他汀类药物在慢性肝病中的应用

对他汀类药物的肝脏安全性及其在慢性肝病中的应用进行评述,包括肝脏病专家对他汀类药物治疗血脂紊乱的肝脏安全性评估意见,以及肝脏转氨酶持续异常、非酒精性脂肪性肝病、慢性丙型肝炎、原发性胆汁性肝硬化、原发性肝细胞癌及肝移植患者使用他汀的效果和安全性.     

Use of statins in patients with peripheral artery disease

Atherosclerotic peripheral artery disease (PAD) is a growing health issue that affects more than 200 million individuals worldwide, conferring a high risk of cardiovascular events and death. In spite of its high prevalence, PAD has often been neglected in the past and the heightened cardiovascular risk of patients with PAD has been consistently under-recognized by practitioners. Considering that an integrated approach to reduce cardiovascular events and lower limb complications is necessary in this setting, statins represent the cornerstone of therapy as reported by current American and European guidelines. Literature has extensive data about the importance of lipid-lowering therapy in patients with PAD demonstrating that statins reduce symptoms, cardiovascular events and mortality. Despite data extrapolated from many studies on coronary artery diseases, moderate-dose statin therapy seems to be safe, and the minor risks posed in terms of myopathy-related symptoms are greatly outweighed by benefits. Other lipid-lowering drugs did not show the same results in terms of outcome and they should not be considered as first line therapy in these patients. The role of anti-PCSK9 inhibitors is emerging in the literature but further data are necessary to understand their superiority over statins.     

老年动脉粥样硬化性心血管疾病患者他汀类药物使用现状

目的探讨他汀类药物在老年动脉粥样硬化性心血管疾病(ASCVD)患者中的使用现状。方法筛选医院电子病历数据,选择2014年1月~2018年12月在解放军第九六〇医院和德州市第二人民医院收治的年龄≥60岁的ASCVD患者15751例,按患者的年龄分为60~69岁组6230例,70~79岁组5192例和≥80岁组4329例。调查3组患者他汀类药物使用现状,分析他汀类药物使用的影响因素,比较患者LDL-C、非HDL-C控制达标的情况。结果≥80岁组外周动脉粥样硬化疾病比例明显高于60~69岁组和70~79岁组(1.6%vs 1.1%和0.8%,P=0.000)。所有患者他汀类药物使用率为67.4%,急性冠状动脉综合征(ACS)患者他汀类药物使用率99.2%、PCI后为98.3%、冠状动脉旁路移植术(CABG)后为95.2%。多因素logistic回归分析显示,ACS、PCI后、CABG后、住院科室、入院时间是影响他汀类药物使用的独立危险因素(P<0.05,P<0.01)。与60~69岁组和70~79岁组比较,≥80岁组LDL-C达标率(48.07%vs 32.98%和30.97%)及非HDL-C达标率(38.99%vs 30.99%和28.76%)均明显升高(P<0.01)。结论他汀类药物在老年ASCVD急症患者中使用率较高,但在慢病管理中的使用及血脂达标情况仍有待提高。     

Use of ursodeoxycholic acid in patients with liver disease

Ursodeoxycholic acid (UDCA), the 7β-epimer of chenodeoxycholic acid, has multiple hepatoprotective activities. UDCA modifies the bile acid pool, decreasing levels of endogenous, hydrophobic bile acids while increasing the proportion of nontoxic hydrophilic bile acids. UDCA has a choleretic effect, increasing hepatocellular bile acid excretion, as well as cytoprotective, antiapoptotic, and immunomodulatory properties. UDCA has been shown to delay development of gastroesophageal varices and progression to cirrhosis as well as to improve long-term survival in patients with primary biliary cirrhosis. Significant improvement of abnormal liver tests may be achieved during UDCA therapy in patients with primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cystic fibrosis-associated liver disease, nonalcoholic fatty liver disease, graft-versus-host disease of the liver, total parenteral nutrition-induced cholestasis, and in some pediatric cholestatic liver diseases. However, unlike the effecs of UDCA in primary biliary cirrhosis, the long-term effects of UDCA in disease progression and survival in these other conditions remain to be established.     

不同他汀类药物治疗非酒精性脂肪性肝病合并高脂血症患者效果分析*

目的 探讨应用不同的他汀类药物治疗非酒精性脂肪性肝病(NAFLD)合并高脂血症患者的近期疗效。方法 2019年9月～2021年5月我院收治的52例NAFLD合并高脂血症患者被分成两组,每组26例,分别给予阿托伐他汀或匹伐他汀治疗6个月。检测空腹胰岛素水平,计算胰岛素抵抗指数 (HOMA－IR) ,采用ELISA法检测血清肿瘤坏死因子-α ( TNF-α) 、白介素-6(IL-6) 、IL-8、超敏C反应蛋白(hs-CRP)水平,使用超声诊断仪检查肝脏声像图变化,使用Fibrotouch-B型诊断仪检测肝脏脂肪受控衰减参数(CAP)和肝硬度检测(LSM)。结果 在治疗6个月末,匹伐他汀治疗组HOMA-IR、血清TC、TG和LDL-C水平分别为(2.1±0.5)、(3.5±0.4)mmol/L、(2.4±0.3)mmol/L和(2.2±0.5)mmol/L,均显著低于阿托伐他汀治疗组【分别为(2.5±0.4)、(4.2±1.0)mmol/L、(2.9±0.4)mmol/L和(2.9±0.7)mmol/L,P＜0.05】,而血清HDL-C水平为(1.6±0.4)mmol/L,显著高于阿托伐他汀治疗组【(1.3±0.3)mmol/L,P＜0.05】;两组血清TNF-α、hs-CRP、IL-6和IL-8水平比较,差异无统计学意义(P＞0.05);匹伐他汀治疗组CAP为(258.4±6.3)dB/m,显著低于阿托伐他汀治疗组【(267.7±10.2)dB/m,P＜0.05】;两组肝脏实质回声表现比较,无显著性差异(P＞0.05)。结论 应用他汀类药物治疗NAFLD合并高脂血症患者近期疗效较好,可能与降低了血脂水平和胰岛素抵抗,改善了机体炎性反应有关,而应用匹伐他汀的效果可能更好,值得进一步观察。     

Use of complementary and alternative medicine in patients with liver disease

OBJECTIVES: Complementary and alternative medicine (CAM) is used by 42% of the U.S. population. Its use among patients with chronic liver disease has not been well defined. Toward that end, we surveyed patients in six geographically diverse liver disease clinics in the United States for use of CAM. METHODS: Patients attending six liver disease clinics were polled via a common questionnaire regarding their use of CAM. Demographic information was obtained to identify predictors of CAM use. Statistical analysis included univariate and multivariate analysis using logistic regression. RESULTS: A total of 989 patients completed the questionnaire. Of these, 389 (39%) admitted to using some form of CAM at least once during the preceding month; 21% admitted to using herbal preparations, and 13% used herbs to treat their liver disease. Five variables were found to be predictive of alternative therapy use: female sex, young age, level of education, annual income, and geographic location. In all, 74% of patients reported using CAM in addition to the medications prescribed by their physician, but 26% did not inform their physician of their CAM use. CONCLUSIONS: CAM use is as common among patients visiting liver disease clinics in the United States as in the general population (39% vs 42%). Many patients are using herbs to treat their liver disease but are declining to discuss this use with their physician.     

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.     

Use of immobilized histidine in assay for endotoxin in patients with liver disease

TheLimulus amebocyte lysate (LAL) test has the disadvantage of being influenced by various inhibitors and activators. We have developed a method for the LAL reaction that involves the specific adsorption and isolation of endotoxin using a membrane filter unit and immobilized histidine; in this present study we used the method to measure endotoxin in the plasma of patients with acute or chronic liver disease. The adsorbed endotoxins are separated from LAL-inhibitors or-activators by the membrane filter unit, and their activity is directly assayed with the LAL reagent in a filter cup without any inhibition or activation. The study population consisted of 23 subjects, 3 with fulminant hepatitis and 20 with cirrhosis (9 with esophageal varices and 11 without). All 3 (100%) of the samples of plasma from patients with fulminant hepatitis were positive for endotoxin, as were the samples of 7 (78%) of the 9 patients with cirrhosis and esophageal varices, and 2 (18%) of the 11 patients with cirrhosis but without such varices. The results suggested that this method appears to be useful for assaying the concentration of endotoxin in patients with fulminant hepatitis or cirrhosis of the liver.     

Non-alcoholic fatty liver disease and the statins treatment

Even if the fatty liver is an entity recognized long time ago, only recently the non-alcoholic liver disease (NAFLD) came in attention. The fact that NAFLD might progress from simple steatosis to steatohepatitis and cirrhosis showed that NAFLD is not always a benign disorder. NAFLD has many etiological factors, but the majority of cases are those in the context of metabolic syndrome, known as primary NAFLD. Statins are well known as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitors, but this class has also pleiotropic actions non-related with HMG-CoA inhibition. Particularly, the possible anti-inflammatory and anti-fibrinogenesis qualities make statins an option in NAFLD. So, regarding the statins treatment in NAFLD, there are two aspects that are important. First of all, if statins (that are essential in the therapy for the improvement of cardiovascular risk) are safe at patients with NAFLD, given their adverse effect of increasing hepatic transaminases. Secondly, considering the strong associations between NAFLD and metabolic syndrome components, like obesity and insulin resistance, if statins could be a therapeutic option for the patients with NAFLD in the absence of dyslipidemia.     

Metabolic bone disease in patients with liver disease

The coexistence of liver disease and osteopenic bone disease has been recognized for many years and is now the subject of increasing attention. Osteoporosis has been characterized well in patients with cholestatic liver disease, but new research suggests that osteopenia and osteoporosis may also be prevalent in patients with other chronic liver diseases. Although the precise mechanism of bone loss remains unclear, advances in treatment and prevention are bringing heightened awareness to this common problem.     

Current questions regarding the use of statins in patients with coronary heart disease

The discovery of statins caused a revolution in the field of lipid intervention. Statins are drugs with a good safety profile. Their clinical benefit has been extensively documented in primary and secondary prevention of coronary heart disease. There is substantial evidence that the clinical outcome can be improved with aggressive statin treatment both in patients with unstable as well as with stable coronary heart disease. Also, early administration of statins in acute coronary syndromes is accompanied by rapid clinical benefits, mainly through their "pleiotropic" action (anti-inflammatory, anti-thrombotic, improvement of endothelial function, etc) which is probably a lipid-independent effect. Moreover, emerging data indicate that statins can achieve additional benefit when low density lipoprotein (LDL) cholesterol reduction is coupled with C-reactive protein reduction (<2 mg/L). The prevailing message from the recent statin trials is that intensive LDL cholesterol lowering treatment with statins achieves further clinical benefit beyond that achieved with standard statin therapy. This should encourage the medical community to consider prescribing statins in every coronary patient, aiming at LDL cholesterol levels <100 mg/dL, preferably in the range of 70-80 mg/dL in stable coronary patients, while in coronary patients at very high risk, the optional target for LDL cholesterol levels should be in the range of 50-70 mg/dL.     

他汀类药物在治疗非酒精性脂肪肝病中的研究进展

近年来,非酒精性脂肪肝病逐渐成为国内肝病相关死亡率的主要因素。非酒精性脂肪肝病的发病机制主要与代谢综合征相关,其危险因素主要包括肥胖、2型糖尿病、脂代谢异常等,这些危险因素与心血管疾病密切相关,心血管疾病死亡率也成为非酒精性脂肪肝病首要的死亡原因。他汀类药物是最主要的降脂药物,有证据表明,非酒精性脂肪肝病患者使用他汀类药物降脂治疗不仅能有效降低肝脏转氨酶水平,降低心血管疾病病死率,而且能有效减轻肝脏脂肪变性程度,同时可能对延缓肝脏纤维化有一定的疗效。     

他汀类药物对老老年冠心病患者的应用分析

目的 研究他汀类药物对80岁以上老老年冠心病患者的疗效及安全性.方法 入选73例80岁以上冠心病患者,入院后给予他汀类药物调脂治疗.按他汀药物不同,分为辛伐他汀组（20 mg/d）27例、阿托伐他汀组（20 mg/d）32例和瑞舒伐他汀组（5 mg/d）14例,分别对比分析用药前及随访12～24（13.8±3.7）个月后血脂参数和安全性指标,以及三组患者治疗后各指标的变化.结果 ①冠心病患者治疗后较治疗前TC、LDL-C、LDL-C/HDL-C均有明显下降[（3.59±0.67） mmol/L比（3.84±0.91） mmol/L、（2.16±0.61）mmol/L比（2.39±0.78）mmol/L及（2.15±0.75）比（2.48±0.85）],差异有统计学意义（P＜0.05）;治疗后较治疗前肝功、肾功、肌酶差异无统计学意义.②三组间调脂疗效无显著差异,并且肝功、肾功、肌酶等指标差异无统计学意义.结论 对于80岁以上老老年冠心病患者,应用常规剂量的他汀类药物调脂疗效好,不良反应少,安全性良好.