Predictors of Treatment Response in Chronic Hepatitis B
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Predictors of Treatment Response in Chronic Hepatitis B Grace L.-H. Wong and Henry L.-Y. Chan Department of Medicine and Therapeutics and Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, the Hong Kong SAR, China
Abstract
The ultimate goal of treatment for chronic hepatitis B is to reduce liver-related complications and mortality. Sustained hepatitis B e antigen (HBeAg) seroconversion and hepatitis B surface antigen (HBsAg) clearance 6–12 months after stopping treatment are the short-term surrogate outcomes for interferon or peginterferon therapy. As most patients require long-term nucleos(t)ide analogue treatment, which also has the risk of drug resistance in the case of incomplete viral suppression, maintained hepatitis B virus (HBV) DNA suppression to an undetectable level is the appropriate surrogate outcome. Because no antiviral treatment is perfect, it is desirable for treatment response to be predicted and the treatment regimen modified accordingly. At baseline, high ALT and low HBV DNA levels can predict response to both (peg)interferon and nucleos(t)ide analogues. Genotype A HBV responds best to peginterferon but HBV genotype has no predictive value for nucleos(t)ide analogue treatment. HBV DNA is a good on-treatment predictor of response for nucleos(t)ide analogues but not for (peg)interferon. The data supporting the use of quantitative HBsAg and HBeAg to predict response to peginterferon is stronger than that for nucleos(t)ide analogues. In conclusion, predictors of response are useful to provide the most appropriate antiviral therapy to the most suitable patients, in order to achieve the best response and improve the clinical outcome of chronic hepatitis B patients.
Hepatitis B virus (HBV) infection is a global health problem, currently affecting about 400 million people worldwide. It is estimated that over 200 000 and 300 000 chronic hepatitis B patients die annually worldwide from liver cirrhosis and hepatocellular carcinoma (HCC), respectively.[1] Persistent viral replication is associated with progression of liver disease. Hence, antiviral therapy is aimed at maximal viral suppression to achieve improved clinical outcomes. As no antiviral treatment is perfect, it is desirable to be able
to predict treatment response and to modify the treatment regimen accordingly.[2] As liver-related complications take decades to develop, most treatment trials use short-term surrogate markers of response as outcome measures. To evaluate predictors of treatment response, one must understand the meaning and importance of each of these surrogate markers. Furthermore, the on-treatment response of nucleos(t)ide analogues must be clearly differentiated from the off-treatment response of interferon (or peginterferon) therapy.
Wong & Chan
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1. Surrogate Markers for Long-Term Outcome 1.1 Hepatitis B Surface Antigen (HBsAg) Clearance
Hepatitis B surface antigen (HBsAg) clearance, with or without the appearance of ant
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