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Lecture - Personalized Hepatology 2012: Therapy of Chronic Hepatitis B and C
FML seminar, December 15, 2012: New Developments in Gastroenterology with Focus on Hepatitis
Personalized Hepatology 2012: Therapy of Chronic Hepatitis B and C
Prof. Dr. Dr. h. c. mult. Hubert E. Blum
University Hospital Freiburg, Germany
The options and modalities of the antiviral treatment of chronic hepatitis B and C have greatly improved during the last few years. This is mainly due to the availability of novel antiviral drugs on the one hand and on the other hand to the increasing identification of viral as well as host factors that allow to individually predict the antiviral response (‚personalized hepatology’).
Chronic hepatitis B. Standard therapy of chronic hepatitis B is based on the monotherapy with pegylated interferon-a (PEG-IFNa2a) or a nucleos(t)ide analogue. The treatment with PEG-IFNa2a has a defined duration of 6-12 months, results in a sustained virological response (SVR) of only about 25% in Caucasian patients and is associated with significant side effects. By comparison, treatment with nucleos(t)ide analogues has only minor side effects but is of undefined duration, generally several years, and carries the the risk of developing drug resistance.
Given the high cost and potential side effects, major efforts were targeted towards the identification of viral factors predicting the individual response to antiviral therapy. Indeed, it is possible to predict the response to PEG-IFNa2a by comparing the level of hepatitis B surface antigen (HBsAg) at week 0 and week 24 of treatment: a drop of the HBsAg level of > 1 log predicts a 92 % chance of a SVR (positive predictive value). By comparison, a drop of < 1 log predicts treatment failure in 97 % (negative predictive value). Further, there are also predictors of the response to treatment with nucleos(t)ide analogues. A 5-year follow-up study of patients treated with lamivudine identified a level < 10'000 copies of HBV DNA / ml serum at week 4 of treatment as a predictor of response.
While these results require confirmation and extension to other antiviral agents, they clearly indicate that personalized therapy of chronic hepatitis B will become reality.
Chronic hepatitis C. Since the late 1980s standard therapy of chronic hepatitis C has greatly improved and is now based on the combination of a pegylated interferon-a (PEG-IFNa) and ribavirin. During recent years 2 major developments have entered clinical practice: predictors of response to antiviral therapy and the availability of new HCV-specific direct antiviral agents (DAAs).
The individual response to antiviral treatment can be predicted by 2 viral (HCV genotype and dynamics of HCV RNA loss) and 3 host factors (interleukin 28B genotype and the serum levelof interferon inducible protein-10 and the vitamin D3, resp.). These factors allow to individually predict the SVR and to individualize the duration of treatment, e.g., shortening or prolonging treatment duration as well as stopping treatment prematurely.
Given the fact that patients infected with HCV genotype 1a or 1b have a SVR to the standard antiviral combination therapy of 40-50 % only, major efforts were directed towards the development of novel DAAs, incl. inhibitors of HCV protease, polymerase and helicase. Recently, the 2 HCV protease inhibitors boceprevir and telaprevir have been licensed for the treatment of both therapy-naive as well as relapse or non-responder patients with hepatitis C genotype 1 infection, in combination with PEG-IFNa and ribavirin. In clinical studies, the triple therapy with telaprevir resulted in therapy-naive patients in a SVR of 75 % vs. 44 % (PEG-IFNa and ribavirin only), in relapse patients of 85 % vs. 24 % and in non-responders of 31 % vs. 5 %. Similar studies with boceprevir showed a SVR in therapy-naive patients of 63 % vs. 38 % and in relapse patients of 72 % vs. 29 %.
In summary, the therapy of chronic hepatitis B and C have greatly improved during recent years, in part due to novel antiviral agents, in part by an increasingly individualized treatment strategy based on viral and/ or host factors (‚personalized hepatology’). Further improvements are to be expected in the near future, e.g., an interferon-free treatment for patients with chronic hepatitis C. Despite these therapeutic advances, the implementation of the available measures to prevent viral hepatitis still have a very high priority.