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Tenofovir Improves Outcomes of HBV Acute-on-Chronic Liver Failure

SUMMARY
Treatment with tenofovir (Viread) lowers HBV viral load, reduces liver injury, and decreases the risk of death in patients with acute-on-chronic liver failure due to hepatitis B reactivation.

By Liz Highleyman

Spontaneous reactivation of chronic hepatitis B virus (HBV) infection can cause acute-on-chronic liver failure (ACLF), or sudden worsening of liver disease in people who already have chronic viral hepatitis. Liver transplantation is an accepted treatment for acute liver failure, but donor livers are in short supply and antiviral therapy would be an attractive option.

As reported in the March 2011 issue of Hepatology, Hitendra Garg and colleagues in India evaluated the efficacy of tenofovir -- one of most potent nucleoside/nucleotide analogs approved for hepatitis B treatment -- and looked at predictors of mortality in patients with ACLF. Prior research has indicated that the older hepatitis B drug lamivudine (Epivir-HBV) is not effective for this purpose.

The study population included 27 patients with ACLF due to spontaneous HBV reactivation who were randomly assigned to receive either tenofovir or placebo. Most (72%) were men and the median age was 45 years. At baseline the median HBV DNA viral load was level was 900,000 IU/mL and 56% were hepatitis B "e" antigen positive.

All patients were followed for at least 3 months or until death. The primary endpoint was survival at 3 months. Liver transplants were unavailable.

Results

At 3 months, the probability of survival was significantly higher in the tenofovir group compared with the placebo group (57% vs 15%, respectively).
The typical cause of death was progressive liver failure leading to multi-organ failure.
HBV DNA levels declined significantly in the tenofovir group, but remained stable in the placebo group.
After 3 months follow-up, 60% of patients in the tenofovir group experienced HBeAg loss, compared with none in the placebo group.
Surviving patients taking tenofovir experienced significant improvement in Child-Turcotte-Pugh (CTP) and MELD liver disease scores, but these did not change in placebo group.
Having more than a 2 log reduction in HBV DNA at week 2 was an independent predictor of survival.

"Tenofovir significantly reduces HBV DNA levels, improves CTP and MELD scores, and reduces mortality in patients with severe spontaneous reactivation of chronic hepatitis B presenting as ACLF," the researchers concluded. "Reduction in HBV DNA levels at 2 weeks should be a desirable goal and is a good predictor of survival."

"The pathogenesis of severe acute exacerbation is believed to be associated with vigorous immune response, which results in severe hepatic necro-inflammation and finally hepatic decompensation," they explained in their discussion. "It is quite likely that [tenofovir] therapy inhibited the ongoing necro-inflammation and might even have permitted hepatic regeneration. Our data convincingly shows that a rapid reduction in HBV DNA was associated with improvement in indicators of injury and even survival."

Investigator affiliations: Department of Gastroenterology, GB Pant Hospital, New Delhi, India; Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India; Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.

5/10/11

Reference
H Garg, SK Sarin, M Kumar, et al. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. Hepatology 53(3):774-780 (abstract). March 2011.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 


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FDA-approved Therapies for Chronic HBV Infection
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