玉米肽对动物实验性肝损伤的保护作用

玉米肽对四氯化碳和硫代乙酰胺引起的小鼠急性肝损伤具有明显的保护作用 ,抑制血清中谷丙转氨酶活性的升高 ,降低丙二醛含量并增加肝糖原含量 。

肝损伤动物模型制作研究进展

肝脏疾病是危害人类健康的常见病,因此,建立和完善肝损伤动物模型,对各种肝脏疾病治疗药物的筛选和发病机制的研究有着重要的意义。将近年来肝损伤动物模型的相关进展作以综述和探讨。

小型动物实验性肝纤维及肝硬化动物模型的研究进展

肝纤维化是由于慢性肝病所致的持续或反复的肝实质炎症坏死而引起纤维结缔组织大量增生,其降解失衡导致肝内过多胶原沉积形成肝纤维化,肝纤维化为肝硬化早期阶段。因此,慢性肝损伤动物模型的制备具有重要的研究意义。肝纤维化的防治是国内外研究的热点,国内外对该模型的研究较多,为此笔者对几种常用的肝纤维化模型复制方法、机制及该模型的优缺点加以综述。

灵芝孢子粉对肝脏保护作用的药理试验研究

灵芝是高等真菌Ganoderma luciaum Leyss ex Fr. Karst的子实体,在我国传统用作补药及镇静药。根据《本草纲目》记载,灵芝为补五脏之气、扶正固本的上品药物,本文系研究灵芝孢子粉混悬液对肝损伤病理模型的药理作用。

红宝治疗乙型肝炎临床观察

开放性应用红宝胶囊治疗各类乙肝93例4周,结果显示,红宝能改善乙肝病人的食欲、腹胀、乏力、头晕、肝痛及睡眠等症状,且具有退黄和降酶作用,但对血请白蛋白及总蛋白影响较微。

美洲大蠊提取物黏糖氨酸对肝纤维化模型大鼠的影响及机制

背景:慢性肝病肝纤维化是可逆转的。有研究表明,美洲大蠊提取物具有一定的抗纤维化作用,其对实验性肝纤维化大鼠起保护作用。目的:观察美洲大蠊提取物黏糖氨酸治疗大鼠肝纤维化效果,初步探讨黏糖氨酸抗肝纤维化的作用机制。方法:采用猪血清诱导免疫性肝纤维化模型大鼠,同时采用0.5,0.25,0.10 g/kg的黏糖氨酸灌胃治疗,放射免疫法检测肝纤4项;免疫组织化学检测肝组织转化生长因子β1、组织金属蛋白酶抑制物蛋白表达强度和阳性细胞率;检测不同浓度的黏糖氨酸与转化生长因子β1、组织金属蛋白酶抑制物相关性。结果与结论:(1)美洲大蠊提取物黏糖氨酸能降低层粘连蛋白、Ⅲ型前胶原、Ⅳ型胶原和透明质酸酶水平(P<0.01),降低转化生长因子β1和组织金属蛋白酶抑制物1在肝组织的表达(P<0.01);(2)黏糖氨酸浓度与转化生长因子β1和组织金属蛋白酶抑制物1的蛋白表达呈明显的负相关(|r|>0.9);(3)结果证实,美洲大蠊提取物黏糖氨酸可逆转肝纤维化的改变,其作用机制与黏糖氨酸抑制转化生长因子β1和组织金属蛋白酶抑制物1的表达有关。

基于肝病临床病症特点的动物模型分析

根据肝病临床病症特点,分析目前常用的肝损伤动物模型,探讨现有肝损伤模型与临床病症的吻合情况及应用前景。现有的肝损伤动物模型主要有化学性、药物性、免疫性、酒精性,在一定程度上代表临床肝纤维化、肝硬化、病毒性肝病、酒精性肝病等病症。肝病造模方法较多,但缺少能反映肝病临床病症特点、体现肝病中医病因的动物模型复制,与临床病症仍存在一定差距。笔者根据现有肝损伤模型与临床病症特点的吻合程度及以中医证候特点,提出了制作与临床症状更为接近的病症结合肝损伤动物模型的设想,为中医药治疗肝病的研究提供可靠的实验方法。

Establishment of an animal model of ischemic type intrahepatic biliary lesion in rabbits

AIM:To explore a method to establish an animal model of ischemic type intrahepatic biliary lesion in rabbits. METHODS:Forty Japanese white rabbits of clean grade were divided randomly into four groups(10 rabbits per group)including sham operation(SO) group,and artery-bile obstruction(ABO)-1 h group, ABO-2 h group and ABO-3 h group.All the rabbits in this study underwent the same initial surgical procedure in which the liver was prepared as for graft removal during liver transplantation.Subsequently in the SO group,no additional vascular intervention was performed,while in groups ABO-1 h,ABO-2 h and ABO-3 h,the animals underwent combined clamping of the hepatic artery and common bile duct with microvascular clips for 1,2 and 3 h,respectively.After the scheduled occlusion time,the clip was removed to recover blood supply.The animals were killed 4 wk after operation.The survival rate,liver function, cholangiography and histopathological manifestation of the rabbits in each group were observed. RESULTS:The survival rate was 100%in groups SO,ABO-1 h and ABO-2 h,while it was 60%in group ABO-3 h.At each observation time,the change degree of the indexes of liver function was proportional to the clamping time(ABO-3 h>ABO-2 h>ABO-1 h> SO,P<0.05).Cholangiographical and histopathologic manifestations both showed that intrahepatic biliary lesion aggravated proportionally with the increase of the clamping time. CONCLUSION:An animal model of ischemic type intrahepatic biliary lesion in rabbits is successfully established,which may provide a reliable technique for basic and clinical research into the etiology, development and prophylaxis of ischemic type intrahepatic biliary lesion after liver transplantation.

Glutamine is highly effective in preventing in vivo cobalt-induced oxidative stress in rat liver

AIM: To evaluate the in vivo effect of glutamine on cobaltgenerated oxidative stress and (HO-1) induction in rat liver.METHODS: Fasted female Wistar rats received a single injection of cobalt chloride (375 μmol/kg body weight) and then were killed at different times. Lipid peroxidation and soluble and enzymatic antioxidant defense system (reduced glutathione (GSH), catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) were measured in liver homogenates. Ferritin and ferritin iron contents as well as heme oxygenase-1 (HO-1) activity and expression were also determined. The antioxidant properties of glutamine (Gin) were also evaluated. RESULTS: Cobalt chloride increased lipid peroxidation (50% over control values) 1 h after treatment. GSH reached a minimum at 3 h (40%) increasing thereafter. Twelve hours after CoCl2 injection, the antioxidant enzymes CAT, GSH-Px and SOD also diminished by about 30%. Heme oxygenase-1 induction was observed 6 h after treatment reaching a maximum value of 14-fold over the controls, 12 h after cobalt treatment. A 1.7-fold increase in ferritin and ferritin-bound iron 24 h after treatment were also obtained. Administration of glutamine (300 mg/kg body weight) by gavage 24 h before CoCl2 treatment entirely prevented the increase in thiobarbituric acid reactive substances (TBARS) content, the decrease in GSH levels, and partially reverted heme oxygenase-1 induction. CONCLUSION: These results suggested that a natural product such as glutamine prevents glutathione depletion and consequently heme oxygenase induction.

Induction of ischemic tolerance in rat liver via reduced nicotinamide adenine dinucleotide phosphate oxidase in Kupffer cells

AIM: To elucidate the mechanisms of hepatocyte preconditioning by H2O2 to better understand the pathophysiology of ischemic preconditioning. METHODS: The in vitro effect of H2O2 pretreatment was investigated in rat isolated hepatocytes subjected to anoxia/reoxygenation. Cell viability was assessed with propidium iodide fluorometry. In other experiments, rat livers were excised and subjected to warm ischemia/ reperfusion in an isolated perfused liver system to determine leakage of liver enzymes. Preconditioning was performed by H2O2 perfusion, or by stopping the perfusion for 10 min followed by 10 min of reperfusion. To inhibit Kupffer cell function or reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, gadolinium chloride was injected prior to liver excision, or diphenyleneiodonium, an inhibitor of NADPH oxidase, was added to the perfusate, respectively. Histological detection of oxygen radical formation in Kupffer cells was performed by perfusion with nitro blue tetrazolium. RESULTS: Anoxia/reoxygenation decreased hepatocyte viability compared to the controls. Pretreatment with H2O2 did not improve such hepatocyte injury. In liver perfusion experiments, however, H2O2 preconditioning reduced warm ischemia/reperfusion injury, which wasreversed by inhibition of Kupffer cell function or NADPH oxidase. Histological examination revealed that H2O2 preconditioning induced oxygen radical formation in Kupffer cells. NADPH oxidase inhibition also reversed hepatoprotection by ischemic preconditioning. CONCLUSION: H2O2 preconditioning protects hepato- cytes against warm ischemia/reperfusion injury via NADPH oxidase in Kupffer cells, and not directly. NADPH oxidase also mediates hepatoprotection by ischemic preconditioning.

血小板反应蛋白1在纤维化模型大鼠肾组织中的表达

背景:在实验性炎症性肾脏疾病模型中血小板反应蛋白1是转化生长因子β1重要的内源活化剂。转化生长因子β1是在许多不同的炎性疾病过程中,导致组织纤维化的主要细胞因子,特别是在肾脏疾病。目的:探讨血小板反应蛋白1在纤维化肾组织中的表达。方法:将健康雄性SD大鼠随机分为假手术组与模型组,模型组大鼠右侧输尿管进行结扎,制备大鼠肾纤维化模型。术后3周,每周取血、取尿,用ELISA与Bradford法检测血清肌酐、血尿素氮水平及尿蛋白含量;处死大鼠后,取结扎侧肾脏固定,用Western blot方法检测血管内皮生长因子、转化生长因子β1和血小板反应蛋白1蛋白的表达,苏木精-伊红检测术后肾组织病理结构改变情况。结果与结论:(1)造模后1周,模型组大鼠尿蛋白、血清肌酐与尿素氮水平显著高于假手术组(P<0.05),3周后,各指标差异更显著(P<0.01),表明肾功能损伤加重;(2)模型组转化生长因子β1蛋白与血小板反应蛋白1蛋白表达量明显高于假手术组,而血管内皮生长因子蛋白表达量显著低于假手术组;(3)苏木精-伊红染色结果显示,结扎肾小管后大鼠肾组织严重病变。(4)结果提示:血小板反应蛋白1蛋白在大鼠纤维化肾组织中表达水平显著升高,且其表达水平与血管内皮生长因子蛋白和转化生长因子β1蛋白密切相关,可能在肾纤维化中发挥重要作用。

CXCL16 participates in pathogenesis of immunological liver injury by regulating T lymphocyte infiltration in liver tissue

AIM： To investigate the role of CXCL16 in the pathogenesis of immunological liver injury and to explore the possible mechanism ofT lymphocyte infiltration regulated by CXCL16. METHODS： Immunological liver injury in murine model was induced by Bacille Calmette-Guerin and lipopolysaccharide. Expression pattern and distribution of CXCL16 were examined by real-time quantitative RT-PCR and immunohistochemical analysis. Anti-CXCL16 antibody was administrated in vivo to investigate its effect on T-cell recruitment and acute hepatic necrosis. The survival of murine model was also evaluated. RESULTS, The murine immunological liver injury model was successfully established, CXCL16 expression increased and predominantly distributed in periportal areas and vascular endothelia in injured liver tissues. Administration of anti-CXCL16 Ab protected the mice from death and acute liver damage. Approximately 70% of the mice survived for 72 h in the anti-CXCL16 Ab treatment group, whereas 80% died within 72 h in control Ab group. The number of liver-infiltrating T lymphocytes was significantly reduced from 1.01×10^7 to 3.52×10^6/liver, compared with control Ab treatment. CONCLUSION： CXCL16 is involved in immunological liver injury by regulating T lymphocyte infiltration in liver tissue.

Tumor necrosis factor-alpha induces apoptosis of enterocytes in mice with fulminant hepatic failure

AIM: To explore the alterations of intestinal mucosa morphology, and the effects of tumor necrosis factor a (TNFα) on enterocyte apoptosis in mice with fulminant hepatic failure (FHF). METHODS: Liver damage was induced by lipopolysaccharide (LPS)/TNF-α in D-galactosamine (GaIN) sensitized BALB/c mice. There were 40 mice in normal saline (NS)-treated group, 40 mice in LPS-treated group, 40 mice in GaIN-treated group, 120 mice in GaIN/ LPS-treated group and 120 mice in GaIN/ TNFα-treated group. Each group was divided into five subgroups of eight mice each. Serum samples and liver, intestinal tissues were respectively obtained at 2, 6,9,12 and 24 h after administration. Anti-TNFa monoclonal antibody was injected intravenously into GaIN/LPS-treated mice. Serum TNFα levels were determined by enzyme linked immunosorbent assays (ELISA). Serum ALT levels were determined using an automatic analyzer. The intestinal tissues were studied under light microscope and electron microscope at 2, 6, 9,12 and 24 h in mice with fulminant hepatic failure, respectively. Enterocyte apoptosis was determined by terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling (TUNEL) method. The expression of tumor necrosis factor receptor 1 (TNFR1) in intestinal tissue was tested by immunohistochemistry Envision Two Steps. RESULTS: Gut mucosa was morphologically normal at all time points in all groups, but typical apoptotic cells could be seen in all experimental groups under electron microscope. Apoptosis rate of gut mucosal epithelial cells were significantly increased at 6, 9 and 12 h, peaked at 12 h in mice with fulminant hepatic failure. TNFa induced apoptosis of enterocytes in mice with FHF. The integrated OD (IOD) levels of TNFa receptor 1 protein expressed in the intestine of mice with GaIN/LPS and GaIN/ TNFα induced FHF at 2, 6, 9, 12 and 24 h after GaIN/LPS and GaIN/TNFα administration were 169.54±52.62/905.79±111.84,11 350.67±2 133.26/28 160.37±4 601.67, 25 781.00±2 277.75/122 352.30±49 412.40, 5 241.53±3 007.24/ 49 157.93±9 804.88, 7 086.13±1 031.15/3 283.45±127.67, respectively, compared with those in control groups (with NS, LPS and GaIN administration, respectively). IOD level of TNFR1 changed significantly at 6, 9 and 12 h after GaIN/LPS and GalN/TNFa administration. The expression of TNFR1 protein was significantly higher at 9 h after GaIN/LPS and GaIN/TNFα administration than that in control groups. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis. CONCLUSION: TNFα can induce apoptosis of enterocytes in mice with FHF. Anti-TNFα IgG can inhibit this role.

Protective effect of fufanghuangqiduogan against acute liver injury in mice

AIM: To study the effects and possible mechanisms of fufanghuangqiduogan (FFHQ) in mice with acute liver injury (ALI). METHODS: ALI was successfully induced by injecting carbon tetrachloride (CCl4) intra peritoneally and by tail vein injection of Bacillus Calmette Guerin (BCG) and lipopolysaccharide (LPS) in mice, respectively. Each of the two model groups was divided into normal group, model group, FFHQ (60, 120 and 240 mg/kg) treatment groups, and bifendate treatment group. At the end of the experiment, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), content of malondialdehyde (MDA), activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in liver homogenate were measured by biochemical methods. The activities of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) were determined by radio-immunoassay. Hepatic tissue sections were stained with hematoxylin and eosin and examined under a light microscope. RESULTS: In the two models of ALI, FFHQ (60, 120, 240 mg/kg) was found to significantly decrease the serum transaminase (ALT, AST) activities. Meanwhile, FFHQ decreased MDA contents and upregulated the lower SOD and GSH-px levels in liver homogenate. Furthermore, in immunologic liver injury model, FFHQ decreased levels of TNF-α and IL-1 in serum. Histologic examination showed that FFHQ could attenuate the area and extent of necrosis, reduce the immigration of inflammatory cells. CONCLUSION: FFHQ had protective effect on liver injury induced by either CCl4 or BCG+LPS in mice, and its mechanisms were related to free radical scavenging, increasing SOD and GSH-px activities and inhibiting the production of proinflammatory mediators.

Oral administration of geranylgeranylacetone plus local somatothermal stimulation: A simple, effective, safe and operable preconditioning combination for conferring tolerance against ischemia-reperfusion injury in rat livers

AIM： To explore a simple, effective, safe and operable pretreatment for conferring tolerance against ischemia- reperfusion （I-R） injury in rat livers. METHODS： Forty-five rats were divided into five groups （each group n = 9）. Group C： control group; group G： geranylgeranylacetone （GGA） was administered without heat stress; group S： local heat stress alone; group WG： GGA plus whole-body heat stress; group SG： GGA administration plus local heat stress. After completion of the I-R procedure, the ischemic-reperfused liver lobes in five groups were resected and tested for heat shock protein （HSP70） by RT-PCR, Western blotting analysis and immunohistochemical staining. The blood samples were collected for ALT and AST measurement at the end of occlusion of blood supply, 30 min after reperfusion, 24, 48, 72 h after surgery from the inferior vena cava. Survival was monitored for 1 wk. RESULTS： The production of HSP70 after I-R injury increased, the liver enzyme levels after reperfusion decreased rapidly, and the survival rates increased in groups C-SG. CONCLUSION： The combination of GGA plus local somatothermal stimulation is a simple, effective, safe and operable pretreatment to induce HSP70 in patients with liver tumor and cirrhosis before hepatectomy and in donors before harvesting graft for liver transplantation.2005 The WJG Press and Elsevier Inc. All rights reserved.

N-acetylcysteine attenuates alcohol-induced oxidative stress in the rat

AIM: There is increasing evidence that alcohol-induced liverdamage may be associated with increased oxidative stress.We aimed to investigate free-radical scavenger effect of n-acetylcysteine in rats intragastrically fed with ethanol.METHODS: Twenty-four rats divided into three groups werefed with ethanol (6 g/kg/day, Group 1), ethanol and n-acetylcysteine (1 g/kg, Group 2), or isocaloric dextrose(control group, Group 3) for 4 weeks. Then animals weresacrificed under ether anesthesia, intracardiac blood andliver tissues were obtained. Measurements were performedboth in serum and in homogenized liver tissues.Malondialdehyde (MDA) level was measured by TBARSmethod. Glutathione peroxidase (GSH-Px) and superoxidedismutase (SOD) levels were studied by commercial kits.Kruskal-Wallis test was used for statistical analysis.RESULTS: ALT and AST in Group 1 (154 U/Land 302 U/L,respectively) were higher than those in Group 2 (94 U/L and155 U/L) and Group 3 (99 U/L and 168 U/L) (P＝0.001 forboth). Serum and tissue levels of MDA in Group 1 (1.84 nmol/mL and 96 nmol/100 mg-protein) were higher than Group 2(0.91 nmol/mL and 64 nmol/100 mg-protein) and Group 3(0.94 nmol/mL and 49 nmol/100 mg-protein) (P＜0.001 forboth). On the other hand, serum GSH-Px level in Group 1(8.21 U/g-Hb) was lower than Group 2 (16 U/g-Hb) andGroup 3 (16 U/g-Hb) (P＜0.001). Serum and liver tissue levelsof SOD in Group 1 (11 U/mL and 26 U/100 mg-protein)were lower than Group 2 (18 U/mL and 60 U/100 mg-protein)and Group 3 (20 U/mL and 60 U/100 mg-protein) (P＜0.001for both).CONCLUSION: This study demonstrated that ethanol-induced liver damage is associated with oxidative stress,and co-administration of n-acetylcysteine attenuates thisdamage effectively in rat model.

Evaluation of CMU-1 preservation solutions using an isolated perfused rat liver model

AIM: CMU-1 is a new preservation solution with a low potassium concentration as well as low viscosity that is highly effective in reducing preservation injury. The purpose of this experiment is to compare the protective effect of CMU-1 solution with that of UW during cold preservation and normothermic reperfusion. METHODS: Wistar rats were divided into two groups according to different preservation solution: CMU-1 group and UW group. After 6, 12 and 24 h cold storage of rat liver in different preservation solutions, the isolated perfused rat liver model was applied to reperfuse the liver for 120 min normothermically (37 癈) with Krebs-Henseleit solution, meanwhile the pH value of the preservation solution was measured. The perfusate was sampled for the evaluation of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). At the end of the reperfusion, all of the bile product was collected, energy metabolic substrate and histological examination were performed. RESULTS: After preserving for 6 h, pH value of both groups did not change; after 12 h, both decreased but with no significant difference. After 24 h, pH value in UW solution group significantly decreased. The total adenine nucleotides level and AEC in liver tissue decreased with preservation time, but they were higher in CMU-1 group. And the amount of bile product after perfusion for 120 min in CMU-1 group was much more than that in UW group. However, there were no significant differences in ALT and LDH levels between two groups. Histology showed no difference. CONCLUSION: The preservation effect of CMU-1 solution is similar with that of UW solution. However, CMU-1 solution shows some advantages over UW solution in energy metabolism, preventing intracellular acidosis and bile product.

Expression of nitric oxide synthase in T-cell-dependent liver injury initiated by ConA in Kunming mice

Objective: To investigate whether nitric oxide synthase (NOS) is expressed in T-cell-dependent liver injury initiated by concanavalin A (ConA) in Kunming mice and study the possible effect of nitric oxide(NO) on liver injury models. Methods: Liver injury in Kunming mice was induced by administration of ConA through tail vein. Expression of NOS in the liver was detected by NADPH diaphorase staining method. The possible effect of NO on liver injury models was obtained by L-NAME injection to suppress synthesis of NO. Results: NOS has a strong expression in hepatocytes after ConA injection, especially in those close to the central vein, while only a weak expression was found in the epithelial cells in control group. Liver injury became more serious when NO synthesis was inhibited by L-NAME, accompanied by great malondialdehyde(MDA) increase in serum and severe intrahepatic vascular thrombosis. Conclusion: NOS markedly expressed in ConA-induced liver injury, which may subsequently promote nitric oxide synthesis. Increasement of nitric oxide has a protective effect on ConA-induced liver injury.

Expression of Egr-1 in the liver of mice following hemorrhagic shock and resuscitation

Objective: To investigate the expression of early growth response gene-1(Egr-1) in the liver following hemorrhagic shock with or without resuscitation(HS or HSR). Methods: Mice were subjected to HS or HSR.Liver expression of Egr-1 mRNA was detected by Northern blotting.DNA binding activity of the Egr-1 protein in liver nuclear extracts(NE) was determined by electrophoretic mobility shift assay(EMSA).Western blot analysis was used to assess the induction of Egr-1 protein in the liver tissue,cytoplasma and NE. Results: Egr-1 mRNA was strongly expressed as early as 1 h after HS,and its level was decreased in the following 2.5 h but still higher than that in 1 h HS group.The Egr-1 DNA binding activity elevated in the liver NE of 2.5 h HS group and 2.5 h HS + 4 h R group,so did the Egr-1 protein in the liver and the liver NE of the same two groups.However,the maximal Egr-1 protein expression was found in the cytoplasma of liver following 2.5 h HS. Conclusion: Our data suggest that both Egr-1 mRNA and protein are strongly elevated and the binding activity of Egr-1 to its cognate DNA site is increased in the liver following HSR,indicating the increases of Egr-1 transcriptional and translational levels.This study provides evidence that Egr-1 gene is activated in the liver during HS and HSR.

Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase

AIM： To identify the proportion, causes and the nature of drug-induced liver injury （DILI） in patients with no- tably elevated alanine aminotransferase （ALT）. METHODS： All the inpatients with ALT levels above 10 times upper limit of normal range （ULN） were ret- rospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT eleva- tions were examined for each patient, including bili- ary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed usingthe Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS： A total of 129 cases with ALT 〉 i0 ULN were identified. Hemodynamic injury （n = 46, 35.7%）, DILl （n = 25, 19.4%） and malignancy （n = 21, 16.3%） were the top three causes of liver injury. Peak ALT val- ues were lower in DILI patients than in patients with hemodynamic injury （14.5 5.6 ULN vs 32.5 ：I： 30.7 ULN, P = 0.001）. Among DILI patients, one （4%） case was classified as definite, 19 （76%） cases were clas- sified as probable and 5 （20%） as possible according to the ClOMS scale. A hepatocellular pattern was ob- served in 23 （92%） cases and mixed in 2 （8%）. The extent of severity of liver injury was mild in 21 （84%） patients and moderate in 4 （16%）. Before discharge, 10 （40%） patients were recovered and the other 15 （60%） were improved. The improved patients tended to have a higher peak ALT （808 ＋ 348 U/L vs 623 ＋ 118 U/L, P = 0.016） and shorter treatment duration before discharge （8 ＋ 6 d vs 28 ~ 12 d, P = 0.008） compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILl. Antibacterials were the most common agents causing DILI in 8 （32%） cases, followed by glucocorticoids in 6 （24%） cases. Twenty-four （96%） cases received treatment of DILl with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs （e.g., glycyr- rhizinate）, antioxidants （e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin）, polyene phospha- tidyl choline and herbal extracts （e.g., protoporphyrin disodium and silymarin）. Diagnosis of DILl was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgi- cal wards had a higher risk of missed diagnosis in dis- charge letter [odds ratio （OR） 32.7, 95%CI （2.8-374.1）,CONCLUSION： DILI is mostly caused by use of anti- bacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT 〉 10 ULN. DILI is underdiagnosed frequently.