Abstract :
Background: Treatment with oral nucleos(t)ide analogues (NA) are associated with improvement of
liver histology and accepted as current standard treatment of patients with chronic hepatitis B (CHB). The emergence
of hepatitis B viral (HBV) resistance to oral NA is common and lead to the worsening of liver disease.
Detection of HBV mutation may be helpful in clinical management. We aimed to evaluate mutation patterns of
HBV polymerase in patients with CHB treating with NA.
Patients and Methods: Patients with CHB receiving one or more of oral NA were enrolled from the
Gastroenterology and Hepatitis Clinic, Siriraj Hospital, Thailand during September 2007 to January 2009. Virologic
breakthrough is defined by an increase of HBV DNA at least 1 log10 copies/mL (or > 1 log10 IU/mL) from
nadir level during treatment. Blood sample was stored at -80˚C until tested. HBV polymerase resistance profile
was preformed by line probe assay (INNO-LiPA HBV DR v2).
Results: Twenty-seven patients were enrolled with 21 men and 6 women. Their mean age was 48 ±
11.6 years. Mean initial HBV viral load before treatment was 1 × 107 IU/ml with mean initial AST and ALT of 125
and 165 IU/mL, respectively. Twenty-four patients were initially treated with lamivudine (LMV) and three patients
were treated with adefovir dipivoxil (ADV). The mutation patterns of HBV polymerase were refractory to LMV
alone (n = 15) and refractory to LMV and other NA (n = 12). Mean HBV viral load at the time of virologic
breakthrough was 2.8 × 107 IU/mL and biochemical breakthrough was found in 8 patients (29.6%). The most
frequent resistant HBV mutation were M204V/I (88.9%), M180/A181 (77.7%), and L80I 9 (33.3%).
Conclusion: In CHB patients with LMV resistance alone, HBV polymerase mutations were predictable
detected in 88% and at least 12% of them had primary ADV resistant mutation. Thus, routine adding of ADV
in these patients may result in treatment failure. The usefulness of line probe assay to identify mutation in the
patients who have failed to multiple NA is helpful but its sensitivity to detect some mutations is still limited. |
file/Thai-Journal-of-gastroenterology-vol-11-no-1-2679220.pdf