A randomized controlled trial of lamivudine to treat acute hepatitis B

Abstract

The role of antivirals in patients with acute viral hepatitis B (AVH-B) has not been evaluated in controlled trials. The aim of this study was to evaluate the efficacy of lamivudine in patients with AVH-B. AVH-B patients with serum bilirubin of more than 5 mg/dL were randomized to receive either 100 mg of lamivudine daily for 3 months (group 1, n ‫؍‬ 31) or placebo (group 2, n ‫؍‬ 40). Patients were considered to have severe AVH-B if they fulfilled 2 of 3 criteria: (1) hepatic encephalopathy; (2) serum bilirubin > 10.0 mg/dL; and (3) international normalized ratio (INR) > 1.6. At week 4, HBV DNA levels were significantly lower (P ‫؍‬ 0.037) in group 1 (median: 3.6721 log copies/mL) than group 2 (median: 4.2721 log copies/mL). Thereafter, HBV DNA levels were comparable in the 2 groups. The improvement in serum bilirubin, ALT, and INR values was similar in the 2 groups. Twenty-two patients (71%) in group 1 and 25 patients (62.5%) in group 2 had severe AVH-B. Results were similar when patients with severe AVH-B were analyzed separately. After 12 and 18 months, 93.5% and 92.5%, respectively, of patients in the lamivudine group and 96.7% and 97.5%, respectively, of patients in the placebo group lost HBsAg. There were no deaths in either group. After 1 year, 21 patients (67.7%) in group 1 and 34 patients (85%) in group 2 developed protective anti-HBs titers (P ‫؍‬ 0.096). All HBeAg-positive patients in both groups lost e antigen and anti-HBe developed in 71% and 87.5% of patients in groups 1 and 2, respectively (P ‫؍‬ 0.132). A cute viral hepatitis B (AVH-B) is successfully cleared in more than 95% of immunocompetent patients. The remainder of patients may develop either chronic HBV infection or, in a small proportion, fulminant hepatitis.The accepted criteria for defining clinical and serologic recovery from acute hepatitis B are clearance of circulating hepatitis B surface antigen (HBsAg) and appearance of the antibodies to HBsAg (anti-HBs), with normalization of serum aminotransferases. Nevertheless, a recent longterm study noted that occult HBV infection might persist in the liver up to 10 years after clinical resolution. 1Lamivudine is a potent inhibitor of HBV replication that works by causing chain termination of an RNA-dependent HBV polymerase. 2 It has been administered successfully to immunocompromised patients with 4 Since a proportion of patients with AVH-B develop severe hepatitis and fulminant hepatic failure, a logical hypothesis is that rapid reduction in the HBV DNA levels through the use of antiviral agents could result in a less intense host response against the hepatitis B virus. However, the experience with lamivudine treatment of immunocompetent patients with AVH-B has been limited to only a few case reports, 5,6 a published abstract of a larger series 7 and a pilot study. 8 The aim of this study was to evaluate the efficacy, utility, and safety of lamivudine in treating immunocompetent patients with AVH-B.

Hepatitis B virus treatment: Which patients require immediate treatment

“…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. 14 A difference in survival was not noted in 27 patients treated with nucleoside analogue therapy compared with untreated patients (67% and 71%, respectively).…”

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

“…Treatment with antivirals is usually recommended in fulminant disease. Small randomized controlled trials with 3TC have demonstrated a more rapid fall in HBV DNA but no difference in outcome in acute infection [143]. In coinfection, fewer (60-80%) patients with acute HBV clear their infection [82,83].…”

Worse Outcomes among African Americans with Liver Cancer: What Might Cause the Disparity?

“…The majority of cases of acute HBV results from horizontal transmission and the vast majority (95%) are cleared and do not result in chronic HBV infection [28]. According to data in the NHANES III (1988)(1989)(1990)(1991)(1992)(1993)(1994)) and a subsequent NHANES (1996-2006) survey, ageadjusted prevalence of chronic HBV infection defined as patients with positive anti-HBc and HBsAg in the non-Hispanic black population increased from 0.83% to 0.89%, the only group studied that showed an increase over the time surveyed [29].…”