他汀(Statins) 治疗对肝硬化患者安全且可能有益

 发布时间：2012/6/4 9:07:00 来源：爱唯医学  一项研究显示，他汀治疗对于肝硬化患者不仅是安全的，还可能延缓肝脏疾病进展至肝功能失代偿，延长患者寿命。因为安全性方面的顾虑，一些临床医生对于晚期肝病患者不给予他汀治疗，或对已使用者停止他汀治疗。为了确定他汀治疗对肝硬化患者肝功能失代偿的真实影响，布里格姆妇女医院的Kumar博士及其同事进行了这项研究。他汀治疗组患者均经活检证实有肝硬化，并曾因血脂异常接受至少3个月的他汀治疗。对照组为未接受过他汀治疗的肝硬化患者，并且年龄、性别和美国联盟医疗系统研究患者数据登记(该系统包含在麻省总医院和布里格姆妇女医院接受治疗的患者的人口统计学和诊断信息)的Child-Pugh分级均与他汀治疗组匹配，与他汀治疗组的患者数之比为2:1。研究的主要终点为肝功能失代偿以及至发生肝功能失代偿的时间，肝功能失代偿定义为发生腹水、黄疸(胆红素超过2.5 mg/dl)、肝性脑病或静脉曲张出血；次要终点为死亡。研究者创建了一个Cox比例风险模型，校正年龄、Child-Pugh分级、糖尿病、冠心病和肝细胞癌对肝功能失代偿的影响，并使用条件逻辑回归的方法评估死亡率。结果显示，在243例肝硬化患者中，81例为他汀使用者，162例为匹配的对照患者。"两组中分别约有70%的患者为Child-Pugh A级，30%为Child-Pugh B/C级，并且两组的MELD(终末期肝病模型)评分、白蛋白、静脉曲张和使用b受体阻滞剂的情况相似，"Kumar医生指出。他汀治疗组平均随访时间为1,756天，31例患者报告失代偿(38.2%)，对照组平均随访时间为1,503天，80例患者(50.62%)报告失代偿。在Cox分析中，"他汀治疗是唯一与失代偿风险降低显著相关的因素，危险比(HR)为0.46"。此外，Kaplan-Meier曲线显示，接受他汀治疗患者至发生失代偿的时间显著延长。在亚组分析中，观察到Child-Pugh A和Child-Pugh B/C级的他汀治疗者至发生失代偿的时间均显著延长。他汀治疗组的总死亡率显著降低，两组总死亡率分别为37.0%和50.6%。在多变量模型中，使用他汀仍与死亡率降低显著相关，比值比(OR)为0.36，而冠心病和肝细胞癌与死亡率增高相关，HR分别为3.6和4.9。两组的死因无统计学差异，"但必须注意的是，约1/3患者的死因未记录，因此难以确定他汀治疗组患者是否较对照组患者更少死于肝脏相关或心血管原因"。研究者认为，他汀具有肝脏保护作用的原因可能为血液动力学和分子学效应的联合效应。他汀可改善外周血管的内皮功能异常，通过增加肝脏的一氧化氮供给，减轻血管功能异常对肝硬化门静脉高压的不良影响，并达到降低门静脉压力的作用。Kumar博士总结称，他汀治疗对于肝硬化患者安全甚至有益，对于有合理心血管适应证的肝硬化患者，应毫不迟疑地给予他汀治疗。Kumar医生披露无相关利益冲突。

 

Statins Appear Safe, Even Beneficial, in Cirrhosis  By: DIANA MAHONEY, Family Practice News Digital NetworkSAN DIEGO – Statin therapy is not only safe for patients with cirrhosis, it may slow the progression of their liver disease to hepatic decompensation and help them live longer, a study has shown.The findings, reported at the annual Digestive Disease Week, should help allay fears that decreased hepatic clearance of statins could lead to complications in patients with advanced liver disease, as was previously hypothesized, said lead investigator Dr. Sonal Kumar."In fact, it seems the opposite may be true," said Dr. Kumar of Brigham and Women's Hospital, Boston, referring to the results of her retrospective study in which statin therapy in cirrhosis patients was associated with a decreased risk of hepatic decompensation, a delay in the time to decompensation, and reduced all-cause mortality, compared with cirrhosis patients not taking statins.The investigators were aware that some clinicians either do not initiate statin therapy or discontinue statins in patients with advanced liver disease because of perceived safety concerns. Dr. Kumar and her colleagues sought to determine the actual effect of statin therapy on the risk of hepatic decomposition in cirrhosis.They identified all patients with biopsy-proven cirrhosis who had taken statins for a minimum of 3 months for treatment of dyslipidemia. A control population of cirrhosis patients not on statins was matched 2:1 for age, gender, and Child-Pugh class from the Partners HealthCare System Research Patient Data Registry, which includes demographic and diagnostic information on patients treated at Massachusetts General Hospital and Brigham and Women's Hospital.The primary outcomes of the study were hepatic decompensation, defined as the development of ascites, jaundice (bilirubin greater than 2.5 mg/dL), hepatic encephalopathy, or variceal hemorrhage, and time to decompensation. Mortality was a secondary outcome, Dr. Kumar explained.The investigators created a Cox proportional hazards model for decompensation to control for age, Child-Pugh class, diabetes, coronary artery disease, and hepatocellular carcinoma, and they used conditional logistic regression to assess mortality, she said.Of 243 cirrhosis patients included in the analysis, 81 were statin users and 162 were matched controls. "In each group, approximately 70% of patients were Child-Pugh A and 30% were Child-Pugh B/C, and the MELD [Model for End-Stage Liver Disease] score, albumin, presence of varices, and beta-blocker use were similar between groups," Dr. Kumar noted. In the statin group, which was followed for a mean of 1,756 days, decompensation was reported in 31 patients (38.2%), compared with 80 patients (50.62%) in the control group.The control patients were followed for a mean of 1,503 days, and on Cox analysis, "statin therapy was the only factor significantly associated with lower decompensation risk, with a hazard ratio of 0.46." Additionally, Kaplan-Meier curves showed a significantly longer time to decompensation in patients receiving statin therapy, she said. In subgroup analyses, significantly longer time to decompensation was observed in Child-Pugh A and Child-Pugh B/C patients.Overall mortality was significantly lower in the statin group, at 37.0%, than in the control group, at 50.6%, said Dr. Kumar. Statin use remained significantly associated with decreased mortality in multivariate analysis, with an odds ratio of 0.36, while coronary artery disease and hepatocellular carcinoma were associated with increased mortality, with respective odds ratios of 3.6 and 4.9.There were no statistically significant differences in cause of death between the two groups, "however it is important to note that cause of death was not documented for approximately one-third of the study patients, so we cannot make definitive statements about whether patients on statins were less likely to die of liver-related or cardiovascular causes than patients in the control group," said Dr. Kumar.The apparent hepatoprotective effect of statin therapy in cirrhosis patients may be a function of previously observed hemodynamic and molecular effects of statins, Dr. Kumar hypothesized. Sinusoidal endothelial dysfunction with decreased nitric oxide production contributes to increased hepatic resistance in cirrhosis, she explained. Just as statins improve endothelial dysfunction in the peripheral vasculature, they may also improve the vascular disturbances that contribute to portal hypertension in cirrhosis by selectively increasing nitric oxide availability in the liver, thus reducing pressures, she said.The retrospective design of the study limits the conclusions that can be taken from it. Specifically, "we can't say that all patients with liver disease should be prescribed statins," Dr. Kumar said. "What we can say is that statin therapy is safe in this population, it may be beneficial for its effects on the liver as well as the cardiovascular system, and clinicians should not hesitate to prescribe it for appropriate cardiovascular indications in cirrhosis patients." The findings also indicate that prospective studies are warranted to clarify the role of statins in advanced liver disease, she stressed.Dr. Kumar disclosed no relevant financial conflicts of interest.