他汀类药物对慢性肝脏疾病进展及预后的影响

慢性肝病严重时可进展为肝纤维化和肝硬化,进而引起门静脉高压,最终可能发展至肝细胞癌。近年来,越来越多的研究发现他汀类药物可以使非酒精性脂肪性肝病患者的肝脏组织学得到改善,延缓肝纤维化进展,降低失代偿事件以及肝细胞癌的发生风险。介绍了他汀类药物在慢性肝病患者中的应用进展,为慢性肝脏疾病的防治提供一定的依据。     

他汀类药物肝脏安全性问题

他汀类药物继1987年问世以来，已成为西方发达国家处方量最大的药物之一，在心脑血管疾病的防治中起着重要作用。随着“早期干预、强化降脂、长期用药”理论的提出，他汀类药物的安全性问题备受关注，当前对他汀类药物肝脏毒性的过分担忧已影响到高脂血症的常规治疗，而对安全性的正确评价则有利于风险管理和心脑血管获益。为此，本文从肝脏病学的角度客观评估他汀类药物的安全性，并探讨与高脂血症密切相关的非酒精性脂肪性肝病（ nonalcoholic fatty liver disease, NAFLD）能否从他汀类药物治疗中获益。     

他汀类与非酒精性脂肪肝病患者的卒中预防

非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)是慢性肝病中的一个重要类型,其发病率日益增高,是代谢综合征的肝脏表现,与心脑血管病的发生关系密切.对NAFLD患者的卒中预防十分重要.他汀类药物是最重要的一类降胆固醇药物,通过抑制羟甲基戊二酰辅酶A(hydroxy-methyl-glutaryl coenzyme A HMG-CoA)还原酶,减少胆固醇合成,上调肝脏低密度脂蛋白(low-density lipoprotein,LDL)受体,降低循环低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)水平,有效降低卒中风险.此外,他汀类的多效性以及对胆同醇相关细胞信号通路的影响,能减缓或防止NAFLD的进展.由于他汀类药物对肝脏有一定的不良作用,是否能应用于慢性肝病患者存在较大争议.现有证据显示,他汀类药物可在NAFLD患者中安全使用,通常无需监测肝酶,过分关注他汀类药物的肝毒性反而可能采取不恰当的停药,导致心血管事件风险的增高.为此,他汀类对NAFLD患者的有效性及安全性尚需进一步评估.     

慢性肝病患者应用他汀治疗的安全性及肝脏获益

<正>他汀是3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂,具有降血脂、抗氧化、抗增殖、抗炎、改善内皮细胞功能等广泛生物学作用,作为一线推荐药物用于动脉硬化性心脑血管疾病的预防和治疗。由于他汀有导致血清丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)升高的风险,传统观点认为慢性肝病患者需谨慎处方他汀以免增加肝脏损伤。然而,临床上罕见他汀导致的严重药物性肝损伤,慢性肝病患者应用他汀并不比普通人群更易出现不良反应,最近不断有研究发现他汀有抗肝脂肪变、抗炎、抗纤维化、降低门静脉压力等功效,有可能让服用他汀的慢性肝病患者心血管和肝脏同时获益[1-2],因此有必要重新认识他汀的肝脏安全性,让更多患者获益于他汀治疗。     

他汀类药物肝脏安全性的研究进展

<正>随着他汀类药物在临床上的广泛使用,他汀类药物的安全性问题也一直备受关注,最常见的问题是血清转氨酶的升高。本文总结了他汀类药物肝脏安全性相关研究进展,为临床正确认识他汀类药物肝脏安全性及合理用药提供参考。他汀类药物,全称3-羟基-3甲基戊二酰辅酶A(HMG-CoA)还原酶抑制药,是现阶段最有效的降脂药物,可显著减少心血管事件或冠心病病死率。目前国内常见的他汀类药物有氟伐他汀、阿托伐他汀、洛伐他汀、辛伐他汀、普伐他汀、瑞舒伐他汀以及匹伐     

基础慢性肝脏疾病对接受免疫检查点抑制剂治疗的肿瘤患者的疗效及安全性的影响

近年来免疫检查点抑制剂(ICI)已经被批准用于多种恶性肿瘤的治疗,与此同时,接受ICI治疗且具有慢性肝脏疾病背景的肿瘤人群大幅增加。慢性肝脏疾病是否影响ICI的疗效和安全性逐渐成为热点问题。本文简要概述合并不同类型慢性肝脏疾病(慢性病毒性肝炎、非酒精性脂肪性肝病、自身免疫性肝病、肝硬化等)基础的肿瘤(原发性肝癌、非小细胞肺癌、黑色素瘤)患者应用ICI的有效性和安全性,并对慢性乙型肝炎患者ICI治疗后HBV再激活的相关文献进行综述,以期对存在慢性肝脏疾病基础的肿瘤患者ICI使用诊疗规范的制订和完善提供依据。     

正确看待他汀类药物的肝脏安全性

要点提示： 1、孤立性转氨酶升高≠肝脏损害。 2、非酒精性脂肪肝（NAFLD）患者应积极应用他汀类药物。 3、综合评价服用他汀类药物的获益与风险后可知，临床中应充分应用他汀类药物。     

Fa基因多态性与自身免疫性肝病的相关性

自身免疫性肝炎(AIH)和原发性胆汁性肝硬化(PBC)均是由免疫介导的病因不明的慢性肝脏炎症性疾病,表现为严重的肝脏病变,并可以进展为肝硬化Ⅲ.为探寻自身免疫性肝病的遗传易感性,我们分析了自身免疫性肝病患者的Fas基因多态性.     

问：降脂治疗前已出现肝功能异常的患者，是否能服用他汀类降脂药？

答：《中国成人血脂异常防治指南》明确指出,胆汁淤积和活动性肝病是使用他汀类药物的禁忌证,而轻度的肝脏转氨酶升高（〈3倍正常上限）并不是他汀治疗的禁忌证。     

他汀类药物防治慢性心力衰竭的研究进展

他汀类药物目前已应用于冠心病的整体防治。随着研究深入,人们发现他汀类药物具有降血脂以外的心血管系统多效性作用(pleiotropic effects)对防治慢性心力衰竭(CHF)可能有效。本文将对他汀类药物防治CHF的作用机制、临床证据及当前存在的争议作一综述。     

Lipid-lowering agents in the management of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.     

Use of statins in patients with liver disease

Opinion statement  Cardiovascular disease is as common in individuals with chronic liver disease as in the general population. Moreover, recent data suggest that patients with nonalcoholic fatty liver disease (NAFLD) may have a cardiovascular risk greater than that conferred by the conventional risk factors. There is unequivocal evidence that cardiovascular disease is an important cause of morbidity and mortality in this patient population and thus requires consideration of aggressive therapy with lipid-lowering agents such as statins. Because all statins are hepatically cleared and can cause elevations in liver biochemistries, there is a concern that patients with underlying liver disease may be at increased risk for hepatotoxicity. However, recent data, along with an assessment of statin safety by the Liver Expert Panel, suggest that statins are generally well tolerated in patients with chronic liver disease such as NAFLD, primary biliary cirrhosis, and hepatitis C virus. These drugs also appear to be safe in patients with stable/compensated cirrhosis. However, decompensated cirrhosis and acute liver failure should be considered contraindications for lipid-lowering therapy as these patients are unlikely to benefit because of their generally grave prognosis. Although routine hepatic biochemical test monitoring is recommended, the cost-effectiveness of this approach has been questioned. The benefit of statins in patients with underlying liver disease who are otherwise important candidates for statin therapy far outweighs the risk of a very rare event of serious liver injury.     

Rhabdomyolysis after midazolam administration in a cirrhotic patient treated with atorvastatin

The administration of statins in patients with liver disease is not an absolute contraindication. Hepatotoxicity is a rare and often dose-related event and in the literature there are only a few described cases of fatal rhab-domyolysis in patients with chronic liver disease after statin administration. During treatment with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors,the factors responsible for myopathy may either be related to the patient,or due to interactions with other medications that are metabolic substrates of the same isozymes and therefore able to increase blood statin concentration. The most important side effects consist of increased transaminase levels,abdominal pain or muscle weakness,increased serum levels of creatine kinase and rhabdomyolysis. In this article we report a case of fatal rhabdomyolysis with acute renal failure after gastric endoscopy,where midazolam was used as a sedation agent in a patient with chronic liver disease treated with a high dose of atorvastatin. Therefore,we suggest paying particular attention to the potential risks of associating atorvastatin and midazolam in patients with chronic liver disease who need to undergo gastric endoscopy.     

非生物人工肝对慢性重型肝炎肝功能支持效果评价

目的评价非生物人工肝支持治疗对慢性重型肝炎患者肝功能的支持效果及安全性。方法253例早、中、晚期慢性重型肝炎患者在综合治疗基础上给予非生物人工肝支持治疗,观察非生物人工肝支持治疗前后患者肝功能、肾功能、凝血酶原活动度（PTA）、血常规及临床症状变化情况。结果253例慢性重型肝炎患者进行非生物人工肝支持治疗后,血清总胆红素（TBIL）及谷丙转氨酶（ALT）下降,PTA上升（P〈0．01）;临床症状明显改善率为9．1％,有效率47．8％,总有效率为56．9％,不良反应轻。治疗后中、晚期慢性重型肝炎的存活率分别为53．1％、10．4％,早期患者存活9例。结论 非生物人工肝支持治疗慢性重型肝炎患者不良反应轻,对肝功能有肯定的支持作用,尤其对早、中期患者支持效果更好。     

慢性肝病患者组织中生存素与VEGF-A的表达

目的研究慢性肝病患者组织中生存素与血管内皮生长因子-A(VEGF-A)的表达意义。方法选取2011年1月-2013年5月广西壮族自治区南溪山医院肝病科收治的原发性肝癌患者50例作为研究对象,所有患者均行手术治疗,同时经病理学检查后证实为原发性肝癌,比较乙肝肝硬化、慢性乙型肝炎、原发性肝癌患者组织中的生存素与VEGF-A的表达。结果生存素在乙肝肝硬化、慢性乙型肝炎、原发性肝癌患者组织中的阳性表达率分别为46.9%、31.6%、84.0%,在三者之间的表达,差异具有统计学意义(P0.05);VEGF-A的表达率分别为75.0%、26.3%、68.0%,VEGF-A在原发性肝癌患者中的阳性表达率比乙肝肝硬化、慢性乙型肝炎患者较高,差异具有统计学意义(P0.05)。结论将生存素与VEGF-A作为早期原发性肝癌的检测标志物,能有效提高肝癌的诊断率,值得临床推广使用。     

Statins in liver disease: a molehill, an iceberg, or neither?

A growing number of chronic liver disease patients, especially those with metabolic syndrome-associated nonalcoholic fatty liver disease or hepatitis C virus-associated dysmetabolic syndrome, will take statins to prevent cardiovascular disease. As a result, clinicians will weigh complex issues raised by the interaction of statins with liver metabolism in these disorders. In this article, we critically review data concerning statins and liver pathophysiology with an emphasis on nonalcoholic fatty liver disease and hepatitis C virus, while also touching on other chronic liver diseases. Basic research interests include statins' mechanism of action and their effects on cholesterol-related cell signaling pathways and angiogenesis. From the clinical standpoint, many chronic liver diseases increase cardiovascular risk and would undeniably benefit from sustained statin use. The false alarms and security accompanying aminotransferase monitoring, however, are disturbing in light of the scarcity of data on statins' long-term effects on liver histology. Although some actions of statins might eventually prove to be particularly useful in nonalcoholic steatohepatitis, hepatitis C virus, or hepatocellular carcinoma, others may prove harmful. The lack of definitive data makes a fully informed decision impossible. Research using histological endpoints is urgently needed to determine the indications and contraindications of this extraordinary class of agents in patients with chronic liver disease.     

The potential role of statins in treating liver disease

Introduction: Statins are commonly use for the management of dyslipidemia, worldwide. Various studies have demonstrated that statins offer significant reduction in the risk of cardiovascular morbidity and mortality. However, this class of drugs has been implicated in potential liver toxicity, thus has been considered as a ‘forbidden-drug’ in patients with increased liver enzymes.

Areas covered: Studies have shown that statins might offer clinical benefits in the setting of viral hepatitis, progression of cirrhosis, and hepatocellular carcinoma. More importantly, this class of drugs was shown to ameliorate liver histological (in both imaging and biopsy studies) and functional alterations in patients with non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. In addition, two large survival studies have demonstrated reduction in the risk for cardiovascular events with statin use in patients with elevated transaminase levels at baseline.

Expert commentary: These benefits were of greater extent compared with patients with normal liver function tests at baseline. However, current international guidelines seem to neglect these findings and are not including statins in the management algorithm of patients with non-alcoholic fatty liver disease or steatohepatitis. Future randomized studies providing biopsy-proven benefits will establish the use of statins in the prevention of cardiovascular events and therapeutic algorithm of these patients.