Objective:To investigate the clinical and pathological characteristics of chronic hepatitis B (CHB) with metabolic dysfunction-associated fatty liver disease (MAFLD), as well as associations with advanced fibrosis.Methods:CHB patients who underwent liver biopsy at Tianjin Second People′s Hospital from June 2016 to September 2019 were included in the study. The patients were divided into two groups based on whether they had concomitant MAFLD; a CHB group and a MAFLD-CHB group. t-tests and Chi-square tests were used to compare pathological characteristics and basic features in the two groups. Logistic regression analysis was used to analyze factors associated with advanced fibrosis. Results:The CHB group included 110 patients, and the MAFLD-CHB group included 272 patients. There were significant differences in smoking, alcohol consumption, hypertension incidence, body metabolic index, alanine aminotransferase, gamma-glutamyl transferase (GGT), high-density lipoprotein, low-density lipoprotein, fasting plasma glucose, and platelets (PLT) between the two groups (all P<0.05). The MAFLD-CHB group had a higher incidence of advanced fibrosis than the CHB group ( P<0.05). In logistic regression analysis MAFLD [odds ratio ( OR)=2.204, 95% confidence interval ( CI) 1.018-4.774, P=0.045], GGT ( OR=1.008, 95% CI 1.002-1.013, P=0.005), and PLT ( OR=0.995, 95% CI 0.991-0.999, P=0.019) were associated with advanced fibrosis (all P<0.05). In the MAFLD-CHB group type 2 diabetes ( OR=3.281, 95% CI 1.375-7.832, P=0.007), GGT ( OR=1.011, 95% CI 1.003-1.018, P=0.005), and PLT ( OR=0.993, 95% CI 0.988-0.998, P=0.004) were associated with advanced fibrosis ( P<0.05). Conclusion:Patients with MAFLD-CHB are more likely to develop advanced fibrosis than patients with CHB alone. In the MAFLD-CHB group type 2 diabetes mellitus was associated with advanced fibrosis. It is important to strictly control relevant risk factors in MAFLD-CHB patients, especially in patients with type 2 diabetes.

Chronic hepatitis C is a kind of viral hepatitis caused by hepatitis C virus infection, which can further progress to cirrhosis, liver failure, hepatocellular carcinoma, and even death. Presently, there is no preventive vaccine yet. Therefore, preventing infection and safe and effective drug treatment are currently the most effective strategies for dealing with hepatitis C virus infection. Since 2014, the clinical application of direct-acting antiviral drugs has brought revolutionary changes to the treatment of chronic hepatitis C. Direct-acting antiviral drugs have an excellent hepatitis C virus clearance effect, are well tolerated, have a good safety profile, and can significantly improve liver function, metabolic disorders, immune dysfunction, etc. However, some studies have pointed out that even if the hepatitis C virus is cleared during the treatment of chronic hepatitis C-related cirrhosis with direct-acting antiviral drugs, a considerable proportion of patients still have severe liver failure, hepatocellular carcinoma, and even liver disease-related death, so there are still some problems in the treatment of chronic hepatitis C- related cirrhosis with direct-acting antiviral drugs that need to be further explored. This article reviews the research progress of direct-acting antiviral drugs so as to provide meaningful references for the treatment of patients with chronic hepatitis C-related cirrhosis.

‍ ObjectiveTo investigate the value of serum complement C3 level in determining the stage of liver fibrosis in primary biliary cholangitis （PBC）. MethodsClinical data were collected from 108 patients with PBC who attended Tianjin Second People’s Hospital and underwent liver biopsy from January 2012 to October 2022. The degree of liver fibrosis （S0-4） was assessed according to the Scheuer scoring system， with ≥S2 defined as significant liver fibrosis， ≥S3 defined as progressive liver fibrosis， and S4 defined as liver cirrhosis. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and a one-way analysis of variance was used for comparison between multiple groups； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The area under the ROC curve （AUC） was used to evaluate the efficacy of complement C3 in the diagnosis of liver fibrosis in patients with PBC. The Spearman correlation analysis was used to investigate the correlation between complement C3 and liver fibrosis stage. ResultsAmong the 108 patients with PBC， there were 87 （80.6%） female patients and 102 patients （94.4%） with positive autoantibody. As for the stage of liver fibrosis， there were 5 patients （4.6%） in S0 stage， 41 （38.0%） in S1 stage， 23 （21.3%） in S2 stage， 25 （23.1%） in S3 stage， and 14 （13.0%） in S4 stage. There was a significant difference in the level of complement C3 between the patients with different liver fibrosis stages （H=42.891， P<0.001）. The level of complement C3 gradually decreased with the aggravation of liver fibrosis， with a negative correlation between them （r=-0.565， P<0.001）. Liver stiffness measurement （LSM）， aspartate aminotransferase/alanine aminotransferase ratio， aspartate aminotransferase-to-platelet ratio index， and fibrosis-4 were negatively correlated with complement C3， with a correlation coefficient of -0.439 （P<0.001）， -0.323 （P=0.001）， -0.206 （P=0.033）， and -0.291 （P=0.002）， respectively. The multivariate logistic regression analysis showed that complement C3 level was an independent predictive factor for significant liver fibrosis， progressive liver fibrosis， and liver cirrhosis， while LSM was an independent predictive factor for significant liver fibrosis and progressive liver fibrosis. The ROC curve analysis showed that complement C3 had an AUC of 0.731， 0.832， and 0.968， respectively， in the diagnosis of significant liver fibrosis， progressive liver fibrosis， and liver cirrhosis， with a corresponding cut-off value of 1.445， 1.235， and 1.005， respectively， and complement C3 combined with LSM had an AUC of 0.811， 0.941， and 0.976， respectively， in the diagnosis of significant liver fibrosis， progressive liver fibrosis， and liver cirrhosis. There was a significant difference in AUC between complement C3 combined with LSM and complement C3 alone in the diagnosis of significant liver fibrosis （Z=2.604， P=0.009）， and there was also a significant difference in AUC between complement C3 combined with LSM and complement C3 alone in the diagnosis of progressive liver fibrosis （Z=3.033， P=0.002）； there was no significant difference in AUC between complement C3 combined with LSM and complement C3 alone in the diagnosis of liver cirrhosis （Z=1.050， P=0.294）， while There was a significant difference in AUC between complement C3 combined with LSM and LSM alone in the diagnosis of liver cirrhosis （Z=2.326， P=0.020）. ConclusionSerum complement C3 level has a certain clinical value in assessing the degree of liver fibrosis in patients with PBC， and complement C3 combined with LSM can further improve the efficacy of complement C3 or LSM in the diagnosis of liver fibrosis in PBC.

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*

For the high-risk population, early screening and diagnosis are important measures to achieve good control of liver cancer and reduce the burden of liver cancer, and determining the high-risk population of liver cancer and formulating appropriate liver cancer screening strategies are the key to realizing the early screening and diagnosis of liver cancer. The risk assessment model for liver cancer is an important method for rapid and convenient identification of the high-risk population of liver cancer. Based on the risk stratification of liver cancer, the methods such as imaging technology, serological markers, liquid biopsy, metabolomics, and glycomics can be used for accurate early screening and diagnosis of liver cancer, so as to achieve the goal of early treatment.

Non-alcoholic fatty liver disease (NAFLD) is not a benign condition, especially in patients with non-alcoholic steatohepatitis (NASH) combined with liver fibrosis grades F2-4, who have a higher risk of liver-related events and mortality. Thus, this population is considered "at-risk" for developing NASH. China has a large NAFLD patient population, so how to screen for those with liver fibrosis is an important socio-economic concern. At the moment, serological models, liver stiffness detection based on vibration-controlled transient elastography, and magnetic resonance elastography (MRE) are the only non-invasive tests (NITs) for liver fibrosis. The prevention and treatment guidelines for NAFLD at home and abroad are reviewed here, based on the research progress of NITs in recent years, so as to suggest screening, evaluation pathways, and management for liver fibrosis in patients with NAFLD.

Objective To investigate the value of the hepatocellular carcinoma (HCC) risk model REAL-B score in predicting the risk of HCC in chronic hepatitis B (CHB) patients receiving antiviral therapy in comparison with mPAGE-B, aMAP and PAGE-B scores. Methods A retrospective analysis was performed for the clinical data of 1160 CHB patients who received entecavir or tenofovir treatment for more than 1 year from January 2013 to December 2015 in Tianjin Second Peolple's Hospital, and the events of HCC were recorded. The area under the ROC curve (AUC) was used to evaluate the value of REAL-B, mPAGE-B, aMAP, and PAGE-B scores in predicting HCC. The Kaplan-Meier method was used to evaluate the cumulative incidence rate of HCC at different time points, and the log-rank test was used to compare the incidence rate of HCC between the groups with different scores. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. Results Among the 1160 CHB patients, 108 (9.8%) progressed to HCC within a median follow-up time of 5.3 (5.0-6.3) years. REAL-B score had an AUC of 0.848 (95% confidence interval [ CI ]: 0.816-0.880) in predicting the onset of HCC within 5 years, followed by aMAP score (AUC=0.823, 95% CI : 0.786-0.860), mPAGE-B score (AUC=0.822, 95% CI : 0.788-0.857), and PAGE-B scores (AUC=0.780, 95% CI : 0.736-0.824). The 5-year cumulative incidence rate of HCC was 0.8% in the low-risk group (with a REAL-B score of 0-3 points), which was significantly lower than the incidence rate of 11.8% in the medium-risk group (with a REAL-B score of 4-7 points) and 35.6% with the high-risk group (with a REAL-B score of 8-13 points) ( P < 0.05). In the low-risk group, REAL-B score had a negative predictive value of 100% and 99.67%, respectively, in predicting HCC within 3 and 5 years. Conclusion REAL-B score accurately predicts the risk of HCC in CHB patients receiving antiviral therapy, with a better predictive value than the other risk models within 3 years of antiviral therapy.

Objective To investigate the value of neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width-to-lymphocyte ratio (RLR), and lymphocyte-to-monocyte ratio (LMR) in predicting the prognosis of early small hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA). Methods A retrospective analysis was performed for 132 patients newly diagnosed with early HCC who underwent RFA in Tianjin Second People's Hospital from September 2011 to December 2020. Preoperative data were collected and the patients were followed up to observe recurrence and overall survival (OS). The X-tile tool was used to determine the optimal cut-off values of NLR, RLR, and LMR based on 5-year survival rate and recurrence-free survival (RFS) rate, and then the patients were divided into N-R-L 0 group with 92 patients, N-R-L 1 group with 29 patients, and N-R-L 2 group with 11 patients. The chi-square test was used for comparison of categorical data between the three groups. The Kaplan-Meier method was used to plot the survival curve, and the log-rank test was used to compare RFS and OS rates between groups. The factors with statistical significance in the log-rank test were included in the multivariate Cox regression analysis to determine the risk factors for RFS and OS rates. Results There were significant differences in Child-Pugh class and albumin between the N-R-L 0, N-R-L 1, and N-R-L 2 groups ( χ 2 2=10.992 and 5.699, both P < 0.05). The 1-, 3-, and 5-year OS rates of the three groups were 100%/96.3%/90.7%, 96.6%/60.4%/41.3%, and 81.8%/46.8%/15.6%, respectively ( χ 2 =38.46, P < 0.000 1), and the 1-, 3-, and 5-year RFS rates of the three groups were 76.9%/52.5%/33.3%, 42.9%/13.1%/0, and 11.1%/0/0, respectively ( χ 2 =35.345, P < 0.000 1). The multivariate Cox regression analysis showed that tumor diameter ≥ 2 cm (hazard ratio[ HR ]=2.10, 95% confidence interval[ CI ]: 1.28-3.43, P =0.003; HR =3.67, 95% CI : 1.58-8.52, P =0.002), N-R-L score of 1 point ( HR =3.14, 95% CI : 1.81-5.46, P < 0.000 1; HR =8.27, 95% CI : 3.15-21.71, P < 0.000 1), and N-R-L score of 2 points ( HR =2.61, 95% CI : 1.06-6.42, P =0.037; HR =14.59, 95% CI : 3.96-53.78, P < 0.000 1) were independent predictive factors for RFS and OS. Conclusion N-R-L, a systemic inflammatory response marker composed of NLR, RLR, and LMR, is an independent risk factor for recurrence and survival of early small HCC after RFA, and it can be used as a useful noninvasive biomarker in combination with tumor features to predict the recurrence and survival of early HCC after RFA.

Objective:To investigate the prognosis and outcome of patients with chronic hepatitis C (CHC) related cirrhosis after achieved sustained virologic response (SVR) treated with direct-acting antiviral agent (DAA).Methods:Ninety-five patients diagnosed with CHC related cirrhosis who had complete data in Tianjin Second People′s Hospital from January 2014 to June 2017 were retrospectively followed up. Among them, 72 patients were treated with DAA and all of them achieved SVR, and the other 23 patients did not receive any antiviral therapy. The differences of mortality and incidence of hepatocellular carcinoma (HCC) between DAA treatment group and non-antiviral treatment group were compared. Statistical analysis was performed by independent sample t test, Mann-Whitney U test and chi-square test. Results:At the end of follow-up for three to 71 months, patients in DAA treatment group had a significant improvements in alanine aminotransferase, aspartate aminotransferase, albumin and liver stiffness measurement compared with those before treatment (42(23, 61) U/L vs 18(13, 28) U/L, 54(37, 75) U/L vs 23(18, 28) U/L, 39(33, 42) g/L vs 45(41, 48) g/L, 26(18, 37) kPa vs 15(11, 26) kPa, respectively, Z=-6.005, -7.008, -6.057 and -3.162, respectively, all P<0.01). However, there were no significant differences in incidence of HCC (12%(9/72) vs 17%(4/23)) and mortality (3%(2/72) vs 13%(3/23)) between the DAA treatment group and non-antiviral treatment group (both P>0.05). There was no significant difference of cumulative incidence of HCC in DAA treatment group compared with non-antiviral treatment group ( P=0.609). The age of patients progressed to HCC was older than those without HCC ((60.3±3.6) years vs (54.4±9.9) years, t=-3.948, P<0.01). In subgroup analysis, among the six patients with HCC, four had diabetes, the prevalence of diabetes in the patients without HCC was 17%(7/42); the level of fasting blood glucose (FBG) ((7.3±1.9) mmol/L vs (5.9±1.1) mmol/L) were higher in patients progressed to HCC than those without HCC in DAA treatment group with compensated cirrhosis ( χ2=7.430 and t=-2.442, respectively, both P=0.019). Conclusions:DAA treatment could notably improve liver function and alleviate liver fibrosis, but could not reduce the mortality and incidence of HCC in patients with CHC related cirrhosis significantly. Diabetes and high level FBG may be the risk factors for occurrence of HCC in patients with CHC related compensated cirrhosis.