By Liz Highleyman

Several nucleoside/nucleotide analogs have potent activity against hepatitis B virus (HBV), but resistance mutations can emerge when these agents are used as monotherapy. Drug resistance is particularly a concern for patients who have experienced multiple prior treatment failures, which can lead to dangerous hepatic flares (worsening liver inflammation) in those with advanced disease.

In an open-label study presented at the recent 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008) in San Francisco, German researchers assessed the safety and efficacy of combination tenofovir (Viread) plus entecavir (Baraclude) initiated as rescue therapy in 12 treatment-experienced chronic hepatitis B patients with cirrhosis.

All participants were men, the median age was 49 years, all were HIV negative, and 9 were hepatitis B "e" antigen (HBeAg) positive. Patients had multidrug-resistant HBV or only partial response to previous treatment (median 3 regimens). At baseline, the median ALT level was 1.6 x the upper limit of normal (ULN) and the median HBV DNA level was 5 x 106 copies/mL.

Results

• The median treatment duration after initiating tenofovir + entecavir was 6 months (range 3-15 months).

• 9 of 12 patients (75%) achieved undetectable HBV DNA (< 400 copies/mL).

• The median HBV DNA level decreased by 4.6 logs (range 1.7-7.8 log) (P < 0.0001).

• ALT also decreased significantly (P = 0.001).

• No significant clinical side effects were reported.

• No patients experienced liver decompensation due to complications of cirrhosis or development of hepatocellular carcinoma (HCC).

• 6 patients became HBV DNA negative for the first time, demonstrating the high antiviral efficacy of this combination despite pre-existing resistance mutations or only partial response to prior therapies.

• However, no patients experienced HBeAg or hepatitis B surface antigen (HBsAg) loss.

Based on these findings, the researchers concluded that, "rescue therapy with entecavir and tenofovir in cirrhotic HBV monoinfected patients harboring complex viral resistance patterns or showing only partial antiviral responses earlier was highly efficient, safe, and well tolerated."

However, they added, "More data are certainly needed to judge about the long-term safety, long-term antiviral efficacy and prevention of emergence of new viral mutations and prevention of clinical decompensation or HCC using this therapeutical approach in HBV patients with advanced liver disease."

Department of Medicine, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Microbiology and Virology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.

11/18/08

Reference
J Schollmeyer, M Lutgehetmann, T Volz, and others. Combination of entecavir and tenofovir as a rescue therapy is safe and highly efficient in cirrhotic HBV mono-infected patients with the history of multiple previous treatment failures. 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2008). San Francisco. October 31-November 4, 2008. Abstract 985.