Tenofovir plus lamivudine as rescue therapy for adefovir-resistant chronic hepatitis B in hepatitis

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Liver Int. 2008 Feb 26 [Epub ahead of print]

Tenofovir plus lamivudine as rescue therapy for adefovir-resistant chronic

hepatitis B in hepatitis B e antigen-positive patients with liver cirrhosis.

Choe WH, Kwon SY, Kim BK, Ko SY, Yeon JE, Byun KS, Kim GH, Lee CH.

Department of Internal Medicine, Konkuk University School of Medicine, Konkuk

University Hospital, Seoul, Korea.

Background/Aims: There is no consensus on the management of patients with

adefovir (ADV)-resistant hepatitis B virus (HBV) infection. The aim of this

study was to investigate whether tenofovir disoproxil fumarate (TDF) combined

with lamivudine (LMV) is effective and safe in patients with resistance to or

non-response to ADV. Methods: Six patients with HBV-related cirrhosis, viral

breakthrough during LMV therapy and viral breakthrough or non-response during

ADV therapy were treated daily with TDF plus LMV for at least 6 months. The HBV

DNA level, alanine aminotransferase (ALT), the Child-Pugh score and serum

creatinine were monitored. Genotypic LMV- or ADV-resistant mutations were

measured in stored samples. Results: In five of six patients, ADV-resistant

mutations at rt181 or rt236 were detected during ADV therapy. At 6 months of

starting TDF/LMV combination, HBV DNA levels became undetectable (detection

limit, 400 copies/ml) in four of six patients. Within 12 months, HBV DNA levels

became undetectable in all patients, and ALT levels were normalized in four of

six patients. These responses persisted up to the end of the observation period

(median duration 16.5 months, range 6-21 months). The Child-Pugh scores improved

in two of three patients with hepatic decompensation. No significant changes in

serum creatinine were observed. Conclusion: Our data demonstrated that TDF plus

LMV safely and markedly suppressed HBV replication in patients with resistance

to or non-response to ADV. This study suggests that this combination may be a

promising rescue therapy for these patients, particularly those with liver

cirrhosis or pre-existing LMV resistance.

PMID: 18312291 [PubMed - as supplied by publisher]

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