Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience

Abstract

Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.

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.…”

“…In a prospective study of lamivudine therapy in 17 patients with severe or fulminant hepatitis B, treatment was associated with a significantly lower rate of encephalopathy and need for transplantation when compared with historical controls. 12 In a randomized controlled trial of lamivudine versus placebo in 71 patients with acute hepatitis and jaundice (bilirubin >5 mg/dL), serum HBV DNA levels decreased more rapidly in the lamivudine group, but higher rates of clinical and biochemical improvement were not observed. 13 Recently, data on 61 patients with fulminant liver failure due to acute hepatitis B was reported from the US Acute Liver Failure Study Group.…”

Entecavir in Severe Acute Hepatitis B

“…Tillman et al [55] reported that Lamivudine may prevent the progression of severe hepatitis B to liver failure by decreasing HBV DNA load, reducing inflammatory reaction and improving liver function when administered early enough.…”

Treatment of special populations with chronic hepatitis B infection

“…These studies are small and LAM has been used in most, which has been found to improve survival. However, a randomized study did not demonstrate any difference in the rate of biochemical improvement or of HBsAg loss [77,78]. Several years ago, a randomized trial was conducted in Greece in patients with acute icteric hepatitis B using IFN-a 2b with no benefit, since all patients lost HBsAg and seroconverted to anti-HBs [79].…”