A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: A nationwide, multicentre study in Taiwan

Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Antiviral therapy (Impact Factor: 3.02). 02/2006; 11(8):985-94.
Source: PubMed


The long-term benefit for chronic hepatitis C (CHC) patients treated with interferon (IFN)/ribavirin (RBV) combination therapy remains unclear. We aimed to evaluate the long-term effects of IFN monotherapy and IFN/RBV combination therapy on reducing hepatocellular carcinoma (HCC) and mortality in patients with chronic hepatitis C virus (HCV) infection, adjusting for risk factors.
A total of 1,619 patients with biopsy-proven CHC, including 1,057 receiving IFN-based therapy (760 on IFN/RBV combination therapy) and 562 untreated controls from three medical centres and one regional core hospital in Taiwan were enrolled in this retrospective-prospective cohort study.
The incidence of HCC and survival during a follow-up period of 1.0-15.3 (mean 5.18) and 1-16 (mean 5.15) years in treated and untreated patients, respectively, was analysed using Cox proportional hazards regression. The cumulative incidence of HCC was 35.2% and 12.2% for untreated and treated groups, respectively (P=0.0013). The cumulative survival rate was 93.1% and 96.2% for untreated and treated groups, respectively (P=0.3928). Significantly lower incidences of HCC and mortality were observed in sustained virological responders (both for IFN monotherapy and IFN/RBV combination) but not in nonresponders when compared with untreated patients. HCV genotype 1 patients had significantly higher incidences of HCC than genotype non-1 patients. In multivariate analysis, pre-existing cirrhosis, non-response, HCV genotype-1 and age were associated with HCC; pre-existing cirrhosis and non-response correlated to mortality.
A sustained virological response secondary to IFN monotherapy or IFN/RBV combination therapy could reduce the risk for HCC and improve survival of CHC patients.

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Available from: Ming-Lung Yu, Oct 14, 2015
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    • "Notably, although HCC occurred in only a minority of non-cirrhotic patients, older noncirrhotic patients with high baseline cGT levels had as great a risk for HCC development as cirrhotic patients. Persistent viremia has been recognized as a strong indicator of HCC development among patients who have received anti-HCV antiviral therapy [7] [8] [9] "
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    ABSTRACT: Background& Aims Hepatitis C virus (HCV)-infected patients with cirrhosis remain at risk of hepatocellular carcinoma (HCC) even after achieving sustained virological response (SVR). The aim of the study was to explore the incidence and risk for HCC among non-cirrhotic patients with an SVR. Methods A total of 642 patients with an SVR after peginterferon/ribavirin therapy were enrolled with a median follow-up period of 53.0 months (range: 6–133 months). Results Thirty-three of the 642 (5.1%) patients developed HCC over 2324.8 person-years of follow-up. Cox regression analysis revealed that the strongest predictive factor of HCC occurrence was liver cirrhosis (HR 4.98, 95% CI. 2.32-10.71, P<0.001), followed by age (HR 1.06, 95% CI. 1.02-1.11, P=0.005) and r-GT levels (HR 1.008, 95% CI. 1.004-1.013, P<0.001). The incidence of HCC did not differ between patients with high and low baseline r-GT levels among patients with cirrhosis (P=0.53), but the incidence of HCC was significantly higher in non-cirrhotic patients with high r-GT levels compared with those with low r-GT levels (P=0.001). Cox regression analysis revealed that the strongest factors associated with HCC development in non-cirrhotic sustained responders were baseline r-GT levels (HR 6.44, 95% CI. 2.20-18.89, P=0.001) and age (HR 3.68, 95% CI. 1.33-10.17, P=0.012). The incidence of HCC was not different between older non-cirrhotic patients with high r-GT levels and cirrhotic patients (P=0.34). Conclusions HCC remains a threat in non-cirrhotic patients with an SVR. Serum r-GT levels helped to identify potential patients at high risk.
    Full-text · Article · Jul 2014 · Journal of Hepatology
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    • "Therefore, we are unable to understand if the discrepancy between the serological and virological diagnostic tests of HBV/HCV would change over time. The present study cannot provide our own data of liver disease deterioration, ie, chronic liver disease to LC or HCC, and effect of anti-viral therapy on their outcome is not known 36. Another study is now underway and we might be able to answer some of the above-mentioned questions. "
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    ABSTRACT: Background and Aim: Viral hepatitis is a health threat for hemodialysis (HD) patients and it may be transmitted during treatment. Some patients categorized to have viral hepatitis were found to be non-viremic. To clarify the discrepancy between the serological tests in HD patients, we conducted the study. Methods: A total of 1681 HD patients was included. Blood samples were analyzed for hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody (anti-HCV). Detection of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA were performed in either HBsAg (+) or anti-HCV (+) samples. HBV DNA/HCV RNA was also measured in a subset of HBsAg (-) and anti-HCV (-) patients. Liver function tests were analyzed and compared with the serological and virological tests. Results: The serological tests showed that 230 patients (13.7%) were HBsAg (+) and 290 (17.3%) were anti-HCV (+). We were unable to detect HBV DNA in 97 of 230 (42.2%) HBsAg (+) patients, and HCV RNA could not be found in 76 of 290 (26.2%) anti-HCV (+) patients. In 167 HBsAg (-) patients, only one showed a trace amount of HBV DNA. None of 151 anti-HCV (-) patients showed detectable HCV RNA. The prevalence rate of viral hepatitis remains high in Taiwanese HD patients: 13.7% for HBV and 17.3% for HCV. However, virological analysis showed 42.2% non-viremic rate for HBsAg and 26.2% non-viremic rate for anti-HCV. Conclusions: The findings might challenge the presently suggested principles of bed and machine dedication and the diagnosis of viral hepatitis in HD patients.
    Full-text · Article · Mar 2014 · International journal of medical sciences
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    • "Successful HCV treatment using antiviral therapy would prevent the consequences of HCV infection.[2], [3] Recently, the introduction of direct antiviral agents (DAA) has greatly improved the sustained virological response (SVR) rate in patients with HCV genotype 1 (HCV-1) infection.[4] On the other hand, pegylated interferon (peginterferon)/ribavirin, which is the standard-of-care for HCV-2 patients, has provided satisfactory results with an SVR rate of 80–93%.[5]–[7] "
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    ABSTRACT: BACKGROUNDAIMS: The impact of virological factors and interleukin-28B (IL-28B) genetic variants on retreatment of hepatitis C virus genotype 2 (HCV-2) treatment-experienced patients remains unknown. On-treatment virological responses and IL-28B rs8099917 genotype were determined in 46 HCV-2 treatment-experienced patients (42 previous relapsers; four previous non-responders) retreated with 24-week peginterferon/ribavirin. Forty (87.0%) patients carried the rs8099917 TT genotype and 6 patients (13.0%) carried the TG/GG genotype. The sustained virological response (SVR; seronegativity of HCV RNA throughout 24 weeks of the post-treatment follow-up period) rate was 71.7%. Compared with previous non-responders, previous relapsers had a significantly higher SVR rate (78.6% vs. 0%, P = 0.004) and a lower relapse rate (17.5% vs. 100%, P = 0.04). All the previous non-responders were with the rs8099917 TT genotype. As for those who relapsed, treatment responses, including the rates of rapid virological response (RVR, 80.6% vs. 66.7%, P = 0.59), early virological response (EVR, 97.2% vs. 83.3%, P = 0.27), end-of-treatment virological response (97.2% vs. 83.3%, P = 0.27) and SVR (80.6% vs. 66.7%, P = 0.59) and relapse rate (17.1% vs. 20.0%, P = 1) did not differ significantly between patients with the rs8099917 TT and those with the non-TT genotype. Multivariate analysis revealed that the most important factor predictive of an SVR in the retreatment of HCV-2 was previous relapse; the only factor predictive of an SVR for previous relapsers was the achievement of an EVR. Compared with the achievement of a RVR, the attainment of an EVR was more accurate in predicting an SVR (88% vs. 74%). Peginterferon/ribavirin is effective in the retreatment of HCV-2 relapsers, especially among those who achieved an EVR.
    Full-text · Article · Mar 2013 · PLoS ONE
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