Randomized Controlled Trial of Tenofovir in Patients of Reactivation of Hepatitis B Presenting as Acute on Chronic Liver Failure
Randomized Controlled Trial of Tenofovir in Patients of Reactivation of Hepatitis B Presenting as Acute on Chronic Liver Failure
Background: Reactivation of hepatitis B is a well-characterized syndrome marked by the abrupt
 reappearance or rise of hepatitis B virus (HBV) DNA in the serum of a patient with previously
 inactive or resolved HBV infection. Reactivation can be spontaneous, but is most commonly
 triggered by cancer chemotherapy, immune suppression, or alteration in immune function.
 Spontaneous acute exacerbation of chronic hepatitis B infection is seen with a cumulative
 probability of 15±37% after 4 years of follow-up.2 Significant number of patients of
 spontaneous acute exacerbation of chronic hepatitis B may present with very high ALT levels,
 jaundice and liver failure.3 This condition should be defined as acute-on-chronic liver
 failure (ACLF) according to a recent Asia-Pacific consensus recommendation.

 The short term prognosis of patients of spontaneous acute exacerbation of chronic hepatitis B
 leading to ACLF like presentation is extremely poor, with a mortality of 30-70% in different
 series.8,9,10 Liver transplantation has been the only definitive therapy available to salvage
 this group of patients. However ,this is not readily available and affordable. Another
 therapeutic option is antiviral therapy but has limited data. The efficacy of lamivudine was
 evaluated and compared by historical control but was not found to be beneficial.8,9,10
 However ,a study from Taiwan showed a survival benefit in a subgroup of patients who were on
 lamivudine and had baseline bilirubin below 342 mmol/L (20 mg/dL).11 Tenofovir disoproxil
 fumarate (TDF) is a potent, rapidly acting, oral acyclic nucleotide analogue, reverse
 transcriptase inhibitor that has been shown to be highly effective in suppressing hepatitis B
 virus replication.12 Tenofovir has also shown excellent activity against HBV in both LAM-
 naïve and LAM-resistant patients.13,14. Its efficacy has not been evaluated in patients of
 reactivation of hepatitis B who present as ACLF Hypothesis: The investigators hypothesis that
 Tenofovir reduces the morbidity and mortality in patients with Spontaneous reactivation of
 hepatitis B by reducing HBV DNA.
Inclusion Criteria:

 -  Reactivation of chronic hepatitis B characterized by rise in ALT level >5 times upper
 limit of normal along with HBV DNA level >105 copies/ml (~1.8x104 IU/ml) presenting as
 ACLF

 -  Acute hepatic insult

 -  Jaundice (bilirubin ≥5 mg/dL) and coagulopathy (INR>1.5)

 -  Complicated within 4 weeks by ascites and/or encephalopathy in a patient with
 previously diagnosed or undiagnosed chronic liver disease.

 Exclusion Criteria:

 -  Superinfection with other viruses (Hepatitis E, A, D and C)

 -  Coexistent hepatocellular carcinoma (HCC)

 -  Portal vein thrombosis

 -  Coexistent renal impairment

 -  Pregnancy

 -  Co-infection with HIV infection or Patients received previous course of any antiviral

 -  Immunomodulator or cytotoxic/immunosuppressive therapy for chronic hepatitis or other
 illness within at least the preceding 12 month.