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

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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.