A Randomized Controlled Trial of Lamivudine in Acute Hepatitis B
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Study type: Interventional
Phase: Phase 4

Summary: 
      Since a proportion of patients with Acute Viral Hepatitis-B develop severe hepatitis and
      fulminant hepatic failure, it is logical to believe that a rapid reduction in the HBV DNA
      levels by using 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 is limited.The aim of the present study was to evaluate the efficacy,
      utility and safety of lamivudine in treating immunocompetent patients with AVH-B.
    

Detailed description: 
      The diagnosis of acute hepatitis B was based on recent onset acute illness including
      prodromal symptoms, jaundice and other typical symptoms. The laboratory investigations
      supporting the diagnosis of acute hepatitis included the presence of >2.5 times the upper
      limit of serum alanine aminotransferase (ALT) and serum bilirubin, and positive IgM anti-HBc
      test. Ultrasound, and esophagogastroduodenoscopy was done to look for any evidence of chronic
      liver disease. All patients had normal alpha-fetoprotein levels.

      Co-infection with hepatitis A, C, D, E and human immunodeficiency virus (HIV) infection was
      looked for by appropriate serologic tests conducted within 7 days of presentation.

      Patients with co-infection, a history of hepatotoxic drug intake or alcohol use >20g/day, or
      any evidence of chronic liver disease in the past, at presentation or during follow-up were
      excluded. Patients were also excluded if they had serum bilirubin < 5 mg/dl at presentation.

      Patients were classified as severe AVH-B if they fulfilled any two of the following criteria:
      (1) hepatic encephalopathy; (2) serum bilirubin ≥10.0 mg/dl; and (3) international normalized
      ratio (INR) ≥1.6.

      The patients were randomized into 2 groups: Group 1: Treatment with lamivudine 100 mg daily
      for 3 months, Group 2: Placebo. Randomization was done using random number table. The initial
      study and randomization was planned to enroll 120 patients or continue the study till three
      years, whichever was earlier. Individual rather than block randomization was done The
      investigators as well as the patients were blinded to the randomisation. The patients in the
      placebo group received a placebo pill.

      All patients were monitored during treatment for clinical evidence and grade of hepatic
      encephalopathy, impaired coagulation (abnormal international normalized ratio, IINR),
      AST/ALT, serum albumin bilirubin levels every week for the first month and then monthly. HBV
      serology, including serum HBsAg, HBeAg, and anti-HBe were checked at baseline and every 3
      months. Anti-HBs titres were checked at 6 and 12 months. Quantitative HBV DNA assay was
      performed on day 0, day 4, week 1, week 2, week 3, week 4, then every month for the next 2
      months and then every 3 months for 12 months.

      All patients were followed for at least 12 months after the onset of AVH-B. Development of
      protective anti-HBs(>10 IU/L) was specifically looked for.

      Exacerbation of chronic hepatitis B was excluded by investigating thoroughly for any evidence
      of chronic liver disease by Ultrasound, Upper GI endoscopy, or low albumin at presentation.
      Ultrasound was repeated at 6 and 12 months, and if there was any suspicion Upper GI endoscopy
      was also repeated. LFTS were done at every hospital visit.

      HBsAg, HBeAg, IgM anti-HBc, anti-HBs, and anti-HBe were tested by commercially available
      enzyme-linked immunoassays. Serum quantitative HBV DNA assay was performed by use of an ultra
      sensitive Hybrid capture assay [Digene Labs, USA] that has a lower limit of detection of
      4,700 copies/ml. An arbitrary value of 4,700 copies/ml was assigned to values < 4,700
      copies/ml for analysis purposes. In such patients HBV DNA was done by an in-house qualitative
      PCR test to indicate negativity or positivity of viral DNA. The lower limit of detection was
      600 copies/ml.
    

Intervention name(s): Lamivudine
Intervention type(s): Drug
Intervention MeSH terms: Lamivudine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Acute Hepatitis B, Lamivudine