长期拉米夫定治疗无效慢性乙肝患者106例

Long-term ineffective treatment of chronic hepatitis B with Lamivudine: an analysis of 106 cases

目的:通过对长期拉米夫定治疗无效的慢性乙型肝炎(CHB)病例分析,寻找可汲取的临床经验和教训．方法:观察和随访长期(12-60 mo)拉米夫定治疗无效的CHB或伴有早期肝硬化患者共106 例．项目包括除临床表现、肝功、乙型肝炎病毒学标志物及YMDD变异检测外,有17例进行了CD细胞检测,43例进行了肝活检．结果:106例患者长期持续服用拉米夫定期间(86例)和停服拉米夫定后(20例)出现 ALT、AST异常率分别为100％(106／106), 92．5％(98／106)．HBsAg阳性106例,HBeAg阳性104例,HBeAb阳性2例．HBV DNA(PCR): ≤108 copies／L 4例,≥109 copies／L 102例,其中YMDD变异65例,变异率61.3％．肝组织病理变化:肝活检43例,轻、中、重度分别为18, 15,10例,其中伴有早期肝硬化23例．病情类型:重度以上22例(20％),余为轻、中度．结论:拉米夫定抑制HBV DNA作用显著,对 CHB患者近期降酶、改善临床症状较快,然而缺乏远期持续效应．伴有早期肝硬化CHB 患者停药与否均有病情加重的风险．

AIM： To summarize the valuable experiences through analysis of long-term ineffective treatment with Lamivudine （LAM） on chronic hepatitis B patients. METHODS： One hundred and six patients, with or without early-stage cirrhosis, were followed up and the clinical data retrospectively analyzed. All the patients were observed in terms of clinical manifestations and received tests of liver function, hepatitis B virus markers and YMDD mutations. Of these patients, 17 also received CD cell examination, and 43 received liver biopsies. RESULTS： The percentages of elevated alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were 100% （106/106） and 92.5% （98/106）, respectively. All the 10^6 patients were HBsAg-positive, and 10^4 were HBeAg-positive while 2 were HBeAb-positive. The level of HBV DNA was lower than or equal to 10^8 copies/L in 4 patients, and higher than or equal to 10^9 copies/L in 102 patients, of which 65 （61.3%） patients had YMDD mutations. Of the 43 patients received liver biopsy, mild histological changes were found in 18 cases, moderate in 15 cases and severe in 10 cases. Of the 43 patients, 23 were accompanied with early-stage liver cirrhosis, of which 22 were severe cases. CONCLUSION： LAM can short-termly inhibit HBV replication, reduce aminotransferase level and improve clinical manifestations effectively in chronic hepatitis B patients. However, it was ineffective in long term. The risks of severe disease increase in patients accompanied by earlystage liver cirrhosis no matter whether LAM treatment is stopped.