Entecavir (Baraclude) and Tenofovir (Viread) Rescue Therapy for Chronic Hepatitis B Patients with Advanced Fibrosis and Prior Treatment Failure

		SUMMARY: A "rescue therapy" regimen combining entecavir (Baraclude) and tenofovir (Viread) is safe and effective for chronic hepatitis B patients with advanced liver disease who have experienced past treatment failure or developed extensive drug resistance, according to a study presented this month in Boston at the 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009).

By Liz Highleyman

In this open-label cohort study, investigators from 8 referral centers in Europe assessed the efficacy and safety of tenofovir plus entecavir in treatment-experienced hepatitis B patients with advanced liver disease.

Past treatment with single nucleoside/nucleotide analog drugs as sequential monotherapy has left many patients with hepatitis B virus (HBV) that harbors multiple resistance mutations, the researchers noted as background. Drug resistance renders older therapies less effective or ineffective, putting patients with advanced liver fibrosis or cirrhosis at risk of further damage due to hepatic "flares," or episodes of worsening disease.

Of the 39 study participants, more than half were hepatitis B "e" antigen (HBeAg) positive. They had multidrug resistant HBV or a history of only partial response to previous treatment. The median age was 48 years, and patients had used an average of 3 (range 1-6) past treatment regimens. At baseline, the median ALT level was 1.2 x upper limit of normal (ULN) and the median HBV DNA level was 1.7 x 10(4) IU/mL.

Results

	The median treatment duration after initiating combination therapy was 10.5 months (range 1-42 months).
	During this period, no significant clinical side effects were observed.
	The median HBV DNA level dropped significantly after starting the combination regimen, by 3.5 log (range 0-8 log; P < 0.0001).
	Nearly 80% (31 of 39 patients) achieved undetectable HBV DNA (< 80 IU/mL).
	HBV DNA decline was accompanied by a significant ALT decrease (median 0.68 x ULN; P = 0.001).
	All patients with detectable HBV DNA were treated for less than 6 months.
	3 patients experienced HBeAg loss (after 18, 21, and 24 months).
	1 person showed hepatitis B surface antibody (HBs) seroconversion.
	Patients with liver cirrhosis at baseline did not develop clinical decompensation.
	However, 2 patients with cirrhosis who had undetectable HBV DNA nevertheless developed hepatocellular carcinoma.
	There was no significant decrease in adherence among patients taking the 2 medications.

Based on these findings, the investigators concluded, "Rescue therapy with entecavir and tenofovir in HBV monoinfected patients harboring complex viral resistance patterns or showing only partial antiviral responses to preceding therapies was highly efficient, safe, and well tolerated in patients with advanced liver disease."

However, they added, "More data are certainly needed to judge about the long-term safety, efficacy and prevention of emergence of new viral mutations in this difficult to treat patient population."

Asklepiosklinik St. Georg, Liver Center Hamburg IFI Institute, University of Hamburg, Germany; University Hospital Hamburg Eppendorf, Hamburg, Germany; Hotel Dieu Hospital Lyon, Lyon, France; University Hospital Hamburg Eppendorf, Hamburg, Germany; University Medical Center, Rotterdam, Netherlands; Charite University Medical Center, Berlin, Germany; Fondazione IRCCS Maggiore Hospital, University of Milan, Italy; Service d Hepato-Gastroenterologie, Universite Pierre et Marie Curie, Paris, France; Hospital Vall de Hebron, Barcelona, Spain; Goethe University Hospital, Frankfurt, Germany.

11/13/09

Reference
J Petersen, M Lutgehetmann, F Zoulim, and others. Entecavir and Tenofovir combination therapy in chronic Hepatitis B: Rescue therapy in patients with advanced fibrosis and multiple previous treatment failures. Results from an international multicenter cohort study. 60th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD 2009). Boston. October 30-November 1, 2009. Abstract 405.