Interleukin-28B rs12979860 C allele: Protective against advanced fibrosis in chronic hepatitis C genotype 1 infection.

Background and Aim: While genetic polymorphisms upstream of the interleukin-28B(IL28B) gene are associated with necroinflammatory activity grade in chronic hepatitis C virus genotype 1 (HCV-1) infection, any association with fibrosis is less definitive. Pretreatment liver biopsies in a cohort of treatment-naïve patients with HCV-1 were analyzed to evaluate associations between liver histology, and the rs12979860 and rs8099917 IL28B single nucleotide polymorphisms.Methods: Two hundred sixty-six patients with HCV-1 infection and pretreatment liver biopsy were tested for the rs12979860 and rs8099917 single nucleotide polymorphisms.Predictors of advanced fibrosis (METAVIR F3/4) and high activity grade (A2/3) were identified using multivariable logistic regression analysis.Results: Forty-four patients (16.5%) had advanced fibrosis and 141 patients (53.0%) high activity grade. Prevalence of rs12979860 IL28B genotype was: CC 45.7%, CT 42.7%, and TT 11.6%. Prevalence of advanced fibrosis was lower in those with IL28B CC genotype compared with those without (11.0% vs 21.3%; P = 0.03), with an increasing number of Talleles associated with a higher frequency of advanced fibrosis: CC 11.0%, CT 18.0%, TT33.3% (P = 0.01). Predictors of advanced fibrosis on multivariate analysis were platelet count (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97­0.99; P < 0.0001), high activity grade (OR 5.68, 95% CI% 1.86­17.32; P = 0.002), IL28B rs12979860 CC genotype(OR 0.36, 95% CI 0.14­0.93; P = 0.03), and aspartate aminotransferase (OR 1.02,95% CI 1.00­1.03; P = 0.046). No association was found between rs8099917 IL28B genotype and liver histology.Conclusions: IL28B rs12979860 CC genotype appears to be independently associated with a lower prevalence of advanced fibrosis stage in HCV-1 infection. This association warrants further evaluation.

Successful treatment of patients with hepatitis C in rural and remote Western Australia via telehealth.

Rural and remote patients at the Royal Perth Hospital were reviewed and treated for hepatitis C by a hepatologist and nurse practitioner using telehealth (videoconferencing). Over a four-year period, 50 patients were treated with pegylated interferon and ribavirin, and participated in a total of more than 500 telehealth sessions. Sustained virological response rates (SVRs) were compared to those in face-to-face (FTF) clinics to assess treatment outcomes. Treatment through telehealth was found to be non-inferior to FTF clinics. Telehealth patients with genotype 1 infection achieved a higher rate of SVR than those attending FTF clinics (73% versus 54%, respectively), although the difference was not significant. SVR rates for genotype 2 and 3 of 72% were similar in telehealth to FTF rates of 74%. A total of 35 telehealth patients completed a satisfaction questionnaire and most indicated that they were happy with the programme and would participate again in the future. The study confirmed that telehealth is an effective option for the treatment of hepatitis C in rural and remote areas.

Early on-treatment viral load and baseline METAVIR score: improved prediction of sustained virological response in HCV genotype 1 patients.

BACKGROUND: On-treatment HCV viral load during early therapy with pegylated interferon (PEG-IFN) and ribavirin is highly predictive of sustained virological response (SVR). We sought to provide further refinement of this prediction through an extensive evaluation of the effect of HCV viral loads at weeks 4, 8 and 12 on SVR, including analysis by liver disease stage grouping. METHODS: A total of 309 patients with genotype 1 chronic HCV and recent liver biopsy enrolled in the CHARIOT study received 180 µg of PEG-IFN-α2a weekly with 1,000/1,200 mg of ribavirin daily. The probability of an SVR was estimated using baseline METAVIR fibrosis stage and HCV viral loads at weeks 4, 8 and 12. RESULTS: HCV RNA was undetectable in 27.5%, 50.3% and 62.6% of patients at weeks 4, 8 and 12, respectively. SVR was 80.0%, 76.8% and 72.4% among patients with undetectable HCV RNA at weeks 4, 8 and 12, respectively. SVR decreased in a progressive fashion with increasing HCV viral loads at each early time point, but was similar for patients with HCV viral load <15 IU/ml, 15-100 IU/ml and 100-1,000 IU/ml. The effect of fibrosis stage on SVR was modest for patients with HCV viral load <1,000 IU/ml at week 4, but more marked for those with week 4 HCV viral load >1,000 IU/ml, and all HCV viral load categories at weeks 8 and 12. CONCLUSIONS: A combination of baseline fibrosis stage and on-treatment HCV viral load at early time points provides improved estimates for treatment response in patients with chronic HCV genotype 1.

Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing.

BACKGROUND & AIMS: The impact of fibrosis stage on chronic hepatitis C virus (HCV) treatment response was explored in CHARIOT, a study of high dose peginterferon alfa-2a (PEG-IFNalpha-2a) induction therapy in treatment naïve genotype 1 infection. METHODS: Eight hundred and ninety-six patients were randomised 1:1 to 360 microg (n=448) or 180 microg (n=448) PEG-IFNalpha-2a weekly with RBV 1000-1200 mg/day for 12 weeks followed by 36 weeks of 180 microg PEG-IFNalpha-2a weekly plus RBV 1000-1200 mg/day. Virological responses were assessed at week 4, 8, 12, 24, 48 (end of therapy), and 24 weeks following therapy (sustained virological response, SVR). As previously reported, there was no significant difference in SVR in the induction (53%) and standard (50%) arms, therefore the pooled study population was used for analysis of SVR and relapse. RESULTS: A marked step-wise decline in SVR was evident by fibrosis stage: F0 (70%); F1 (60%); F2 (51%); F3 (31%); F4 (10%) (p<0.0001). Early virological responses were lower among F3/4 patients, including rapid virological response (RVR) (21% vs. 34% for F3/4 and F0-2, respectively) (p=0.0072), and the RVR positive predictive value was also lower (63% vs. 80%). Virological relapse rates were similar in early disease stages (F0, 16%; F1, 23%; F2, 26%), but increased markedly in advanced fibrosis (F3, 50%; F4, 80%) (p<0.0001). Cumulative PEG-IFNalpha-2a and ribavirin doses were similar among patients with F3/4 and F0-2 within treatment arms through week 4, 8, 12, and week 24. CONCLUSIONS: Low virological response in hepatitis C genotype 1 patients with advanced fibrosis is not explained by inadequate cumulative PEG-IFN and ribavirin doses.