阿德福韦酯联合拉米夫定治疗YMDD变异乙型肝炎初步临床研究

目的:观察阿德福韦酯联合拉米夫定治疗YMDD乙肝患者1年的疗效。方法:40例因拉米夫定治疗而发生YMDD变异的慢性乙肝患者,ALT为正常上限的2～10倍,HBV-DNAㄒ105copies/ml,胆红素水平小于正常上限的2倍,接受阿德福韦酯10mg/d同时拉米夫定100mg/d治疗,同期38例慢性乙肝初治患者接受阿德福韦酯10mg/d治疗,疗程均为1年,分别观察ALT、HBV-DNA、乙肝标志的变化。结果:治疗前后两组ALT、HBV-DNA水平均显著下降,ALT复常率联合治疗组为82.5%,初治组为84.2%,HBV-DNA阴转率前者为32.5%,后者为34.2%,乙肝标志两组均无变化。治疗9月时YMDD变异治疗组3例患者出现A181V位点变异,但未出现ALT的波动。结论:阿德福韦酯联合拉米夫定治疗YMDD变异乙肝患者疗效显著,与阿德福韦酯初治乙肝患者疗效无显著差异,但易出现对阿德福韦酯的耐药。

Hepatitis B virus genotypes and lamivudine resistance mutations in Jordan

AIM:To investigate and identify prevalent hepatitis B virus(HBV) genotypes and to explore lamivudine-resistant mutations among treated and untreated patients in Jordan.METHODS:A total of 107 cases with chronic hepatitis B were recruited from different medical centers in Jordan.Serological tests were preformed for all cases using a microparticle enzyme immunoassay.HBV Genotyping was performed for 70 cases using Line probe genotyping assay.The YMDD mutations were explored for 20 cases(4 were lamivudine naive) using the INNO-LiPA HBV DR assay.RESULTS:Genotype D was the only detected genotype.A total of 6 YMDD mutations were detected in 5 treated patients(31%) while one mutation was detected in the naive patients.Seventeen percent of cases were positive for HBeAg and had statistically significant higher levels of serum aminotransferases.CONCLUSION:HBV genotype D appears to be the only circulating type in Jordanian patients.The YMDD mutations were detected in 31% of lamivudine-treated cases with similar patterns to those found in the literature.We also found a relatively low prevalence of HBeAg expression among examined cases(17%).Awareness of these serologic,genotypic and resistance patterns might help in the formulation of management plans and for predicting clinical outcomes.Further larger scale studies are needed to confirm our results and to examine possible associations among clinical,serologic,and genetic patterns of HBV infections in Jordan.

Clinical features of chronic hepatitis B patients with YMDD mutation after lamivudine therapy

Objective: To study the clinical features of chronic hepatitis B (CHB) patients with tyrosine-methionine-aspartateaspartate (YMDD) mutation after lamivudine therapy. Methods: This investigation was a retrospective study of 63 CHB patients with YMDD mutation during lamivudine therapy. Clinical data, including period and types of YMDD mutation; hepatitis B virus (HBV) DNA levels and alanine aminotransferase (ALT) levels before and after YMDD mutation were measured. YMDD mutation in the HBV DNA polymerase gene was determined using polymerase chain reaction (PCR) and direct sequencing. HBV DNA quantification was determined using real-time PCR. Relevant serum markers of HBV were measured. The follow-up period was 12 months after YMDD mutation. Results: YMDD mutation occurred 7～44 months (median, 21.5 months) after the start of lamivudine therapy. The majority of the cases (42/63, 66.6%) had YMDD mutants detected between 12 and 24 months. Four types of YMDD mutation were observed in this study, rtL180M/M204V mutation was the predominant type (26/63, 41.3%). A proportion of patients (16/63, 25.4%; 12/63, 19.1%) had higher HBV DNA levels and ALT levels (after mutation vs before mutation),respectively. Conclusion: The majority of patients with YMDD mutants had similar or lower HBV DNA levels and ALT levels compared with baseline values. This subset of patients might have benefited from the continued lamivudine therapy. The patients with increased ALT and HBV DNA levels (breakthrough hepatitis) should benefit from the addition of a newer nucleotide analogue (e.g. adefovir).

YMDD variants of HBV DNA polymerase gene: Rapid detection and clinicopathoiogical analysis with long-term Iamivudine therapy after liver transplantation

AIM: To look for a rapid low-cost technique for the detection of HBV variants.METHODS: Two patients who underwent orthotopic liver transplantation (OLT) for HBV infection were treated with lamivudine (100 mg daily) and HBV infection recurred in the grafted livers. The patients were monitored intensively for liver enzymes, hepatitis B surface antigen (HBsAg) and HBV DNA in serum. Liver biopsy was performed regularly. HBV DNA in a conserved polymerase domain (the YMDD locus) was amplified from serum of each patient by PCR and sequenced. HBV genotypes were analyzed by restriction fragment length polymorphism (RFLP) of the PCR products generated from a fragment of the polymerase gene.RESULTS: YMDD wild-type HBV was detected in one patient by PCR-RFLP and DNA sequencing 19 mo after OLT, and YIDD mutant-type HBV in the other patient, 16 mo after OLT.CONCLUSION: PCR-RFLP assay is an accurate and simple method for genotyping lamivudine-resistant HBV variants.