C.-F. Huang

Interleukin-28B genetic variants in identification of hepatitis C virus genotype 1 patients responding to 24 weeks peginterferon/ribavirin

BACKGROUND & AIMSnA substantial proportion of hepatitis C virus genotype 1 (HCV-1) patients achieved a sustained virological response (SVR, HCV RNA seronegative throughout 24 weeks of post-treatment follow-up) after 24 weeks peginterferon/ribavirin therapy. We explored the role of interleukin-28B genotype in identifying patients who responded to the regimen.nnnMETHODSnInterleukin-28B rs8099917 genotype was determined in 226 HCV-1 patients with 24 weeks peginterferon/ribavirin.nnnRESULTSnCompared to patients with rs8099917 TG/GG genotype, those with TT genotype had significantly higher rapid virological response (RVR, HCV RNA seronegative at treatment week 4, 54.0% vs. 17.9%, p<0.001) and SVR (64.7% vs. 25.6%, p<0.001) rates, and lower relapse rate (28.0% vs. 54.5%, p=0.01). Logistic regression analysis revealed that the strongest factor predictive of a RVR was the carriage of rs8099917 TT genotype (odds ratio/ 95% confidence intervals [OR/CI]: 6.24/2.34-16.63), followed by lower viral loads (OR/CI: 5.29/2.81-9.93) and age (OR/CI:0.94/0.91-9.97). The most important factor predictive of an SVR was the attainment of a RVR (OR/CI: 22.23/9.22-53.58), followed by the carriage of rs8099917 TT genotype (OR/CI: 3.38/1.18-9.65), lower viral loads (OR/CI: 2.23/1.00-4.93) and ribavirin exposure dose (OR/CI: 1.17/1.06-1.30). The determinant power of rs8099917 genotype on SVR was mainly restricted to non-RVR patients, particularly those with higher baseline viral loads. Combination of the two pretreatment predictors, interleukin-28B genotype and baseline viral loads, could predict treatment efficacy with a positive predictive value of 80% and a negative predictive value of 91%.nnnCONCLUSIONSnInterleukin-28B genotype could help identifying patients who are or are not candidates for an abbreviated regimen before treatment.

Pegylated-Interferon Alpha Therapy for Treatment-Experienced Chronic Hepatitis B Patients

Background Studies are limited on pegylated interferon (Peg-IFN) therapy for chronic hepatitis B (CHB) patients who failed or relapsed on previous antiviral therapy. Objectives We aimed to investigate the effect of Peg-IFN therapy in treatment-experienced CHB patients. Study Design A total of 57 treatment-experienced CHB patients at two medical centers were enrolled. All of the patients were treated with Peg-IFN α-2a at 180 μg weekly for 24 or 48 weeks. The hepatitis B serological markers and viral loads were tested every 3 months until 1 year after stopping Peg-IFN therapy. The endpoints were HBV DNA <2000IU/mL, hepatitis B e antigen (HBeAg) seroconversion, and a hepatitis B surface antigen (HBsAg) loss at 12 months post-treatment. Results In HBeAg-positive patients, 25.0%, 29.2%, and 12.5% of the patients achieved HBeAg seroconversion, HBV DNA <2000 IU/mL and a combined response, respectively, at 12 months post-treatment. Prior IFN therapy, a high baseline ALT level, a low creatinine level, undetectable HBV DNA at 12 weeks and a decline in HBV DNA >2 log10 IU/mL at 12 weeks of therapy were factors associated with treatment response. In HBeAg-negative patients, 9.1%, 15.2%, and 6.1% of the patients achieved undetectable HBV DNA, HBV DNA <2000 IU/mL, and an HBsAg loss, respectively, at 12 months post-treatment. No factor was significantly associated with the treatment response in the HBeAg-negative patients. The median HBsAg level declined from 3.4 to 2.6 log10 IU/mL in all the patients, and the 5-year cumulative rate of the HBsAg loss was 9.8% in the HBeAg-negative patients. Overall, none of the patients prematurely discontinued the Peg-IFN therapy. Conclusions Peg-IFN re-treatment is effective for a proportion of HBeAg-positive treatment-experienced patients; it has limited efficacy for HBeAg-negative treatment-experienced patients. Peg-IFN might facilitate HBsAg loss in HBeAg-negative treatment-experienced patients.

Rapid Prediction of Treatment Futility of Boceprevir with Peginterferon-Ribavirin for Taiwanese Treatment Experienced Hepatitis C Virus Genotype 1-Infected Patients.

The efficacy and safety of the boceprevir (BOC)-containing triple therapy in Taiwanese treatment-experienced patients remains elusive. After 4 weeks of peginterferon/ribavirin lead-in therapy, patients with cirrhosis or previous null-response received triple therapy for 44 weeks; whereas others received 32 weeks of triple therapy followed by 12 weeks of peginterferon/ribavirin therapy. Patients with HCV RNA > 100 IU/mL at week 12 or with detectable HCV RNA at week 24 of treatment were viewed as futile. A total of 123 patients received treatment. The rates of sustained virological response (SVR) and relapse were 66.7% and 8.9%, respectively by using intention-to-treat analysis. Multivariate analysis revealed that factors associated with SVR included HCV-1b (odds ratio [OR]/ 95% confidence intervals [CI]: 19.23/1.76–525.15, P = 0.01), BOC adherence (7.69/1.55–48.78, P = 0.01), serum albumin (OR/CI:6.25/1.14–40.07, P = 0.03) levels and HCV RNA levels (OR/CI:0.34/0.12–0.79, P = 0.01). Twenty-six (21.1%) patients experienced severe adverse events (SAEs). Multivariate analysis revealed that APRI > 1.5 was the single factor associated with occurring SAEs (OR/CI: 3.77/ 0.97–14.98, P = 0.05). Merging the cut-off values of HCV RNA > 7 log IU/mL at baseline and HCV RNA > 6 log IU/mL at week 4 provided the earliest and best combing viral kinetics in predicting week 12/24 futility with the PPV of 100% and accuracy of 93.5%. HCV-1 treatment experienced Taiwanese patients treated with boceprevir-containing triple therapy in real world had comparable efficacy and safety profiles with those reported in clinical trials. Early viral kinetics before week 4 of treatment highly predicted futility at week 12 or 24 of treatment.

More advanced disease and worse survival in cryptogenic compared to viral hepatocellular carcinoma.

Although hepatitis B virus (HBV) and hepatitis C virus (HCV) infections remain major risk factors for hepatocellular carcinoma (HCC), non‐viral causes of HCC, particularly non‐alcoholic fatty liver disease (NAFLD), are becoming increasingly prevalent. The aim of this study was to compare the clinical characteristics and survival of cryptogenic and viral HCC.

Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance

Background/Aims Both spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by anti-viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC). The current study aimed to compare the risk of HCC between the two patient groups Methods A total of 313 subjects with spontaneous HCV clearance (SC) and 564 age- and sex-matched patients in the treatment-induced SVR group were enrolled for analysis. Results Nineteen (2.2%) of the 877 patients developed HCC during 6,963 person-years of follow-up. Fourteen (2.5%) SVR patients and 5 (1.6%) SC patients developed HCC (P=0.004). Cox regression analysis of factors predictive of HCC included SVR (versus SC: hazard ratio [HR]/ 95% confidence interval [CI]: 5.83/1.27-26.88), diabetes (HR/CI:3.41/1.21-9.58), and age (HR/CI: 1.07/1.01-1.14). Of the 564 SVR patients, eleven (5.9%) of the 187 patients with fibrosis stage 2-4 (F2-4) and 2 (0.9%) of the 226 patients with F01 developed HCC (P=0.01). Compared to SC subjects, only SVR patients with F2-4 (P<0.001) but not F0-1(P=0.60) had a higher risk of HCC development. Cox-regression analysis using liver fibrosis as a variable demonstrated that factors associated with HCC included SVR with F2-4 (versus SC: HR/CI: 10.06/2.20-45.98), diabetes (HR/CI:3.23/1.14-9.19), and age (HR/CI: 1.08 1.02-1.15). Conclusions Compared to subjects with spontaneous viral clearance, subjects with antiviral treatment-induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis. These results may provide important information for decision-making regarding the prioritization of current direct antiviral agents in resource-limited countries.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects survival after HCC diagnosis.