Maya Gambarin-Gelwan

Resistance-Associated Variants in Chronic Hepatitis C Patients Treated with Protease Inhibitors

Direct-acting antiviral agents in combination with pegylated interferon (PEG-IFN) and ribavirin (RBV) significantly improve sustained virologic response rate and reduce duration of therapy among both treatment-naïve and treatment-experienced patients with genotype 1 chronic hepatitis C. One of the most important considerations with both boceprevir and telaprevir is the potential development of resistant variants with therapy. Patients with poor intrinsic responsiveness to interferon, and those with incomplete virological suppression on protease inhibitor therapy, appear to be at higher risk for resistance. In this article we will define antiviral resistance and review the data on both in vitro and in vivo resistance to protease inhibitors, concentrating on data on boceprevir and telaprevir. We will also explore the significance of resistant variants present at the baseline, as well as the fate of the resistant variants and the ways to minimize the development of resistance to protease inhibitors.

Chronic hepatitis C genotype 2 and 3: Are we ready for personalized medicine?

Over the last several years, efforts have been made in patients with genotypes 2 and 3 chronic hepatitis C (CHC) to assess whether shortening the duration of therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV) might preserve the efficacy of the standard 24 week treatment duration while decreasing sideeffects and improving tolerability. Data on viral kinetics have shown that both the effectiveness of IFN in blocking production of the virus in the first phase of viral decline (rapid decline) and the rate of decline in the second phase (slower decline) differ in patients with hepatitis C virus (HCV) genotype 1 and in those with genotypes 2 or 3 [1,2]. This led several investigators to the hypothesis that in patients with CHC genotype 2 or 3 and rapid virologic response (RVR, i.e. HCV RNA undetectable after 4 weeks of therapy), 12–16 weeks of treatment with PEG-IFN and RBV may be as effective as a course of 24 weeks [3,4], which induces sustained virologic response (SVR) in about 80% of patients [5,6]. While several European studies [3,7–9] and a study from Taiwan [10] appeared to support this hypothesis, the results were somewhat different in the ACCELERATE [11] and NORTH-C [12] trials. The conflicting results may have been due to differences in the study design, prevalence of advanced fibrosis and cirrhosis, baseline viral counts, predominant genotype, ethnic background of the study population, and different RBV dosing schedules. The earlier trials by Dalgard et al. [7] and VonWagner et al. [8] included a relatively young HCV population with mostly earlystage fibrosis, while almost 25% of patients in ACCELERATE (a large prospective randomized, multinational non-inferiority trial) had bridging fibrosis or cirrhosis [11]. The absence of bridging fibrosis/cirrhosis was shown to be an independent predictor of SVR among genotype 2 and 3 patients by both Dalgard et al. [7] and Shiffman et al. [11], although this has not been reported by others [3,8,13]. Unlike most prior studies which evaluated truncation of treatment duration to less than 24 weeks in genotype 2 and 3 patients, ACCELERATE used a fixed dose RBV (800 mg/d). Since the mean body weight of ACCELERATE patients with genotype 2, for example, was about 84 kg [11], that resulted in a mean daily dose

S2085 Non-Invasive Hepatic Fibrosis Assay Scores Increase with Increasing Age in Patients with Chronic Hepatitis C

Purpose:Patients with Chronic Hepatitis C (CHC) may develop fulminant hepatitis if coinfected with Hepatitis A virus (HAV) or Hepatitis B virus (HBV). We sought to determine if our African-American (AA) and Hispanic population with CHC were tested and vaccinated as per AASLD guidelines. We also studied immunity patterns in HIV co-infected patients. Methods:We conducted a retrospective study at our university affiliated community health care center involving CHC patients seen in the hepatitis clinic from January 2004 to December 2007. Data on demographics, HIV status, HAV and HBV serology and vaccination was recorded. Patients with decompensated liver disease, acute HAV and active HBV were excluded. Results:Among 174 patients with CHC, 131 (75.2%) were Hispanics and 38 (21.8%) were AA. The prevalence of HAV immunity was higher than that of HBV (65% vs.40%,p 0.05). AA subjects were more likely to be tested for HAV and HBV immunity compared to Hispanics (76% vs. 59% p=NS; 92% vs. 82% p=NS respectively), though this difference did not reach statistical significance. Among 28 subjects co-infected with HIV (16%, n=174), the likelihood of being tested for immunity to HAV was higher than non-HIV subjects (93% vs. 61% p<0.0001). The prevalence of immunity to HAV or HBV did not differ in the two groups (p=NS). Conclusion:Among AA and Hispanics with CHC, we found a significantly higher prevalence of immunity to HAV than previously reported. Interestingly, immunity to HAV was higher than that to HBV. There is a disparity in the practice of testing for immunity to HAV compared to HBV. Despite established AASLD vaccination guidelines, HAV and HBV vaccination rates are yet sub-optimal. Increased physician awareness is necessary to ensure implementation of AASLD vaccination guidelines for HAV and HBV in minority patients with Chronic hepatitis C.