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
