Current remarks and future directions on the interactions between metabolic dysfunction-associated fatty liver disease and COVID-19

During the outbreak of the coronavirus disease 2019(COVID-19)pandemic,particular interest rose regarding the interaction between metabolic dysfunctionassociated fatty liver disease(MAFLD)and the COVID-19 infection.Several studies highlighted the fact that individuals with MAFLD had higher probability of severe acute respiratory syndrome coronavirus 2 infection and more severe adverse clinical outcomes.One of the proposed mechanisms is the inflammatory response pathway,especially the one involving cytokines,such as interleukin 6,which appeared particularly elevated in those patients and was deemed responsible for additional insult to the already damaged liver.This should increase our vigilance in terms of early detection,close follow up and early treatment for individuals with MAFLD and COVID-19 infection.In the direction of early diagnosis,biomarkers such as cytokeratin-18 and scoring systems such as Fibrosis-4 index score are proposed.COVID-19 is a newly described entity,expected to be of concern for the years to come,and MAFLD is a condition with an ever-increasing impact.Delineating the interaction between these two entities should be brought into the focus of research.Reducing morbidity and mortality of patients with COVID-19 and MAFLD should be the ultimate objective,and the optimal way to achieve this is by designing evidence-based prevention and treatment policies.

drug-induced autoimmune liver disease:a diagnostic dilemma of an increasingly reported disease

The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-ground mainly consisting of some risk alleles of the major histocompatibility complex(HLA).Many drugs have been linked to AIH phenotypes,which sometimes persist after drug discontinuation,suggesting that they awaken latent autoimmunity.At least three clini-cal scenarios have been proposed that refers to drug- induced autoimmune liver disease(DIAILD):AIH with drug-induced liver injury(DILI); drug induced-AIH(DI-AIH); and immune mediated DILI(IM-DILI).In addi-tion,there are instances showing mixed features of DI-AIH and IM-DILI,as well as DILI cases with positive autoantibodies.Histologically distinguishing DILI from AIH remains a challenge.Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however,a detailed standard-ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag-nosis between both entities.Growing information on the relationship of drugs and AIH is being available,being drugs like statins and biologic agents more fre-quently involved in cases of DIAILD.In addition,there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepa-totoxicity.Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of

Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease

The use of non-steroidal anti-inflammatory drugs(NSAIDs) is widespread worldwide thanks to their analgesic, anti-inflammatory and antipyretic effects. However, even more attention is placed upon the recurrence of digestive system complications in the course of their use. Recent data suggests that the complications of the lower gastro-intestinal tract may be as frequent and severe as those of the upper tract. NSAIDs enteropathy is due to enterohepatic recycling of the drugs resulting in a prolonged and repeated exposure of the intestinal mucosa to the compound and its metabolites. Thus leading to so-called topical effects, which, in turn, lead to an impairment of the intestinal barrier. This process determines bacterial translocation and toxic substances of intestinal origin in the portal circulation, leading to an endotoxaemia. This condition could determine a liver inflammatory response and might promote the development of nonalcoholic steatohepatitis, mostly in patients with risk factors such as obesity, metabolic syndrome and a high fat diet, which may induce a small intestinal bacterial overgrowth and dysbiosis. This alteration of gut microbiota may contribute to nonalcoholic fatty liver disease and its related disorders in two ways: firstly causing a malfunction of the tight junctions that play a critical role in the increase of intestinal permeability, and then secondly leading to the development of insulin resistance, body weight gain, lipogenesis, fibrogenesis and hepatic oxidative stress.

Thinking outside the liver: Induced pluripotent stem cells for hepatic applications

The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications.

Hepatic complications induced by immunosuppressants and biologics in inflammatory bowel disease

The incidence of inflammatory bowel diseases(IBD)is rising worldwide.The therapeutic options for IBD are expanding,and the number of drugs with new targets will rapidly increase in coming years.A rapid step-up approach with close monitoring of intestinal inflammation is extensively used.The fear of side effects represents one the most limiting factor of their use.Despite a widespread use for years,drug induced liver injury(DILI)management remains a challenging situation with Azathioprine and Methotrexate.DILI seems less frequent with anti-tumor necrosis factor agents and new biologic therapies.The aim of this review is to report incidence,physiopathology and practical guidelines in case of DILI occurrence with the armamentarium of old and new drugs in the field of IBD.

Hepatobiliary manifestations in inflammatory bowel disease: The gut,the drugs and the liver

Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic challenge.Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis(UC),and typically do not correlate with intestinal activity.Primary sclerosing cholangitis(PSC)is the most common hepatobiliary manifestation of IBD,and is more prevalent in UC.Approximately 5%of patients with UC develop PSC,with the prevalence reaching up to 90%.Cholangiocarcinoma and colon cancer risks are increased in these patients.Less common disorders include autoimmune hepatitis/PSC overlap syndrome,IgG4-associated cholangiopathy,primary biliary cirrhosis,hepatic amyloidosis,granulomatous hepatitis,cholelithiasis,portal vein thrombosis,liver abscess,and non-alcoholic fatty liver disease.Hepatitis B reactivation during immunosuppressive therapy is a major concern,with screening and vaccination being recommended in serologically negative cases for patients with IBD.Reactivation prophylaxis with entecavir or tenofovir for 6to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen(HBsAg)positive,independently from viral load.HBsAg negative and anti-HBc positive patients,with or without anti-HBs,should be closely monitored,measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy,and should be treated if the viral load increases.On the other hand,immunosuppressive therapy does not seem to promote reactivation of hepatitis C,and hepatitis C antiviral treatment does not influence IBD natural history either.Most of the drugs used for IBD treatment may induce hepatotoxicity,although the incidence of serious adverse events is low.Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant.Methotrexaterelated hepatotoxicity has been described in 14%of patients with IBD,in a dose-dependent manner.Liver biopsy is not routinely recommended.Biologics-related hepatotoxicity is rare,but has been shown most frequently in patients treated with infliximab.Thiopurines have been associated with veno-occlusive disease,regenerative nodular hyperplasia,and liver peliosis.Routine liver biochemical tests are recommended,especially during the first month of treatment.All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement.Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.

Extracellular vesicles in liver disease and beyond

Extracellular vesicles(EVs) are membrane-derived vesicles which can be released by different cell types, including hepatocytes, hepatic stellate cells and immune cells in normal and pathological conditions. EVs carry lipids, proteins, coding and non-coding RNAs and mitochondrial DNA causing modifications on the recipient cells. These vesicles are considered potential biomarkers and therapeutic agents for human diagnostic and prognostic due to their function as intercellular mediators of cell-cell communication within the liver and between other organs. However, the development and optimization of methods for EVs isolation is required to characterize their biological functions as well as their potential as a treatment option in the clinic. Nevertheless, many questions remain unanswered related to the function of EVs under physiological and pathological conditions. In the current editorial, the results obtained in different studies that investigated the role of intrahepatic EVs during liver diseases, including drug-induced liver injury, non-alcoholic fatty liver, nonalcoholic steatohepatitis, alcoholic liver disease and hepatocellular carcinoma and extrahepatic EVs in remote organs during pathological events such as pulmonary disease, cardiovascular diseases, neurodegenerative disorders e.g., Alzheimer's disease, Parkinson's disease and multiple sclerosis as well as in immunopathological processes, are discussed. Although much light needs to be shed on the mechanisms of EVs, these membranederived vesicles represent both a novel promising diagnostic, and a therapeutic tool for clinical use that we emphasize in the current editorial.

Liver manifestations and complications in inflammatory bowel disease:A review

Hepatobiliary manifestations are common in inflammatory bowel disease(IBD),with 30%of patients presenting abnormal liver tests and 5%developing chronic liver disease.They range from asymptomatic elevated liver tests to lifethreatening disease and usually follow an independent course from IBD.The pathogenesis of liver manifestations or complications and IBD can be closely related by sharing a common auto-immune background(in primary sclerosing cholangitis,IgG4-related cholangitis,and autoimmune hepatitis),intestinal inflammation(in portal vein thrombosis and granulomatous hepatitis),metabolic impairment(in non-alcoholic fatty liver disease or cholelithiasis),or drug toxicity(in drug induced liver injury or hepatitis B virus infection reactivation).Their evaluation should prompt a full diagnostic workup to identify and readily treat all complications,improving management and outcome.

肠道菌群及其代谢与肝脏疾病

正常状态下,人体与肠道微生物群互利共生。肠道微生物群已被证实与多种疾病相关,而肝脏作为肠道的比邻器官,无论是在解剖学上还是在功能上都与肠道密切相关。罹患肝病时,肠道微生物群组成发生显著变化,且该变化还会进一步促进肝病进展。本文介绍不同肝病状态下肠道菌群及其代谢物的变化和这种变化对肝病进展的影响,以帮助同人深入认识肠道菌群变化与肝病发生发展之间的关联,进而共同探索基于肠道微生态的肝病预防和治疗新策略。

Nrf2-ARE信号通路参与肝脏疾病病理机制研究进展

核因子NF-E2相关因子2(Nrf2)是细胞抵御氧化应激的一个重要转录因子,它能够在活性氧或亲电试剂的刺激下,转位进入细胞核,并与抗氧化反应元件(ARE)相互作用,从而诱导下游保护性Ⅱ相解毒酶和抗氧化酶的表达,达到细胞保护的作用。氧化应激是诸多肝脏疾病共同的发病机制,而Nrf2-ARE是体内一条极为重要的抗氧化应激信号通路,该通路在肝脏疾病的发生、发展及预防过程中起着非常重要的作用,Nrf2或将成为肝脏疾病治疗的新靶点。该文综述了Nrf2-ARE信号通路参与肝脏疾病病理机制的最新研究进展,以期为日后相关研究提供参考。

S-腺苷蛋氨酸治疗药物性胆汁淤积性肝病伴抑郁/焦虑患者的研究

目的研究S-腺苷蛋氨酸对药物性胆汁淤积性肝病伴抑郁/焦虑患者的治疗作用。方法 38例不同病因的药物性胆汁淤积性肝病并抑郁/焦虑患者予S-腺苷蛋氨酸治疗,应用SDS/SAS量表分别评估、比较治疗前后各组患者抑郁/焦虑情况。结果 S-腺苷蛋氨酸治疗后,中草药致药物性肝病伴抑郁/焦虑患者以及抗生素、他汀类药物致药物性肝病伴抑郁患者胆汁淤积明显改善,抑郁/焦虑症状改善有显著差异(P值分别为0.001、0.011、0.018),而在抗肿瘤药物致药物性肝病患者中无显著性差异。结论 S-腺苷蛋氨酸在中草药以及抗生素、他汀类药物性胆汁淤积性肝病并抑郁/焦虑患者中具有保肝及抗抑郁的双重作用,这将为人类"生理-心理"疾病的全面治疗奠定基础。

老年药物性肝损伤患者临床特征分析

目的分析老年药物性肝损伤(DILI)患者的临床特征,以为临床干预提供依据。方法2018年12月~2024年2月我院老年医学科诊治的老年多种疾病患者181例,常规行临床分型和疾病程度分度。应用单因素和多因素Logistic回归分析影响DILI病情严重程度的危险因素。结果在181例老年患者中,发现DILI者44例(24.3%),其中肝细胞损伤型28例,胆汁淤积型12例,混合型4例;轻度25例,中度10例,重度8例,死亡1例;可疑药物为中草药占27.3%,保健类药物占22.7%,内分泌系统疾病用药占13.6%,心脑血管疾病用药占11.4%,等;DILI组年龄为72(66,76)岁,显著大于非DILI组【67(65,69),P<0.05】,多种疾病、饮酒、脂肪肝和高脂血症占比分别为79.6%、27.3%、56.8%和84.1%,显著高于非DILI组(分别为11.7%、3.6%、12.4%和8.7%,均P<0.05);9例≥3级肝损伤患者年龄为73(67,75)岁,显著大于35例≤2级肝损伤者【67(66,70)岁,P<0.05】,饮酒、多种疾病和合并脂肪肝占比分别为88.9%、100.0%和88.9%,均显著大于≤2级肝损伤者(分别为11.4%,74.3%和48.6%,均P<0.05),多因素Logistic回归分析表明,高龄【OR:1.67,95%CI:1.26~3.05】、饮酒【OR:2.43,95%CI:1.35~3.17】和脂肪肝【OR:2.14,95%CI:1.50~4.75】均是影响老年DILI患者病情严重程度的独立危险因素(P<0.05)。结论中草药、保健类药物、内分泌和心脑血管系统疾病用药容易导致老年基础疾病多的患者发生DILI,戒酒、降低脂肪肝程度和控制好疾病发作可能减轻DILI严重程度,值得临床深入研究。

组织病理、免疫组化及荧光在自身免疫性肝病诊断及鉴别诊断中的应用探究

目的 以自身免疫性肝炎(autoimmune hepatitis,AIH)、原发性胆汁性胆管炎(primary biliary cholangitis,PBC)、AIH-PBC重叠综合征(overlap syndrome,OS)和药物诱发性自身免疫样肝炎(drug-induced autoimmune-like hepatitis,DI-AILH)为研究对象,结合临床特征、组织病理、免疫组织化学染色和免疫荧光染色展开多方面研究,以探寻有助于鉴别诊断它们的临床病理特征。方法 对各组患者的肝穿刺标本进行HE、免疫组化和免疫荧光染色,结合判读结果量化分析AIH、PBC和OS之间及AIH和DI-AILH之间的组织学、免疫组织化学和免疫荧光差异;并针对DI-AILH和AIH之间显著性差异因子建立Logistic回归模型。结果 组织学评估中,AIH出现显著的界面性肝炎、Rosette花环形成、界板处成簇的浆细胞浸润;PBC出现汇管区浆细胞浸润、明显的淋巴细胞性小叶间胆管炎;OS出现更高的汇管区和肝小叶内炎症分级。免疫组化和免疫荧光半定量评分显示,AIH和PBC在汇管区和界板处阳性细胞有显著性差异、AIH出现IgG小叶内和汇管区沉积、PBC出现IgA沿小叶间胆管线状沉积。DI-AILH和AIH浆细胞、中性粒细胞浸润和界板处炎症差异明显,Logistic回归模型曲线下面积>0.80。结论 尽管在临床病理特点方面存在重叠,AIH、PBC和AIH-PBC OS仍存在有助于各自诊断的组织学、免疫组化及荧光特点,根据肝组织损伤模型,病理医师也可以给出关于AIH和DI-AILH较为准确的诊断。

阿托伐他汀药物性肝损伤的临床特征分析

背景药物性肝损伤是常见的药物不良反应之一,阿托伐他汀是临床上广泛应用的他汀类降脂药物之一,易引发肝损伤,目前对其所导致的药物性肝损伤的临床特征研究数据较少。目的探讨阿托伐他汀药物性肝损伤的临床特征,以提高临床医生对阿托伐他汀药物性肝损伤的认识。方法选取广西医科大学第一附属医院2012年1月—2022年8月住院且使用阿托伐他汀治疗,出现肝损伤且经Roussel Uclaf因果关系评估法评估为阿托伐他汀药物性肝损伤的患者,分析其临床特征。结果经Roussel Uclaf因果关系评估法评估,共确诊84例阿托伐他汀药物性肝损伤。阿托伐他汀药物性肝损伤患者中男性较多(72.6%),平均年龄为(60.2±11.5)岁,且均合并基础疾病(100.0%);达到中度肝损伤2例(2.4%),经治疗治愈或好转率达到100.0%。根据病程分型,主要表现为急性病程(100.0%);根据受损靶细胞分型以混合型最多(60.7%),其次是胆汁淤积型(26.2%)、肝细胞型(11.9%)。78.6%的患者服用阿托伐他汀发生肝损伤的时间在3个月内,且以第1~2周内居多;81.0%的患者在累积服用阿托伐他汀80个药物限定日剂量时发生肝损伤。结论阿托伐他汀药物性肝损伤多发生于男性、中老年、合并基础疾病的患者,多为轻度肝损伤,预后较好;临床分型以混合型、胆汁淤积型居多;肝损伤发生时间主要在3个月内,且阿托伐他汀药物性肝损伤的发生有一定剂量依赖性。

药物性肝病患者中医体质分布和临床特点分析

目的:分析药物性肝病患者的性别、年龄、中医体质、中医证型等分布规律。方法:选取2020年8月至2022年8月解放军总医院第五医学中心中医肝病科收治的药物性肝病患者368例,收集患者相关临床资料,分析药物性肝病患者的性别、年龄、中医体质、中医证型等分布规律和临床特征。结果:药物性肝病患者中医体质分布以气郁质(19.02%)最为多见,其次依次为阴虚质(18.21%)、湿热质(15.22%)、阳虚质(13.32%)、血瘀质(11.14%)、平和质(7.61%)、痰湿质(6.25%)、气虚质(5.16%)、特禀质(4.08%)。药物性肝病患者中医体质在性别、年龄等方面均具有差异性,男性以湿热质、阴虚质为多见;女性以气郁质、阴虚质为多见,而阴虚质在男性、女性均多见;青年中以气郁质和湿热质较多见,中年中以痰湿质较多见、老年以血瘀质较多见。药物性肝病患者在中医证型分布中主要为湿热内蕴证125例(34%),其次分别为肝郁脾虚证98例(27%)、肝肾阴虚证56例(15%)、气滞血瘀证46例(12%)、寒湿中阻证43例(12%);药物性肝病患者在体质与证型存在相关性,体质类型决定了该病证型的易感性。结论:根据药物性肝病患者的中医体质以及证型的分布特点以及相关临床特征,提示可以通过调节情志、合理饮食以及药物防治等方面做到“未病先防”“既病防变”,做到“辨体”“辨证”“辨病”的有机结合。

TNF-α在对乙酰氨基酚所致大鼠药物性肝损伤中的作用

目的探讨TNF-α在对乙酰氨基酚所致大鼠急性药物性肝损伤中的作用。方法 40只SD大鼠随机分成空白对照组、益赛普对照组、对乙酰氨基酚组、对乙酰氨基酚+益赛普组,每组10只。单次给药,24 h后采集血液测定生化指标,之后处死大鼠,取肝脏组织做病理检查以及应用ELISA试剂盒检测血清TNF-α。结果对乙酰氨基酚组肝损伤明显,阻断TNF-α后肝损伤减轻。对乙酰氨基酚组肝功生化值及TNF-α水平较空白对照组升高,差异有统计学意义(P<0.05),对乙酰氨基酚+益赛普组肝功生化值及TNF-α水平较对乙酰氨基酚组下降,差异有统计学意义(P<0.05)。结论 TNF-α的表达在对乙酰氨基酚所致大鼠急性肝损伤肝组织中明显升高,阻断TNF-α后肝损伤减轻,TNF-α可能参与对乙酰氨基酚所致肝损伤。

C-藻蓝蛋白对肝脏损伤的保护作用及机制研究进展

C-藻蓝蛋白(C-PC)是一种来自海洋藻类的含色素蛋白质,在多种炎性疾病和肿瘤治疗中表现出良好的效果。其对药物或毒性物质引起的肝损害、非酒精性脂肪性肝病、肝纤维化和肝脏缺血再灌注损伤等多种肝病具有保护作用。C-PC对肝损伤的保护作用主要是通过调节核因子(NF)-κB、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)和AMP依赖的蛋白激酶(AMPK)等信号通路及抑制氧化应激等机制实现的,且对正常细胞没有毒性。因此,C-PC作为一种潜在的天然保肝海洋活性物质具有广阔的应用前景。就近年来C-PC对肝脏损伤的保护作用及机制的研究进展进行综述。

褐藻胶寡糖对D-半乳糖诱导的衰老模型小鼠肝脏损伤的保护作用及其机制

目的探讨褐藻胶寡糖(AOS)对D-半乳糖(D-gal)诱导的衰老模型小鼠肝脏损伤的保护作用及其可能的机制。方法将32只雄性C57BL/6J小鼠随机分为对照组(A组)、AOS组(B组)、D-gal组(C组)和D-gal+AOS组(D组)。C、D组小鼠颈背部皮下注射D-gal[200 mg/(kg·d)],其余各组注射等量生理盐水,连续8周。从第5周开始B、D组小鼠用AOS[200 mg/(kg·d)]进行灌胃处理,其余各组用等量生理盐水灌胃处理,连续4周。实验结束后,收集小鼠血液和肝脏组织样本,测定小鼠血清中ALT、AST的水平,检测肝脏组织中衰老相关蛋白p21和还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)的氧化酶亚基gp91 phox、p67 phox的表达情况,以及核因子E2相关因子2(Nrf 2)、血红素氧化酶-1(HO-1)mRNA和超氧化物歧化酶1(SOD1)蛋白的含量。结果小鼠血清中ALT、AST和肝脏组织中衰老蛋白p21检测结果显示,单用D-gal诱导小鼠肝脏衰老和肝脏损伤的效果最显著(F=77.05~836.38,P<0.05),AOS对D-gal诱导的小鼠肝脏衰老和肝脏损伤有改善作用(F=20.29~138.67,P<0.05)。Western blot检测结果显示,单用D-gal可提高小鼠肝脏组织中NADPH的氧化酶亚基gp91 phox、p67 phox的水平(F=690.11、66.68,P<0.05),降低抗氧化酶SOD1的水平(F=24.85,P<0.05),而AOS可抑制D-gal的作用(F=12.28~123.18,P<0.05)。RT-qPCR检测结果显示,单用D-gal可明显抑制肝脏组织中Nrf 2、HO-1 mRNA的表达(F=380.07、253.34,P<0.05),而AOS可抑制D-gal的作用(F=62.04、41.21,P<0.05)。结论AOS可有效抑制D-gal诱导的衰老小鼠肝脏损伤,保护肝脏的生理功能,其作用机制可能与调控肝脏细胞中Nrf2/HO-1信号通路,抑制肝脏组织中的氧化应激有关。

Glutathione-S-transferases genes-promising predictors of hepatic dysfunction

diseases pathogenesis are genes that encodes the synthesis of glutathione-Stransferase(GST),known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins,through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products.The group of GST enzymes consists of cytosolic,mitochondrial and microsomal fractions.Recently,eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known:α-,ζ-,θ-,κ-,μ-,π-,σ-,andω-.The GSTs gene family in the Human Gene Nomenclature Committee,online database recorded over 20 functional genes.The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins.Nevertheless,human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene.Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases,particularly non-alcoholic fatty liver disease,hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma.Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology,and correlations with the natural course of the diseases were subsequently postulated.

解放军总医院第五医学中心2002年-2018年常见非感染性肝病构成比及变化趋势分析

目的对比分析住院的4种常见非感染性肝病住院患者2002年-2018年构成比及变化趋势。方法收集2002年-2018年解放军总医院第五医学中心收治的37973例非感染性肝病患者[出院病历的病案首页第一诊断为酒精性肝病(n=14971)、药物性肝损伤(药物性肝损害)(n=11406)、非酒精性脂肪性肝病(n=1776)和自身免疫性肝病(n=9820)]的病历资料,包括年龄、性别分布特征并对变化趋势进行对比分析。计数资料组间比较采用χ^2检验。结果药物性肝损伤患者占常见非感染肝病患者的30.04%,排在第2位,仅次于酒精性肝病。2011年以前药物性肝损伤患者占总住院肝病患者的比例呈上升趋势,2012年后该构成比开始呈一过性下降趋势。不同年龄段男女分布有显著差异(χ^2=113.087,P<0.05)。男性发病年龄主要集中在40~49岁,女性主要集中在50~59岁。不同住院年份的药物性肝损伤男性和女性患者,在不同高发年龄段分布均存在显著差异(男性:χ^2=369.252,P<0.001;女性:χ^2=663.490,P<0.001)。男性患者发病年龄峰值区间无明显变化,而女性患者发病年龄峰值区间呈老龄化趋势,由原来的40~49岁为主逐渐过渡到近6年的50~59岁年龄段。结论药物性肝损伤已构成非感染性肝病主要部分,中老年女性为主要高发人群,须重视药物性肝损伤的防控和诊治,尤其是中老年女性群体应加强安全用药指导宣教,建议在服药期间密切监测肝功能。