Value of serum complement C3 in the diagnosis of liver fibrosis associated with primary biliary cholangitis / 临床肝胆病杂志

‍ 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.

Hepatocyte apoptosis fragment product cytokeratin-18 M30 level and non-alcoholic steatohepatitis risk diagnosis: an international registry study / 中华医学杂志(英文版)

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.

Research advances in early screening and diagnosis of hepatocellular carcinoma / 临床肝胆病杂志

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.

Value of inflammatory biomarkers in predicting the prognosis of early small hepatocellular carcinoma after radiofrequency ablation / 临床肝胆病杂志

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.

Value of external validation of REAL-B score in predicting the risk of hepatocellular carcinoma in chronic hepatitis B patients treated by antiviral therapy / 临床肝胆病杂志

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.

A retrospective follow-up study of hepatitis C virus related cirrhosis treated with direct-acting antiviral agent / 中华传染病杂志

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.

Factors associated with significant liver fibrosis in chronic hepatitis B patients with non-alcoholic fatty liver disease / 中华传染病杂志

Objective:To investigate the influencing factors of significant liver fibrosis in patients with chronic hepatitis B (CHB) concurrent with non-alcoholic fatty liver disease (NAFLD).Methods:Those who underwent liver pathological examination and confirmed diagnosis of CHB and NAFLD in Tianjin Second People′s Hospital from August 2014 to September 2017 were enrolled. Data regarding their demographic information, laboratory tests results, and liver pathology results were analyzed. The latter results were used to categorize the patients either in non-significant liver fibrosis group (Metavir stage<F2) or in significant liver fibrosis group (Metavir stage≥F2). The measurement data were compared using t test or Mann-Whitney U test, and the count data using chi-square test.The factors influencing the onset of significant liver fibrosis were subsequently explored with binary logistic regressions. Results:Out of 273 patients screened, 160 and 113 patients respectively belonged to the non-significant fibrosis group and the significant fibrosis group. Age, histologic activity, NAFLD type, liver stiffness measurement, hepatitis B e antigen (HBeAg) status (positive/negative), hepatitis B virus (HBV) DNA, aspartate aminotransferase, γ-glutamyl transpeptidase, total bilirubin, high blood glucose (with/without) and platelet count between the two groups were statistically significant( t=2.232, χ2=44.276, χ2=4.808, t=2.096, χ2=5.299, t=3.191, U=7 041.500, U=6 873.500, t=2.989, χ2=5.588, t=3.429, all P<0.05). Logistic regression showed that non-alcoholic steatohepatitis (NASH), histologicactivity, HBV DNA and platelet count were the independent influencing factors for significant liver fibrosis (odds ratio ( OR)=2.809, 6.730, 0.843, 0.995, respectively, all P<0.05). Patients were divided into two subgroups according to their HBeAg status, the results showed that for patients with negative HBeAg, NASH, histologic activity, HBV DNA and platelet count were the independent influencing factors for significant liver fibrosis ( OR=8.629, 3.626, 0.740, 0.992, respectively, all P<0.05). For patients with positive HBeAg, histologic activity and high blood glucose were the independent risk factors for significant liver fibrosis ( OR=12.738, 4.223, respectively, both P<0.01). Conclusion:Liver inflammation, NASH and high blood glucose are the serious risk factors during the onset and progression of significant liver fibrosis in patients with CHB and NAFLD, while HBV DNA and platelet count levels are negatively correlated with significant liver fibrosis.

Trends of CD4+T lymphocyte counts in acquired immune deficiency syndrome patients in Tianjin from 2005 to 2017 / 中华传染病杂志

Objective To assess the trends and characteristics of CD 4 +T lymphocyte counts among patients with acquired immune deficiency syndrome ( AIDS) in Tianjin City.Methods The demographic and clinical characteristics of AIDS patients diagnosed in Tianjin Second People′s Hospital from 2005 to 2017 were analyzed.The CD4 +T lymphocyte count and the frequency of CD 4+T lymphocyte count ＜200 cells／μL were analyzed according to age , transmission route and education level.The chi-square test was used for counting data.The rank sum test was used for the data that did not conform to normal distribution .Results The 3 062 patients were aged (38.2 ±11.9) years.There were 2 867 males (93.6%) aged (37.8 ±11.8) years, and 195 female patients ( 6.4%) aged (43.3 ±12.6) years.The CD4+T lymphocyte counts of these patients presented an increasing trend from 2005 to 2017, with statistically significant differences among different years (Z＝18.871, P＜0.05).The frequency of CD4 +T lymphocytes ＜200 cells／μL showed a decreasing trend , with statistically significant difference in different years (χ2 ＝7.017,P＜0.05).The CD4+T lymphocyte counts in patients of all age groups showed an increasing trend from 2005 to 2017, with statistically significant differences (Z＝6.849, 9.532, 7.146, 6.874, 8.038, 11.249, and 10.059, respectively, all P＜0.05).The CD4+T lymphocyte counts in homosexual patients presented an increasing trend , with statistical significance in different years (Z＝8.038, P＜0.05).The CD4+T lymphocyte counts in patients who received education more than 13 years (include 13 years) presented an increasing trend , with statistical significance (Z＝4.573, P＜ 0.05).Conclusions The median CD4+T lymphocyte counts of AIDS patients receiving primary treatment in Tianjin city are increasing by years , while the proportion of severe immunosuppression is decreasing.Patients who are infected through homosexual transmission and those with high level of education seek medical care earlier.

Clinical value of noninvasive method in diagnosing hepatic fibrosis about chronic HBV carriers / 中华肝脏病杂志

Objective@#To compare the clinical value of FibroScan, FIB-4, APRI and AAR diagnosing hepatic fibrosis in chronic hepatitis B virus (HBV) carriers. @*Methods@#A total of 213 patients with chronic HBV carriers diagnosed by clinical and liver biopsy were selected. And according to HBeAg status, 149 patients were divided into HBeAg-positive group and 64 patients were divided into HBeAg-negative group. The liver stiffness measurements (LSM) was measured by FibroScan (FS), FIB-4, APRI and AAR values were calculated using FIB-4, APRI and AAR formula. And all patients underwent liver biopsy in the same period. According to the degree of hepatic fibrosis in Knodell, one decision point was set: significant hepatic fibrosis (S ≥ 2). The Spearman correlation analysis method was used to analyze the correlation of indicators and the area under receiver operator characteristic curves (AUROCs) of LSM, FIB-4, APRI and AAR were drawn according to liver biopsy pathology results as gold standard. The value of LSM, FIB-4, APRI and AAR diagnosing hepatic fibrosis in chronic HBV carriers was retrospectively analyzed. Retrospective analysis of FS, FIB-4, APRI and AAR were divided into 149 HBeAg-positive chronic HBV carriers (HBeAg-positive group) and 64 HBeAg-negative chronic HBV carriers (HBeAg) in 213 patients with chronic HBV carriers and HBeAg Negative group) in the diagnosis of liver fibrosis. @*Results@#The LSM of 213 patients with chronic HBV carriers, 149 patients with HBeAg-positive chronic HBV carriers and 64 patients with HBeAg-negative chronic HBV carriers were significantly correlated with liver fibrosis grade≥ 2 (P < 0.001). Regardless of HBeAg status, only LSM in the three groups had moderate evaluation efficacy for evaluating significant fibrosis(S≥2), and the positive predictive value was more than 94%, but the diagnostic accuracy was not high, the minimum was 46.31% (HBeAg-positive group), the maximum value of 67.19% (HBeAg-negative group), while the remaining three kinds of serum noninvasive liver fibrosis diagnostic model indicators and diagnostic efficacy are low. The LSM in the three groups showed a significant positive correlation with liver fibrosis grade (S)≥2. @*Conclusion@#LSM is more accurate than FIB-4, APRI and AAR in diagnosing chronic HBV carriers. Dynamically monitoring changes of LSM can earlier understand the progress of liver fibrosis than the three kinds of serology noninvasive diagnostic model and is contributed to the choice of liver biopsy timing.

Clinical value of diagnosing hepatic fibrosis by Mohamadnejad model and FibroScan in the HBeAg negative chronic hepatitis B virus carriers / 中华实验和临床病毒学杂志

Objective@#To investigate the clinical value of diagnosing hepatic fibrosis in the HBeAg negative chronic hepatitis B virus (HBV) carriers by hepatic fibrosis model of Mohamadnejad (M model) and the hepatic instantaneous elastic detector (FibroScan, FS).@*Methods@#A total of 217 patients were included: they were diagnosed as the HBeAg negative chronic HBV carriers. The value of the hepatic fibrosis was calculated by M model formula, liver stiffness measurements (LSM) was surveyed by FS, and all patients underwent liver biopsy in the same period. According to the degree of hepatic fibrosis in Knodell, one decision point was set: significant hepatic fibrosis (S ≥ 2). The Spearman correlation analysis method was used to analyze the correlation of indicators and the area under receiver operator characteristic curve (AUROC) of M model and FS was drawn.@*Results@#LSM and M model were positively correlated with the fibrosis stage of liver biopsy (r=0.64, 0.80, P=0.000, 0.000, <0.01). The diagnostic sensitivity, positive likelihood ratio, specificity and negative predictive value of M model and FS for the HBeAg negative chronic HBV carriers with significant hepatic fibrosis were 88.10%, 13.02, 93.23%, 92.50% and 82.14%, 5.20, 84.21%, 88.20%, respectively. The diagnostic AUROC of significant hepatic fibrosis were 0.927 and 0.858, respectively. It had significant statistical difference (Z=2.12, P<0.05).@*Conclusions@#M model and FS are noninvasive and ideal tools for screening HBeAg negative chronic HBV carriers with significant hepatic fibrosis. The value of diagnosing significant hepatic fibrosis in the HBeAg negative chronic HBV carriers by M model was remarkably higher than that of FS.

The significance of 8-hydroxy-deoxyguanosine acid in the diagnosis of nonalcoholic steatohepatitis / 中华内科杂志

Objective To evaluate the significance of serum 8-hydroxy-deoxyguanosine acid ( 8-OHdG) in the diagnosis of nonalcoholic steatohepatitis ( NASH).Methods Patients or healthy subjects were enrolled at the Second Hospital of Tianjin Medical University and the Second People ′s Hospital of Tianjin from May 2013 to December 2015.A total of 41 patients with nonalcoholic fatty liver disease were enrolled in the study , including 20 nonalcoholic simple fatty liver ( NAFL) patients and 21 NASH patients whose diagnosis were proven by liver biopsy.The other 32 healthy subjects were studied as controls.Serum 8-OHdG, ALT, AST and GGT were tested.Nonalcoholic fatty liver disease activity score ( NAS ) and expression of 8-OHdG in liver was investigated between NAFL patients and NASH patients.The correlations between serum 8-OHdG and serum ALT , AST, GGT, and 8-OHdG in liver tissue in NASH group were investigated.In addition , the receiver operating characteristic ( ROC) curve analyses for ALT and 8-OHdG levels were performed in NAFL patients and NASH patients , and the cut-off value was determined.Results Serum 8-OHdG values in healthy controls , NAFL and NASH patients were (0.19 ±0.16) μg/L, (0.22 ±0.16) μg/L, (0.42 ±0.21) μg/L respectively.The serum 8-OHdG and serum ALT, GGT and 8-OHdG in liver tissue were all positively correlated in NASH group with respective correlation coefficient r values as 0.454 7, 0.382 9, and 0.497 6.AUC of 8-OHdG was 0.901 with cut-off value 0.39 μg/L.Its sensitivity was 88.3%and specificity was 81.5%, which were higher than those of ALT.Conclusion The value of serum 8-OHdG would be used as a marker for the diagnosis of NASH.

A serum lipidomic study of patients with non-alcoholic fatty liver disease / 中华肝脏病杂志

Objective@#To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease (NAFLD), and to analyze the lipid metabolism characteristics of NAFLD.@*Methods@#The subjects were divided into control group (23 patients) and pathologically confirmed NAFLD group (42 patients), and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis (PLS-DA) model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis.@*Results@#A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model (R2 = 0.753, Q2 = 0.456) and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group (VIP > 1, P < 0.05), including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol (LPI), choline plasmalogen (PlsCho), ethanolamine plasmalogen (PlsEtn), ceramide (Cer), sphingomyelin, and triglyceride (TG). Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids (increased by 39%, t = -3.954, P < 0.05) and TGs (increased by 36%, Z = -2.662, P < 0.05), mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI (increased by 223%, t = -3.858, P < 0.05) and Cer (increased by 21%, t = -2.481, P < 0.05) and significant reductions in PlsCho (reduced by 18%, t = 3.184, P < 0.05) and PlsEtn (reduced by 20%, t = 2.363, P < 0.05).@*Conclusion@#There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.

Clinical value of Serum CK-18 M30 levels in patients with nonalcoholic steatohepatitis / 实用医学杂志

Objective To detect the level of serum fragmented cytokeratin 18 (CK-18 M30) in patients with nonalcoholic steatohepatitis (NASH), to explore the relationship between the expression of CK-18 M30 and NASH. Methods 33 healthy people as control group, 24 nonalcoholic simple fatty liver (NAFL) patients, and 21 NASH patients were included in this study. CK-18 M30, ALT, AST and GGT were detected in all patients’ vein blood. NAFLD activity points (NAS) was examined in biopsy specimens of NAFL patients and NASH patients. Pearson correlation was applied to analyze the correlations between serum CK-18 M30, ALT, AST, GGT and the NAS of liver tissue in NASH group. Results Serum CK-18 M30 level of healthy control, NAFL and NASH group were (96.557 2 ± 41.226 8)U/L, (104.321 7 ± 45.167 3)U/L, (263.125 5 ± 61.578 1)U/L respectively. Serum CK-18 M30 level in NASH patients positively correlated with both NAS of liver tissue and serum ALT, which correlation coefficient r values were 0.601 5 and 0.420 6. Conclusion The concentration of serum CK-18 M30 could be used as a marker in the diagnosis of NASH.

Value of controlled attenuation parameter in diagnosis of fatty liver using FibroScan / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the value of controlled attenuation parameter (CAP) in the diagnosis of fatty liver using FibroScan in patients with chronic liver disease (CLD).</p><p><b>METHODS</b>A prospective cohort study was performed for the patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD) who underwent liver pathological examination followed by CAP measurement within 1 week in The Second People's Hospital of Tianjin from February 2013 to May 2014. According to related guidelines, hepatocyte steatosis was classified as S0: <5%, S1: 5%-33%, S2: 34%-66%, or S3: ≥67%. The receiver operating characteristic (ROC) curves were plotted with positive results as the diagnostic criteria, and the optimal cut-off values were determined at the maximum Youden index. Single linear regression and multiple stepwise regression were applied to analyze the influencing factors for CAP.</p><p><b>RESULTS</b>A total of 427 patients were enrolled, consisting of 19 patients (4.4%) with NAFLD, 383 (89.7%) with CHB, and 25 (5.9%) with CHC. The optimal cut-off values for CAP in the diagnosis of steatosis ≥5%, ≥34%, and ≥67% were 230 dB/m, 252 dB/m, and 283 dB/m, respectively, and the areas under the ROC curve were 0.803, 0.942, and 0.938, respectively (Z = 14.194, 28.385, and 16.486, respectively, all P < 0.01). CAP differentiated S0 from S1, S1 from S2, S0 from S2, S0 from S3, and S1 from S3 (Z = 10.109, 10.224, 47.81, 29.917, and 10.999, all P < 0.01), but was not able to differentiate S2 from S3 (Z = 0.656, P = 0.5116). The single linear regression and multiple stepwise regression analyses showed that only body mass index (BMI; B = 4.001, P < 0.01) and hepatic steatosis (B = 33.015, P = 0.000) were correlated with CAP. The coincidence rates between CAP and liver pathological diagnosis were 77.4%, 81.0%, and 96.2% for S0, S3, and ≥S2, respectively.</p><p><b>CONCLUSION</b>CAP has a good value in the diagnosis of fatty liver in CLD patients, and can well differentiate between all stages of fatty liver except S2 and S3. CAP is influenced by BMI, but is not found to be associated with liver fibrosis, inflammation, liver stiffness measurement, and etiology.</p>

Diagnostic value of alcoholic liver disease (ALD)/nonalcoholic fatty liver disease (NAFLD) index combined with γ-glutamyl transferase in differentiating ALD and NAFLD

BACKGROUND/AIMS: This study aimed to verify the reliability of the alcoholic liver disease (ALD)/nonalcoholic fatty liver disease (NAFLD) index (ANI) for distinguishing ALD in patients with hepatic steatosis from NAFLD, and to investigate whether ANI combined with γ-glutamyl transferase (GGT) would enhance the accuracy of diagnosis in China. METHODS: A hundred thirty-nine cases of fatty liver disease (FLD) were divided into two groups of ALD and NAFLD. The ANI was calculated with an online calculator. All indicators and ANI values were analyzed using statistical methods. RESULTS: ANI was significantly higher in patients with ALD than in those with NAFLD (7.11 ± 5.77 vs. -3.09 ± 3.89, p 0.05). CONCLUSIONS: ANI can help distinguish ALD from NAFLD with high accuracy; when ANI was combined with GGT, its effectiveness improved further.

Impact of liver steatosis on the curative effect of pegylated interferon-alpha-2a in patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the impact of hepatic steatosis on virologic response to treatment with pegylated interferon-alpha-2a (PEG-IFNα-2a) in chronic hepatitis B (CHB) patients.</p><p><b>METHODS</b>We retrospectively analyzed 50 biopsy-proven cases of CHB in patients who had been administered a 48-week course of PEG-IFNα-2a in our hospital between 2005 and 2009. The patients were stratified according to presence of steatosis confirmed by pathological findings, with 28 in the non-steatosis group and 22 in the steatosis grouP(21 with mild steatosis,and 1 with moderate steatosis).</p><p><b>RESULTS</b>from blood routine test,hepatic and renal function tests, fasting blood glucose test, thyroid function test and blood lipid test were collected for analysis, as were results from hepatitis B viral load test and detection of hepatitis B virus (HBV) markers and autoantibodies. The efficacy of antiviral treatment and side effects were compared between the stratified groups by statistically comparing the results from before and after the 48 weeks of treatment.</p><p><b>RESULTS</b>At the end of treatment, the non-steatosis group had 42.9% of patients with undetectable HBV-DNA ( less than 500 copies/ml), a hepatitis B e antigen (HBeAg) seroconversion rate of 31.6% and a complete response rate of 39.3%. The steatosis group had a lower rate of patients with undetectable HBV-DNA (40.9%) and higher rates of HBeAg seroconversion (33.3%) and complete response (40.9%), but none of the differences reached the threshold for statistical significance (x2=0.012, 0.019, 0.014 and P=0.560,0.600,0.568 respectively). Both groups showed significant increases in triglyceride levels after treatment (steatosis group:t =-2.164, P=0.040; non-steatosis group:t =-2.863, P=0.009), and there was a significant difference between the two groups (t=2.41, P=0.020).</p><p><b>CONCLUSION</b>Our study did not show that mild hepatic steatosis affected the efficiency of a 48-week course of PEG-IFNα-2a treatment for patients with CHB.</p>

Cross-section study of early renal damage in patients with chronic hepatitis B / 天津医药

Objective To investigate early renal damage of chronic hepatitis B (CHB) patients and the risk factors related to their renal function. Methods CHB patients who visited the second people’s hospital but did not receive systemic treatment were enrolled in our study. Those who visited for general check-up with no hepatic findings during the same period were selected as control group. Glomerular filtration rate (GFR) of all the participants were estimated by simplified MDRD equation and CKD-EPI equation (designated as M-eGFR and C-eGFR respectively). Influence factors of eGFR were statistically analyzed. Results In the total 528 cases in CHB group, 88 (16.67%) and 62 (11.74%) suffered declined M-eGFR and C-eGFR respectively. By contrast, 10 (8.77%) and 6 (5.26%) cases in the total 114 cases in control group present declined M-eGFR and C-eGFR ac?cordingly. Percentages of renal function impairment, estimated by both M-eGFR and C-eGFR, were higher in the CHB group than those in control group. The difference was statistically significant (χ2=4.518, P<0.05;χ2=4.156, P<0.05). Multiple linear regression analysis indicated that age, HBsAg and body mass index (BMI) were risk factors of M-eGFR while age, HBsAg, gender and serum albumin were risk factors of C-eGFR. On the other hand, HBV-DNA and HBeAg were not risk factors for M-eGFR or C-eGFR. Conclusion HBV infection can lead to early renal damage. Age and HBsAg are main risk factors of renal function impairment. Therefore, renal function should be scrutinized in CHB patients.

A multi-center clinical study of a novel controlled attenuation parameter for assessment of fatty liver / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the controlled attenuation parameter (CAP) assessment of fatty liver and choose a cut-off value of hepatic steatosis more than 5%.</p><p><b>METHODS</b>Consecutive patients, 18 years or older, who had undergone percutaneous liver biopsy and CAP measurement were recruited from five liver healthcare centers in China. All enrollees were categorized as hepatic steatosis grade S0 (<5%) or S1 (5%). An M-probe equipped FibroScan 502 was used to capture CAP values. Receiver operating characteristic (ROC) curves were plotted, and the areas under (AU) the curves were calculated to determine the diagnostic efficacy. The CAP cut-off values at the optimal thresholds were defined by maximum Youden indices; sensitivity and specificity were also calculated.</p><p><b>RESULTS</b>A total of 332 patients were enrolled in the study, including 67 patients with non-alcoholic fatty liver disease (NAFLD) and 265 with chronic hepatitis B (CHB) viru: infection. The median age (inter quartile range, IQR) of the study cohort was 39.0 (32.0-50.5) years-old. There were 46 males (68.7%) in the NAFLD group, with a median age of 37.0 (28.0-45.0) years-old, and 182 males (68.7%) in the CHB group; the differences between the two groups in median age and male: female ratio did not reach statistical significance. Multivariate linear regression analysis identified steatosis grade and body mass index (BMI) as independently associated with CAP. The median (IQR) CAP values among patients with S0 and S1 grade steatosis were 215.0 (190.0-241.0) dB/m and 294.0 (255.0-325.5) dB/m (P<0.001), respectively. For all patients, when BMI was <25 kg/m2, the ability of the AUROC of the CAP to discriminate hepatic steatosis more than or equal to 5% was 0.853, and the optimal cut-off value was 244.5 dB/m; however, when BMI≥25 kg/m2, the AUROC was 0.835 and the optimal cut-off value 269.5 dB/m.</p><p><b>CONCLUSION</b>CAP can identify hepatic steatosis more than or equal to 5% and is applicable for the diagnosis of fatty liver if it is adjusted for BMI.</p>

Analysis of clinical and pathological features of chronic hepatitis B in combination with hepatic steatosis in the elderly / 中华老年医学杂志

Objective To explore the clinical and pathological characters of chronic hepatitis B (CHB) in combination with hepatic steatosis in the elderly.Methods Totally 223 elderly patients with CHB and hepatic steatosis diagnosed by liver biopsy were retrospectively analyzed and 220 nonelderly patients with CHB and hepatic steatosis were randomly selected as control group.Clinical and pathological features and change in liver histology were compared between the two groups.Results The incidences of hypertension,coronary heart disease,type 2 diabetes mellitus and metabolic syndrome were increased in elderly groups (all P＜0.01 or 0.05),while the proportion of patients with hyperlipemia and obesity were decreased as compared with non-elderly group (both P＜0.01).The levels of body mass index,serum triglyceride and HBV-DNA were lower in elderly group than in non-elderly group (all P＜0.01).The ratio of mild degree of CHB was elevated in elderly group as compared with non-elderly group (P＜0.05).Liver histopathological examination showed that the proportion of patients with the inflammation grade less than G2 and fibrotic stages exceeding S2 were increased,while the positive rate of HBcAg by immunohistochemistry was reduced in elderly group as compared with non-elderly group (both P＜0.05).Conclusions The degree of inflammatory liver injury and inflammation grade are slighter,but the fibrotic stage is more serious in elderly patient with CHB and hepatic steatosis,which indicating a slower progress of liver injury.It is still to be investigated whether metabolic syndrome,hypertension,coronary heart disease and type 2 diabetes mellitus are easily complicated in elderly patient with CHB and hepatic steatosis.The serum hepatitis B virus DNA replication may be negatively correlated with ageing.

The association between hepatic steatosis and HBsAg and HBcAg in chronic hepatitis B patients / 中华消化杂志

ObjectiveTo explore the association between hepatic steatosis and the liver tissue expression of HBsAg and HBcAg in chronic hepatitis B (CHB) patients.MethodsFrom January 2005 to June 2008,a total of 147 CHB patients with hepatic steatosis diagnosed by liver biopsy and other 149 CHB patients without hepatic steatosis but with similar HBV DNA titer were enrolled.The differences of HBsAg and HBcAg immunostaining and liver injury in these two groups were compared.The data were analysed using t test and chi square test.ResultsCompared with non-steatosis group,the average age and body weight index of hepatic steatosis group were higher (t values were -3.31and -6.57,both P＜0.01).The percentage of moderate to severe hepatic inflammation in liver,obvious hepatic fibrosis and the strong positive HBsAg staining was lower (30.6％ vs 15.4％ ； 26.5％vs 12.8％； 23.1 ％ vs 6.7 ％； x2=9.63,8.92,15.76； all P＜0.01),and the percentage of strong positive HBcAg staining was also in downtrend.Compared with degree F1 and F2 of liver steatosis,the percentage of HBsAg and HBcAg strong positive staining in liver tissues of degree F3 and F4 was in downtrend.ConclusionsHepatic steatosis affected the expression of HBsAg and HBcAg in liver tissue of CHB patients.As hepatic steatosis appeared and became more severe,both expression of HBsAg and HBcAg and the degree of liver injury were in downtrend.