Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus: A case report

Abstract

We present a case of fetal liver failure caused by the activation of lamivudine-resistant hepatitis B virus (HBV) nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decompensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase (ALT) decreased transiently. However, after the start of α-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtL80I/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtL80I/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.

Hepatitis B virus with the rtL80V/I mutation is associated with a poor response to adefovir dipivoxil therapy

“…In patients infected with HBV genotype C, several polymerase mutations, including rtL80V/I, rtL180M and rtM204I, were associated with significantly higher viral loads, increased LAM resistance and disease exacerbation (9). In addition, the coexistence of rtM204V/I with rtL80V/I occurred at the time of viral breakthrough in a patient with fatal liver failure caused by the activation of LAM‐resistant HBV 9 months after LAM treatment (27). To clarify the adverse effects of the rtL80V/I mutation on clinical outcomes, further studies are needed in patients harbouring rtL80V/I.…”

trans-Complementation of HBV rtM204I mutant replication by HBV wild-type polymerase

“…In contrast, in vivo , as drug-resistant mutants emerge, there is an increase in viral load and serum alanine aminotransferase levels as well as a deterioration of liver histology. Indeed, lamivudine-resistant mutants have also been associated with death in several case studies (Kagawa et al, 2004; Kim et al, 2001; Suzuki et al, 2007; Wang et al, 2002). …”

Construction and expression of eukaryotic plasmids containing lamivudine-resistant or wild-type strains of Hepatitis B Virus genotype C

“…In YMDD variants, the methionine of the YMDD motif in HBV polymerase is substituted with either isoleucine, designated as YIDD, or valine, designated as YVDD. Much clinical data has indicated that patients who have developed HBV YMDD mutations show deterioration of their physical condition, and rebound of virus load in their serum [12][13][14] . In this study, we constructed the eukaryotic expression plasmids of HBV genotype C full-length genome, which contained wild-type, YVDD mutation or YIDD mutation, respectively.…”