Treatment of Hepatitis B Virus Cirrhosis

Article type: Editorial Implication for health policy/practice/research/medical education: Untreated Hepatitis B Virus (HBV) cirrhosis runs a progressive course to liver failure and death. However, new antivirals that adequately control HBV replication can interrupt this ominous clinical course, are capable of reverting liver fibrosis and may avoid liver transplantation. Therefore indefinite treatment with the latest generation antivirals (Entecavir, Tenofovir) has become mandatory in all HBV viremic patients with compensated and decompensated cirrhosis An analysis of cohorts of patients with compensated cirrhosis caused by the Hepatitis B Virus (HBV) indicates that the disease decompensates at an annual rate of 1.5% to 5%. Following decompensation, the 5-year survival rate has varied from 14% to 35% (1); the 5-year survival rate in untreated patients is higher in patients decompensating from variceal bleeding than in those decompensating from ascites (29 vs. 16%) (2). Given its ominous course, it is of no surprise that international guidelines recommend treating HBV cirrhosis to control HB viremia, prevent the dire complications of the disease, and increase survival. Interferon is an unfit treatment solution. It is contrain-dicated in decompensated cirrhosis and of limited use in compensated cirrhosis (3, 4). HBV can usually only be controlled for temporarily; the cytokine cannot be given for long because of side effects and bacterial infection; and exacerbation of liver disease can decompensate the disease. Antiviral therapy for HBV cirrhosis entered common practice following the seminal study of Dr. Liaw (5), who showed that the treatment of compensated HBV cirrhosis with Lamivudine significantly diminishes the risk of decompensation and complications; specifically, after 36 months of therapy, only 9% of the patients in Lamivudine treatment experienced progression of the disease, versus 21% of those in the placebo group, a difference so significant that it prompted early termination of the trial. Unfortunately, Lamivudine treatment is aggravated by a high risk of viral resistance and hepatitis flares; these conditions can cause rapid deterioration of the liver disease and death (6). Adefovir, the next antivi-ral to be developed, confirmed the efficacy of treatment for HBV cirrhosis, in particular in the transplantation setting. In two studies, patients with lamivudine-refractory-decompensated HBV were given Adefovir for 1 year; at the 1-year mark, these patients had significantly improved the Meld score versus baseline (7, 8). However Adefovir was not perfect, as it had a potential for nephrotoxicity (a particular risk in cirrhotic patients) and suppressed HBV replication only slowly. Furthermore, the patients' experience …