Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure

Abstract

Background and aims: The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF.

Methods: The US Acute Liver Failure Study Group, a 23-site registry, prospectively enrolled 1,413 patients with ALF with different etiologies between 1998 and 2008. Of those, 105 patients were identified as HBV-ALF patients, of whom we excluded those without data on NA use or with co-infection with hepatitis C, leaving 85 patients, 43 of whom had received NA treatment. HBV-DNA on admission was quantified by real time polymerase chain reaction.

Results: The treated and untreated groups were similar in most respects but differed significantly in regard to higher aminotransferase and bilirubin levels and hepatic coma grades, all being observed in the untreated group. Median duration of NA treatment was 6 days (range, 1-21 days). Overall survival in the NA treated and untreated groups were 61 and 64%, respectively (P = 0.72). Rates of transplant-free survival were 21 and 36% in the treated and untreated groups, respectively (P = 0.42). Multivariate analysis revealed that not using a NA [odds ratio (OR) 4.4, 95% CI 1.1-18.1, P = 0.041], hepatic coma grade I or II [OR 14.4, 95% CI 3.3-62.8, P < 0.001] and prothrombin time (PT) [OR 0.59, 95% CI 0.39-0.89, P = 0.012] were predictors of improved transplant-free survival.

Conclusions: Patients who are admitted with established HBV-ALF do not appear to benefit from viral suppression using nucleoside(tide) analogues presumably because of rapid disease evolution and short treatment duration. Despite the lack of benefit, NAs should still be given to transplantation candidates since viral suppression prevents recurrence after grafting.

Figure 1

Study schema of NA use in HBV-ALF indicating patient groups and outcomes. Of the 105 patients with HBV-ALF enrolled, 12 were excluded because of either co-infection with hepatitis C (2) or lack of NA data (10). Eight additional patients were excluded because treatment had been started either >3 weeks prior to study admission or >3 weeks after study admission. NA: Nucleoside (tide) analogues; SS: Spontaneous Survival; OLTx: Transplantation; OS: overall survival; CG: coma grade

Figure 2

Receiver operator characteristic (ROC) curve for a logistic regression model using admission hepatic coma grade, prothrombin time/INR, creatinine, age and the two groups (NA use vs. No NA use) as covariates. The area under the curve was 0.891 which was highly significant.