ObjectiveTo investigate the histological features as well as the factors influencing liver disease progression in Chinese patients with chronic hepatitis C (CHC). MethodsA total of 102 CHC patients who underwent percutaneous liver biopsy between August 2007 and May 2010 were recruited. Age, gender, body mass index (BMI) and transmission route of recruited patients were recorded. Serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), HCV genotypes, HCV viral load and liver histological changes were detected. Statistical analysis was done by t test and Logistic regression. ResultsThe serum levels of ALT and AST in CHC patients with histological activity index (HAI) ≥4 were much higher, while platelet (PLT) counts were lower than those with HAI ＜4(t=2.209, 2. 298 and 2. 565, respectively; all P＜0.05). Likewise, in patients with F≥3, the serum levels of ALT and AST as well as the mean age and the duration of infection were significantly elevated compared with F ＜ 3 group ( t = 3.497, 2. 758, 2. 340 and 2. 570,respectively; all P＜0. 05), while PLT counts were much lower (t = 2. 761, P=0. 007). The unvariate predictors for HAI≥4 were female, ALT＞1 × upper limits of normal (ULN), AST level,F≥3, HCV RNA≥6 lgIU/mL and PLT counts. By mutivariate analysis, the Ishak stage score was the only independent predictor for HAI≥4 (OR 3.098, 95％CI 1.884-5. 092; P＜0.01). Finally,the univariate predictors for F≥3 were age, BMI≥24 kg/m2 , ALT＞1 × ULN, AST level, HAI≥4,PLT counts and duration of infection≥ 15 years. Multivariate analysis revealed that age (OR 1. 074,95％CI 1.006-1. 146; P=0.033), ALT level (OR 1. 035, 95％CI 1.015－1.055; P＜0.01), ASTlevel (OR 0. 969, 95％CI 0. 948－0. 990; P=0. 005), the duration of infection ≥15 years (OR 37. 215, 95％CI 5. 816－238. 127; P＜0.01) and HAI≥4 (OR 1. 939, 95％CI 1. 426－2. 636; P＜0.01) were independent predictors for F≥ 3. ConclusionAge, ALT level, AST level, duration of infection≥15 years, HAI≥4 are independent predictors for liver fibrosis.

Objective To identify the histological features as well as factors influencing the course of HBeAg-negative chronic hepatitis B virus ( HBV)-infected patients with persistently normal alanine amino-transferase (ALT) levels (PNAL). Methods Ninety-eight HBeAg-negative chronic HBV-infected patients with PNAL who underwent percutaneous liver biopsy were recruited from October 2003 to March 2008. The ALT level, HBV markers, HBV DNA level and liver histological changes were detected. Comparison of means was done by t test and single factor analysis of variance. Nonparametric statistics was done by Marm-Whitey U test and Kruskal-Wallis test. Analysis of independent risk factor was done using Logistic model. The dianostic value of ALT level to significant liver histological changes was evaluated by receiver performance curve. Results Twenty-two point four percent and 17.3% of subjects had the histological activity index (HAI)≥4and fibrosis (F) score≥3 respectively. Subgroup analysis showed that subjects with ALT＞0.50 × upper limit of normal (ULN) had a significantly higher rate of HAI≥4 and F score≥3 than those with ALT≤0.50×ULN (HAI≥4:36.4% vs 11.1%, χ2 =8.881, P=0.003;F score≥3:27.3% vs 9.3%, χ2 =5.487, P= 0.019, respectively), and older subjects (more than 45 years old) had a higher proportion of HAI ≥4 than the younger (33.3% vs 13.4%, χ2 =4.923, P=0.027). Multivariate Logistic regression analysis revealed that a decade increase in age was the independent predictor of HAI≥4 (OR=2.410, P=0.023).Receive operating characteristic (ROC) curve showed that 87.0% and 90.7% of subjects with ALT＜0.50× ULN had histological changes of HAI＜4 and F score＜3 respectively. The proportions of HAI≥4 and F score≥3 in subjects with HBV DNA＜1×104 copy/mL were 14.9% and 12.8%, respectively. Conclusions Significant histological changes may be present in part of the subjects with persistently normal ALT and different HBV DNA levels, so that liver biopsy is very important, especially in those with age ＞45 years.Half time the ULN may serve as an appropriate cutoff value of normal ALT level for managing Chinese HBeAg-negative chronic HBV-int'ected patients.

Objective To explore the expressions of circulating microRNAs (miRNAs) in acute liver failure mice induced by D-galactosamine (GalN)/lipopolysaccharides (LPS) and the correlation with miRNAs in the liver.Methods Forty clean grade Balb/C mice,with 32 in the model group and 8 in the control group were enrolled in the study.Liver failure was induced by intraperitoneally injection of D-GalN and LPS in mice of the model group,while mice of the control group were intraperitoneally injected with 1 mL 0.9 ％ sodium chloride solution.Serum and liver samples were collected at 0,3,5,7 hours following administration,and eight mice should be supplied to each sample,and changes of alanine aminotransferase (ALT),aspartate aminotransferase (AST) and histopathology of the liver were observed.miRNA from both the serum and the liver was extracted,miRNA expression profile in the liver at 0,5,7 hours by locked nucleic acid (LNA)-miRNA microarray was analyzed and miRNA by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) was detected.Means of the two groups were compared using one-way ANOVA and correlation analyses were performed using Pearson and Spearman correlation.Results Expression of miRNAs in the liver tissue changed significantly over time with the occurrence of acute liver failure in the mice.Twenty-one miRNAs were up-regulated and 27 were down-regulated,among which miRNA-122 and miRNA-1187 were down-regulated while miRNA-146a and miRNA-155 were up-regulated.It was confirmed by the PCR assay that the expression of miRNA-122 and miRNA-1187 in the liver gradually decreased,while those in the serum were up-regulated over time.However,the expressions of inflammation associated miRNA-155 and miRNA-146a were up-regulated both in the serum and the liver after administration.The expressions of miRNA-122 and miRNA-1187 were negatively correlated between serum and liver (r=-0.477,P=0.0089,r=-0.420,P=0.231),while the expressions of miRNA-155 in serum and liver were positively correlated (r=0.678,P=0.0001).Moreover,the expressions of miRNA-122 (r=0.571,0.554) and miRNA-1187 (r=0.471,0.542) were also positively correlated with serum levels of ALT and AST (all P＜0.05).Liver and serum levels of miRNA-122 and miRNA-1187 changed significantly at 5 hours after administration,which preceded the changes of ALT/AST.Conclusions The expressions of miRNA-122 and miRNA-1187 in serum are well inversely correlated with the corresponding expressions in liver tissues during acute liver failure in mice.The changes of miRNA-122 and miRNA-1187 in the serum precede those of ALT/AST.These data suggest that serum miRNA-122 and miRNA-1187 might be the candidate serum biomarkers for early prediction of liver injury.

ObjectiveTo investigate the efficacy and safety of Fuzheng Huayu tablets (FZHY) combined with entecavir (ETV) in the treatment of chronic hepatitis B (CHB) liver fibrosis. MethodsA total of 52 patients with CHB liver fibrosis with an Ishak stage of ≥F3 who were treated in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from April 2011 to January 2013 were enrolled and divided into FZHY combined with ETV group (combination group) and placebo combined with ETV group (control group), with 26 patients in each group, and the course of treatment was 48 weeks for both groups. Liver biopsy was performed before and after these treatment; clinical outcome was determined based on the reversal rate of Ishak stage for liver fibrosis and the improvement rate of histological activity index (HAI) for inflammation grade, and safety was evaluated based on electrocardiographic findings. Three datasets (full analysis set, per-protocol set, and safety dataset) were identified for analysis; the t-test or the Wilcoxon test was used for comparison of continuous data between two groups, and the CMH chi-square test, the chi-square test, or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsOf all 52 patients, 46 underwent the two liver biopsies before and after treatment, with 22 in the combination group and 24 in the control group. At week 48 of treatment, there was a significant difference in the proportion of patients with Ishak stage reduced by ≥1 stage between the combination group and the control group (81.8% vs 54.2%, χ2=5.297, P=0.021). There was also a significant difference in the improvement rate of HAI grade between the combination group and the control group were (59.1% vs 25.0%, χ2=6.822, P=0.009). There were no significant differences between the two groups in the incidence rates of adverse events and serious adverse events, the safety analysis of vital signs, and laboratory safety indicators (all P＞0.05). ConclusionFZHY combined with ETV has significant advantages over ETV alone in improving liver fibrosis and inflammation, and antiviral therapy combined with anti-fibrosis therapy can bring better hepatic histological improvement for CHB patients. FZHY combined with ETV has good safety in the treatment of patients with CHB liver fibrosis.

Objective To investigate the diagnostic accuracy of FibroScan-AST (FAST) score in patients with high-risk nonalcoholic steatohepatitis (NASH) with a nonalcoholic fatty liver disease (NAFLD) activity score of ≥4 and significant liver fibrosis (F ≥2), along with comparison with other serological models. Methods A total of 84 consecutively admitted patients hospitalized in Ruijin Hospital from January 2015 to December 2020 and biopsy-confirmed NAFLD/NASH were included in this study, and FibroScan (liver stiffness measurement and controlled attenuation parameter) and blood biochemical tests were performed at one week before and after liver biopsy. A Kruskal-Wallis H analysis of variance was used for comparison between multiple groups, and Spearman's correlation coefficient was used to analyze the correlation between variables. The receiver operating characteristic (ROC) curve was plotted with pathological results as the "gold standard", and the area under the ROC curve (AUC) was calculated. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and classification accuracy were calculated based on the cut-off values determined by previous studies. In subgroup analysis, the patients were divided into subgroups based on different clinical indices to evaluate the diagnostic accuracy of each model, which was expressed as AUC (95% confidence interval [ CI ]). Results Among the 84 patients, 43 had high-risk NASH. The FAST score was 0.54(0.04-0.93) for all patients, and the FAST score for liver fibrosis stages F0-F4 was 0.26(0.06-0.73), 0.48(0.04-0.82), 0.61(0.13-0.75), 0.64(0.09-0.93), and 0.82(0.75-0.89), respectively, with a significant difference between stages ( H =23.360, P < 0.001). FAST score was positively correlated with liver fibrosis stage ( r =0.491, P < 0.001). NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index were positively correlated with liver fibrosis stage ( r =0.230, 0.346, and 0.281, all P < 0.05), with a weaker correlation than FAST score. FAST score had an AUC of 0.725 (95% CI : 0.617-0.834, P < 0.001) in evaluating high-risk NASH. According to the low cut-off value determined by previous studies, FAST score ≤0.35 excluded high-risk NASH in 21 patients (25%) with an NPV of 71%; according to the high cut-off value, FAST score ≥0.67 helped to make a confirmed diagnosis of high-risk NASH in 19 patients (22.6%) with a PPV of 74%. NFS and FIB-4 had an AUC of 0.633(95% CI : 0.513-0.753) and 0.686(95% CI : 0.570-0.803), respectively, in the diagnosis of high-risk NASH ( P < 0.05). Conclusion FAST score can accurately determine the presence or absence of high-risk NASH in NAFLD patients with or without metabolic risk factors, and selection of appropriate cut-off values can help some patients avoid liver biopsy.