Detection of lamivudine and adefovir resistance mutations among Filipino patients with chronic hepatitis B using line probe assay

Abstract

Background: Hepatitis B virus (HBV) mutations conveying resistance to antivirals are a major health concern worldwide in the treatment of chronic hepatitis B infection. The availability of a sensitive assay that can detect emerging HBV antiviral resistance mutations is important for individualized monitoring of response to standard of care treatment. The risk of developing lamivudine (LAM) resistance is 14% to 70% after 1 to 5 years of treatment, which is sufficiently high to justify HBV antiviral resistance mutation testing. On the other hand, resistance to adefovir (ADV) is slow to emerge, ranging from 3% to 29% following 1 to 5 years of treatment. Mutation analysis helps in decision-making for clinical management of chronic HBV infection and molecular epidemiological studies as well. This study seeks to determine the presence of LAM and ADV resistance mutations among Filipino patients clinically diagnosed with chronic hepatitis B from July 2008 to December 2011.Methods: A total of fourteen samples were examined for the presence of antiviral resistance mutations using line probe assay, INNO-LiPA HBV DR v2. There were 9 (64%) males and 5 (36%) females with ages ranging from 17 to 69 years old.Results: Among the fourteen samples, 5 (36%) had wild-type, 4 (28%) had HBV mutant strain DNA not detected, and 5 (36%) had HBV DNA mutations. Out of the 5 HBV DNA mutant strains, one or 20% had one-drug resistance mutation detected (rtA181T for ADV). Three or 60% had 3-drug resistance mutations pattern detected. The first patient had rtG173L for LAM compensatory mutation, rtL180M for LAM, and rtM204V for LAM. The second patient had rtL80I for LAM compensatory mutation, rtL180M for LAM, and rtM204I for LAM, telbivudine (TBV). The third patient had L180L/A181T upcoming resistance for ADV, M204I upcoming resistance for LAM, emtricitabine, TBV, and N236T upcoming resistance for ADV. The remaining one or 20% had 4 drug-resistance mutations detected (rtA181T for ADV, rtL180M for LAM, rtM204V for LAM, and rtM204I for LAM, TBV).Conclusion: The most frequently encountered LAM-resistant mutant was rtM204V/I. Overall, the line probe assay provides a useful tool for the detection of lamivudine and adefovir resistance mutations among HBV-infected Filipino patients. http://dx.

A critical review of diagnostic and prognostic markers of chronic hepatitis B infection

“…Table 3 illustrates that the HBV genotype does not seem to have a substantial impact on the clinical manifestations of hepatitis B patients [ 65 ]. Numerous investigations have demonstrated that there is no meaningful correlation between HBV genomes and clinical characteristics such as liver histology, ALT levels, liver fibrosis, and HBeAg status [ 66 , 67 ]. Nonetheless, some research has indicated that a greater viral load may be linked to specific HBV genotypes [ 68 ].…”