Clinical trial NCT01074645: Randomized Controlled Trial of Tenofovir in Patients of Reactivation of Hepatitis B Presenting as Acute on Chronic Liver Failure
Official title: Tenofovir Reduces Morbidity and Mortality in Patients With Spontaneous Reactivation of Hepatitis B Presenting as Acute-on-chronic Liver Failure (ACLF): A Randomized Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Acute on Chronic Liver Failure
Hepatitis B
Keywords: Acute-on -chronic liver failure
Reactivation of hepatitis B
Spontaneous reactivation of chronic hepatitis B presenting as to acute-on-chronic liver failure
Lead sponsor: Govind Ballabh Pant Hospital
Sponsor class: OTHER_GOV
First posted: 2010-02-24
Enrollment: 27
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Reduction in HBV DNA levels, survival
timeFrame: 3 Month
Secondary outcomes:
measure: Improvement in CTP, MELD scores
timeFrame: 3 Month
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Department of Gastroenterology, GB Pant Hospital,
state: Delhi
Study officials:
affiliation: G.B. Pant Hospital, New Delhi, India
name: Shiv K Sarin, MD,DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garg H, Sarin SK, Kumar M, Garg V, Sharma BC, Kumar A. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. Hepatology. 2011 Mar;53(3):774-80. doi: 10.1002/hep.24109. Epub 2011 Feb 3.