CAJ | 학술논문

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HBeAg阳性患者中4例出现HBeAg 血清学转换，1例HBsAg 血清学转换；12例 HBeAg 阴性患者中3例发生 HBsAg 血清学转换；HBeAg及HBsAg转换时间平均为26.5个月及33.7个月。NA维持治疗中未见HBeAg或HBsAg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。
목적：탐토핵감（산）유사물（NA）여간우소（IFN）연합치료조기을형간염간경화실대상기환자적료효。방법선택부합부유소량복수（경B초학인）일항병발증，차간경화Child-pugh평분범위위8~11분적만성을형간염간경화환자22례，균여NA항병독치료。실대상기간경화전변위대상기후，의거환자정황선택가용소제량IFN（300×104U혹500×104U）연합치료，진행불소우4년적장기수방，관찰료효、질병진전정황급안전성。결과22례환자응용NA항병독치료후균유종실대상기전변위대상기，3례（13.6%）재치료적2~3년간출현질병진전；소유환자응용NA 3개월후HBV-DNA균저우검측치하한，장기수방중미견병독학돌파화림상내약정황。7례을간HBeAg양성환자중4례출현HBeAg 혈청학전환，1례HBsAg 혈청학전환；12례 HBeAg 음성환자중3례발생 HBsAg 혈청학전환；HBeAg급HBsAg전환시간평균위26.5개월급33.7개월。NA유지치료중미견HBeAg혹HBsAg복양。22례환자중유11례재치료전갑태단백（AFP）유불동정도적승고，연합치료후AFP 균강지정상，기중2례발생간세포암，단미견AFP승고。1례환자재응용IFN과정중재차출현간공능실대상，정용IFN후간공능우전위대상。기타불량반응기본동IFN단약치료。결론조기적만성을형간염간경화실대상기환자응용NA후가이역전위대상기，NA+IFN연합치료가이개선예후、감소내약。
Objective To investigate the therapeutic efficacy and the mechanism of treatment of Interferon (IFN)-α combined with nucleos (t)ide analogues (NA)in patients with early HBV decompensated cirrhosis. Methods A total of 22 decompensated cirrhosis patients with only few ascites (confirmed by B-type ultrasound) and the Child-Pugh ranged from 8~11 points were treated with NA, liver function protective drugs, diuretics and supportive treatment. When decom-pensated cirrhosis transformed to compensated stage, low doses of IFN, such as IFN 300 IU or IFN 500 IU, was combined with NA, the NA based treatment regimen, while the course of treatment with IFN were uncertain. In addition, all patients were followed for disease progression and assessed for the safety for more than 4 years. Results All of the 22 patients who transformed from decompensated cirrhosis to compensated stage were treated with NA. Three cases (13.6%) showed pro-gression of cirrhosis during 2 to 3 years of follow-up. HBV DNA levels in all patients declined to the lower limits of detec-tion (<500 copies/ml) after 3 monthsˊ therapy, and in the whole course of treatment, virology breakthrough and resistance were not observed. In 7 of the HBeAg positive patients, 4 patients achieved HBeAg seroconversion, and 1 patient achieved HBsAg seroconversion. In 12 of HBeAg negative patients, 3 achieved HBsAg seroconversion. The average time to HBeAg seroconversion was 26.5 months and 33.7 months for HBsAg seroconversion. No one who had initially lost HBsAg or HBeAg subsequently became HBsAg or HBeAg positive. The high level of AFP in the 11 patients at baselines returned to normal with combined treatment. Two patients who progressed to hepatocellular carcinoma did not show elevating level of AFP during the follow-up period. Only 1 patient who progressed to decompensated stage with the treatment of IFN, and became compensated when transformed to NA. Other adverse effects were similar to the group who received IFN alone. Conclusion Early decompensated cirrhosis patients can be reversed to compensate stage when treated with NA, and the combined NAs and IFN treatment can also be tried. The majority of patients could tolerate different doses of IFN therapy well, the combination treatment of NA and IFN can reduce resistance and improve the prognosis.