www.HepCChallenge.org
June 2009
Clinical Trials, Cohort Studies, Pilot Studies 1-8
Basic and Applied Science, Pre-Clinical Studies 8-12
HIV/HCV Coinfection 12-17
Complementary and Alternative 17
Epidemiology, Diagnostics & Miscellaneous Works 17-31
Clinical Trials, Cohort Studies, Pilot Studies
Response to
therapy with pegylated interferon and ribavirin for chronic hepatitis C in
hispanics compared to non-hispanic whites. Yu S, Douglass
JM, Qualls C, Arora S, Dunkelberg JC. Am J Gastroenterol. 2009 May 12. [Epub
ahead of print]
OBJECTIVES: Ethnicity has been shown to play an important role in hepatitis C virus
(HCV) treatment response. However, few studies have examined the treatment
response of Hispanics to combination therapy with pegylated interferon and
ribavirin. The aim of this study was to compare the treatment responses of
Hispanics and non-Hispanic whites (NHW) treated with pegylated interferon and
ribavirin for chronic HCV. METHODS: A retrospective review was conducted
of all treatment-naive Hispanics and NHW with HCV who were treated at the
University of New Mexico Hospital or Albuquerque VA Medical Center between
October 2001 and January 2007. Genotype 1 patients received 48 weeks of therapy
with pegylated interferon and ribavirin; genotype 2 and 3 patients received 24
weeks of treatment. RESULTS: A total of 396 patients were included in
the analysis, consisting of 179 Hispanics and 217 NHW. Overall, fewer Hispanics
completed therapy compared with NHW (64.8% vs. 80.2%, P<0.001). In genotype
1 patients, early virologic response (EVR), end-of-treatment response (ETR),
and sustained virologic response (SVR) did not differ significantly between the
two ethnic groups. In genotype 2 and 3 patients, Hispanics had similar EVR
compared with NHW (81.3% vs. 88.2%, P=0.25), but lower ETR (64.1% vs. 83.1%,
P=0.01) and SVR (45.3% vs. 75.3%, P<0.001). After correcting for patients
who prematurely discontinued therapy, genotype 2 and 3 Hispanics continued to
have a reduced SVR compared with NHW (65.9% vs. 87.3%, P=0.014). The attenuated
SVR in Hispanics was because of a higher relapse rate after achieving ETR
compared with NHW (25% vs. 7.5%, P=0.02).CONCLUSIONS: Hispanics with
genotype 2 and 3 HCV infection treated with pegylated interferon and ribavirin
are less likely to achieve SVR compared with NHW. The lower rate of SVR in
Hispanic patients is, in part, because of an increased rate of relapse after
ETR.
Positive and
negative prediction of sustained virologic response at weeks 2 and 4 of
treatment with albinterferon alfa-2b or peginterferon alfa-2a in
treatment-naďve patients with genotype 1, chronic hepatitis C. Neumann AU, Pianko S, Zeuzem S, Yoshida EM, et al. J Hepatol. 2009 Mar
11. [Epub ahead of print]
BACKGROUND/AIMS: Albinterferon alfa-2b is a novel, long-acting, fusion polypeptide that
is dosed q2wk or q4wk. The predictive value of early virologic response during
albinterferon alfa-2b or peginterferon alfa-2a treatment was investigated in
interferon-naďve patients with genotype 1, chronic hepatitis C. METHODS:
Four hundred and fifty-eight patients were randomized to: albinterferon 900 or
1200mug q2wk, or 1200mug q4wk, or peginterferon 180mug qwk. HCV RNA was
measured by real-time PCR. A linear exhaustive search algorithm was used to
determine the best SVR prediction algorithm in the per-protocol population
(n=368), with inclusion of key ITT analyses to assess impact. RESULTS:
SVR rate: 54-67% (P=NS between arms). Rapid initial virologic response rate at
week 2 (RIVR; viral decline >2log(10)IU/mL) was 32-50% and gave rise to
positive predictive value of 88-97% for SVR. No initial virologic response at
week 4 (NIVR; viral decline <2log(10)IU/mL; viral load >5.5log(10)IU/mL)
demonstrated a 100% negative predictive value for SVR. A sequential prediction
algorithm based on viral kinetics at weeks 2 and 4 identified four prediction
groups that reliably predicted SVR, positively or negatively, in 65-72% of
patients. CONCLUSIONS: Improved SVR prediction was obtained by
integrating absolute levels and reduction of HCV RNA at treatment week 2 and 4.
Patients with RIVR had a high likelihood of achieving SVR.
Overestimation
of liver fibrosis staging using transient elastography in patients with chronic
hepatitis C and significant liver inflammation. Vispo E, Barreiro P, Del Valle J, et al.
Antivir Ther. 2009;14(2):187-93.
BACKGROUND: Transient elastography (TE) is a non-invasive method that allows liver
fibrosis staging on the basis of hepatic stiffness measurements. Little is
known about the influence of chronic liver inflammation on the stiffness of
hepatic tissue. METHODS: A total of 112 patients with chronic hepatitis
C underwent a liver biopsy and TE. RESULTS: Mean values of liver
stiffness (in kPa) by inflammation strata were 4.8, 6.4, 9.4 and 12.6 for A0,
A1, A2 and A3, respectively, in hepatitis C virus (HCV)-monoinfected
individuals (P=0.018). These figures were 8.0, 10.4, 12.9 and 12.6 for A0, A1,
A2 and A3, respectively, in HIV-HCV-coinfected patients (P=0.35). In
HCV-monoinfected patients with fibrosis staging F3-F4, mean liver stiffness was
greater if inflammation was >/=A2 versus A0-A1 (14.6 versus 6.2 kPa;
P=0.04). By contrast, no differences in liver stiffness according to
inflammation were seen in HCV-monoinfected patients with <F3 or in
HIV-HCV-coinfected patients regardless of liver fibrosis staging. Among
HCV-monoinfected patients, mean liver stiffness was greater for alanine
aminotransferase >100 versus <100 IU/l (10.5 versus 8.5 kPa; P=0.04).
CONCLUSIONS: The extent of liver inflammation might affect the accuracy of
TE for staging liver fibrosis, particularly in HCV-monoinfected patients with
advanced fibrosis on liver biopsy and/or increased alanine aminotransferase
levels.
Epidemiological,
immunological and clinical characteristics of acute hepatitis C. Boykinova OB, Stoilova YD, Tsvetkova TZ, Baltadjiev IG. Folia Med
(Plovdiv). 2009 Jan-Mar;51(1):61-9.
The aim of the study was to make a clinical and epidemiological and
immunological characteristic of patients with acute hepatitis C infection
(AHC). PATIENTS AND METHODS: The study included 178 patients with AHC;
they were studied in terms of clinical course, biochemical constellations, T
and B lymphocyte subpopulations, level of TNF-alpha in the blood serum,
presence of autoantibodies, and the outcome of the disease in a five-year
follow-up period. Methods: anti-HCV (EIA), HCV-RNA (PCR), HCV genotyping; ALT,
AST, AP, gamma-GT; ultrasonography and liver biopsy. RESULTS: AHC
incidence increased six-fold between 2000 and 2006. The prevalence of the
disease among intravenous drug-users (IDUs) was 46.07%. Young people (31.71 +/-
1.21) and males (67.98%) were prevalent. The genotype HCV-1 was prevalent. AHC
ran with icterus in 70.22% of all cases, while it was anicteric in 29.78%;
ALT-activity was high--it was mean 1007.94 +/- 59.87 U/l; intrahepatic
cholestasis was found in 38.80%. A light form of the disease was found in
43.26%, mild--in 50.56%, and severe--in 6.18%, without reaching acute liver
failure. In the acute stage of the disease, an increase of helper/inducer
CD3+CD4+ (p = 0.001), memory T helper CD4+CD29+ (p < 0.0001), activated
CD3+HLA-DR+ (p <0.0001), mature CD3+ T cells (p < 0.05), naive CD2+T (p
< 0.01), and B-lymphocytes CD19+ (p < 0.001) was found, together with a
non-significant increase of the suppressor/cytotoxic CD3+CD8+ T lymphocytes in
comparison with the controls. The total killer CD56+ were reduced, as well as
the MHC restricted killer cells CD8+CD56+. TNF-alpha was elevated in the serum
in the light and mild forms (p < 0.0001). The participation of non-organ-specified
antibodies (NOSAs) was minimal. Anti-MLA titer was 1/80 in two patients. Five
years after the outset of AHC, a spontaneous viral clearance was established in
36.67% and chronic hepatitis in 63.33%. CONCLUSION: Despite the
initially activated immune cellular response strongly correlating with a well
expressed cytolytic syndrome around 2/3 of the AHC patients develop a chronic
form of the disease.
Weight
related effects on disease progression in the hepatitis C antiviral long-term
treatment against cirrhosis trial. Everhart JE, Lok AS, Kim HY, Morgan TR, et
al. Gastroenterology. 2009 May 12. [Epub
ahead of print]
BACKGROUND
AND AIMS: With the limited efficacy of current therapy for chronic
hepatitis C, modifiable risk factors for liver disease progression are
important to identify. Because obesity is associated with liver disease, we
examined the effects of weight related conditions on disease outcomes in the
HALT-C trial. METHODS: Of 1050 patients, 985 could be evaluated for
pre-defined progression of liver disease not related to hepatocellular
carcinoma. Clinical outcomes were determined over 3.5 years for all patients
and progression to cirrhosis on protocol biopsy among patients who had bridging
fibrosis (56.5% of cohort) at entry. RESULTS: At study entry, median BMI
was high (29.2 kg/m(2)) and accompanied by other weight related conditions,
including diabetes (24.9%), high median waist circumference, and insulin
resistance (by HOMA 2 IR). Among non-invasive measures, HOMA 2 IR was most
strongly associated with outcomes with hazard ratio (HR) of 1.26 per quartile
increase (95% confidence interval (CI) 1.09-1.45). Presence of steatosis on
baseline biopsy was associated with an increased outcome rate among patients
with bridging fibrosis (p <0.0001) and a decreased rate among patients with
cirrhosis (p = 0.006). Presence of Mallory bodies was associated with outcomes
(HR = 1.59, 95% CI 1.10-2.31) as was significant weight change of at least 5
percent in the first year after randomization (HR=1.25 per category increase in
weight, 95% CI 1.01-1.55). CONCLUSIONS: Insulin resistance, histological
features of fatty liver disease, and weight change were associated with
outcomes of chronic hepatitis C. Improvement in these weight related factors
might modify disease progression.
Evaluation of
VCH-759 monotherapy in hepatitis C infection. Cooper C, Lawitz EJ, Ghali P, Rodriguez-Torres M, et al. J Hepatol. 2009
Apr 23. [Epub ahead of print]
BACKGROUND: VCH-759 is a non-nucleoside inhibitor of HCV RNA-dependent polymerase
with sub-micromolar IC(50) values versus genotype 1a/1b replicons. METHODS:
The antiviral activity, pharmacokinetics and tolerability of VCH-759
administered as monotherapy for 10 days with a 14 day follow-up period were
evaluated in 31 treatment-nai ve genotype 1 participants. Three cohorts
received: 400mg thrice (t.i.d.), 800mg twice (b.i.d.), 800mg t.i.d or placebo. RESULTS:
VCH-759 was well tolerated with the most frequent adverse event being
gastrointestinal upset in both the active and placebo groups attributable, in
part, to the dosing vehicle. VCH-759 was rapidly absorbed and trough plasma
levels were at or above the IC(90) (non protein-adjusted) for all dosing
regimens. The mean maximal decrease in HCV RNA log(10) (IU/mL) was 1.97, 2.30
and 2.46 for 400mg t.i.d., 800mg b.i.d. and 800mg t.i.d. doses. Viral
polymerase genotypic sequencing revealed emergence of HCV variants in a
majority of participants that coincided with on-treatment viral rebound. CONCLUSIONS:
VCH-759 was well tolerated and achieved a2 log(10) decline in HCV RNA with
800mg b.i.d. and t.i.d doses. In a subset of participants, viral rebound was
observed and associated with resistant variants. This data supports further
evaluation of VCH-759 in combination with interferon-ribavirin treatment.
Treatment of
hepatitis C virus carriers with persistently normal alanine aminotransferase
levels with peginterferon alpha-2a and ribavirin: a multicentric study. Puoti C, Pellicelli AM, Romano M, et al. Liver Int. 2009 Apr 17. [Epub
ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/19422478?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
Abstract Background/Aims: To evaluate, in clinical practice, the
efficacy and safety of combined antiviral treatment in hepatitis C virus (HCV)
carriers with normal alanine aminotransferase (ALT) levels. Methods: Eighty-eight HCV carriers
with persistently normal ALT levels were enrolled. All patients received
peginterferon (PEG-IFN) alpha-2a 180 mug once weekly plus ribavirin (RBV) 800
mg/day for 24 weeks (HCV-2 and -3) or 1000-1200 mg/day for 48 weeks (HCV-1). Results: Rapid virological response
(RVR) was seen in 66/88 patients (75%): 19/32 HCV-1 (59%), 40/46 HCV-2 (87%)
and 7/10 HCV-3 patients. Younger patients, leaner subjects and patients with
non-1 genotype or lower baseline HCV RNA levels were more likely to achieve an
RVR. Sustained virological response (SVR) was seen in 69/88 patients (78%):
20/32 HCV-1 patients (62%), 41/46 HCV-2 patients (89%) and 8/10 (80%) HCV-3
patients. The overall SVR rate was 88% in patients with RVR (58/66) and 50% in
those without RVR. Conclusions:
The combination of PEG-IFN alpha-2a and RBV produces, in patients with normal
ALT, virological response rates that are comparable or even higher than those
obtained in patients with elevated ALT levels. Thus, we suggest that in
selected cases immediate therapy might be preferred to a 'wait-and-see' policy.
Improvement
of liver function in liver cirrhosis patients after autologous mesenchymal stem
cell injection: a phase I-II clinical trial.
Kharaziha P, Hellström PM, Noorinayer B, et al. Eur
J Gastroenterol Hepatol. 2009 May 16. [Epub ahead of print]
BACKGROUND: End-stage liver disease is a medical problem with high morbidity and
mortality. We have investigated the feasibility, safety, and efficacy of using
autologous mesenchymal stem cells (MSCs) as a treatment. METHODS: Eight
patients (four hepatitis B, one hepatitis C, one alcoholic, and two
cryptogenic) with end-stage liver disease having Model for End-Stage Liver
Disease score >/=10 were included. Autologous MSCs were taken from iliac
crest. Approximately, 30-50 million MSCs were proliferated and injected into
peripheral or the portal vein. Liver function and clinical features were
evaluated at baseline and 1, 2, 4, 8, and 24 weeks after injection. RESULTS:
Treatment was well tolerated by all patients. Liver function improved as
verified by the Model for End-Stage Liver Disease score, which decreased from
17.9+/-5.6 to 10.7+/-6.3 (P<0.05) and prothrombin complex from international
normalized ratio 1.9+/-0.4 to 1.4+/-0.5 (P<0.05). Serum creatinine decreased
from 114+/-35 to 80+/-18 mumol/l (P<0.05). Serum albumin changed from 30+/-5
to 33+/-5 g/l and bilirubin from 46+/-29 to 41+/-31 mumol/l. No adverse effects
were noted. CONCLUSION: Our data show that MSCs injection can be used
for the treatment of end-stage liver disease with satisfactory tolerability.
Furthermore, this treatment may improve clinical indices of liver function in
end-stage liver disease.
Association
of hepatitis C virus seropositivity with inflammatory markers and heart failure
in persons with coronary heart disease: data from the heart and soul study. Tsui JI, Whooley MA, Monto A, Seal K, Tien PC, Shlipak M. [ ]5: J Card
Fail. 2009 Jun;15(5):451-6. Epub 2009 Feb 10.
BACKGROUND: How hepatitis C virus (HCV) affects coronary heart disease (CHD) risk
factors and outcomes is largely unknown. METHODS AND RESULTS: Among a
cohort of patients with stable CHD, we examined the association between HCV
seropositivity and levels of inflammatory markers (C-reactive protein [CRP],
fibrinogen, interleukin-6, and tumor necrosis factor [TNF]-alpha) and risk for
the following outcomes: death, cardiovascular (CV) events, and heart failure
events. A total of 84 (8.6%) participants were found to be seropositive for
HCV. HCV-seropositive patients were found to have significantly lower adjusted
mean levels of CRP (2.6 vs. 4.4; P < .01) and fibrinogen (340 vs. 398; P
< .01), but higher levels of TNF-alpha (7.1 vs. 4.8; P < .01).
Age-adjusted rates for HCV seropositive vs. seronegative were as follows: death
93 vs. 42/1,000p-y (P < .01), CV events 62 vs. 40 (P=.13), and heart failure
76 vs. 29 (P < .01). After adjustment for demographic and clinical factors,
HCV remained significantly associated with an increased risk for heart failure
events (HR=2.13; 95% CI: 1.19-3.80). CONCLUSIONS: In this cohort with
CHD, HCV seropositive participants had higher rates of death, CV events, and
heart failure hospitalizations during follow-up. After adjustment for CV risk
factors, HCV seropositivity remained independently associated with risk for
heart failure events.
Peginterferon
alpha-2b and ribavirin for the treatment of chronic hepatitis C in Japanese
pediatric and young adult patients: a survey of the Japan Society of Pediatric
Hepatology.
Tajiri H, Inui A, Kiyohara Y, Suzuki M, Kagimoto S, Etani Y, Shimizu T,
Fujisawa T. Eur J Gastroenterol Hepatol. 2009 May 23. [Epub ahead of print]
OBJECTIVES: Only a few studies on the treatment with peginterferon-2b and ribavirin
are available in children with chronic hepatitis C virus (HCV). The aim of this
study was to evaluate both the efficacy and the safety of the treatment in
Japanese children and young adults. METHODS: Twenty-two of 41 members of
the Japan Society of Pediatric Hepatology reported on 37 cases who were treated
with peginterferon and ribavirin. RESULTS: Of the 37 patients, 29 have
completed the treatment and all of them cleared the HCV virus. Three patients
are still being treated, whereas the remaining five failed to complete the
treatment. Cessation of the treatment was because of the nonresponsiveness
(n=3), the expense of the treatment (n = 1), or lethargy (n=1). After excluding
the three patients, who were continuing the treatment and one who has not
completed the 24-week follow-up period, from the 37 patients, 33 were available
for sustained virologic response (SVR) analysis. After 4 weeks of follow-up,
one of the 33 relapsed. An intention-to-treat analysis showed that 27 of the 33
(81.8%) achieved a SVR. The only factor significantly associated with SVR was
their virologic response status at week 4. CONCLUSION: The results
showed that the present patients infected with HCV and treated with
peginterferon-2b and ribavirin achieved a remarkably high SVR rate. In
addition, most of the patients achieved a SVR once they showed a virologic
response at week 4. The combination of peginterferon-alpha with ribavirin may
be considered as a standard therapy for children and young adults.
Multiple
cytokine profiling of the therapeutic responses to ribavirin and pegylated
interferon-alpha2b using an "induction" approach with natural
interferon-beta in difficult-to-treat chronic hepatitis C. Kishida Y, Haruna Y, Naitoh M, Katayama K, Kashiwagi T. J Interferon
Cytokine Res. 2009 Jun;29(6):353-68.
Cyclic and periodic IFN treatment (CPIT) consisting of induction
treatment with nIFN-beta followed by maintenance treatment with IFN-alpha could
prevent viral breakthrough and achieve rapid virological response (RVR) and
early virological response (EVR) in chronic hepatitis C (CHC). The efficacy and
immune response of RBV+PEG-IFN-alpha2b using induction approach with CPIT
(novel combination treatment: NCT) in 7 CHC patients with genotype 1b and high
viral load were evaluated. A biometric multiplex serum cytokine assay was utilized
to characterize the immunomodulatory effect. RVR and EVR were 7/7 and 7/7,
respectively. Viral titers dropped below detectable levels in five patients
with sustained virological response (SVR) before the end of CPIT (early
virological responder: EAVR), and two patients without SVR after the end of
CPIT (late virological responder: LAVR). At baseline, in EAVR compared with the
controls, IL-6 and IL-15, CXCL-8 and CXCL-10 levels were significantly higher
(P < 0.05); IL-10 and IL-13 levels were significantly lower (P < 0.05);
and the IL-12 level was lower. In LAVR, GM-CSF, CXCL-8 and CXCL-10, and CCL-4
levels were significantly higher (P < 0.05); and IL-10 and IL-12 were lower
than the controls. In EAVR but not LAVR, the IL-12 increased and the CCXL-8 decreased
significantly (P < 0.05). In conclusion, NCT-induced viral clearance leading
to improvement in the innate immune response resulting in SVR in CHC with
genotype 1b and high viral load.
Short-term
prolongation of pegylated interferon and ribavirin therapy for genotype 1b
chronic hepatitis C patients with early viral response. Ikeda H, Suzuki M, Okuse C, Yamada N, Okamoto M, Kobayashi M, Nagase Y,
et al. Hepatol Res. 2009 May 7. [Epub
ahead of print]
Aim: We tailored extended treatments using
pegylated interferon (PEG IFN) and ribavirin (RBV) to viral responses after
initiation of therapy and investigated the efficacy and safety of its therapy
for chronic hepatitis C (CHC) patients. Methods:
Eighty-two genotype 1b CHC patients were enrolled in the present study. All
patients received PEG IFN-alpha-2b and weight-based RBV therapy. We defined a
viral response in which serum HCV-RNA is undetectable at week 4 as rapid viral
response (RVR), detectable at week 4 and undetectable by week 12 as early viral
response (EVR), and detectable at week 12 and undetectable by week 24 as late
viral response (LVR). We set the treatment duration depending on viral
response; 48 weeks for RVR patients and 72 weeks for LVR. Furthermore, EVR
patients received a short-term extension of treatment duration to 52-60 weeks.
We prospectively investigated sustained viral response (SVR) rates of these
groups. Results: Overall
SVR rate for the total patient group was 57.3%. SVR rates of the RVR, EVR and
LVR patients were 100%, 80.5% and 40.0%, respectively. Nine patients could not
complete this treatment protocol. Baseline platelet count and mutation in the
interferon sensitivity-determining region of NS5A were significant independent
predictors of SVR, and amino acid substitution of the core region was a
significant independent predictor of non-viral response by multivariate
logistic regression analyses. Conclusion:
The results indicate that short-treatment extension of PEG IFN plus RBV
treatment protocols in EVR patients can improve overall SVR rates.
Interleukin
18 promoter variants (-137G>C and -607C>A) in patients with chronic hepatitis
C: Association with Treatment Response. Haas SL,
Weiß C, Bugert P, Gundt J, Witt H, Singer MV, Berg T, Böcker U. J Clin Immunol. 2009 May 20. [Epub ahead of
print]
BACKGROUND: Recently, two functional IL18 promoter variants, -607C>A (rs1946518)
and -137G>C (rs187238), were associated with viral clearance in patients
with hepatitis C. The present study focused on their relevance for treatment
response. METHODS: Seven hundred fifty-seven chronically infected
European patients and 791 controls were enrolled in the study. IL18 genotyping
was performed by allele-specific PCR. Liver histology was available in 67.9%. RESULTS:
Genotype and allele frequencies were equally distributed in patients and
controls. No significant association with various disease characteristics was
observed. However, when comparing patients with sustained virological response
(SR) and non-SR, statistically significant associations were found for both
variants (p = 0.0416 and p = 0.0274, respectively). In viral genotype 1, the
-607A allele was positively associated with treatment response (p = 0.0190; OR
1.537; 95% CI, 1.072-2.205) and the -137G allele with a higher rate of
nonresponse (p = 0.0302; OR 1.524; 95% CI, 1.040-2.233). CONCLUSIONS:
The association of IL18 variants with treatment response in genotype 1
hepatitis C patients implies a predictive and modifying role of these genetic
variants.
Effects of smoking on survival for patients with end-stage liver
disease. Lee
DS, Mathur AK, Acker WB 2nd, et al. [ ]6: J Am Coll Surg. 2009
Jun;208(6):1077-84. Epub 2009 Apr 24.
BACKGROUND: Smokers with chronic liver disease can become eligible for
transplantation, but some insurers refuse reimbursement pending smoking
cessation. STUDY DESIGN: Our
hypothesis is that liver transplantation candidates and recipients who smoke
have inferior survival compared with nonsmokers. Using a retrospective cohort
study design, three Cox proportional hazards models were constructed to
determine covariate-adjusted mortality from transplantation evaluation and
transplantation based on smoking status at evaluation, transplantation, and
posttransplantation followup. RESULTS:
From 1999 to 2007, 2,260 patients were evaluated. Seven hundred sixty were
active smokers, and 1,500 were nonsmokers. Smokers at evaluation were younger
(49.3 versus 51.7 years), were more likely to be men (65.9% versus 58.7%), have
hepatitis C (54.2% versus 30.1%), have a lower Model for End-Stage Liver
Disease score (10.5 versus 12.3), and less likely to receive transplant (12.2%
versus 18.6%) (all p < 0.05). The postevaluation multivariate model
indicated that substance use, higher Model for End-Stage Liver Disease score, hepatitis
C, and older age increased mortality risk (all p < 0.05), and liver
transplantation (hazards ratio = 0.986; 95% CI, 0.977 to 0.994) was associated
with lower mortality. Smoking was not associated with increased mortality risk
at any time point in those evaluated or receiving transplants. CONCLUSIONS: Providers should continue
encouraging potential liver transplantation candidates to stop smoking, but
insurer-driven mandated smoking cessation might not improve survival.
Basic and Applied Science, Pre-Clinical Studies
Novel serum markers of fibrosis progression for the follow-up of hepatitis
C virus-infected patients. Caillot F, Hiron M, Goria O, et al. [ ]4: Am J Pathol. 2009 May
28. [Epub ahead of print]
Liver biopsy
is considered the gold-standard method for the assessment of liver fibrosis
during follow-up of hepatitis C virus-infected patients, but this invasive
procedure is not devoid of complications. The aim of the present study was to
identify novel non-invasive markers of fibrosis progression. By microarray
analysis, we compared transcript levels in two extreme stages of fibrosis from
16 patients. Informative transcripts were validated by real-time PCR and used
for the assessment of fibrosis in 23 additional patients. Sixteen transcripts
were found to be dysregulated during the fibrogenesis process. Among them, some
were of great interest because their corresponding proteins could be
serologically measured. Thus, the protein levels of inter-alpha inhibitor H1,
serpin peptidase inhibitor clade F member 2, and transthyretin were all
significantly different according to the four Metavir stages of fibrosis. In
conclusion, we report here that dysregulation, at both the transcriptional and
protein levels, exists during the fibrogenesis process. Our description of
three novel serum markers and their potential use as serological tests for the
non-invasive diagnosis of liver fibrosis open new opportunities for better
follow-up of hepatitis C virus-infected patients.
Diabetes pattern on the 75 g oral glucose tolerance test is a risk
factor for hepatocellular carcinoma in patients with hepatitis C virus. Konishi I,
Hiasa Y, Shigematsu S, et al. Liver Int. 2009 Apr 17. [Epub ahead of print]
Abstract Background: Patients
with hepatitis C virus (HCV) frequently show glucose intolerance. Diabetes
mellitus (DM) has been proposed to be a risk factor for hepatocellular
carcinoma (HCC). Aims: The aim of this study is to clarify the influence
of glucose intolerance as evaluated by the 75 g oral glucose tolerance test
(OGTT) on hepatocarcinogenesis in patients with HCV. Methods: This study
was carried out in a cohort of 197 patients with HCV who had not been
previously diagnosed as having DM. All patients underwent the 75 g OGTT at
entry. They were also screened for HCC and, thereafter, the rate of
hepatocarcinogenesis was compared between the patients with and without glucose
intolerance. Results: Based on the results of the 75 g OGTT, 125 (63%)
had normal glucose tolerance (NGT), 49 (25%) had impaired glucose tolerance
(IGT) and 23 (12%) had the DM pattern. HCC occurred more frequently in patients
with the DM pattern than in patients with either NGT or IGT. Even in patients
without advanced liver fibrosis, HCC was more frequently observed in patients
with DM than in patients with NGT. A multiple logistic regression analysis
showed advanced liver fibrosis, the DM pattern on the 75 g OGTT, an older age
and gamma-glutamyltransferase to all be independent risk factors related to
hepatocarcinogenesis. Conclusions: A DM pattern on the 75
g OGTT was thus found to be associated with hepatocarcinogenesis and the 75 g
OGTT is considered to be useful for identifying this risk factor for HCC in
patients with HCV.
Progress towards improving antiviral therapy for hepatitis C with
hepatitis C virus polymerase inhibitors. Part I: Nucleoside analogues. Brown NA. Expert
Opin Investig Drugs. 2009 May 9. [Epub ahead of print]
Background: With an
increasing worldwide burden of liver failure and liver cancer from chronic
hepatitis C virus (HCV) infection, discovery and development efforts for new antiviral
medicines for HCV are expanding rapidly. Two HCV protease inhibitors (PIs),
telaprevir (VX950) and boceprevir (SCH503034), are now furthest along in
clinical development, with Phase II data suggesting a potential treatment
advance with triple combination regimens comprising a protease inhibitor,
pegylated interferon and ribavirin. However, the current data suggest that such
regimens will fail to produce sustained virologic responses in >/= 30 - 40%
of patients, and tolerance of interferon/ribavirin treatment regimens is often
problematic; hence, there is a need for continued development of new anti-HCV
agents to further optimize treatment efficacy and safety. The HCV polymerase
(HCV Pol) is an attractive target for antiviral therapy because the gene sequences
encoding HCV Pol are relatively conserved across the six main HCV genotypes and
the emergence of viral resistance is expected to be relatively slow for
pharmaceutical agents, such as nucleoside analogues, that are targeted to the
active (catalytic) site of HCV Pol. Methods: This review (Part I) of
HCV Pol inhibitors focuses on the scientific rationale and recent development
progress for nucleoside-type HCV Pol inhibitors; a subsequent review (Part II)
will assess progress with non-nucleosidic HCV Pol inhibitors. Results/conclusions:
Early clinical data for several nucleosides targeted to HCV Pol indicate marked
antiviral effects and a likelihood of relatively slow HCV resistance,
consistent with the profile of nucleosidic inhibitors of HIV and hepatitis B
virus infection and supporting potentially important roles for nucleoside
agents in optimizing combination therapies for HCV infection. Optimally
effective future anti-HCV therapies are likely to be based on multi-class
treatment regimens combining polymerase and PIs, together with pegylated
interferon and ribavirin or pharmaceutical agents from other mechanistic
classes.
Prediction of asymptomatic cirrhosis in chronic hepatitis C
patients: accuracy of artificial neural networks compared with logistic
regression models. Cazzaniga M, Salerno F, Borroni G, Ceriani R, Stucchi G, et al. Eur
J Gastroenterol Hepatol. 2009 Jun;21(6):681-7.
OBJECTIVE: Models based on logistic regression analysis are proposed as
noninvasive tools to predict cirrhosis in chronic hepatitis C (CHC) patients.
However, none showed to be sufficiently accurate to replace liver biopsy.
Artificial neural networks (ANNs), providing a prediction based on nonlinear
algorithms, can improve the diagnosis of cirrhosis, a syndrome characterized by
complex, nonlinear biological alterations. We compared ANNs with two logistic
regression analysis-based models in predicting CHC histologically proven
cirrhosis. METHODS: Liver biopsy was
obtained in CHC patients of two different cohorts (an internal cohort including
244 patients and an external cohort including 220 patients). One hundred and
forty-four patients from the internal cohort served as a training set to
construct ANNs and a logistic regression model (LOGIT). These two models and
the aspartate aminotransferase-to-platelet ratio index (APRI) were tested in
the remaining 100 patients (internal validation set) and in the external cohort
(external validation set). Diagnostic performances were evaluated by standard
indices of accuracy. RESULTS: In the
internal validation set, ANNs, LOGIT, and APRI showed similar discrimination
powers (0.88, 0.87, and 0.87 respectively). However, ANNs showed the best
positive predictive value (0.86 vs. 0.67 and 0.56) and positive likelihood
ratio (40.2 vs. 13.4 and 8.4). In the external validation set, the
discrimination power of ANNs (0.76) was significantly higher than those of
LOGIT (0.67) and APRI (0.67). CONCLUSION:
Compared to conventional models, ANNs performance in predicting CHC cirrhosis
is slightly better and more reproducible.
T(CD8) response in diverse outcomes of recurrent exposure to
hepatitis C virus. Bharadwaj M, Thammanichanond D, Aitken CK, et al. Immunol Cell
Biol. 2009 May 12. [Epub ahead of print]
To analyse the immune correlates in a setting of recurrent exposure to
hepatitis C virus (HCV), we studied T(CD8) responses in injecting drug users
(IDUs) with different disease outcomes. Ex vivo HCV-specific T(CD8) responses
assessed by interferon-gamma (IFNgamma) enzyme-linked immunospot (ELISPOT) were
comparable in human lymphocyte antigen (HLA)-matched IDUs with spontaneous HCV
clearance or persistent infection. A detailed characterization of these T(CD8)
cells in age and HLA-matched IDUs demonstrated that HCV clearance and
protection from reinfection correlated with HCV-specific T(CD8) cells that
could proliferate in vitro, possessed cytotoxic potential and produced IFNgamma
and tumour-necrosis factor-alpha, rather than with the circulating frequency of
responding T(CD8) cells determined ex vivo. While validating the importance of
multifunctional T(CD8) in mediating protection in IDUs with recurrent exposure
to HCV our findings highlight that the magnitude and/or breadth of HCV-specific
T(CD8) determined in ex vivo ELISPOT may not be the sole determinant of
protection especially in a setting of recurrent exposure.
Circulating levels of interferon-gamma in course of hepatitis C
virus-related arthritis.
Tarantino G,
Sabatini P, Soriente I, Amato P, Sangiolo MG, Riccio A. J Interferon Cytokine
Res. 2009 May 18. [Epub ahead of print]
The aim was to weigh the serum concentrations of interferon gamma
(IFN-gamma), a cytokine that enhances Th1-cell differentiation and suppresses
collagen synthesis and angiogenesis, in two apparently distinct diseases,
hepatitis C virus-related arthritis (HCVrA) and rheumatoid arthritis (RA),
which share some overlapping immunological features. In this study, IFN-gamma
serum levels were assayed by an ELISA method in 21 HCVrA patients and in 16
with RA. Very low IFN-gamma serum levels were found in five out of 21 patients
with HCVrA and only in three out of 16 RA patients. Median value (range)
resulted decrease in both HCVrA and RA groups, that is, 0.29 (0.04-1.49) versus
0.20 (0.05-1.18) IU/mL), P = 0.58. No correlation was evidenced with hepatic
and arthritic involvements, nor between IFN-gamma serum levels and viral
replication and moreover with the positivity of antinuclear antibody,
rheumatoid factor, and anti-cyclic citrullinated peptides antibodies. These results show that IFN-gamma
behavior appears similar in HCVrA and RA groups reinforcing the lack of
significant differences between HCVrA and RA patients. Low circulating levels
could be explained with the fact that IFN-gamma is not an isolate cytokine, but
a piece of composite system regulated in a complex fashion, with many different
factors contributing.
Modeling hepatitis C virus kinetics: the relationship between the
infected cell loss rate and the final slope of viral decay. Dahari H,
Shudo E, Cotler SJ, Layden TJ, Perelson AS. Antivir Ther. 2009;14(3):459-64.
BACKGROUND: Patients infected with hepatitis C virus (HCV) who respond to
treatment with interferon-alpha plus ribavirin exhibit biphasic or triphasic
viral load decreases. While the rapid first phase is indicative of the
effectiveness of therapy in blocking viral production (epsilon), the slope of
the final phase (lambda), that is, the second phase in biphasic decreases and
the third phase in triphasic decreases, depends on the infected cell loss rate
(delta). In standard models, lambda is approximately epsilondelta when the
viral clearance rate c>>delta, as has been previously estimated. METHODS: The relationship among
epsilon, delta, lambda and the baseline fraction of HCV-infected hepatocytes
(pi) was investigated in a model that included proliferation of hepatocytes. RESULTS: We found that lambda was not
proportional to epsilon, but rather obeyed a complex relationship that could
lead to dramatic increases in estimates of delta as epsilon increased. In
particular, when epsilon<99%, lambda moderately underestimated delta in
patients with a small pi, whereas delta might be up to 10-fold larger than
lambda in patients with a large pi. Interestingly, when epsilon>99%,
delta~lambda regardless of pi. CONCLUSIONS:
Our results indicated that in patients undergoing therapy who achieved a 2
log(10) reduction in viral load (epsilon<99%), previously estimated delta
values might represent only a minimal estimate of the infected cell loss rate.
Moreover, combining interferon-alpha with new antiviral agents to achieve
epsilon>99% should allow for a more accurate estimate of delta in HCV RNA
kinetic studies. This might be important when using viral kinetics to estimate
the effect of the immune response on viral elimination and the attainment of
sustained virological response.
Natural killer cell functional dichotomy in chronic hepatitis B
and chronic hepatitis C virus infections.Oliviero B, Varchetta S, Paudice
E, et al. Gastroenterology. 2009 May 23.
[Epub ahead of print]
BACKGROUND AND AIMS: The phenotypic and functional characteristics of natural killer
(NK) cells in chronic hepatitis B virus (HBV) and hepatitis C virus (HCV)
infections are incompletely defined and largely controversial. METHODS AND RESULTS: We studied NK cell
receptor (NKR) expression, cytotoxic activity and cytokine production in
peripheral blood mononuclear cells (PBMC) from 35 patients with chronic
hepatitis C, 22 with chronic hepatitis B and 30 healthy controls. Patients with
chronic HBV infection had an increased proportion of NKG2C+ NK cells with
normal inhibitory receptor expression and a lower proportion of activated NK
cells compared with HCV+ patients, which was associated with normal or reduced
cytolytic activity and markedly dysfunctional TNF and IFN production. Patients
with chronic HCV infection showed a predominantly activating phenotype,
featuring a decreased percentage of cells expressing the inhibitory receptor KIR3DL1
and a concomitant increase in the proportion of NKG2D+ NK cells. Expression of
the CD69 early activation antigen on NK cells positively correlated with serum
alanine aminotransferase and HCV RNA values, suggesting participation of
virus-induced effector NK cells in liver necroinflammation. Phenotypic changes
in HCV+ patients were associated with enhanced cytokine-induced cytolytic
activity and increased usage of natural cytotoxicity and NKG2D receptor
pathways, accompanied by defective cytokine production, although to a lesser
extent than patients with chronic HBV infection. CONCLUSIONS: These findings provide evidence for a functional
dichotomy in patients chronic HBV and HCV infections, featuring conserved or
enhanced cytolytic activity and dysfunctional cytokine production which may
contribute to virus persistence.
Rifampicin as an oral angiogenesis inhibitor targeting hepatic cancers.
Shichiri
M, Fukai N, Kono Y, Tanaka Y. Cancer Res. 2009 May 19. [Epub ahead of print]
Angiogenesis
is an important therapeutic target in cancer, and to fully exploit its
therapeutic potential, combination chemotherapeutic/antiangiogenic regimens
should be optimized and delivered earlier to more patients. Ideally, this could
be done by a single potent oral agent with established safety. Rifampicin, a
semisynthetic antibiotic derived from the rifamycins, is one of the most
commonly used pharmaceutical compounds worldwide in the treatment of
tuberculosis. Here, we present the effects of oral rifampicin on human cancer
progression and its antiangiogenic properties, which were comparable to the
angiogenesis inhibitor endostatin. Clinically, low-dose p.o. administration of
rifampicin to six high-risk patients with hepatitis C virus-related liver
cirrhosis resulted in a single occurrence of hepatocellular carcinoma during
the follow-up period of 97.3 +/- 29.1 (mean +/- SD) months. Experimentally,
rifampicin rapidly and markedly down-regulated the expression of a wide
spectrum of angiogenesis-associated genes in growing human microvascular
endothelial cells, thereby suppressing endothelial cell proliferation and
migration. Rifampicin, at higher concentrations, also directly inhibited the
growth of a variety of human cancer cells. P.o. administration of rifampicin
significantly inhibited in vivo growth and metastases of subcutaneous human
cancer xenografts. Thus, the potent antiangiogenic properties of oral
rifampicin therapy were effective in suppressing cancer progression. It
provides a promising new addition to antiangiogenic strategies for designing
human cancer therapies. Considering the clinical pharmacokinetics of
rifampicin, which enters the enterohepatic circulation and undergoes subsequent
hepatic accumulation, it may be especially beneficial as an antitumor agent
targeting hepatobiliary tumors.
Toward the back-up of boceprevir (SCH 503034): discovery of new
extended P(4)-capped ketoamide inhibitors of hepatitis C virus NS3 serine protease
with improved potency and pharmacokinetic profiles. Bogen SL, Pan
W, Ruan S, Nair LG, Arasappan A,et al. J
Med Chem. 2009 May 20. [Epub ahead of print]
Hepatitis C
is the most prevalent liver disease. Viral hepatitis C (HCV), a small (+)-RNA
virus, infects chronically an estimated 300 million people worldwide. Results
of Phase I clinical studies with our first generation HCV inhibitor Boceprevir,
SCH 503034 (1), presented at the 56th Annual Meeting of the American
Association for the Study of Liver Diseases (AASLD) were encouraging, and thus,
additional human clinical studies are underway. In view of the positive data
from our first generation compound, further work aimed at optimizing its
overall profile was undertaken. Herein, we report that extension of our earlier
inhibitor to the P(4) pocket and optimization of the P(1)' capping led to the
discovery of new ketoamide inhibitors of the HCV NS3 serine protease with
improved in vitro potency. In addition to being potent inhibitors of HCV
subgenomic RNA replication, some of the new P(4)-capped inhibitors were also
found to have improved PK profile.
HIV/HCV Coinfection
Characteristics
of hepatitis C virus co-infection in a human immunodeficiency virus-infected
population with lower reported rates of injection drug use. Burton MJ, Olivier J, Mena L. Am J Med Sci. 2009 May 26. [Epub ahead of print]
BACKGROUND: Injection drug use (IDU) is considered the major risk factor for human
immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection. We
examined risk factors for HIV/HCV coinfection in a region with a low reported
rate of IDU. METHODS: We identified 146 HIV/HCV coinfected patients in
Jackson, Mississippi. Medical records were reviewed for demographics, social
history, and risk factors for HIV and HCV acquisition. A randomly selected
group of HIV-monoinfected patients from the same clinic served as a control
group. RESULTS: History of IDU (P < 0.0001), crack cocaine use (P
< 0.0001), incarceration (P < 0.0001), and syphilis (P < 0.0001) were
significantly associated with HCV infection in this cohort of HIV patients.
However, the reported rate of IDU (32.5%) is lower than other published HIV/HCV-infected
cohorts. CONCLUSIONS: HIV/HCV patients in Mississippi are less likely to
report a history of IDU than other coinfected populations, suggesting an
alternative means of HCV transmission. Further studies are needed to examine
the role of syphilis, crack cocaine use, and incarceration as risk factors for
HCV infection in this population of HIV patients.
HAART is
associated with lower hepatic necroinflammatory activity in HIV-hepatitis C
virus-coinfected patients with CD4 cell count of more than 350 cells/microl at
the time of liver biopsy. Pascual-Pareja JF, Caminoa A, Larrauri
C, González-García J, Montes ML, Díez J, Grande M, Arribas JR. AIDS. 2009 May
15;23(8):971-5.
OBJECTIVE: To evaluate the impact of HAART on the
liver damage of HIV-hepatitis C virus (HCV)-coinfected patients with relatively
preserved immune status. DESIGN: Cross-sectional study of liver biopsies. METHODS: HIV-HCV-coinfected
patients who underwent liver biopsies and had a CD4 cell count of at least 350
cells/microl at the time of liver biopsy were included. Exclusion criteria
included positive hepatitis B surface antigen and prior anti-HCV therapy.
Necroinflammatory activity and fibrosis was scored by the Scheuer fibrosis
staging system. Steatosis was scored according to the percentage of hepatocytes
affected. Logistic regression analysis was used to assess determinants of
necroinflammatory activity of at least 3. RESULTS:
One hundred and nineteen HIV-HCV coinfected patients were included. In the
univariate analysis, alcohol abuse, serum alanine aminotransferase levels,
steatosis and a high fibrosis score were significantly associated with higher
necroinflammatory activity. In the multivariate analysis, a high level of
alanine aminotransferase, advanced fibrosis and absence of HAART were
associated with higher necroinflammatory activity. CONCLUSION: Use of HAART was associated with lower levels
of necroinflammatory activity. Necroinflammatory activity was strongly
associated with higher fibrosis scores. These results suggest that HAART might
decrease hepatitis C activity in HIV-HCV-coinfected patients with CD4 cell
count of more than 350 cells/microl.
Effect of
antiviral treatment on serum markers of liver fibrosis in HIV-hepatitis C
virus-coinfected patients: the Fibrovic 2 Study - ANRS HC02. Halfon P, Carrat F, Bédossa P, Lambert J, Pénaranda G, Perronne C, Pol S,
Cacoub P. Antivir Ther. 2009;14(2):211-9.
BACKGROUND: Non-invasive liver fibrosis scores have been proposed as alternatives to
liver biopsy (LB) in hepatitis C virus (HCV)-infected patients. Here, we aimed
to assess the effect of antiviral treatment on non-invasive serological markers
of liver fibrosis in HIV-HCV-coinfected patients. METHODS: We included
114 HIV-HCV-coinfected patients with LBs performed before and 6 months after
the end of treatment (week 72; W72). Fibrotest, the Forn's index, age-platelet
ratio index, SHASTA, FIB-4, Hepa-score and Fibrometer scores were assessed.
There were 29 (25%) patients who achieved sustained virological response (SVR).
RESULTS: At baseline (BL), all non-invasive fibrosis scores except the
Forn's index did not show significantly lower values in SVR patients. At W72,
all non-invasive scores, except Hepascore, showed a significant decrease in SVR
patients (P<0.01). There was a significant difference in fibrosis stages on
LBs between BL and W72 in SVR and non-SVR patients. CONCLUSIONS: In
HIV-HCV-coinfected patients, HCV clearance is associated with a significant
reduction in non-invasive fibrosis serological markers, which most likely
reflect the histological improvement associated with SVR. If confirmed, such
results will reinforce the reliability of these markers in the follow-up after
HCV treatment.
Psychiatric
and substance use disorders comorbidities in veterans with hepatitis C virus
and HIV coinfection. Fuller BE, Loftis JM, Rodriguez VL,
McQuesten MJ, Hauser P. Curr Opin Psychiatry. 2009 May 11. [Epub ahead of
print]
PURPOSE OF
REVIEW: A growing number of veterans in theVeterans Health
Administration are coinfected with HIV and hepatitis C virus. This review
covers timely research relative to comorbid conditions that are common in this population
including psychiatric diagnoses, substance use disorders and neurocognitive
problems. RECENT FINDINGS: Current literature on the psychiatric,
substance use disorders and cognitive problems of the coinfected population
show that not only are rates of morbidity higher in the coinfected population
but that this affects antiviral treatments as well. There is new evidence that
brain injuries and infiltration of the virus into the central nervous system
may be responsible for cognitive dysfunction. Cotesting, particularly in
hepatitis C infected individuals, is not done routinely despite shared risk
factors. SUMMARY: With this understanding of the comorbidities of the
coinfected population, integrated healthcare models involving mental health,
internal medicine, substance abuse treatment and internal medicine are crucial
to work with these medically and psychologically complex patients.
Chronic
hepatitis C in patients coinfected with human immunodeficiency virus in Japan:
a retrospective multicenter analysis. Yotsuyanagi H, Kikuchi Y, Tsukada K,
Nishida K, et al. Hepatol Res. 2009 Apr 3. [Epub ahead of print]
Aim: A nationwide survey in Japan revealed that nearly one-fifth of human
immunodeficiency virus (HIV)-positive patients are co-infected with hepatitis C
virus (HCV). We conducted a study to further analyze the features of liver
disease in HIV-HCV co-infected patients. Methods:
We analyzed 297 patients from eight hospitals belonging to the HIV/AIDS Network
of Japan. Results: HCV
genotypes 1, 2, 3, 4 and mixed genotypes were detected in 55.2, 13.7, 18.9, 0.9
and 11.3% of patients, respectively, in contrast to the fact that only
genotypes 1 and 2 are detected in HCV mono-infected patients in Japan. This is
compatible with the transmission of HCV through imported blood products
contaminated by HCV. Sixteen of 297 HIV-HCV co-infected patients had advanced
liver disease accompanied by ascites, hepatic encephalopathy or hepatocellular
carcinoma. The average age of such patients was 41.1 +/- 14.0 years, which was
much younger than that of HCV mono-infected patients with the same
complications. The progression speed of liver disease estimated from the
changes in the levels of serum albumin, bilirubin, or platelet was slower in
patients who achieved sustained virological response with interferon treatment
than in those who did not receive it. The overall sustained virological
response rate to interferon treatment was 43.3%. Conclusions: Our findings suggest that liver disease is
more advanced in HIV-HCV co-infected patients than in HCV mono-infected
patients, and interferon treatment may retard the progression of liver disease
in such patients.
HCV treatment
decision-making substance use experiences and hepatitis C treatment
decision-making among HIV/HCV coinfected adults. Fink Ogawa LM, Bova C. Subst Use Misuse. 2009 May 13:1. [Epub ahead of
print]
Hepatitis C virus (HCV) infection is a major source of morbidity and
mortality among substance users and persons living with human immunodeficiency
virus (HIV) infection. Treatment for chronic HCV infection involves complex
decision-making. These decisions are even more complicated in persons with HIV
and substance use related problems. A secondary analyses of qualitative data
collected in the United States (2004-2005) with 31 HIV/HCV coinfected adults
(48% women; mean age 44.7 years) revealed three themes related to substance use
(substance use evolution, revolving door: going back out and reconstructing
life) and two HCV treatment decision-making themes (HCV infection treatment
issues: not a priority, fear, misinformation and get clean and try it). Study
limitations and implications are discussed.
Kidney
diseases in HIV/HCV-coinfected patients. Izzedine
H, Sene D, Cacoub P, Jansen H, Camous L, Brocheriou I, Bourry E, Deray G. AIDS.
2009 May 12. [Epub ahead of print]
BACKGROUND: Hepatitis C virus (HCV) co-infection
occurs in 25% of HIV-infected persons. The impact of HIV/HCV coinfection on
renal and patient outcomes is unclear.
METHODS: The main objective of the study is the comparison of
outcomes (progression to advanced renal failure, initiation of dialysis, and
death) in patients with HIV (n = 40), HCV (n = 30) or coinfection (n = 30)
during the period between January 1999 and December 2007. RESULTS: Patients were
predominantly white men with a mean creatinine clearance of 50.6 +/- 32.2 ml
per min per 1.73 m. Membranoproliferative glomerulonephritis (MPGN) and
HIV-associated nephropathy were found in 34 and 9%, respectively. Seventeen
patients needed transitory or definitive hemodialysis after 2, 2.5, and 12
months in HIV/HCV (n = 5), HIV (n = 6) and HCV (n = 6) infections,
respectively. In multivariate analysis, variables found to independently
predict outcome in HIV/HCV coinfected patients were younger age, a longer delay
to kidney biopsy, cryoglobulinemia and MPGN. Twenty-one patients died, mostly
in the HCV (n = 8) and/or HIV/HCV coinfected (n = 12) groups. The relative risk
of death for HIV/HCV co-infected patients was 2.1 times more than for
HCV-infected patients and 7.5 times more than for HIV-infected patients.
HIV/HCV co-infection [odds ratio (OR), = 4; 95% confidence interval (CI),
1.3-12.9; P = 0.015] and MPGN (OR, 6; 95% CI, 2-18.8; P = 0.0018) were
independently associated with death. CONCLUSION: Kidney disease is a
relatively frequent complication in HIV or HCV monoinfected individuals. The
impact of kidney disease on survival of HIV/HCV coinfected patients seems
deleterious but remains largely unknown.
Long-term
outcomes after treatment with interferon and ribavirin in HCV patients. Aronsohn A, Reau N. J Clin Gastroenterol. 2009 May 14. [Epub ahead of
print]
Hepatitis C is a leading indication for transplantation and a common
cause of liver-related death worldwide. Treatment for hepatitis C has evolved
from interferon therapy alone, which yielded relatively poor response rates
compared with the currently recommended and more effective combination of
pegylated interferon and ribavirin. Factors such as hepatitis C viral genotype,
pretreatment viral load, race, renal function, degree of hepatic fibrosis, and
comorbid conditions such as HIV coinfection have clinical importance in that
they influence viral kinetics, which play a large role in determining a
sustained response to therapy or virologic "cure." However, the goal
of therapy is to reduce liver-related morbidity and mortality by decreasing
rates of progression or improvement of fibrosis, reducing risk of
hepatocellular carcinoma, improving posttransplant graft and patient survival,
and resolving or improving some of the extrahepatic manifestations of hepatitis
C. Studies generally infer long-term success from the more tangible goal of
sustained viral suppression; however, increasing data suggest that effective
therapy does result in decreased morbidity and mortality. Given the
heterogeneity of patients who are infected with hepatitis C, treatment
decisions should be specifically tailored to each individual patient on the
basis of their predisposing conditions and anticipated clinical outcomes.
Plasma HCV-RNA
decline in the first 48 h identifies hepatitis C virus mono-infected but not
HCV/HIV coinfected patients with an undetectable HCV viral load at week 4 of
peginterferon-alfa-2a/ribavirin therapy. Arends
JE, Stuart JC, Baak LC, van der Ende ME, et al. J Viral Hepat. 2009 May 11.
[Epub ahead of print]
SUMMARY: During peginterferon-alfa-2a/ribavirin therapy, plasma hepatitis C virus
(HCV)-RNA decreases with a rapid first phase and a slower second phase. We
compared the viral load decrease and slope in the first 48 h in patients with a
rapid viral response (RVR, i.e. HCV-RNA < 50 IU/mL at week 4) with patients
not achieving an RVR. From 23 HCV-infected (14 mono-infected and nine
HCV/HIV-coinfected) genotype 1 or 4 positive
peginterferon-alfa-2a/ribavirin-treated patients, plasma HCV-RNA was determined
at baseline, 48 h, weeks 1, 2, 4, 8, 12, 48 and 72. The HCV viral load decrease
(Delta0-48), the slope (lambda(1)) and the efficiency factor (epsilon) were
determined in the first 48 h after the start of therapy. Five (36%) HCV
mono-infected patients and three (33%) HIV/HCV-coinfected patients achieved an
RVR whereas six (43%) HCV mono-infected patients and five (56%)
HIV/HCV-coinfected patients reached a sustained viral response (SVR). In
contrast to HIV/HCV-coinfected patients, five HCV mono-infected patients with
an RVR showed both a larger Delta0-48 and steeper lambda(1) (-1.77log(10) IU/mL
+/- 0.66 and -2.04/day +/- 0.76) compared to nine non-RVR patients
(-0.66log(10) IU/mL +/- 0.39; P = 0.019 and -0.76/day +/- 0.41; P = 0.019).
When divided by SVR, a greater Delta0-48 and steeper lambda(1) were also seen
in both HCV mono-infected and HIV/HCV-coinfected patients. Thus, in the first
48 h after the start of therapy, HCV mono-infected patients with an RVR have a
larger viral load decrease, steeper viral slope and a higher efficiency factor
as compared with non-RVR patients.
Systematic
review of HIV and HCV infection among drug users in China. Bao YP, Liu ZM.
Int J STD AIDS. 2009 Jun;20(6):399-405.
To determine the HIV and hepatitis C virus (HCV) geographical
distribution among drug users in China, a systematic literature review of 40
peer-reviewed publications (comprising 15,565 drug users) was conducted. Of the
total drug users, 10,724 were found to be injection drug users (IDUs) and 4841
were non-injection drug users (non-IDUs). Various studies identified that among
IDUs and non-IDUs, the overall HIV prevalence rates were 12.55% and 1.05%, and
the HCV prevalence rates were 66.97% and 18.30%, respectively. The HIV
prevalence rate ranged from 0% (Anhui and Inner Mongolia) to 52.51% (Yunnan)
among IDUs, and from 0% to 19.80% among non-IDUs correspondingly. The HCV
prevalence rate ranged from 11.43% (Shannxi) to 90.77% (Hubei) among IDUs, and
from 0% (Anhui) to 40.00% (Fujian) among non-IDUs. Based on the high prevalence
of HIV and HCV among drug users, scaling-up harm reduction was required from
'heroin trafficking areas' to other areas in China.
Complementary and Alternative
Artichoke leave extract for chronic hepatitis C - A pilot study. Huber R,
Müller M, Naumann J, Schenk T, Lüdtke R. Phytomedicine. 2009 May 7. [Epub ahead
of print]
BACKGROUND: Artichoke leave extracts (ALE) have hepatoprotektive properties
and are used by patients with chronic liver disease. Effects in patients with
chronic hepatitis C are unclear. METHODS:
17 patients with chronic hepatitis C and persistently elevated aminotransferase
levels were treated for 12 weeks with 3200mg standardized ALE per day. Primary
outcome parameter was the rate of alanine aminotransferase (ALT) normalisation
after 12 weeks. Secondary parameters were the course of ALT, aspartate
aminotransferase and gamma glutamyltransferase levels, quantitative HCV RNA,
subjective symptoms frequently associated with chronic hepatitis C (fatigue,
discomfort upper abdomen, joint problems) and safety. RESULTS: None of the patients had normalized ALT levels after 12
weeks of treatment. There was no significant change of aminotransferase levels
or viral load compared to baseline levels. Fatigue and joint problems
significantly improved after 4 weeks of treatment. However, after 12 weeks,
there was no significant difference to baseline. Tolerability of ALE was rated
as good to excellent. Severe side effects did not occur. CONCLUSION: ALE seem not to be effective to improve
aminotransferase levels in patients with chronic hepatitis C.
Epidemiology, Diagnostics, and Miscellaneous Works
Donor livers with steatosis are safe to use in hepatitis C
virus-positive recipients. Burra P, Loreno M, Russo FP, Germani G, et al. Liver Transpl. 2009 May 28;15(6):619-628.
[Epub ahead of print]
Whether donor
graft steatosis affects liver function and influences survival after liver
transplantation is still open to debate. The aim of this study was to assess
the impact of donor graft steatosis on long-term liver histology after liver
transplantation. One hundred sixteen consecutive liver transplants were
performed in 56 hepatitis C virus-positive (HCV+) patients and 60 HCV- patients
who had protocol liver biopsies at 6, 12, 24, and 36 months after liver
transplantation. Liver biopsies were obtained from all grafts. No steatosis was
seen in 50.9% of the biopsies taken at the back table before implantation,
whereas steatosis was mild in 39.6% of the samples and moderate/severe in 9.5%
of the samples. In the 56 HCV+ recipients, fibrosis stage 3 was seen in 22.2%
and stage 4 was seen in 2.2% of 45 biopsies at 36 months after liver
transplantation. There was no correlation between donor graft steatosis and
fibrosis after liver transplantation, regardless of the etiology of liver
disease. No difference in 36-month survival after liver transplantation was
seen, regardless of whether the etiology of the patient's liver disease was
HCV-related or non-HCV-related (80.3% versus 75%; P = 0.4) and whether the
steatosis in the graft was reportedly absent, mild, or moderate/severe (79.7%
versus 73.9% versus 81.1%; P = 0.7). In conclusion, nearly one-quarter of HCV+
recipients have precirrhosis/cirrhosis 3 years after liver transplantation.
Steatotic grafts do not seem to exacerbate the progression of fibrosis in HCV+
recipients, nor do they seem to negatively affect 3-year patient survival.
Impact of the donor risk index on the outcome of hepatitis C
virus-positive liver transplant recipients. Maluf DG, Edwards EB, Stravitz RT,
Kauffman HM. Liver Transpl. 2009 May 28;15(6):592-599. [Epub ahead of print]
We have
investigated the impact of the donor risk index (DRI) on the outcome of
hepatitis C virus (HCV)-infected patients undergoing liver transplantation
(LTx). Retrospective analysis was performed from the Organ Procurement and
Transplantation Network database (January 1, 2000 to June, 2006). The DRI was
calculated as described by Feng et al. (Am J Transplant 2006;6:783-790). Model
for End-Stage Liver Disease (MELD) exceptions were excluded from the analysis.
Relative risk (RR) estimates of patient and graft loss were derived from Cox
regression models. The Wald test was used to test the effect of the MELD score
at transplant on the HCV-DRI interaction. Of the LTx recipients (16,678), 76.1%
were Caucasian, and 66.7% were male; the median age was 52 (range, 18-80
years), and the mean follow-up time was 1148 days (range, 0-2959 days).
Forty-six percent (n = 7675) of LTx recipients were HCV(+). The median DRI was
1.3 (range, 0.77-4.27). Increasing DRI was associated with a statistically
significant increase in the RR of graft failure and patient death for both
HCV(+) and HCV(-) recipients. However, HCV(+) recipients demonstrated a
significantly higher increase in the RR of patient and graft loss as a function
of the DRI than HCV(-) subjects, even after adjustments for several recipient
factors, including MELD. In conclusion, a synergistic interaction between donor
DRI and recipient HCV status exists, such that an allograft from a high-DRI
donor more adversely affects the outcome of an HCV(+) recipient than that of an
HCV(-) recipient.
Surveillance for acute viral hepatitis --- United States, 2007. Daniels D, Grytdal S, Wasley A; Division of Viral Hepatitis,
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC.
MMWR Surveill Summ. 2009 May 22;58(3):1-27.
Problem: In the
United States, acute viral hepatitis most frequently is caused by infection
with any of three distinct viruses: hepatitis A virus (HAV), hepatitis B virus
(HBV), or hepatitis C virus (HCV). These unrelated viruses are transmitted
through different routes and have different epidemiologic profiles. Safe and
effective vaccines have been available for hepatitis B since 1981 and for
hepatitis A since 1995. No vaccine exists against hepatitis C. HBV and HCV can
persist as chronic infections and represent a leading cause of chronic liver
disease and hepatocellular carcinoma in the United States. Reporting Period
Covered: Cases in 2007, the most recent year for which data are available, are
compared with those from previous years. Description of System: Cases of acute
viral hepatitis are reported voluntarily to CDC by state and territorial health
departments via CDC's National Notifiable Disease Surveillance System (NNDSS).
Reports are received electronically via CDC's National Electronic
Telecommunications System for Surveillance (NETSS). Results: Acute hepatitis A
incidence has declined 92%, from 12.0 cases per 100,000 population in 1995 to
1.0 case per 100,000 population in 2007, the lowest rate ever recorded.
Declines were greatest among children and in those states where routine
vaccination of children was recommended beginning in 1999. Acute hepatitis B
incidence has declined 82%, from 8.5 cases per 100,000 population in 1990 to
1.5 cases per 100,000 population in 2007, the lowest rate ever recorded. Declines
occurred among all age groups but were greatest among children aged <15
years. Following a peak in 1992, incidence of acute hepatitis C declined;
however, since 2003, rates have plateaued. In 2007, as in previous years, the
majority of these cases occurred among adults, and injection-drug use was the
most common risk factor. Interpretation: The results documented in this report
suggest that implementation of the 1999 recommendations for routine childhood
hepatitis A vaccination in areas of the United States with consistently
elevated hepatitis A rates has reduced rates of infection. In addition,
universal vaccination of children against hepatitis B beginning in 1991 has
reduced disease incidence substantially among younger age groups. Higher rates
of hepatitis B continue among adults, particularly among males aged 30--44
years, reflecting the need to vaccinate adults at risk for HBV infection. The
decline in hepatitis C incidence after 1992 was attributable primarily to a
decrease in incidence among injection-drug users. The reasons for this decrease
were unknown but probably reflected changes in behavior and practices among
injection-drug users. Public Health Actions: The expansion in 2006 of
recommendations for routine hepatitis A vaccination to include all children in
the United States aged 12--23 months is expected to reduce hepatitis A rates
further. Ongoing hepatitis B vaccination programs ultimately will eliminate
domestic HBV transmission, and increased vaccination of adults with risk
factors will accelerate progress toward elimination. Further prevention of
hepatitis B and hepatitis C relies on identifying and preventing transmission
of HBV or HCV in hospital and nonhospital health-care associated settings. In
addition, prevention of hepatitis C relies on identifying and counseling
uninfected persons at risk for hepatitis C (e.g., injection-drug users)
regarding ways they can protect themselves from infection. Public health
management of persons with chronic HBV or HCV infection will help to interrupt
the transmission to susceptible persons, and their medical management will help
to reduce the development of the sequelae from chronic liver disease.
Epidemic spread of hepatitis C virus genotype 3a and relation to
high incidence of hepatocellular carcinoma in Pakistan. Khan A,
Tanaka Y, Azam Z, et al. J Med Virol. 2009 May 27;81(7):1189-1197. [Epub ahead
of print]
Studies
conducted in different populations worldwide revealed an association between
HCV genotype 1 and the development of hepatocellular carcinoma (HCC) than in
infection with other HCV genotypes. There are reports which reveal the
association of HCV genotype 3a (HCV-3a) with hepatic steatosis and fibrosis but
its relation with the development of HCC has not been investigated. In
Pakistan, where the incidence of HCC is increasing, 189 patients with chronic
liver disease including 82 with HCC were enrolled. HCV genotypes were
determined by phylogeny in the NS5B region and the epidemic history of HCV-3a
was examined using coalescent theory based methods. HCV-3a was the predominant
genotype (81.4%) in the cohort studied, followed by 3b (9.3%), 3k (2.3%), 1a
(1.5%), 1c (1.5%), 1b (0.8%), and 2a (0.8%) where 76% of HCC and 86% of non-HCC
were infected with HCV-3a. The significant factors associated with HCC were
older age (mean +/- SD) 55.8 (+/-9.9) (P < 0.0001), and male gender (P <
0.001). HCV RNA was significantly higher in patients with HCC and chronic
hepatitis than in liver cirrhosis (P < 0.0001). Molecular evolutionary
analysis revealed a distinct phylogenetic cluster of HCV-3a in Pakistan and an
estimation of the effective number of HCV infections indicated the appearance
of HCV-3a in this region around 1920s and a rapid exponential growth in the
1950s. This indicates that the epidemic spread of HCV-3a occurred earlier in
Pakistan than in other countries in which this genotype has been reported.
HCV-3a which spread earlier in Pakistan may be associated with an increasing
incidence of HCC.
A neuropsychological study comparing patients infected with HCV
and HBV without psychiatric comorbidities. Quarantini LC, Miranda-Scippa A,
Batista-Neves S, et al. J Med Virol. 2009 May 27;81(7):1184-1188. [Epub ahead
of print]
Hepatitis C
is one of the most common chronic infectious diseases worldwide, with
well-documented extra-hepatic manifestations, such as a broad number of
cognitive deficits. These impairments may be explained by psychiatric
comorbidities, which have not been investigated properly in the literature. In
order to elucidate a specific hepatitis C virus (HCV) induced cognitive
impairment not related to mental disorders, neuropsychological performance of
patients infected with HCV was compared with that of patients infected with
hepatitis B virus cognitive impairment, especially psychiatric comorbidities. A
total of 33 patients infected with HCV and 22 patients infected with HBV were
included in the study. There were no significant differences between the two
groups with regard to age or years of education. The group of patients infected
with HCV performed significantly worse on visuo-spatial memory tasks after
adjusting for years of education and age. There were no significant differences
between patients infected with HCV and patients infected with HBV with regards
to other neuropsychological functions. The data indicate that patients infected
with HCV patients have poorer visuo-spacial memory performance than patients
infected with HBV, suggesting that the cognitive deficit may be specific to HCV
infection and not to secondary comorbid psychiatric disorders.
Hepatitis C virus infection in the family setting of patients with
occult hepatitis C. Castillo I, Bartolomé J, Quiroga JA, Barril G, Carreńo V. J Med
Virol. 2009 May 27;81(7):1198-1203. [Epub ahead of print]
Family
members of patients with chronic hepatitis C virus (HCV) infection are at
increased risk of HCV infection but the prevalence of HCV among family members
of patients with occult HCV infection is not known. Anti-HCV, serum HCV RNA and
levels of liver enzymes were determined in 102 family members of 50 index
patients with occult HCV infection and in 118 family members of 59 chronic
hepatitis C index patients. HCV RNA and/or anti-HCV were detected in 10/102
(9.8%) relatives of patients with occult HCV infection and in 4/118 (3.4%) of
patients with chronic hepatitis C. Fourteen additional family members (seven
were relatives of index patients with occult HCV infection) had abnormal values
of liver enzymes without serological markers of HCV infection. Two of these
patients (who were relatives of two index patients with occult HCV infection) underwent
a liver biopsy and were diagnosed with an occult HCV infection because HCV RNA
was detected in the liver cells in the absence of serological HCV markers. In
conclusion, the prevalence of HCV infection among family members of patients
with occult HCV infection was similar to that found among family members of
patients with chronic hepatitis C. This stresses the need to adopt strategies
to prevent the transmission of HCV in the family setting of patients with
occult HCV infection.
Future directions for investigation of fatigue in chronic
hepatitis C viral infection. Seaman K, Paterson BL, Vallis M, Hirsch G, Peltekian KM. [Chronic
Illn. 2009 Jun;5(2):115-28.
Fatigue is a
common and often debilitating symptom for people living with chronic hepatitis
C viral infection. Numerous published reports in the past decade have attempted
to address the nature and aetiology of fatigue in chronic hepatitis C; however,
this field is plagued with lack of clarity about how hepatitis C virus
(HCV)-related fatigue occurs and when it is experienced by the infected person.
Consequently, both patients and clinicians alike are unclear about how to
mediate or prevent the negative consequences of HCV-related fatigue. In the
following article, the authors identify areas of ambiguity and incongruity that
have evolved primarily from the underlying assumptions and methodological
decisions of researchers in the field of HCV-related fatigue. Research related
to fatigue in chronic illness is drawn upon to suggest future directions for
investigations and interventions in the field of HCV-related fatigue. Future
research needs to move beyond the subjective symptomatology of HCV-related
fatigue and begin to account for the multidimensional and contextualised nature
of the fatigue experience.
Undiagnosed hepatitis C on the general medicine and trauma
services of two urban hospitals. Brady KA, Weiner M, Turner BJ. J Infect. 2009 May 3. [Epub ahead
of print]
The inpatient
medical service may be an important location to identify undiagnosed hepatitis
C virus (HCV) infection. We conducted a cross-sectional HCV prevalence study in
consecutive patients aged 18-65 admitted in a three-month period to two urban
hospitals' general internal medicine and trauma services. Patient sera were
anonymously screened for anti-HCV antibody with an enzyme-linked immunoassay
and, when anti-HCV positive (+), for HIV. Health system records were examined
for prior HCV testing or diagnosis or an HIV diagnosis then linked anonymously
to test results. Multivariate logistic regression was used to examine
associations of patient and health care factors with unknown HCV+ status. Of
786 unique patients tested (60.3% of all admitted patients), 62 (7.9%) were
HCV+ without a prior HCV+ test or diagnosis while 61 patients (7.8%) tested
HCV+ but had prior HCV+ test or diagnosis. Of 62 patients with unknown HCV+, 6
(9.7%) were HIV+ but only 3 had a prior HIV diagnosis; of 61 patients with
known HCV+, all 9 (14.8%) HIV+ had been diagnosed. Among the 640 patients with
prior unknown HCV status, an HCV+ test was strongly associated with age: 50-65
(adjusted odds ratio [AOR] 5.44, CI 2.20-13.48) and age 36-49 (AOR 4.65, CI
1.91-11.32) versus. 18-35. In this anonymous study, we could not obtain HCV
risk factor data but the positive and negative predictive values of HCV testing
all in-patients with an unknown HCV status were 99.3% and 99.0%, respectively.
In similar urban general medicine and trauma services, broader efforts to test
for HCV in inpatients aged 36-65 may be warranted.
Transplantation of high-risk donor organs: a survey of US solid
organ transplant center practices as reported by transplant infectious diseases
physicians. Ison MG,
Stosor V. Clin Transplant. 2009 May 18. [Epub ahead of print]
Public Health
Service (PHS) guidelines developed in 1994 provide guidance to minimize the
risk of HIV transmission and to monitor recipients following the
transplantation of "high-risk" organs. There are no data on current
practices or opinions of these policies by transplant infectious diseases (TID)
physicians. An electronic survey was sent to all US solid organ transplatation
centers with identified TID expertise as self-reported to the American Society
of Transplantation and Infectious Diseases Society of America. A total of 108
surveys were sent in December 2007 and 32 responses were received (30%).
Thirty-three percent of centers obtain only verbal, 52% verbal and written, and
14% do not obtain any special consent from recipients of organs from high-risk
donors (ROHRD). Post-solid organ transplantation serologies for HIV, hepatitis
B (HBV), and hepatitis C virus (HCV) are obtained at 40% of centers in ROHRD
only, 20% in all recipients, and not performed in 40%; post-solid organ
transplantation nucleic acid testing (NAT) testing is carried out in 36-45% of
centers in ROHRD, 11% in all recipients, and not performed in approximately 50%
of centers. Only 22.7% of respondents believed current guidelines accurately
represent what they consider to be high-risk donors. There is significant
variability in the acceptance and management of ROHRD in the US. Most TID
experts do not feel that the current PHS guidelines accurately define high-risk
donors.
Antiviral resistance and specifically targeted therapy for HCV
(STAT-C). Thompson AJ, McHutchison JG. J Viral Hepat. 2009 Jun;16(6):377-87.
As health
care providers, we find ourselves on the verge of a new era in the treatment of
chronic hepatitis C virus (HCV) infection. A number of directly acting
antiviral agents are now in the latter stages of clinical development. The more
promising candidates include direct inhibitors of the HCV nonstructural 3
protease, as well as both nucleoside and non-nucleoside inhibitors of the NS5B
RNA-dependent RNA polymerase. Although these agents have demonstrated potent
antiviral effect, monotherapy has been complicated by rapid virological
breakthrough due to the selection of drug-resistant mutants. As for HIV and
HBV, combination therapy will therefore be necessary. This brief review
summarizes the current literature concerning resistance and directly acting
antiviral agents, and identifies key challenges facing this emerging field.
Access to care of patients with chronic hepatitis C virus
infection in a university hospital: Is opioid dependence a limiting condition? Perut V,
Labalette C, Sogni P, Ferrand I, Salmon-Céron D, Vidal-Trecan G. Drug Alcohol
Depend. 2009 May 20. [Epub ahead of print]
BACKGROUND: We aimed to examine access to care of opioid-dependent patients
with chronic hepatitis C. METHODS: A
standardized form was used to conduct a retrospective survey from 1999 to 2003
in a French university hospital. All HCV RNA positive in- or outpatients who
had not had a liver biopsy or anti-HCV treatment were included.
Opioid-dependence was defined as active opioid drug use or being on opioid
substitution treatment. RESULTS: The
survey included 580 patients; 137 (23.6%) were opioid-dependent. Fewer patients
with than without current opioid dependence had had genotyping (40.1% versus
67.7%, p<0.001), liver biopsy (51.8% versus 62.8%, p=0.022), and anti-HCV
treatment (8.8% versus 18.3%, p=0.008). Genotyping was independently,
negatively, associated with: (1) current opioid-dependence (OR=0.3,
95%CI=0.2-0.5), (2) former opioid-dependence (OR=0.5, 95%CI=0.3-0.9), (3)
unemployment (OR=0.5, 95%CI=0.3-0.7), and (4) HCV infection discovered by
screening (OR=0.5, 95%CI=0.3-0.7). Access to liver biopsy was independently,
negatively associated with current opioid-dependence (OR=0.6, 95%CI=0.4-0.9),
but positively associated with alcohol consumption (OR=2.0, 95%CI=1.2-3.4) and
abnormal ALT level (OR=2.2, 95%CI=1.5-3.2). Access to anti-HCV treatment was independently,
negatively associated with HCV infection discovered by screening (OR=0.5,
95%CI=0.3-0.9), but positively associated with moderate hepatitis (OR=6.8,
95%CI=2.8-16.8), extensive fibrosis or cirrhosis (OR=12.3, 95%CI=5.5-27.5),
abnormal ALT level (OR=2.1, 95%CI=1.3-3.6) and age (40-64 years) (OR=1.9,
95%CI=1.0-3.4). CONCLUSIONS:
Genotyping and liver biopsies were performed less frequently on current opioid
dependent patients. Absence of genotyping was also independently associated
with unemployment and former opioid-dependence. Alcohol consumption or abnormal
ALT levels favored access to biopsy. Histological grade strongly conditioned
access to anti-HCV treatment.
Insulin resistance, serum adipokines and risk of fibrosis
progression in patients transplanted for hepatitis C. Veldt BJ,
Poterucha JJ, Watt KD, Wiesner RH, Hay JE, et al. Am J
In the
nontransplant setting diabetes mellitus is a risk factor for disease
progression in patients with chronic hepatitis C virus (HCV) infection. The
impact of early insulin resistance on the development of advanced fibrosis,
even in the absence of clinically apparent diabetes mellitus, is not known. Our
aim was to determine whether the Homeostasis Model Assessment of Insulin
Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk
for rapid fibrosis progression. Cohort study including patients transplanted
for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty
patients were included; 25 patients (16%) were treated for diabetes mellitus
and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5.
Multivariate Cox regression analysis showed that insulin resistance (hazard
ratio (HR) 2.07; confidence interval (CI) 1.10-3.91, p = 0.024), donor age (HR
1.33;CI 1.08-1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI
1.01-1.05, p < 0.001) were significantly associated with a higher
probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or
4, whereas steatosis (HR 0.94;CI 0.46-1.92, p = 0.87) and acute cellular
rejection (HR 1.72;CI 0.88-3.36, p = 0.111) were not. In conclusion,
posttransplant insulin resistance is strongly associated with more severe
recurrence of HCV infection. HOMA-IR is an important tool for the
identification of insulin resistance among patients at risk for rapid fibrosis
progression after liver transplantation for HCV.
Hepatitis C virus compartmentalization and infection recurrence
after liver transplantation. Ramirez S, Perez-Del-Pulgar S, Carrion JA, et al. Am J Transplant. 2009 May 20. [Epub ahead of
print]
Hepatitis C
virus (HCV) compartmentalization may have important implications in the
pathogenesis of HCV infection. The aim of this study was to investigate the
presence and relevance of HCV compartmentalization in the setting of liver
transplantation (LT). We collected samples of serum, peripheral blood
mononuclear cells (PBMC), perihepatic lymph nodes (PLN) and liver explant at
the time of LT, and serum and PBMC after transplantation from 57 HCV-infected
cirrhotic patients undergoing LT: 38 individuals received antiviral treatment
before LT and 19 were untreated controls. HCV-RNA levels were determined by
real-time PCR and the hypervariable region 1 (HVR-1) was sequenced. HCV-RNA was
detected in all samples from control patients. In virological responders,
recurrence after LT was associated with residual HCV-RNA in the liver explant.
Within the entire cohort, 47% of patients harbored differences in direct
sequences from distinct compartments. Quasispecies analysis revealed that in
most cases, HVR-1 sequences recovered after infection recurrence were identical
or closely related to those isolated from the liver explant and serum at the
time of LT. Our study shows that a significant proportion of HCV-infected
cirrhotic patients exhibit compartmentalization. Viral variants originating
within the liver appear to be the main cause of HCV recurrence after LT.
Management and treatment of patients with cirrhosis and portal
hypertension: Recommendations from the Department of Veterans Affairs Hepatitis
C Resource Center Program and the National Hepatitis C Program. Garcia-Tsao
G, Lim J. Am J Gastroenterol. 2009 May 19. [Epub ahead of print]
Cirrhosis
represents the end stage of any chronic liver disease. Hepatitis C and alcohol
are currently the main causes of cirrhosis in the United States. Although
initially cirrhosis is compensated, it eventually becomes decompensated, as
defined by the presence of ascites, variceal hemorrhage, encephalopathy, and/or
jaundice. These management recommendations are divided according to the status,
compensated or decompensated, of the cirrhotic patient, with a separate section
for the screening, diagnosis, and management of hepatocellular carcinoma (HCC),
as this applies to patients with both compensated and decompensated cirrhosis.
In the compensated patient, the main objective is to prevent variceal
hemorrhage and any practice that could lead to decompensation. In the
decompensated patient, acute variceal hemorrhage and spontaneous bacterial
peritonitis are severe complications that require hospitalization. Hepatorenal
syndrome is also a severe complication of cirrhosis but one that usually occurs
in patients who are already in the hospital and, as it represents an extreme of
the hemodynamic alterations that lead to ascites formation, it is placed under
treatment of ascites. Recent advances in the pathophysiology of the
complications of cirrhosis have allowed for a more rational management of
cirrhosis and also for the stratification of patients into different risk
groups that require different management. These recommendations are based on
evidence in the literature, mainly from randomized clinical trials and
meta-analyses of these trials. When few or no data exist from well-designed
prospective trials, emphasis is given to results from large series and
consensus conferences with involvement of recognized experts. A rational
management of cirrhosis will result in improvements in quality of life,
treatment adherence, and, ultimately, in outcomes.
Factors associated with awareness of infection status among
chronic hepatitis B and C carriers in Korea. Shin A, Cho ER, Kim J, Sung J,
Park KW, Lim MK, Shin HR. Cancer Epidemiol Biomarkers Prev. 2009 May 19. [Epub
ahead of print]
Hepatitis B
(HBV) and hepatitis C (HCV) viral infections are the most important risk
factors for hepatocellular carcinoma (HCC), which is responsible for 17.5% of
cancer deaths in Korea. The objectives of this study were to identify
demographic characteristics that may affect hepatitis carriers' awareness of
their infection status, and to assess whether health-related behaviors differed
by awareness of the infection. Among 18,636 persons who were recruited from a
cancer screenee cohort, 904 were HBV carriers and 146 were HCV carriers. Among
the HBV carriers, 74.2% were aware of their infection status. Higher education
(odds ratio, 1.8; college versus middle school or less), family history of
liver cancer or disease, and marriage were associated with awareness of HBV
infection status. Participants who were aware of their HBV carrier status were
more likely to be former smokers or drinkers than those who were not aware of
their status. Only 34.9% of HCV carriers were aware of their HCV infection
status. No demographic characteristics were related to awareness of HCV
infection status among HCV carriers. However, HCV carriers who were aware of
their infection status were more likely to be former drinkers (odds ratio, 9.2;
95% confidence interval, 1.8-47.2). In conclusion, two thirds of HCV carriers
and one fourth of HBV carriers in this study population were not aware of their
infection status, and awareness of hepatitis infection status was significantly
associated with other risk behaviors, such as alcohol consumption and cigarette
smoking.
Holiday haemodialysis and imported hepatitis C virus infection: A
series of sixteen cases in two large haemodialysis units. Bhattacharya
S, Price N, Boxall E, Adu D, Lipkin G, Smith S, Osman H. J Clin Virol. 2009 May
16. [Epub ahead of print]
BACKGROUND: Patients in haemodialysis units are at an increased risk of blood
borne virus infections. Birmingham city (West Midlands, UK) has a large number
of its population from an ethnic origin other than white (30%). Recently due to
the increase in number of haemodialysis centres abroad and particularly in the
Indian Subcontinent, a large number of haemodialysis patients from these ethnic
minorities are encouraged to take holidays in their countries of origin. OBJECTIVES: To present the data on a
series of cases of holiday haemodialysis acquired hepatitis C virus (HCV)
infections from two large dialysis units in Birmingham. STUDY DESIGN: In this retrospective study we have reviewed the case
records of all patients in two large dialysis units who had holiday dialysis
abroad and developed HCV infection after returning to the UK. RESULTS: A total of 16 patients from
two large dialysis units in Birmingham who developed HCV infection after
haemodialysing abroad mainly in the Indian Subcontinent are being described.
This constituted 44% of the total HCV positive patients in the two
haemodialysis units (16/36). The cases occurred over a period of 9 years
between 2000 and 2008. The last twelve of these fifteen cases had been
diagnosed in the past 17 months. There were 10 male patients with a mean age
62.8 years (range 26-84 years) and 6 female patients with a mean age of 57
years (range 44-68 years). HCV genotypes 1, 3 and 4 were found in 9, 4 and 3
patients, respectively. CONCLUSION:
These cases underline the importance of enhanced surveillance and infection
control procedures in haemodialysis units for patients who return after
dialysing in resource poor countries. To the best of our knowledge this
represents the largest series of imported HCV infection after holiday
haemodialysis, and demonstrates clearly the significance of the perceived risk
with increasing number of incident infections.
Thoracic complications of liver cirrhosis: radiologic findings. Kim YK, Kim
Y, Shim SS. Radiographics. 2009 May-Jun;29(3):825-37.
Patients with
chronic liver disease exhibit various cardiovascular and pulmonary
complications. Hepatopulmonary syndrome results in dyspnea due to
intrapulmonary arteriovenous shunting and ventilation-perfusion mismatch.
Portopulmonary hypertension occurs in patients with portal hypertension.
Intrathoracic portosystemic collateral vascular pathways develop in patients
with portal hypertension to allow decompression of the portal vein into the
systemic circulation. Hepatic hydrothorax may develop in patients with
cirrhosis and ascites. Massive necrosis of the liver from any cause may be
associated with acute hypoxic respiratory failure, necessitating ventilatory
support. Bacterial infection is common in cirrhotic patients because of a
compromised host defense system. Hepatocellular carcinoma may produce
hematogenous lung metastases, intrathoracic lymph node metastases, direct
intracardiac extension, and pulmonary embolism. Interferon therapy for
treatment of chronic active hepatitis C may disturb cellular immune activation
in some patients and contribute to the onset and progression of sarcoidosis.
Awareness of the various thoracic manifestations in chronic liver disease can
be helpful for making a differential diagnosis and planning proper management.
Efficacy of chronic hepatitis C therapy in community-based trials.
Marotta
P, Hueppe D, Zehnter E, Kwo P, Jacobson I. Clin Gastroenterol Hepatol. 2009 May
14. [Epub ahead of print]
Prospective,
randomized, controlled, phase 3 clinical trials establish pegylated interferon
(PEG-IFN) alfa plus ribavirin as the standard of care for patients with chronic
hepatitis C. Such clinical trials are conducted in a highly regimented manner;
patients must meet strict inclusion/exclusion criteria, and treatment is
administered under rigid protocols with close monitoring by study personnel.
Whether the results of phase 3 trials can be generalized or achieved in
everyday clinical practice is questioned in several therapeutic areas. The
efficacy of PEG-IFN alfa plus ribavirin therapy observed in pivotal phase 3 trials
has been confirmed in several community-based trials conducted in North America
and Europe, demonstrating consistent overall rates of sustained virologic
response across a wide range of patient populations. Sustained virologic
response rates stratified by genotype, viral load, fibrosis score, age, and
ethnicity-factors known to impact treatment outcome-are consistent between
these trials and comparable to those reported in clinical trials. The United
Statesbased WIN-R trial confirmed the value of combining weight-based ribavirin
dosing with weight-based PEG-IFN alfa-2b dosing across a spectrum of patient
body weights. Large Canadian trials (POWeR and EAP), a German trial (AWB), a
French study (Hepatys), and an Italian study demonstrated that PEG-IFN alfa plus
ribavirin produces excellent efficacy in difficult-to-treat patient
populations. Collectively, these results confirm the efficacy of current
standard treatment regimens in a wide range of community-based settings,
affording clinicians confidence that they can attain results similar to those
of rigidly controlled randomized trials.
Glucose abnormalities in non-alcoholic fatty liver disease and
chronic hepatitis C virus infection: the role of iron overload. Lecube A,
Hernández C, Simó R. Diabetes Metab Res Rev. 2009 May 14. [Epub ahead of print]
Non-alcoholic
fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are
major causes of liver disease frequently described in outpatient patients with
glucose abnormalities. Hyperferritinemia, which suggests that iron overload
plays a decisive role in the pathophysiology of insulin resistance and
hyperglycemia, is a common finding in both disorders. However, the role of the
hepatic iron deposition differs from one to the other. In NAFLD, a moderate
liver iron accumulation has been observed and molecular mechanisms, including
the downregulation of the liver iron exporter ferroportin-1, have been
described. Iron overload will enhance intrahepatic oxidative stress that
promotes hepatic fibrosis, interfere with insulin signalling at various levels
and may hamper hepatic insulin extraction. Therefore, liver fibrosis,
hyperglycemia and hyperinsulinemia will lead to increased levels of insulin
resistance and the development of glucose abnormalities. Furthermore, iron
depletion by phlebotomy removes liver iron content and reduces serum glucose
and insulin resistance in NAFLD patients. Therefore, it seems that iron
overload participates in those glucose abnormalities associated with NAFLD.
Concerning chronic HCV infection, it has been classically assumed that iron
overload contributes to insulin resistance associated with virus infection.
However, recent evidence argues against the presence of iron overload in these
patients and points to inflammation associated with diabetes as the main
contributor to the elevated ferritin levels. Therefore, glucose abnormalities,
and specially type 2 diabetes, should be taken into account when evaluating serum
ferritin levels in patients with HCV infection.
Relative and combined effects of chronic alcohol consumption and
HCV infection on serum zinc, copper, and Selenium. González-Reimers
E, Martín-González MC, Alemán-Valls MR, et al. Biol Trace Elem Res. 2009 May
15. [Epub ahead of print]
In alcoholic
hepatitis, Kupffer cells are activated by intestinal gram-bacteria, leading to
cytokine production and free radicals release, which, enhancing cytokine
secretion, create a positive feedback loop which contributes to liver
inflammation. Free radicals also damage the liver in chronic hepatitis C virus
(HCV) infection, a condition frequently associated to alcohol consumption. In
both situations, activity of antioxidant enzymes and of its cofactors zinc
(Zn), selenium (Se), and copper (Cu) is important. This study was performed to
assess the relative and combined effects of chronic alcoholism and HCV
infection on serum Se, Zn, and Cu, and its relation with serum malondialdehyde
(MDA) and tumor necrosis factor-alpha, interferon-gamma, and interleukins (IL)
4, 6, and 8, in 19 HCV- alcoholic patients, 12 HCV+ alcoholic patients, nine
HCV+ non-alcoholic patients, and 20 controls. Serum Zn and Se were lower in
both HCV+ and HCV- alcoholic patients, whereas serum Cu was lower in HCV+
individuals. Serum Zn and Se were related to liver function derangement. MDA
levels were higher in alcoholics, but no relation was observed between trace
elements and MDA or cytokines, so that our results do not support a relevant
role of the analyzed trace elements in the pathogenesis of chronic liver
disease.
HCV-related mortality among male prison inmates in Texas, 1994-2003.
Harzke
AJ, Baillargeon JG, Kelley MF, Diamond PM, Goodman KJ, Paar DP. Ann Epidemiol.
2009 May 12. [Epub ahead of print]
PURPOSE: The prevalence of hepatitis C virus (HCV) infection is high among
adult incarcerated populations, but HCV-related mortality data are lacking. The
study purpose was to assess HCV-related mortality over time and across
racial/ethnic categories from 1994 through 2003 among male prisoners in the
Texas Department of Criminal Justice (TDCJ). METHODS: TDCJ decedent data were
linked with Texas Vital Statistics multiple-cause-of-death data. Crude annual
HCV death rates, age- and race-adjusted summary rates, and average annual
percent changes were estimated. The proportion of deaths due to chronic liver
disease/cirrhosis, liver cancer, hepatitis B, and HIV for which HCV was
identified as an intervening or contributing cause of death was calculated. RESULTS: Among Texas male prisoners,
HCV death rates were high and increased over the 10-year study period by an
average 21% annually, with the largest increase occurring among Hispanic
prisoners. HCV was identified as an intervening or contributing cause of death
in 15% of chronic liver disease/cirrhosis deaths, 33% of liver cancer deaths,
81% of hepatitis B deaths, and 7% of HIV deaths. CONCLUSIONS: Because HCV-related deaths among Texas male prisoners
are high and increasing, particularly among Hispanics, targeted prevention,
screening, and treatment of HCV infections should be among the priorities of
U.S. correctional healthcare systems.
Hepatitis B virus and hepatitis C virus in medical waste handlers
in Tripoli, Libya.
Franka E,
El-Zoka AH, Hussein AH, Elbakosh MM, Arafa AK, Ghenghesh KS. J Hosp Infect.
2009 May 12. [Epub ahead of print]
Medical waste
handlers (MWHs) are at risk of exposure to serious viral infections. No data
are available on the prevalence of hepatitis B virus (HBV), hepatitis C virus
(HCV) or human immunodeficiency virus (HIV) among MWHs in Libya. During a
one-year period (January to December 2004) blood samples from 300 (59 females)
MWHs employed by a local contractor in Tripoli and 300 blood samples from
non-medical waste handlers (NMWHs) who had no direct or indirect contact with
medical waste were examined for HBV, HCV and HIV using enzyme-linked
immunosorbent assays. HBV was detected in 7 (2.3%) and 1 (0.3%) and HCV in 8
(2.7%) and 0 (0.0%) of MWHs and NMWHs, respectively. Significant differences
were observed in the detection rates of HBV (OR: 7.14; P<0.04) and HCV (OR:
undefined; P<0.005) in MWHs when compared with NMWHs. HIV was not detected
in both groups. Of the MWHs studied, 21% were immunised against HBV and 7% were
trained to handle medical waste. In addition, 99.7% wore overalls, 57.7% thick
disposable gloves, 55% boots and 17.7% masks while handling medical waste. In
conclusion, prevalence rates of HBV and HCV were significantly higher in MWHs
than those in NMWHs examined. Training, immunisation, and post-exposure
protection of MWHs, in addition to proper management of medical waste by the
health authorities, may significantly reduce the risk of acquiring infectious
agents by MWHs in Libya.
CXCL10 and CCL2 chemokine serum levels in patients with hepatitis
C associated with autoimmune thyroiditis. Antonelli A, Ferri C, Fallahi P,
et al. J Interferon Cytokine Res. 2009 Jun;29(6):345-51.
To evaluate
CXCL10 and CCL2 in patients with hepatitis C virus chronic infection in
presence/absence of autoimmune thyroiditis (AT). CXCL10 was significantly
higher in: (1) patients with AT than controls without AT (control 1) (P <
0.001; ANOVA); (2) patients with hepatitis C infection than control 1 and
patients with AT (P < 0.001); (3) patients with hepatitis C virus chronic
infection and AT (HCV+AT) than control 1 and patients with AT (P < 0.001)
and hepatitis C (P = 0.004). By defining a high CXCL10 level as a value >218
pg/mL, 2% of control 1, 14% of patients with AT, 68% of patients with hepatitis
C infection, 81% of HCV+AT had high CXCL10 (P < 0.0001; chi-square). CCL2
was similar in control 1 and patients with AT. CCL2 was significantly higher
in: (1) patients with hepatitis C infection than control 1 (P = 0.04; ANOVA);
(2) HCV+AT than patients with AT (P = 0.03) and control 1 (P = 0.02); no
difference was observed between HCV with or without AT. Our study demonstrates:
(1) higher circulating CXCL10 and CCL2 in patients with hepatitis C virus
chronic infection than in controls; (2) higher CXCL10 in HCV+AT than in
patients with hepatitis C infection, suggesting a stronger Th1 immune response
in these patients.
Specialty care and education associated with greater
disease-specific knowledge but not satisfaction with care for chronic hepatitis
C. Beste
LA, Straits-Troster K, Zickmund S, Larson M, Chapko M, Dominitz JA. Aliment
Pharmacol Ther. 2009 May 6. [Epub ahead of print]
Background: Little is
known about differences among hepatitis C virus (HCV) patients managed by
generalists versus specialists with respect to patient-centered outcomes, such
as disease-specific knowledge, health-related quality of life (HRQoL), and
satisfaction with care. Aim: To examine selected
patient-centered outcomes of HCV-related care provided in primary care,
specialty care, or both. Methods: 629 chronic HCV patients
completed a survey including an HCV knowledge assessment and validated
instruments for satisfaction and HRQoL. Multivariable linear regression was
used to compare outcomes between groups. Results: Adjusted total HCV
knowledge score was lower among patients who did not attend specialty care
(p<.01). Primary care and specialty patients did not differ in adjusted
general HRQoL or satisfaction. Sixty percent of specialty patients underwent
formal HCV education, which was associated with 5% higher knowledge score
(p=0.01). General HRQoL and patient satisfaction did not differ between primary
care and specialty groups. Disease-specific knowledge and care satisfaction
were independent of mental illness, substance abuse, socio-economic variables,
history of antiviral treatment, formal HCV education, and duration of time
between last visit and survey completion. Conclusions: Primary care patients
with chronic HCV have lower adjusted disease-specific knowledge than specialty
patients, but no difference in general HRQoL or patient satisfaction.
Health-related quality of life in patients with different stages
of liver disease induced by hepatitis C. Bjornsson E, Verbaan H, Oksanen A,
et al. J Gastroenterol. 2009 May 12:1-10. [Epub ahead of print]
Objective: Patients
with hepatitis C have been shown to have impaired health-related quality of
life (HRQoL). The aim of this study was to determine HRQoL in patients in
different stages of hepatitis C virus (HCV) and to compare HRQoL in HCV
cirrhosis with non-HCV-induced cirrhosis. Material and methods: Out of 489
consecutive patients who fulfilled the inclusion criteria, 472 (96%) agreed to
participate in the study: 158 patients with mild/moderate fibrosis with chronic
hepatitis C (CHC group), 76 patients with HCV compensated cirrhosis (CC), 53
patients with HCV decompensated (DC) cirrhosis, 52 non-cirrhotic patients with
sustained viral response (SVR), and a control group consisting of 32 patients with
non-HCV CC and 101 with non-HCV DC who completed the Short Form-36 (SF-36) and
EQ-5D questionnaire. Results: The CHC group had
significantly lower SF-36 scores than healthy controls, with the exception of
scores for the dimensions physical function and bodily pain. HCV patients with
DC had lower scores in all SF-36 dimensions in comparison with those of the CHC
group, as well as in physical and mental component summaries (p<0.001). In
comparison with the CHC group, the HCV CC group had lower scores on the SF-36
general health dimension (p<0.05) and lower SF-36 physical component summary
(PCS) scores (p<0.05). No major differences were seen in patients with HCV-
and non-HCV-induced cirrhosis. Conclusions: Impairment in HRQoL in
patients with HCV was associated with the severity of liver disease, patients
with decompensated cirrhosis exhibiting the highest impairment in HRQoL. The
etiology of liver disease does not seem to be important in determining HRQoL in
cirrhosis.
Quality of life in hemodialysis patients: hepatitis C virus
infection makes sense. Afsar B, Elsurer R, Sezer S, Ozdemir NF. Int Urol Nephrol. 2009
May 9. [Epub ahead of print]
PURPOSE: Hepatitis C virus (HCV) infection impairs quality of life (QOL)
in patients who are not on dialysis therapy. In dialysis patients, how HCV
infection affects QOL is unknown. In our study, we investigated the independent
relationship between HCV infection and QOL. METHODS: Sociodemographic and laboratory variables were recorded.
Severity of depressive symptoms and QOL were assessed by Beck Depression
Inventory (BDI) and Short Form-36 (SF-36), respectively. RESULTS: Among 165 patients, 83 were anti-HCV antibody positive and
82 were anti-HCV antibody negative. Anti-HCV antibody positive patients had
higher BDI scores than anti-HCV antibody negative patients (P = 0.011). Other
than the social functioning subscale, all SF-36 subscales were lower in
anti-HCV antibody positive patients when compared with anti-HCV negative
patients. Anti-HCV antibody positive patients had lower physical (P = 0.003)
and mental component summary scores (P = 0.018) than negative patients.
Physical component summary score was independently associated with hemodialysis
duration (P = 0.003), sleep disturbance (P = 0.046), BDI score (P = 0.027),
albumin (P = 0.002), and serum hemoglobin (P < 0.0001). Physical component
summary score was not associated with anti-HCV antibody positivity. Mental
component summary score was independently associated with BDI score (P =
0.001), anti-HCV antibody positivity (P = 0.016), and serum hemoglobin (P <
0.0001). CONCLUSION: HCV infection
impairs QOL, especially in mental aspects, in hemodialysis patients.
The
longitudinal quantitative assessment by transient elastography of chronic
hepatitis C patients treated with pegylated interferon alpha-2b and ribavirin. Ogawa E, Furusyo N, Toyoda K, Takeoka H, Maeda S, Hayashi J. Antiviral
Res. 2009 Apr 14. [Epub ahead of print]
The aim of this study was to assess the association between liver
stiffness measured by transient elastography (FibroScan((R))) and the efficacy
of pegylated interferon alpha-2b plus ribavirin combination treatment for
patients with chronic hepatitis C virus (HCV) infection. We prospectively
studied 145 Japanese patients with chronic HCV infection. FibroScan was done at
baseline, at the end of treatment, and at 48 and 96 weeks after the end of treatment.
The FibroScan values were significantly decreased for sustained virological
response (SVR) patients (the mean rate of change; -16.2%, -32.2% and -43.5%) in
comparison with non-SVR patients (-7.2%, -2.1% and +17.3%) at the end of
treatment (P=0.0127), and 48 weeks (P<0.0001) and 96 weeks (P<0.0001)
after the end of treatment. Among the non-SVR patients, the FibroScan values
were significantly decreased for patients with biochemical response (BR)
(-17.9%, -30.0% and -27.1%) in comparison with non-BR (-4.1%, +6.4% and +30.6%)
at the end of treatment (P=0.0270), and 48 weeks (P<0.0001) and 96 weeks
(P<0.0001) after the end of treatment. The FibroScan values may predict a
progressively better clinical outcome for patients with successful virological
and biochemical responses.
Absence of
intrafamilial transmission of hepatitis C virus and low risk for sexual
transmission in rural central Africa indicate a cohort effect. Ndong-Atome GR, Njouom R, Padilla C, et al. J Clin Virol. 2009 May 25. [Epub ahead of
print]
BACKGROUND: Intrafamilial and sexual transmission of hepatitis C virus (HCV) are
still being debated, and little is known about such transmission in central
Africa. OBJECTIVE: To examine the rate of intrafamilial transmission of
HCV between patients and their household members. STUDY DESIGN: A
cross-sectional study was conducted in Dienga, a remote village in Gabon,
involving 195 household members of 14 index cases of HCV infection. After a
questionnaire on the risk factors for parenteral exposure, blood samples were
obtained and tested for antibody to HCV by an enzyme immunoassay (Monolisa
anti-HCV plus version 2). Positive samples were tested for HCV RNA and
genotyped by amplification and phylogenetic analysis of a fragment of the NS5B
gene. RESULTS: HCV antibody was found in 13/195 (6.7%) household contacts,
comprising 5/14 (35.7%) sexual partners and 8/114 (7%) relatives. None of the
children of index patients tested positive. HCV RNA was detected in only five
household members with HCV antibody. The same genotypes were found in only two
of five couples, both couples being sexual partners. Parenteral risk factors
were not more likely to be reported by people positive for HCV antibody than by
those who were negative. Age over 50 years was the only independent predictor
of positivity for HCV antibody. CONCLUSIONS: This study indicates, as
previously suggested, that the spread of HCV in central Africa is due to a
cohort effect, with previous, possibly iatrogenic, transmission rather than
intrafamilial or sexual transmission.
King's Score: an accurate marker of cirrhosis in chronic hepatitis
C. Cross
TJ, Rizzi P, Berry PA, Bruce M, Portmann B, Harrison PM. Eur J Gastroenterol
Hepatol. 2009 May 7. [Epub ahead of print]
OBJECTIVES: Histological assessment of patients with chronic hepatitis C
infection is no longer performed routinely; consequently, a simple test is
needed to identify patients with significant hepatic fibrosis. METHODS: Data were collected,
retrospectively, on 923 consecutive patients undergoing percutaneous liver
biopsy for chronic hepatitis C at King's College Hospital between 1 January
2000 and 30 June 2006; 602 patients were accepted to form the training set and
a further 105 patients to form the validation set. RESULTS: On liver biopsy, 132 (22%) had cirrhosis (Ishak F5-6) in
the training set and 19 (18%) in the validation set. Factors found by
multivariate analysis to be associated with fibrosis in the training set were
used to construct the King's Score: agexaspartate
aminotransferasexinternational normalized ratio / platelets. Area under
receiver operating characteristic curves for predicting cirrhosis and
significant fibrosis (F3-6) were 0.91 and 0.79, respectively. A King's Score of
greater than or equal to 16.7 predicted cirrhosis in 34% of patients (odds
ratio 36.2, 95% confidence interval, 22.0-59.6; P<0.0001) with sensitivity
86%, specificity 80% and a high negative predictive value of 96%; a score
greater than or equal to 12.3 predicted F3-6 (odds ratio 33.9, 95% confidence
interval, 15.2-34.4; P<0.001). The validation set confirmed the utility of
this index, area under receiver operating characteristic curves 0.94 and 0.89
for cirrhosis and F3-6, respectively. CONCLUSION:
The King's Score is a simple and accurate index for predicting cirrhosis in
chronic hepatitis C. Patients with a score of less than 16.7 have a low risk of
cirrhosis.
Age- and sex-related reference ranges of alanine aminotransferase
levels in children: European Paediatric HCV Network. England K,
Thorne C, Pembrey L, Tovo PA, Newell ML. J Pediatr Gastroenterol Nutr. 2009 May
19. [Epub ahead of print]
BACKGROUND: Serum alanine aminotransferase (ALT) levels are commonly used to
indicate liver damage. Although elevated levels indicate possible liver injury,
abnormalities, or disease, some patients with "normal" ALT levels
have minimal to mild liver disease. Recently, ALT reference ranges for adults
were queried and revised ranges proposed with lower upper limits of normality.
The appropriateness of current paediatric ALT reference ranges is unclear. MATERIAL AND METHODS: Hepatitis C virus
(HCV)-uninfected children from the European Paediatric HCV Network represent a
large population of healthy children born to HCV-infected mothers, with ALT
observations collected prospectively from birth. Linear regression identified
factors associated with ALT levels while accounting for within-child repeated
measurements. ALT centiles stratified by sex were calculated using maximum
penalized likelihood methods and LMS software. RESULTS: A total of 1293 HCV-uninfected children had 5011 ALT
measurements during follow-up. ALT levels significantly decreased with
increasing age, whilst ALT levels were significantly lower in girls than boys.
Reference cutoffs representing the 95th centiles before 18 months of age were
60 U/L for boys and 55 U/L for girls, decreasing to 40 U/L for boys and 35 U/L
for girls after 18 months of age. CONCLUSIONS:
These reference ranges represent a unique investigation of ALT levels in a
healthy child population. We show lower and more detailed age-related cutoffs
of normality than available. Additionally, we demonstrate a significant effect
of sex on ALT reference ranges, which has not previously been described in
children younger than 5 years of age.