Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

Objective:To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD)on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods:A total of 155 patients with CHB-related HCC who received ICI–based therapy(in the Department of Hepatology,Tianjin Second People’s Hospital and Department of Hepatobiliary Oncology,Tianjin Medical University Cancer Institute&Hospital)between April 2021 and December 2023 were evaluated.Patients were divided into two groups:MASLD concurrent with CHB[MASLD-CHB](n=38),and CHB(n=117).Results:The median progression-free survival(PFS,6.9 months vs.9.3 months;P=0.001),progressive disease(57.89%vs.37.61%;P=0.028),and disease control rate(42.11%vs.62.39%;P=0.028)in the MASLD-CHB group were significantly worse than the CHB group.The median overall survival was not attained.The percentage of CD4+PD1+(17.56%vs.8.89%;P<0.001)and CD8+PD1+T cells(10.50%vs.7.42%;P=0.005)in patient samples from the MASLD-CHB group were significantly higher than the CHB group.Concurrent MASLD[hazard ratio(HR)=1.921;95%CI,1.138–3.245;P=0.015]and alpha-fetoprotein levels after 3 months of treatment(HR=2.412;95%CI,1.360–4.279;P=0.003)were independent risk factors for PFS in all patients.Conclusions:ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease

BACKGROUND Although many studies have investigated the impact of chronic hepatitis B virus(HBV)infection and nonalcoholic fatty liver disease(NAFLD)on liver disease,few have investigated the relationship between nonalcoholic steatohepatitis(NASH)defined by liver pathology and the prognosis of chronic HBV infection.Most patients were followed up for a short time.This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection.AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events[cirrhosis,hepatocellular carcinoma(HCC),and death]in patients with chronic hepatitis B(CHB)virus infection.METHODS We enrolled patients with chronic hepatitis B virus(HBV)infection who underwent liver biopsy at the Third People’s Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020.Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected.Propensity score matching(PSM)was used to balance baseline parameters,Kaplan-Meier(K-M)survival analysis was used to evaluate the risk of clinical events,and Cox regression was used to analyze the risk factors of events.RESULTS Overall,456 patients with chronic HBV infection were included in the study,of whom 152(33.3%)had histologically confirmed NAFLD.The median follow-up time of the entire cohort was 70.5 mo.Thirty-four patients developed cirrhosis,which was diagnosed using ultrasound during the follow-up period.K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis(log-rank test,P>0.05).Patients with CHB with fibrosis at baseline were more prone to cirrhosis(log-rank test,P=0.046).After PSM,multivariate analysis showed that diabetes mellitus,ballooning deformation(BD),and platelet(PLT)were independent risk factors for cirrhosis diagnosed using ultrasound(P<0.05).A total of 10 patients(2.2%)developed HCC,and six of these patients were in the combined NAFLD group.K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher(log-rank test,P<0.05).Hepatocyte ballooning,and severe liver fibrosis were also associated with an increased risk of HCC(log-rank test,all P<0.05).Cox multivariate analysis revealed that hepatocyte ballooning,liver fibrosis,and diabetes mellitus were independent risk factors for HCC.CONCLUSION There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD.Diabetes mellitus,BD,and PLT were independent risk factors for liver cirrhosis.Patients with chronic HBV infection and NASH have an increased risk of HCC.BD,liver fibrosis,and diabetes mellitus are independent risk factors for HCC.

Evaluation of the diagnostic efficacy of noninvasive diagnosis in patients with chronic viral hepatitis B complicated with nonalcoholic fatty liver disease and significant liver fibrosis

Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combined models,and to explore their clinical features.Methods:A total of 104 inpatients with CHB diagnosed and complicated with NAFLD(hepatic steatosis suggested by liver biopsy)were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University.Liver biopsy was performed in all patients.General data,laboratory test results,liver hardness(LSM),FIB-4,APRI,GGT/PLT,AST/PLT and other results of patients were collected and grouped according to different fibrosis stages(S)to explore the clinical and pathological characteristics of patients with<S2 and S2 stages.Receiver operating characteristic curve was used to evaluate the diagnostic value of LSM,FIB-4,APRI,GGT/PLT,AST/PLT and their combined models in patients with significant liver fibrosis in CHB patients with NAFLD.Results:Among the 104 patients,there were 55 patients had S1 fibrosis,32 patients had S2 fibrosis,11 patients had S3 fibrosis and 6 patients had S4 fibrosis.Patients had<S2 fibrosis,ALT 33.75±17.15 U/L,AST 24.00(19.77,29.00)U/L,inflammation above G2 stage accounted for 92.72%,GGT/PLT 0.07(0.10,0.15),AST/PLT 0.09(0.10,0.15),LSM 8.70(6.80,10.10)kPa,FIB-41.07±0.51,APRI 0.26(0.22,0.28).In patients S2 fibrosis,ALT 42.14±21.39 U/L,AST 29.04(24.00,40.32)U/L,inflammation above G2 stage accounted for 97.95%,GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26),GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26).LSM 11.80(8.50,16.65)kPa,FIB-41.39±0.72,APRI 0.35(0.26,0.66),the difference between the two groups was statistically significant(P<0.05).The area under the receiver operator characteristic curves of the subjects of LSM,FIB-4,APRI,GGT/PLT and AST/PLT were 0.716,0.623,0.669,0.644 and 0.669(P<0.05),respectively.In the combined model,the area under the receiver operator characteristic curves of LSM combined with FIB-4,LSM combined with APRI,LSM combined with GGT/PLT and LSM combined with AST/PLT were 0.712,0.719,0.715 and 0.719,respectively(P<0.05).Conclusion:Although the currently commonly used Noninvasive diagnosis of liver fibrosis has certain diagnostic efficacy for significant liver fibrosis in CHB complicated with NAFLD,it cannot replace liver biopsy.Noninvasive Diagnosis can be used as an auxiliary method for regular clinical evaluation of liver biopsy.

Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin

BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

Autoimmune Hepatitis Prevalence among Patients from Saudi Arabia with Chronic Liver Disease Referred for Transient Elastography

Background and study aim: Autoimmune hepatitis (AIH) is a chronic liver disease that can lead to progressive liver damage. The prevalence of AIH among the general population and among chronic liver disease (CLD) patients is variable worldwide. Currently, no published data on the prevalence of AIH among Saudi or among liver disease patients from the region. In this study, we aimed to assess the prevalence of AIH among CLD patients who were referred for transient elastography (FibroScan) in Saudi Arabia. Patients and methods: A retrospective study was conducted among CLD patients who had a transient elastography (FibroScan) during the 3-year study period. We obtained demographic data and test results for serum alanine aminotransferase (ALT), bilirubin, hemoglobin (Hgb), platelets, and international normalized ratio (INR) from all patients. We compared the results of the AIH patients to those of the non-AIH patients with CLD. In addition, for AIH patients, we measured serum immunoglobulin G (IgG), antinuclear antibody (ANA), smooth muscle antibody (SMA) and ALT at 2 - 6 weeks and at 3 - 4 months. Results: We included 494 patients, who were predominantly female (271 (60%)) and Saudi (299 (60.5%)). Thirty patients (6.1%) had AIH, which represented the 4th most common liver disease. Compared to non-AIH patients, AIH patients were younger (mean ages 49.9 years, SD 14.22 years, and 40.4 years, SD 13.94 years, respectively, P = 0.001). Patients with AIH had significantly lower Hgb and platelets (P = 0.008 for both) and higher ALT, bilirubin and INR (P = 0.05, 0.047 and 0.019, respectively). More than 50% of the AIH patients had cirrhosis. Older age was not associated with advanced disease stage among the AIH patients (P < 0.001). AIH represents the 4th most common cause of CLD in patients referred for transient elastography in Saudi Arabia. AIH tends to be severe in patients at a young age, with a marked biochemical response to steroids and azathioprine treatment.

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients

This letter to the editor relates to the study entitled“Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study”,which was recently published by Peng et al.Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer.The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects,so it is crucial to identify safe and effective drugs to inhibit viral replication.

Psychometrics of the chronic liver disease questionnaire for Southern Chinese patients with chronic hepatitis B virus infection

AIM： To test the psychometric properties of a Chinese [（Hong Kong） HK] translation of the chronic liver disease questionnaire （CLDQ）. METHODS： A Chinese （HK） translation of the CLDQ was developed by iterative translation and cognitive debriefing. It was then administered to 72 uncomplicated and 78 complicated chronic hepatitis B （CriB） patients in Hong Kong together with a structured questionnaire on service utilization, and the Chinese （HK） SF-36 Health Survey Version 2 （SF-36v2）. RESULTS： Scaling success was ≥ 80% for all but three items. A new factor assessing sleep was found and items of two （Fatigue and Systemic Symptoms） subscales tended to load on the same factor. Internal consistency and test-retest reliabilities ranged from 0.58-0.90 for different subscales. Construct validity was confirmed by the expected correlations between the SF-36v2 Health Survey and CLDQ scores. Mean scores of CLDQ were significantly lower in complicated compared with uncomplicated CHB, supporting sensitivity in detecting differences between groups.CONCLUSION： The Chinese （HK） CLDQ is valid, reliable and sensitive for patients with CHB. Some modifications to the scaling structure might further improve its psychometric properties,

TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

AIM:To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea,to investigate the association of TTV and HGV infections with blood transfusion,and to assess the correlation between TTV and HGV viremia and hepatic damage. METHODS:A total of 391 serum samples were examined in this study.Samples were obtained from healthy blood donors(n=110),hepatitis B surface antigen(HBsAg)-positive donors(n=112),anti-hepatitis C virus(anti-HCV)-positive donors(n=69),patients with type B chronic liver disease (n=81),and patients with type C chronic liver disease(n=19). Trv DNA was detected using the hemi-nested PCR.HGV RNA was tested using RT-PCR.A history of blood transfusion and serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were also determined. RESULTS:TTV DNA was detected in 8.2%of healthy blood donors,16.1%of HBsAg-positive donors,20.3%of anti- HCV-positive donors,21.0%of patients with type B chronic liver disease,and 21.1%of patients with type C chronic liver disease.HGV RNA was detected in 1.8%of healthy blood donors,1.8%of HBsAg-positive donors,17.4%of anti-HCV-positive donors,13.6%of patients with type B chronic liver disease,and 10.5%of patients with type C chronic liver disease.The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors(P<0.05), except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors.There was a history of transfusion in 66.7%of TTV DNA-positive patients and 76.9%of HGV RNA-positive patients(P<0.05).No significant increase in serum ALT and AST was detected in the TTV or HGV-positive donors and patients. CONCLUSION:TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors.However,there is no significant association between TTV or HGV infections and liver injury.

Serum neopterin levels in children with hepatitis-B-related chronic liver disease and its relationship to disease severity

AIM:To evaluate serum neopterin levels and their correlations with liver function tests and histological grade in children with hepatitis-B-related chronic liver disease. METHODS:The study population comprised 48 patients with chronic active hepatitis B,32 patients with hepatitis-B-related active liver cirrhosis and 40 normal controls. Serum neopterin was measured using an enzyme-linked immunosorbent assay. RESULTS:The mean ± SD serum neopterin levels were 14.2 ± 5.6 nmol/L in patients with chronic hepatitis,20.3 ± 7.9 nmol/L in patients with liver cirrhosis and 5.2 ± 1.4 nmol/L in control group. Serum neopterin levels were signif icantly higher in patients with chronic hepatitis (P = 0.005) and cirrhosis patients (P = 0.008),than in control subjects. Cirrhotic patients had signif icantly higher serum neopterin levels than patients with chronic hepatitis (P = 0.004). There was a positive correlation between serum neopterin levels and alanine aminotransferase levels in patients with chronic hepatitis (r = 0.41,P = 0.004) and cirrhotic patients (r = 0.39,P = 0.005). Positive correlations were detected between serum neopterin levels and inflammatory score in patients with chronic hepatitis (r = 0.51,P = 0.003) and cirrhotic patients (r = 0.49,P = 0.001). CONCLUSION:Our results suggest that serum neopterin levels can be considered as a marker of inflammatory activity and severity of disease in children with hepatitis-B-related chronic liver disease.

Total cholesterol to high-density lipoprotein ratio and nonalcoholic fatty liver disease in a population with chronic hepatitis B

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is characterized by hypertriglyceridemia,increased low-density lipoprotein cholesterol levels,and reduced highdensity lipoprotein cholesterol(HDL-C)particles.Previous studies have shown that the total cholesterol to high-density lipoprotein cholesterol ratio(TC/HDL-C)was superior to other lipid metabolism biomarkers for predicting NAFLD risk and could be a new indicator of NAFLD.However,the association between TC/HDL-C and NAFLD in patients with hepatitis B virus(HBV)has not yet been determined.AIM To investigate the association between TC/HDL-C and NAFLD in a population with chronic hepatitis B(CHB).METHODS In this study,183 HBV-infected patients were enrolled.All participants underwent blood chemistry examinations and abdominal ultrasound.Univariate and multivariate logistic regression models,curve fitting analysis,and threshold calculation were used to assess the relationship between TC/HDL-C and NAFLD.RESULTS The overall prevalence of NAFLD was 17.49%(n=32)in the 183 CHB participants.The TC/HDL-C of non-NAFLD and NAFLD patients were 3.83±0.75 and 4.44±0.77,respectively(P<0.01).Logistic regression analysis showed that TC/HDL-C was not associated with NAFLD after adjusting for other pertinent clinical variables.However,at an optimal cutoff point of 4.9,a non-linear correlation between TC/HDL-C and NAFLD was detected.The effect size of the left and right sides of the inflection point were 5.4(95%confidence interval:2.3-12.6,P<0.01)and 0.5(95%confidence interval:0.1-2.2,P=0.39),respectively.On the left side of the inflection point,TC/HDL-C was positively associated with NAFLD.However,no significant association was observed on the right side of the inflection point.CONCLUSION This study demonstrated a non-linear correlation between TC/HDL-C and NAFLD in a population with CHB.TC/HDL-C was positively associated with NAFLD when TC/HDL-C was less than 4.9 but not when TC/HDL-C was more than 4.9.

Metabolic-associated fatty liver disease is associated with low muscle mass and strength in patients with chronic hepatitis B

BACKGROUND Although the prognostic relevance of sarcopenia has been increasingly recognised in the context of liver disease,there is a paucity of data evaluating body composition in patients with chronic hepatitis B(CHB).Beyond virus-related factors,nutritional and metabolic aspects can be associated with skeletal muscle abnormalities in these patients and should not be disregarded.AIM To evaluate the association between components of sarcopenia and demographic,clinical,lifestyle,nutritional,and biochemical variables in CHB patients.METHODS Dual-energy X-ray absorptiometry(DXA)was used to assess muscle mass by quantifying appendicular lean mass(ALM)adjusted for body mass index(ALMBMI).Muscle function was evaluated by hand grip strength(HGS)and the timed up and go test.Metabolic-associated fatty liver disease(MAFLD)was defined according to the criteria proposed by an international expert panel.A body shape index and the International Physical Activity Questionnaire were used to assess central obesity and physical activity level,respectively.RESULTS This cross-sectional study included 105 CHB outpatients followed at the tertiary care ambulatory centre(mean age,48.5±12.0 years;58.1%males;76.2%without cirrhosis;23.8%with compensated cirrhosis).The DXA-derived fat mass percentage was inversely correlated with the ALMBMI(r=-0.87)and HGS(r=-0.63).In the multivariable analysis,MAFLD,sedentarism and central obesity were positively and independently associated with low ALMBMI.MAFLD and central obesity were independently associated with low HGS.CONCLUSION MAFLD and central obesity were associated with low muscle mass and strength in patients with chronic hepatitis B,independent of the liver disease stage.

Analysis of influencing factors of chronic hepatitis B complicated with nonalcoholic fatty liver disease

Objective:To investigate the influencing factors of chronic hepatitis B with nonalcoholic fatty liver disease,and to provide a reference for screening and clinical treatment of high-risk groups.Methods:A case-control study was conducted.According to the inclusion and exclusion criteria,133 cases of newly diagnosed patients with CHB combined with NAFLD were enrolled in the Affiliated Hospital of North China University of Technology and Tangshan Infectious Disease Hospital from January 2015 to January 2018.139 cases of newly diagnosed patients with CHB diagnosed in the same period were selected as the control group.The clinical data,initial laboratory examination and imaging findings of the two groups of patients were compared to analyze the influencing factors of chronic hepatitis B combined with nonalcoholic fatty liver disease.Results:1 The BMI,ALT,AST,GGT,FBG,TG and CAP in the case group were significantly higher than those in the control group,the difference was statistically significant(P<0.05).The control group HDL-C,HBcAb,type III procollagen amino terminal peptide,The type IV collagen,laminin and LSM were higher than the case group,the difference was statistically significant(P<0.05).The case group was more likely to be associated with complications,and the difference was statistically significant(P=0.01).2 Univariate analysis showed that About the author:Zhang Guoshun,male,chief physician,professor,master's tutor,doctoral,mainly engaged in research and prevention of liver diseases,13930565676,zguoshun@sina.com.Fund Project:China Hepatitis Prevention Foundation Funded Project(No.:TQGB20170015);Hebei Province Medical Science Research Key Project(No.20170933);North China University of Technology Graduate Innovation Project(No.2019S49)patients in the case group had BMI≥25Kg/m2,GGT>45U/L,type IV collagen≤140ng/ml,laminin≤140ng/ml,CAP≥283dB/m,hyperglycemia,high glycerol The proportion of patients with lipemia was significantly higher than that of the control group,the difference was statistically significant(P<0.05);3 binary logistic regression analysis showed that GGT,FBG,BMI,laminin,CAP were predictive of chronic hepatitis B combined with non-An effective indicator of alcoholic fatty liver disease.Conclusion 1GGT,BMI,FBG,laminin and CAP are the influencing factors of CHB combined with NAFLD.The occurrence of 2NAFLD is closely related to obesity,hyperglycemia and hypertriglyceridemia.The HBcAb and liver fibrosis indexes are decreased when CHB combined with NAFLD,and the mechanism is still unclear.

Factors Associated with Hepatic Steatosis in Black African Subjects with Chronic Viral Hepatitis B in Côte d’Ivoire

Context/Objectives: With the progression of the global epidemic of obesity and metabolic syndrome, the coexistence of hepatic steatosis in patients with chronic viral hepatitis B (VHB) is becoming significant. The aim of this work was to determine the factors associated with hepatic steatosis assessed by a Fibroscan with Controlled Attenuation Parameter (CAP) in patients with chronic viral hepatitis B in Côte d’Ivoire. Methods: This was a cross-sectional and analytical study. Data was collected from February 15 to July 31, 2020 in a private hospital structure in the city of Abidjan in Côte d’Ivoire. We included 83 patients with chronic viral hepatitis B. These were black patients, having performed a Fibroscan/CAP during the recruitment period and consenting to participate in the study. Patients with significant alcohol consumption, a secondary cause of hepatic steatosis, or other liver disease regardless of the etiology associated with hepatitis B were not included. Results: The frequency of hepatic steatosis in chronic VHB carriers assessed by the CAP in our study population was 48.19% including 24.10% severe steatosis. Obesity and high LDL cholesterol were statistically correlated with the presence of steatosis in our patients. Patients who had steatosis on ultrasound were 5 times more likely to have steatosis on CAP. Significant fibrosis was not significantly associated with steatosis. Conclusion: Obesity and LDL hypercholesterolemia are the main factors associated with hepatic steatosis detected by Fibroscan/CAP in patients with chronic viral hepatitis B.

Psychometrics of chronic liver disease questionnaire in Chinese chronic hepatitis B patients

AIM: To evaluate psychometrics of the Chinese (mainland) chronic liver disease questionnaire (CLDQ) in patients with chronic hepatitis B (CHB). METHODS: A cross-sectional sample of 460 Chinese patients with CHB was selected from the Outpatient Department of the Eighth Hospital of Xi'an, including CHB (CHB without cirrhosis) (n = 323) and CHB-related cirrhosis (n = 137). The psychometrics includes reliability, validity and sensitivity. Internal consistency reliability was measured using Cronbach's α. Convergent and discriminant validity was evaluated by item-scale correlation. Factorial validity was explored by principal component analysis with varimax rotation. Sensitivity was assessed using Cohen's effect size (ES), and independent sample t test between CHB and CHB-related cirrhosis groups and between alanine aminotransferase (ALT) normal and abnormal groups after stratifying the disease (CHB and CHB-related cirrhosis).RESULTS: Internal consistency reliability of the CLDQ was 0.83 (range: 0.65-0.90). Most of the hypothesized item-scale correlations were 0.40 or over, and all of such hypothesized correlations were higher than the alternative ones, indicating satisfactory convergent and discriminant validity. Six factors were extracted after varimax rotation from the 29 items of CLDQ. The eligible Cohen's ES with statistically significant independent sample t test was found in the overall CLDQ and abdominal, systematic, activity scales (CHB vs CHBrelated cirrhosis), and in the overall CLDQ and abdominal scale in the stratification of patients with CHB (ALT normal vs abnormal). CONCLUSION: The CLDQ has acceptable reliability, validity and sensitivity in Chinese (mainland) patients with CHB.

Clinical characteristics and 28-d outcomes of bacterial infections in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure (ACLF),which includes hepatic and multiple extrahepatic organ failure,is a severe emergency condition that has high mortality.ACLF can rapidly progress and requires an urgent assessment of condition and referral for liver transplantation.Bacterial infections (BIs) trigger ACLF and play pivotal roles in the deterioration of clinical course.AIM To investigate the clinical characteristics and 28-d outcomes of first Bis either at admission or during hospitalization in patients with hepatitis B virus (HBV)-ACLF as defined by the Chinese Group on the Study of Severe Hepatitis B(COSSH).METHODS A total of 159 patients with HBV-ACLF and 40 patients with acute decompensation of HBV-related chronic liver disease combined with first BIs were selected for a retrospective analysis between October 2014 and March 2016 The characteristics of BIs,the 28-d transplant-free survival rates,and the independent predictors of the 28-d outcomes were evaluated.RESULTS A total of 194 episodes of BIs occurred in 159 patients with HBV-ACLF.Among the episodes,13.4 To were community-acquired,46.4 To were healthcare-associated,and 40.2% belonged to nosocomial BIs.Pneumonia (40.7%),spontaneous bacterial peritonitis (SBP)(34.5%),and bloodstream infection (BSI)(13.4%) were the most prevalent.As the ACLF grade increased,the incidence of SBP showed a downward trend (P=0.021).Sixty-one strains of bacteria,including 83.6% Gramnegative bacteria and 29.5% multidrug-resistant organisms,were cultivated from 50 patients with ACLF.Escherichia coli (44.3%) and Klebsiella pneumoniae (23.0%)were the most common bacteria.As the ACLF grade increased,the 28-d transplant-free survival rates showed a downward trend (ACLF-1,55.7%;ACLF-2,29.3%;ACLF-3,5.4%;P <0.001).The independent predictors of the 28-doutcomes of patients with HBV-ACLF were COSSH-ACLF score (hazard ratio[HR]=1.371),acute kidney injury (HR=2.187),BSI (HR=2.339),prothrombin activity (HR=0.967),and invasive catheterization (HR=2.173).CONCLUSION For patients with HBV-ACLF combined with first BIs,pneumonia is the most common form,and the incidence of SBP decreases with increasing ACLF grade.COSSH-ACLF score,acute kidney injury,BSI,prothrombin activity,and invasive catheterization are the independent predictors of 28-d outcomes.

The effect of NAFLD (non-alcoholic fatty liver disease) on long-term outcome of chronic hepatitis B in Iranian patients

Background: The influence of Non-Alcoholic Fatty Liver Disease on the outcome of chronic hepatitis B disease, including viral, biochemical and histologic characteristics, in Iranian patients is not yet fully un- derstood. Aim: To evaluate the effect of Non-Alcoholic Fatty Liver Disease (NAFLD) on long-term histology- cal, biochemical and viral outcome of chronic he- pa-tictis B in Iranian patients. Methods: We retro- spec-tively evaluated 94 “e Ag” negative chronic hepatitis B patients (with NAFLD: 44, without NAFLD: 50). Non-Alcoholic Fatty Liver Disease was diagnosed based on liver biopsy according to Kleiner classifica-tion. Liver biopsy was done for all patients. Serologi-cal and biochemical variables were evaluated with repeated measure analysis. Results: Non-Alcoholic Fat- ty Liver Disease (NAFLD) was present in 47% of the patients (44 out of 94 patients). In the NAFLD group, increase in AST, ALT, stage (P = 0.002), grade, and total score of liver biopsy were independently related to non-alcoholic fatty liver disease, while HBV-DNA viral load did not correlate with the presence of a fatty liver. Conclusion: Abnormalities of liver enzymes and liver histopathology are more prevalent in concurrent chronic hepatitis B and Non-Alcoholic Fatty Liver Disease (NAFLD).

Increased CD163 expression is associated with acute-on-chronic hepatitis B liver failure

AIM: To assess CD163 expression in plasma and peripheral blood and analyze its association with disease in acute-on-chronic hepatitis B liver failure (ACHBLF) patients. METHODS: A retrospective study was conducted from January 1, 2011 to January 1, 2012. Forty patients with ACHBLF (mean age 44.48 ± 12.28 years, range 18-69 years), 40 patients with chronic hepatitis B (CHB) (mean age 39.45 ± 12.22 years, range 21-57 years) and 20 ageand sex-matched healthy controls (mean age 38.35 ± 11.97 years, range 28-60 years) were included in this study. Flow cytometry was used to analyze the frequency of CD163+ peripheral blood mononuclear cells (PBMCs) and surface protein expression of CD163. Real-time transcription-polymerase chain re-action was performed to assess relative CD163 mRNA levels in PBMCs. Plasma soluble CD163 (sCD163) levels were measured by enzyme-linked immunosorbent assay. Clinical variables were also recorded. Comparisons between groups were analyzed by Kruskal-Wallis H test and Mann-Whitney U test. Statistical analyses were performed using SPSS 15.0 software and a P value < 0.05 was considered statistically significant. RESULTS: Flow cytometry showed that the population of CD163+ PBMCs was significantly greater in ACHBLF patients than in CHB patients and healthy controls (47.9645% ± 17.1542%, 32.0975% ± 11.0215% vs 17.9460% ± 6.3618%, P < 0.0001). However, there were no significant differences in mean fluorescence intensity of CD163+ PBMCs within the three groups (27.4975 ± 11.3731, 25.8140 ± 10.0649 vs 20.5050 ± 6.2437, P = 0.0514). CD163 mRNA expression in ACHBLF patients was significantly increased compared with CHB patients and healthy controls (1.41 × 10 -2 ± 2.18 × 10 -2 , 5.10 × 10 -3 ± 3.61 × 10 -3 vs 37.0 × 10 -4 ± 3.55 × 10 -4 , P = 0.02). Plasma sCD163 levels in patients with ACHBLF were significantly increased compared with CHB patients and healthy controls (4706.2175 ± 1681.1096 ng/mL, 1089.7160 ± 736.8395 ng/mL vs 435.9562 ± 440.8329 ng/mL, P < 0.0001). In ACHBLF patients, plasma sCD163 levels were significantly positively associated with model for end-stage liver disease scores (r = 0.5075, P = 0.008), hepatitis B virus-DNA (r = 0.6827, P < 0.0001), and negatively associated with prothrombin activity (r = -0.3348, P = 0.0347), but had no correlation with total bilirubin (r = 0.2551, P = 0.1122). Furthermore, sCD163 was obviously elevated in non-surviving patients compared with surviving patients with ACHBLF (5344.9080 ± 1589.5199 ng/mL vs 3641.7333 ± 1264.5228 ng/mL, P = 0.0321). CONCLUSION: CD163 and sCD163 may be related to disease severity and prognosis in ACHBLF patients.

Hepatitis B virus genotypes in chronic liver disease patients from New Delhi,India

AIM: To study the Hepatitis B virus (HBV) genotypes and their effect on the progression and outcome in patients with chronic liver diseases from New Delhi, India. METHODS: Sera from 100 HBV-related chronic liver disease (CLDB) cases were tested for HBV genotype using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and Type-specific primers-based PCR (TSP-PCR) targeting to the surface (S) gene encoding hepatitis B surface antigen. RESULTS: Only genotypes A and D were present and genotype D was dominant. Genotype D was present in all CLDB patient categories. The genotype distribution for the 100 patients with CLDB was as follows: genotype A, 16/100 (16%) (7/40- 17% chronic hepatitis B (CHB); 8/47, 17%, HBV-related cirrhosis (CRB); 1/13, 7.6%, HBV-related hepatocellular carcinoma (HCCB); genotype D- 84/100 (84%) (32/40- 80% CHB; 38/47- 81%, CRB; 11/13, 85%, HCCB); genotype A + D, 3/100 (3%) (1/40- 3% CHB; 1/47- 2%, CRB; 1/13, 7.6%, HCCB); C, 0; B, 0; E, 0; F, 0; G 0, H 0; (P < 0.01, genotype D vs A). CONCLUSION: Only HBV genotypes A and D were present in patients with CLDB from New Delhi, India. Compared with genotype D, genotype A patients had no significant clinical or biochemical differences (P > 0.05). Mixed infection with genotype A and D were seen in 3% of the cases. Genotype D was the dominant genotype prevalent in all patient categories.

Chronic hepatitis B-associated liver disease in the context of human immunodeficiency virus co-infection and underlying metabolic syndrome

Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden restricted to the Western Pacific and sub-Saharan African regions.Amidst this is a growing burden of metabolic syndrome(MetS)worldwide.A disproportionate co-burden of human immunodeficiency virus(HIV)infection is also reported in sub-Saharan Africa,which poses a further risk of liver-related morbidity and mortality in the region.We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection.While the mechanistic association between CHB and MetS remains poorly resolved,the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB.Among HIV infected individuals,MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy(ART).It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection.However,this remains to be explored through rigorous longitudinal studies,especially in sub-Saharan Africa.Ultimately,there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV coinfected individuals.

Non-invasive assessment of liver fibrosis in chronic liver diseases:Implementation in clinical practice and decisional algorithms

Chronic hepatitis B and C together with alcoholic and non-alcoholic fatty liver diseases represent the major causes of progressive liver disease that can eventually evolve into cirrhosis and its end-stage complications,including decompensation,bleeding and liver cancer.Formation and accumulation of fibrosis in the liver is the common pathway that leads to an evolutive liver disease.Precise definition of liver fibrosis stage is essential for management of the patient in clinical practice since the presence of bridging fibrosis represents a strong indication for antiviral therapy for chronic viral hepatitis,while cirrhosis requires a specif ic follow-up including screening for esophageal varices and hepatocellular carcinoma.Liver biopsy has always represented the standard of reference for assessment of hepatic fibrosis but it has some limitations being invasive,costly and prone to sampling errors.Recently,blood markers and instrumental methods have been proposed for the non-invasive assessment of liver fibrosis.However,there are still some doubts as to their implementation in clinical practice and a real consensus on how and when to use them is not still available.This is due to an unsatisfactory accuracy for some of them,and to an incomplete validation for others.Some studies suggest that performance of non-invasive methods for liver fibrosis assessment may increase when they are combined.Combination algorithms of non-invasive methods for assessing liver fibrosis may represent a rational and reliable approach to implement non-invasive assessment of liver fibrosis in clinical practice and to reduce rather than abolish liver biopsies.