Precore mutant HBV-infection in a cirrhotic patient experiencing lamivudine-resistance and adefovir-nonresponse: no histological and immuno-histochemical evidence of re-infection treating with tenofovir plus lamivudine over 1 post-transplant year

Aims: Antiviral-drug-resistance is a common phenomenon in chronic hepatitis B therapy. Lamivudine-resistant mutants are mostly sensitive to the nucleoside analogue adefovir dipivoxil. Adefovir-resistant mutants are rare and retain sensitive to lamivudine. Patients with cirrhosis and precore mutant infection have an increased risk for exacerbation of liver disease due to drug-resistance. Viral resistance against both drugs is an indication for switching treatment to experimental antiviral regimes. Main therapeutic need is to prevent virological failure as well as to reach sufficient viral suppression before liver transplantation.

Case report: A 51-year-old homosexual male [BMI: 32kg/m2] with liver cirrhosis developed resistance to lamivudine [2 mutations: rtS219A and sS210R] after 5 years of treatment. Sequential HBV-DNA analysis showed a precore mutant infection with virological failure [HBV-DNA>17 860 000 IU/ml] and only slightly elevated ALT values. The antiviral therapy was immediately switched to Adefovir [10mg/d]. During the next three months, the infection remained highly replicative without any detectable adefovir-resistant mutations or any changes of the ALT-levels. Daily dose of Adefovir was increased to 20mg. After three more months of therapy, the patient developed liver failure due to continuous virological non-response. By switching therapy to lamivudine plus tenofovir, an absolute decline of HBV-DNA (5 log) was detected within 39 days. However, this treatment could not prevent liver failure and the patient underwent cadaveric liver transplantation.

Conclusion: Tenofovir plus lamivudin were well tolerated and resulted in quick, effective and permanent viral suppression before as well as after liver transplantation. No histological or immuno-histochemical evidences of re-infection could be found after 1 year of treatment. Thus, we highly recommend combined treatment of lamivudine plus tenofovir in liver failure patients due to chronic HBV-infection caused by precore mutants with non-response to lamivudine- and adefovir-therapy.

Key words: HBV-infection, precore mutants, lamivudine-resistance, adefovir-non-response, liver transplantation, tenofovir