Use of Nucleoside (Tide) Analogues in Patients with Hepatitis B-Related Acute Liver Failure

Abstract

Background & 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 (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], prolonged 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.

Hepatitis B virus treatment: Which patients require immediate treatment

“…This explains why some patients present with borderline or nondetectable HBV DNA, a situation that may be anticipated more often when a prolonged delay exists between the onset of symptoms and first assessment. 12,14 It can be argued that complete clinical recovery in these instances may depend more on the adequacy of hepatocellular regeneration rather than the rate or degree to which viral replication is suppressed by antiviral therapy.…”

Acute Liver Failure

“…48 A large retrospective review, however, found no difference in spontaneous and overall survival in patients with ALF from hepatitis B infection who were and were not treated with a nucleoside(-tide) analogue. 49 The role of corticosteroids in AIH ALF is unclear. Immunosuppression, usually steroids followed by azathioprine, is recommended for chronic AIH; however, the use in ALF is controversial.…”

Therapy of Acute and Fulminant Hepatitis B

“…Most of these studies recruited patients before they had progressed to more advanced hepatic encephalopathy (HE stages 3 or 4). In a study recruiting patients with more advanced liver failure, no benefit of nucleoside on survival was observed [37], but those authors still concluded that nucleos(t)ide analogues would be indicated in such patients to reduce viral load prior to potential liver transplantation. It is likely that early intervention is crucial.…”