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目的探讨核苷(酸)类似物(NA)与干扰素(IFN)联合治疗早期乙型肝炎肝硬化失代偿期患者的疗效。方法选择符合仅有少量腹水(经B超确认)一项并发症,且肝硬化Child-pugh评分范围为8~11分的慢性乙型肝炎肝硬化患者22例,均予NA抗病毒治疗。失代偿期肝硬化转变为代偿期后,依据患者情况选择加用小剂量IFN(300×104U或500×104U)联合治疗,进行不少于4年的长期随访,观察疗效、疾病进展情况及安全性。结果 22例患者应用NA抗病毒治疗后均由从失代偿期转变为代偿期,3例(13.6%)在治疗的2~3年间出现疾病进展;所有患者应用NA 3个月后HBV-DNA均低于检测值下限,长期随访中未见病毒学突破和临床耐药情况。7例乙肝HBe Ag阳性患者中4例出现HBe Ag血清学转换,1例HBs Ag血清学转换;12例HBe Ag阴性患者中3例发生HBs Ag血清学转换;HBe Ag及HBs Ag转换时间平均为26.5个月及33.7个月。NA维持治疗中未见HBe Ag或HBs Ag复阳。22例患者中有11例在治疗前甲胎蛋白(AFP)有不同程度的升高,联合治疗后AFP均降至正常,其中2例发生肝细胞癌,但未见AFP升高。1例患者在应用IFN过程中再次出现肝功能失代偿,停用IFN后肝功能又转为代偿。其他不良反应基本同IFN单药治疗。结论早期的慢性乙型肝炎肝硬化失代偿期患者应用NA后可以逆转为代偿期,NA+IFN联合治疗可以改善预后、减少耐药。
Objective To investigate the efficacy of combination of nucleoside (NA) analogue (NA) and interferon (IFN) in the treatment of patients with decompensated liver cirrhosis in the early stage. METHODS: Twenty-two patients with chronic hepatitis B cirrhosis who had a complication of only a small amount of ascites (confirmed by B-ultrasound) and who had a Child-pugh score of 8 to 11 with cirrhosis were selected for NA antiviral therapy. Decompensated cirrhosis into compensatory phase, depending on the patient choose to add a small dose of IFN (300 × 104U or 500 × 104U) combination therapy, for not less than 4 years of long-term follow-up, observation of efficacy, disease progression And safety. Results All of the 22 patients turned from decompensation to compensatory phase after NA antiviral treatment, and 3 cases (13.6%) showed disease progression within 2-3 years of treatment. All patients were treated with NA- DNA were lower than the lower limit of detection, no long-term follow-up virological breakthrough and clinical resistance. HBe Ag seroconversion occurred in 4 out of 7 HBeAg-positive patients and HBsAg seroconversion in 1 HBsAg seroconversion in 3 out of 12 HBeAg-negative patients. HBe Ag and HBs Ag conversion time was 26.5 months and 33.7 months. No HBeAg or HBsAg complex was found in NA maintenance therapy. Eleven of the 22 patients had elevated levels of AFP before treatment. After treatment, the AFP levels dropped to normal. Two of them developed hepatocellular carcinoma but no AFP was detected. One patient had recurrent hepatic decompensation during the course of IFN application, and the liver function was switched to compensatory after IFN was stopped. Other adverse reactions with IFN monotherapy. Conclusions In patients with decompensated cirrhosis of the early stage, NA can be reversed to compensatory phase. Combined treatment with NA + IFN can improve prognosis and reduce drug resistance.