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Autoimmune liver diseases (AILDs),including mainly autoimmune hepatitis (AIH),primary biliary cholangitis (PBC),primary sclerosing cholangitis (PSC),IgG4-related sclerosing cholangitis (IgG4-SC),and overlap syndromes,are characterized by circulating autoantibodies,inflammatory liver histology,and increased level of serum immunoglobulins. Early diagnosis and management can significantly improve the prognosis of patients and their quality of life. This editorial focused on the research progress and difficulties encountered in studies on AILDs in China.
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ObjectiveTo explore the role of fatty acid on endoplasmic reticulum (ER) stress and to detect the influence of tauroursodeoxycholic acid (TUDCA) on the expression of ER related genes in steatosis hepatocytes by establishing different models of hepatic steatosis.MethodsHealthy adult hepatocyte cell line HL-7702 was taken as research object.The model of hepatic steatosis was established with palmitic acid alone or mixed fatty acids.The cell viability was measured and calculated through CCK-8 positive cell proliferation assay.The cell morphology and steatosis was observed.The intracellular triglyceride content was tested with the triglyceride determination kit.With TUDCA intervention,the relative expression of Glucose-regulated protein 78 (GRP78) and CCAAT/Enhancer binding protein homologous protein (CHOP) at mRNA level was determined by real-time PCR.ResultsThe viability of hepatocyte was influenced once the concentration of mixed fatty acid reached 0.5 mmol/L or palmitic acid was 0.125 mmol/L.The effect of palmitic acid alone was stronger than that of mixed fatty acid on hepatocyte injury.The content of intra-hepatocyte triglyceride gradually increased in mixed fatty acid group,which only significantly increased after treated for 12 hours in palmitic acid alone group and then there was no significant change.There was no significant difference in relative expression of GRP78 and CHOP at mRNA level in various concentrations and treated time of mixed fatty acid group.After treated with palmitic acid at 0.5 mmol/L,intra-hepatocyte relative expression of CHOP at mRNA level increased obviously,however there was no effect on GRP78mRNA expression.After treated with palmitic acid at 1.0 mmol/L,both intra-hepatocyte GRP78 and CHOP mRNA relative expression increased.There was no significant difference in GRP78 and CHOP mRNA relative expression before and after ER stress in TUDCA intervented low dose palmitic acid group.There was significant difference in CHOP mRNA relative expression before and after ER stress in TUDCA intervented high dose palmitic acid group (at 12hrs:8.6400 to 5.1032; at 24hrs:13.7948to 6.4928,P=0.042 and 0.017),while no significant difference in GRP78 mRNA expression.ConclusionAt same fatty acid concentration,the larger propotion palmitic acid has,the more severe injury hepatocyte has.The regulation of palmitic acid on intra-hepatic ER stress is a time and dose dependent manner.TUDCA may improve palmitic acid induced ER stress to some degree.
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Objective To evaluate the relationship between fatty liver disease and liver metastases from colorectal cancer.Methods Eight hundred and ninety patients with colorectal cancer,who were submitted to hospital from 1993 to 2002 and had complete clinical data,were retrospectively analyzed.Of 890 patients,127 were diagnosed as fatty liver(FL)by ultrasonography,and the other 763 who were without fatty liver were served as controls(NFL).The clinical data including pathology,liver matastasis or mortality after surgery were analyzed.The survival rate and liver matastasis after surgery were followed up and statistically analyzed.Results The liver metastases was lower in FL group than that in NFL group(7 cases vs 102 cases,P=0.012).The tumor size was smaller in FL group than that in NFL group[(4.15±1.80)crn vs(4.77±2.25)cm,P=0.0016].The Dukes B(247/732,33.74%)and C(232/732,31.83%)patients were more common in NFL group,whereas Dukes A(41/121,33.61 %)and B(40/121,32.77%)were more common in FL group with significant difference(P＜0.05).No significant difference was found in 7-year survival rate between two groups who had been followed up(P=0.3024).Conclusion The lower incidence of liver metastases is found in FL group,which indicate that fatty liver disease may inhibit liver metastases from colorectal cancer by underlying mechanisms.
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Objective To study the expression of metabolism related genes in peripheral blood mononuclear cells in patients of non alcoholic fatty liver diseases (NAFLD)with cholelithiasis.Methods Patients who had BMI ≥ 27 were divided into obese ( n = 10),the NAFLD ( n = 7) and NAFLD with cholelithiasis (n= 16) groups.The subjects who had BM1<25 (n = 10) and cholelithiasis (n = 16) were served as controls.The expression of peroxisome proliferator-activated receptors (PPAR)α,sterol regulatory element-binding protein(SREBP)-lc and Leptin Rb in peripheral blood mononuclear cells were measured.Results The expressions of PPARα,SREBP-lc and Leptin Rb in peripheral blood mononuclear cells were different in five groups.The significant difference was found in expression of leptin Rb between NAFLD with cholelithiasis group and the obese group,NAFLD with cholelithiasis group and the cholelithiasis group,NAFLD with cholelithiasis group and NAFLD group,the obese group and controls (P values= 0.037,0.050,0.044and 0.038,respectively).The leptin Rb mRNA expression in NAFLD with choletethiasis group was the lowest.Conclusions The low expression of leptin Rb mRNA was found in NAFLD patients with cholelithiasis.Cholelithiasis may increase the extent of insulin resistance and cause NAFLD progression.
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<p><b>OBJECTIVE</b>To analyze the association between alleles of HLA-DRB1 and type I autoimmune hepatitis (AIH) in patients from Shanghai, China.</p><p><b>METHODS</b>In 32 Chinese patients with type I AIH and 48 healthy controls in Shanghai area, polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) was performed to examine the association of the alleles of HLA-DRB1 and its subtypes with type I AIH.</p><p><b>RESULTS</b>HLA-DRB1 typing by PCR-SSP showed that DR4 had a significantly increased frequency among patients with AIH versus healthy control (46.9% versus 20.8%; relative risk=3.35, chi(2)=5.99, P=0.014). No other alleles differed significantly between the two groups. In subtypes of DRB1*04, there was a trend for an increase in gene frequency of DRB1*0405 increased in patients with type I AIH versus healthy controls (21.9% vs 6.3%, chi(2)=4.23, P=0.04, but Pc=0.08). The frequency of arginine at position HLA-DR beta 71 of third hypervariable region significantly increased among patients with AIH versus healthy control (46.9% versus 18.8%, chi(2)=7.14, P=0.008).</p><p><b>CONCLUSIONS</b>Type I AIH in Chinese patients of Shanghai area is associated with HLA-DR4 and arginine at position DR beta 71 of third hypervariable region</p>
Subject(s)
Humans , Alleles , Asian People , China , DNA Primers , Gene Frequency , HLA-DR4 Antigen , HLA-DRB1 Chains , Genetics , Hepatitis, Autoimmune , Genetics , Polymerase Chain ReactionABSTRACT
Objective To evaluate the efficacy and safety of orlistat combined with low calorie diet in the treatment of obesity with non-alcoholic fatty liver disease. Methods Orlistat 120 mg, three times a day, combined with low calorie diet for a cause of 24 weeks, were given to the 60 non-alcoholic fatty liver disease (NAFLD) patients whose body mass index (BMI) were between 27 and 40. Results ①The percentage of mean weight loss and mean decreased BMI were both (10.76? 4.52 )% of their initinal weight at 24 weeks treatment. ②ALT, AST, GGT and total bilirubin was significantly decreased ( P
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Objective To investigate the role of apoptosis in hepatocyte injury in tyep Ⅰ autoimmune hepatitis (AIH). Methods Using transferase mediated UTP biotin nick end labling (TUNEL) technique and immunohistochemistry with anti Fas antibody, we detected apoptosis cells in 10 liver biopsy samples and 3 control livers obtained from normal subjects. Result Hepatocytes in all AIH liver tissues were positively stained by TUNEL and anti Fas antibody in various degree. In contrast, control tissues did not show DNA fragmentation or positive stain with anti Fas antibody. A significant correlation was seen between apoptosis index (AI) and necroinflammatory grading ( r =0.45, P
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Objective To investigate the expression of CD14, the receptor of lipopolysaccharide (LPS) on Kupffer cell membrane during the course of CCl4-induced liver injury and its role in activation of Kupffer cells. Methods The experimental rats were hypodermically administered CCl4 twice weekly for up to 8 weeks. Kupffer cells were isolated from the liver of normal and CCl4-treated rats by the combined ‘collagenase-pronase’ perfusion method and discontinuous density gradient centrifugation. On the following day after isolation, the cells were incubated with RPMI-1640 containing various doses of LPS for 6 h. The tumor necrosis factor (TNF-?) in the supernatants was measured by ELISA. The expression of CD14 mRNA on Kupffer cells was determined by RT-PCR. The plasma levels of endotoxin were determined by chromogenic substrate limulus amebocyte lysate assay. Results Baseline TNF-? production of Kupffer cells isolated from CCl4-treated rats in 4 and 6 weeks was significantly higher than that of controls (P
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Objective We screened autoimmune hepatitis (AIH) from patients who had abnormal liver function without any viral marker in serum, and investigated the clinical and pathological features of AIH type Ⅰ. Methods According to the revised descriptive criteria and scoring system for diagnosis of autoimmune hepatitis proposed by the International Autoimmune Hepatitis Group, we examined the clinical and pathological characteristics of the patients who were diagnosed as AIH type Ⅰ. Results All patients (32 cases) diagnosed as AIH type Ⅰ were female. The age distribution showed a single peak in the decades of the fifties and sixties. Liver function test of these patients showed hepatic profile. Twenty eight patients (87.5%) had hypergammaglobulinemia, 26(81.3%) and elevated serum IgG level. Twenty six cases were positive for antinuclear antibody (ANA). Twelve patients (37.5%) had concurrent autoimmune diseases. Among fifteen patients who underwent liver biopsy, interface hepatitis and lobular hepatitis were observed in 11(73.3%) and 5(33.3%) patients, respectively. Rosetting of liver cells and liver fibrosis or cirrhosis were also detected in 3(20%) and 6(40%) patients respectively. Twenty one patients (65.5%) were considered to have a complete response to immunosuppressive therapy; 9(28.1%) relapsed; and 12(37.5%) sustained remission. Conclusions Autoimmune hepatitis type Ⅰ is mainly diagnosed in middle aged women, characterized by interface hepatitis on histologic examination, the presence of circulating autoantibody, hypergammaglobulinemia and response to immunosupressive treatment.
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Objective To observe the morphological characteristics of oval cells in human chronic liver diseases, and determine whether there is a relationship between the number of oval cells and liver fibrotic stage. Methods Oval cells were detected in paraffin bedded liver sections of 3 normal subjects (as controls) and 29 chronic liver diseases, using histoimmunochemistry. Cells were counted if they fulfiled the morphological criteria for oval cells and showed cytoplasmic staining. Results Oval cells were not observed in normal livers. In chronic liver diseases, oval cells were located predominantly in the periportal region and fibrosis septa, characterized by an ovoid nucleus, small size, and scant cytoplasmic. The number of oval cells increased significantly ( F=22.60, P