Analysis of changes of hepatic function in opioid addicts during rehabilitation

目的 探讨阿片类依赖者脱毒治疗结束后康复阶段内肝功能状况及其影响因素.方法 采用多中心临床试验方法,以上海市、四川省西昌市及河南省新乡市三地强制隔离戒毒所脱毒治疗结束后康复阶段的阿片类依赖者为研究对象,记录其人口学资料、药物滥用史和戒断症状.戒断症状采用稽延性戒断症状评定量表、汉密顿焦虑量表(HAMA)和汉密顿抑郁量表(HAMD)进行评估.检测研究对象入组时(脱毒治疗后第15天)、康复第4、12、18和24周末血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)及总胆红素(TBil)水平.结果 共130例处于康复阶段的阿片类依赖者纳入研究.其中男性106例(81.5％),女性24例(18.5％);平均年龄(43.8±15.3)岁.滥用毒品时间为1 ～ 242个月,平均(83.2±4.9)个月;脱毒治疗前l周毒品日用量为0.10 ～6.00 g,平均(1.02±0.09)g.入组时稽延性戒断症状评分为10 ～ 52分,平均(20.2±0.9)分,HAMA评分为4～41分,平均(13.7±0.6)分,HAMD评分为4～31分,平均(12.3±0.5)分.入组时受试者ALT、AST及TBil的异常率分别为22.3％(29例)、9.9％(8例)及2.3％(3例).第4周ALT异常率升至36.8％,与入组时比较,差异有统计学意义(P＜0.01).此后呈波动下降,第24周为16.7％,明显低于第4周(P＜0.01).第4周AST异常率也呈上升趋势,但其后随康复时间的延长波动性降低,第24周降至4.9％.康复第12周时TBil异常率为8.4％,明显高于入组时和第4周(均P＜0.05),之后迅速下降,第24周降至0.ALT发生有临床意义降低的例数由第4周的7例(5.6％)升至第24周的10例(16.7％),同期有临床意义升高的例数则由16例(12.8％)降至2例(3.3％).入组时稽延性戒断症状重症者发生ALT异常的风险为轻症者的0.907倍.24周康复期内女性出现ALT异常的风险是男性的4.51倍,抑郁倾向严重者是轻者的1.12倍.结论 阿片类依赖者脱毒治疗结束后康复初期肝功能可能出现异常性升高现象,随康复时间延长可逐步好转.对该类人群需持续监测肝功能指标,以便指导后续的康复及防复吸治疗.Objective To investigate the hepatic function condition and influencing factors in opioid addicts during rehabilitation after detoxification.Methods Opioid addicts abstained from opioid in duration of rehabilitation were recruited from Shanghai,Sichuan and Henan Compulsory Isolated Detoxification Center.The subjects' demographics,drug abuse histories,and withdrawal symptoms were recorded.The protracted withdrawal symptoms scale,Hamilton Anxiety scale (HAMA),and Hamilton Depression scale (HAMD) were used to assess withdrawal symptoms.Hepatic function tests including alanine aminotransferase (ALT),aspartate aminotransferase (AST) and total bilirubin (TBil) were performed at baseline (the 15th day after detoxification),4th,12th,18th,and 24th weeks of rehabilitation.Results A total of 130 subjects were enrolled into the study,comprising 106 (81.5％)male and 24 (18.5％) female with average age of (43.8 ± 15.3) years.Their duration of drug abuse was (83.2 ± 4.9) months ranging from 1 to 242 months and average daily dose taken during the last week before abstinence was (1.02 ± 0.09) g ranging from 0.10 to 6.00 g.At the beginning of rehabilitation,the protracted withdrawal symptoms scale averaged (20.2 ± 0.9) ranging from 10 to 52,HAMD averaged (13.7 ±0.6) ranging from 4 to 41,and HADA averaged (12.3 ± 0.5) ranging from 4 to 31.The initial percentage of abnormal ALT,AST,and TBil in the subjects were 22.3％ (29 cases),9.9％ (8 cases),and 2.3 ％ (3 cases),respectively.Compared with the baseline,the percentage of cases with abnormal ALT increased to 36.8％ at the 4th week of rehabilitation (P ＜ 0.01) and then fluctuated and dropped to 16.7％at the 24th week.The change between the 4th and the 24th weeks was statistically significant (P ＜ 0.01).The percentage of cases with abnormal AST showed a trend of increase at the 4th week and then fluctuated and reduced to 4.9％ at the 24th week.The percentage of cases with abnormal TBil at the 12th week was 8.4％,which was much higher than that at the baseline and the 4th week of rehabilitation (all P ＜ 0.05),and rapidly decreased to zero at the 24th week.The number of subjects who had clinically significant decrease in ALT levels increased from 7 cases (5.6％) at the 4th week to 10 cases (16.7％) at the 24th week,while the number of subjects who had clinically significant increase in ALT levels was decreased from 16 cases (12.8％) to 2 cases (3.3％) at the same time.The risk for abnormal ALT levels in the patients with graver withdrawal symptoms at the beginning of rehabilitation was 0.907 times higher than that with lighter withdrawal symptoms.The risk of abnormal ALT levels in the female patients was 4.51 times higher than that in the male patients.The risk of abnormal ALT levels in patients with severe depression was 1.12 times higher than that with lighter depression during 24 weeks of rehabilitation (OR were 4.51 and 1.12,respectively).Conclusions The levels of hepatic function parameters in opioid addicts may be abnormally increased during initial rehabilitation and may improve gradually with prolongation of rehabilitation.Continuous monitoring of hepatic function of opioid addicts should be performed and it is a good strategy for both rehabilitation and prevention of relapse.国家科技支撑计划项目; 国家重点基础研究发展计划(973计划)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)04192-1971