Clinical and pathological features of drug-induced liver injury with different types of bile duct injury: An analysis of four cases / 临床肝胆病杂志

Objective To investigate the clinical, biochemical, pathological, disease course, and prognostic features of drug-induced liver injury (DILI) patients with different types of bile duct injury. Methods Four patients who were diagnosed with bile duct injury-type DILI by liver biopsy in Shijiazhuang Fifth Hospital, from March 2015 to October 2010 were selected, and related data were collected, including clinical data, laboratory examinations, radiological examination, and prognosis.The semi-quantitative score was determined for liver pathological morphology, and each indicator was compared between the four patients. Results Bile duct injury-type DILI was more common in female patients, and most patients tended to have a good prognosis.Clinical symptoms, liver biochemical parameters, and prognosis varied with the site, grade, scope, regeneration, and repair of bile duct injury. Conclusion Liver biopsy is still the gold standard for making a definite diagnosis of bile duct injury-type DILI, understanding the condition of lesions, and judging the prognosis of this disease.

Clinical and biochemical features of bile duct injury type of drug-induced liver injury / 临床肝胆病杂志

ObjectiveTo investigate the pathological and biochemical features of each pathological subtype of bile duct injury type of drug-induced liver injury (DILI), and to verify the value and significance of pathological classification of DILI. MethodsA retrospective analysis was performed for the clinical data of 112 patients with bile duct injury type of DILI who were admitted to Shijiazhuang Fifth Hospital from January 2006 to January 2016 and China-Japan Friendship Hospital from October 2003 to June 2014. According to the pathological subtype, the patients were divided into mixed hepatitis group with 40 patients, cholestatic hepatitis group with 40 patients, and simple cholestasis group with 32 patients, and the three groups were compared in terms of types of drugs used, course of disease, R value, and peak values, changing trend, time to peak, and recovery time of liver biochemical indices. The independent-samples Kruskal-Wallis H test was used for comparison of continuous data between multiple groups, and the Mann-Whitney U test was used for further comparison between two groups; the chi-square test was used for comparison of categorical data between groups. ResultsAmong the drugs inducing DILI, traditional Chinese medicine and Western medicine each accounted for half of the cases of bile duct injury type of DILI. Traditional Chinese medicine mainly included the drugs for osteoarthropathy, intervertebral disc bulge, alopecia, calculus-removing and cholagogic treatment, Yang-tonifying therapy, and skin diseases; 26 patients (65%) in the cholestatic hepatitis group had DILI caused by traditional Chinese medicine, while 16 patients (40%) in the mixed hepatitis group and 13 (40.6%) in the simple cholestasis group had such DILI. Antibiotics and antipyretic and analgesic drugs were the most common Western medicines for DILI. The mixed hepatitis group had the highest peak values of ALT and AST and R value, followed by the cholestatic hepatitis group and the simple hepatitis group (χ2=54.77, 44.21, and 5195, all P＜0.001), and there were no significant differences in the peak values of the other liver biochemical parameters between the three groups (all P＞0.05). In the mixed hepatitis group and the cholestatic hepatitis group, the time to peak of TBil was longer than that of ALT. There were no significant differences in course of disease, time to peak of liver biochemical parameters, and recovery time between the three groups (all P＞0.05). ConclusionEach subtype of bile duct injury type of DILI has unique clinical and biochemical features, and an understanding of such features may help to accurately judge clinical typing, pathological changes of targets, and degree of injury.

Clinicopathologic features of drug-induced vanishing bile duct syndrome / 中华肝脏病杂志

Vanishing bile duct syndrome (VBDS) manifests as progressive destruction and disappearance of the intrahepatic bile duct caused by various factors and cholestasis. VBDS associated with drug-induced liver injury (D-VBDS) is an important etiology of VBDS, and immune disorder or immune imbalance may be the main pathogenesis. According to its clinical symptoms, serological markers, and course of the disease, D-VBDS is classified into major form and minor form, and its clinical features are based on various pathomorphological findings. Its prognosis is associated various factors including regeneration of bile duct cells, number of bile duct injuries, level and range of bile duct injury, bile duct proliferation, and compensatory shunt of bile duct branches. This disease has various clinical outcomes; most patients have good prognosis after drug withdrawal, and some patients may experience cholestatic cirrhosis, liver failure, and even death. Due to the clinical manifestation and biochemical changes are similar to the primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), it need to identify by clinical physician.

Effects of Rimonabant on Cannabinoid Receptor 1 andα-Smooth Muscle Actin in C57 Mice with Experimental Hepatic Fibrosis / 天津医药

Objective To study the effect of rimonabant, cannabinoid receptor 1(CB1) antagonist, on the expressions of CB1 andα-smooth muscle actin (α-SMA) in C57 mice with experimental hepatic fibrosis, and their mechanisms in liver fibrosis progression thereof. Methods Thirty C57 mice were randomly divided into three groups, normal control group, mod-el control group and model+rimonabant group, 10 mice for each group. The mouse model of experimental hepatic fibrosis was induced by intraperitoneal injection with 10%CCl4 for two weeks. The normal saline was delivered by gavage daily in normal control group and model control group. Rimonabant was given to mice in model+rimonabant group. Mice were sacri-ficed at the end of eight weeks. Samples of liver tissue were collected. The expressions of CB1 andα-SMA in liver tissue of mice were observed by immunohistochemical staining. The score of fibrosis stage (S) in liver tissue was also analyzed. Re-sults The positive expressions of CB1 andα-SMA and the score S were significantly higher in model control group and model+rimonabant group than those in normal control group (P<0.05). The positive expressions of CB1 andα-SMA and the score S were significantly lower in rimonabant group than those in model control group (P<0.05). There were positive corre-lations in CB1,α-SMA and S scores between normal control group, model control group and model+rimonabant group (P<0.05). Conclusion The activation of CB1 can promote the formation of liver fibrosis. The anti-fibrotic effect of rimonabant, CB1 antagonist, related with the inhibiting of the proliferation and activation of hepatic stellate cells (HSC), and the inhibit-ing of the expression of CB1.

Hepatic expression of cannabinoid receptor 1 and 2 in C57 mice with experimental cirrhosis / 中国综合临床

Objective To investigate hepatic expressions and significances of cannabinoid receptor 1 (CB1) and cannabinoid receptor 2(CB2) in C57 mice with experimental cirrhosis.Methods Thirty C57 mice were randomly divided into three groups,i.e.normal control group,model control group and model colchicine group.Hepatic fibrosis model was prepared by intraperitoneal injection of carbon tetrachloride.The expressions of CB1 and CB2 in liver tissue of mice were observed by immunohistochemistry.The scores of inflammation grade (G) and fibrosis stage (S) were simultaneously performed.Results The scores of G and S in model control group and model colchicine group were significantly higher than those in normal control group( F =125.41,P =0.00; F =99.18,P =0.00).The scores of G and S in model control group were significantly higher than those in model colchicine group(P ＜0.01 ).The scores of CB1 and CB2 expressions in model control group and model colchicine group were significantly higher than those in normal control group ( F =29.27,P =0.00; F =36.99,P =0.00).The scores of CB1 and CB2 in model control group were significantly higher than those in model colchicine group( P ＜ 0.05 or P ＜ 0.01 ).There were significant relationships among scores of CB1,CB2,G and S in model control group and model colchicine group(Ps ＜0.05).As the scores of G and S became higher,the expressions of CB1 and CB2 gradually became more intensive.Conclusion The hepatic expressions of CB1 and CB2 in C57 mice with experimental cirrhosis increased significantly and have significant relationship with the grades of liver tissue inflammation and fibrosis.

Expression of cannabinoid receptor 1 in liver tissue of patients with chronic hepatitis B and its relationship with the serum levels of TGF-β1 and Leptin / 中国综合临床

Objective To observe expression and location of cannabinoid receptor 1 (CB1) in liver tissue of patients with chronic hepatitis B (CHB) ,and analyze the relationship of it with the liver fibrosis score,the serum levels of TGF-β1 and Leptin. Methods Liver biopsies were performed in 118 patients with CHB.The expression of CB1 in liver tissue was observed by immune histochemical staining, and semi-quantitative analysis was carried out to devide the CB1 score into four grades: -, +, + +, + + +. Serum levels of TGF-β1 and Leptin were determined by ABC-ELISA double-antibody sandwich method. Results The expression of CB1 in liver tissue with CHB had significant relationship with the fibrosis score. As the expression of the CB1 increased, the fibrosis score became higher ( F = 23. 369,P = 0. 000). Moreover, the expression of CB1 in liver tissue with CHB had significant relationship with the serum levels of TGF-β1 and Leptin( F values were 8. 762 and 5. 749;P values were 0. 001 and 0. 027, respectively). Conclusion CB1 may play promotive role in the process of hepatic fibrosis through regulation of TGF-β1 and Leptin.