5-8 The liver is a rapidly regenerating organ, and persistent liver injury leads to a process of healing and scar tissue formation resulting in fibrosis and eventually cirrhosis. Liver injury leads to fibrosis through the transformation of hepatic stellate cells from vitamin A storage cells to activated hepatic stellate cells that secrete fibrillar collagens.9-11 Although fibrosis was previously thought to be irreversible and relentlessly progressive, recent studies have challenged these ideas.

Animal models selleck chemicals of liver fibrosis have shown that removing the underlying source of liver injury results in clearance of the activated hepatic stellate cells, which allows resorption of the extracellular matrix and, consequently, reversal of fibrosis.12-14 Treatment of the underlying cause of inflammation has been shown clinically to result in reversal of fibrosis and cirrhosis in patients with liver disease from both viral and nonviral causes.15-20 Short-term antiviral therapy for CHB results in the suppression of viral replication21, 22 and has been associated with improvements of liver histology in randomized clinical trials.23 Treatment for 3 years with the oral antiviral agent lamivudine has also been shown to slow the clinical progression of liver disease in patients with advanced fibrosis and cirrhosis.24 However, in this landmark study, disease progression was assessed clinically

and not histologically,

and serum HBV DNA results were not reported. Longer term histological data exist from studies in nucleoside-naive www.selleckchem.com/products/BEZ235.html CHB patients treated with lamivudine or adefovir.25-27 The emergence of antiviral drug resistance negatively affected the histological benefits that were observed with lamivudine, and the impact of resistance on histological response was not reported in the adefovir studies. Viral replication is now recognized as the key driver of liver injury and disease progression, so the primary aim of treatment for chronic HBV infection is long-term suppression of HBV replication to undetectable levels.1, 28, 29 Entecavir is a potent HBV antiviral that, in comparison with lamivudine selleck inhibitor or adefovir in nucleoside-naive patients, has led to superior virological, histological, and biochemical outcomes after 48 weeks of therapy.21, 22, 30 In a study of nucleoside-naive Japanese patients, 3 years of entecavir therapy resulted in potent virological suppression and additional improvements in necroinflammatory and fibrosis scores in comparison with the baseline and week 48 values.31 Virological suppression increased with 5 years of entecavir treatment in long-term rollover studies, and there was minimal emergence of resistance.32-34 The aim of the present evaluation was to determine whether long-term treatment with entecavir is associated with continued histological improvement and reversal of fibrosis or cirrhosis.