Evaluation of anti-HBV drug resistant mutations among patients with acute symptomatic hepatitis B in the United States.

BACKGROUND & AIMS: Reported HBV drug resistance mutations among previously untreated patients with chronic hepatitis B are variable. Whether resistant HBV strains are transmitted in the acute setting is uncertain. We sought to document the presence of antiviral resistance (AVR) mutations in patients with acute HBV (AHB) infection. METHODS: AHB infection was defined by HBsAg/IgM anti-HBc positivity, ALT>10X ULN and compatible clinical history. The TRUGENE HBV kit was used to perform genotyping and direct sequencing of the viral polymerase. INNO-LiPA HBV DRv2 and DRv3 were used to detect AVR mutations. Clonal sequencing was conducted on selected specimens. RESULTS: Twenty-three patients were evaluated (mean age, 43 years; 54% male; 39% African American, 39% Caucasian, 13% Hispanic and 4% Asian). The mean peak ALT was 1554.2IU/L and mean peak total serum bilirubin was 12 mg/dl. The HBV DNA median viral load (N = 15) was 5.14 log(10)IU/ml. Nineteen patients were genotype A, and 1 each were genotype C, D, E and G. HBV drug resistance mutations were not detected by direct sequencing or INNO-LiPA. Clonal sequencing was conducted on 192 clones isolated from three patients and showed rtA181T, rtM250V and rtS202G mutations at an overall frequency of 1.54%, 1.39%, and 1.67% respectively. CONCLUSIONS: We detected adefovir/lamivudine and entecavir relevant mutations in a minor population (<2%) of viral clones by clonal sequencing only. The clinical significance of these mutations is uncertain and may represent small populations of quasi-species vs. transmission of drug resistant strains.

Fatal lactic acidosis associated with the use of combination oral medications to treat reactivation of hepatitis B.

Oral nucleos(t)ide analogs for the treatment of hepatitis B virus (HBV) infection are well tolerated with minimal side effects. These agents do carry a Food and Drug Administration "black box" warning about the development of fatal lactic acidosis on the basis of data from the human immunodeficiency virus literature. However, no previously published cases of this lethal side effect have been reported in patients undergoing HBV treatment using the current Food and Drug Administration-approved HBV medications. We report a case of HBV reactivation after chemotherapy for leukemia, and the development of fatal lactic acidosis attributed to the use of combination oral HBV medications.