Hepatitis B-associated Acute Liver Failure: Life-saving Immediate Treatment with Entecavir Inhibits the Replication of Hepatitis B Virus and its Sequelae

Hepatitis B virus (HBV) remains a major cause of acute liver failure (ALF) necessitating a high rate of emergency liver transplantation. Acute infection is followed by high viral replication rates leading to hepatocyte death and, ultimately, ALF. The objective of treating HBV-induced ALF thus is to eliminate, or significantly suppress, HBV replication. In patients, the guanosine nucleoside analogue, entecavir, has demonstrated superior anti-HBV activity when, for example, compared with lamivudine in chronic HBV infection. Objective: To test whether efficient suppression of viral replication in patients with HBV-induced ALF prevents apoptotic and necrotic cell death as critical events in the pathogenesis of ALF. Methods / Results: This prospective study (02/2008–08/2008) included five patients [1f and 4m at 36.8±13.8 years of age] with ALF. Before treatment, transaminases were highly elevated (ALT: 5,366.6±2,635.3 U/l / AST: 5,366.6±5,010.4 U/l); bilirubin was increased (13.52±4.99mg/dl), and Quick methodology (36.2±15.5%) revealed impaired liver function. HBV DNA levels were >5×106IU/ml. Hepatocyte death was quantified in patients’ sera by (i) M65 ELISA (detecting overall death), and (ii) M30 Apoptosense® ELISA (measuring only apoptotic cell death via caspase-cleaved cytokeratin 18): in HBV+ ALF patients, both M65 (18,010±6,229 U/l) and M30 (10,228±6,581 U/l) were highly elevated. All patients recovered under entecavir treatment. Upon treatment, pathologic parameters rapidly decreased and returned to reference values or trace amounts (HBV DNA) after 6–13 days in all of the cases. The treatment-induced decrease in transaminase levels correlated highly significantly (p<0.005) with M65 and M30 serum values. Conclusion: Immediate treatment of HBV-induced ALF with entecavir inhibits HBV replication whereby abrogating hepatocyte death, reduced liver function, and the continuously elevated systemic transaminase and virus titers.

Acute liver failure - Cell death - HBV