Association of chronic viral hepatitis B with insulin resistance

AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean adults.METHODS:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this study.Subjects diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were rejected.Anthropometry,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all subjects.Homeostasis model assessment(HOMA),quantitative insulin check index(QUICKI),and Mf fm index were used for determining insulin sensitivity.Each participant was categorized into a negative,recovery,or CVHB group.To compare variables between groups,a t-test and/or one-way analysis of variance were used.Partial correlation coefficients were computed to present the association between insulin resistance and other variables.Multiple logistic regression analysis was used to assess the independent association between CVHB and IR.RESULTS:The mean age of men and women were 48.9 and 48.6 years,respectively.Subjects in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P = 0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P 0.001 in women)],cystatin C [(0.96 ± 0.15 mg/dL vs 1.02 ± 0.22 mg/dL,P 0.001 in men),(0.84 ± 0.15 mg/dL vs 0.90 ± 0.16 mg/dL,P 0.001 in women)],fasting insulin [(5.47 ± 3.38 U/mL vs 6.12 ± 4.62 U/mL,P 0.001 in men),(4.57 ± 2.82 U/mL vs 5.06 ± 3.10 U/mL,P 0.001 in women)] and HOMA index [(1.24 ± 0.86 vs 1.43 ± 1.24,P 0.001 in men),(1.02 ± 0.76 vs 1.13 ± 0.87,P = 0.033 in women)] compared to control group.The HOMA index revealed a positive correlation with body mass index(BMI)(r = 0.378,P 0.001),waist circumference(r =0.356,P 0.001),percent body fat(r = 0.296,P 0.001),systolic blood pressure(r = 0.202,P 0.001),total cholesterol(r = 0.134,P 0.001),triglycerides(r = 0.292,P 0.001),cystatin C(r = 0.069,P 0.001) and uric acid(r = 0.142,P 0.001).The QUICKI index revealed a negative correlation with BMI(r =-0.254,P 0.001),waist circumference(r = 0-0.243,P 0.001),percent body fat(r =-0.217,P 0.001),systolic blood pressure(r =-0.132,P 0.001),total cholesterol(r =-0.106,P 0.001),triglycerides(r =-0.205,P 0.001),cystatin C(r =-0.044,P 0.001) and uric acid(r =-0.096,P 0.001).For subjects identified with IR,the odds ratio of an accompanying diagnosis of chronic hepatitis B was 1.534(95% CI:1.158-2.031,HOMA index criteria) or 1.566(95% CI:1.124-2.182,QUICKI criteria) after adjustment for age,gender,BMI,and amount of alcohol consumption.CONCLUSION:Our study demonstrates that CVHB is associated with IR.CVHB may need to be monitored for occurrence of IR and diabetes mellitus.     

Prolonged QT dispersion in inflammatory bowel disease

AIM:To investigate the frequency and factors of prolonged QT dispersion that may lead to severe ventricular arrhythmias in patients with inflammatory bowel disease(IBD).METHODS:This study included 63 ulcerative colitis(UC) and 41 Crohn’s disease(CD) patients.Forty-seven healthy patients were included as the control group.Heart rate was calculated using electrocardiography,corrected QT dispersion(QTcd) and the Bazett’s formula.Homeostasis model assessment(HOMA) was used to determine insulin resistance(IR).HOMA values < 1 were considered normal and values > 2.5 indicated a high probability of IR.RESULTS:Prolonged QTcd was found in 12.2% of UC patients,and in 14.5% of CD patients compared with the control group(P < 0.05).A significant difference was found between the insulin values(CD:10.95 ± 6.10 vs 6.44 ± 3.28,P < 0.05;UC:10.88 ± 7.19 vs 7.20 ± 4.54,P < 0.05) and HOMA(CD:2.56 ± 1.43 vs 1.42 ± 0.75,P < 0.05;UC:2.94 ± 1.88 vs 1.90 ± 1.09,P < 0.05) in UC and CD patients with and without prolonged QTcd.Disease behavior types were determined in CD patients with prolonged QTcd.Increased systolic arterial pressure(125 ± 13.81 vs 114.09 ± 8.73,P < 0.01) and age(48.67 ± 13.93 vs 39.57 ± 11.58,P < 0.05) in UC patients were significantly associated with prolonged QTcd.CONCLUSION:Our data show that IBD patients have prolonged QTcd in relation to controls.The routine followup of IBD patients should include determination of HOMA,insulin values and electrocardiogram examination.     

Contrast-enhanced ultrasound evaluation of hepatic microvascular changes in liver diseases

AIM:To assess if software assisted-contrast-enhanced ultrasonography (CEUS) provides reproducible perfusion parameters of hepatic parenchyma in patients affected by chronic liver disease. METHODS:Forty patients with chronic viral liver disease, with (n = 20) or without (n = 20) cirrhosis, and 10 healthy subjects underwent CEUS and video recordings of each examination were then analysed with Esaote's Qontrast software. CEUS dedicated software Qontrast was used to determine peak (the maximum signal intensity), time to peak (TTP), region of blood value (RBV) proportional to the area under the time-intensity curve, mean transit time (MTT) measured in seconds and region of blood flow (RBF). RESULTS:Qontrast-assisted CEUS parameters displayed high inter-observer reproducibility (k coefficients of 0.87 for MTT and 0.90 TTP). When the region of interest included a main hepatic vein, Qontrast-calculated TTP was significantly shorter in cirrhotic patients (vs non-cirrhotics and healthy subjects) (71.0 ± 11.3 s vs 82.4 ± 15.6 s, 86.3 ± 20.3 s, P 0.05). MTTs in the patients with liver cirrhosis were significantly shorter than those of controls (111.9 ± 22.0 s vs 139.4 ± 39.8 s, P 0.05), but there was no significant difference between the cirrhotic and non-cirrhotic groups (111.9 ± 22.0 s vs 110.3 ± 14.6 s). Peak enhancement in the patients with liver cirrhosis was also higher than that observed in controls (23.9 ± 5.9 vs 18.9 ± 7.1, P = 0.05). There were no significant intergroup differences in the RBVs and RBFs. CONCLUSION:Qontrast-assisted CEUS revealed reproducible differences in liver perfusion parameters during the development of hepatic fibrogenesis.     

IL28B polymorphism as a predictor of antiviral response in chronic hepatitis C

AIM:To evaluate the effect of single nucleotide polymorphisms of interleukin(IL)-28B,rs12979860 on progression and treatment response in chronic hepatitis C.METHODS:Patients(n = 64;37 men,27 women;mean age,44 ± 12 years) with chronic hepatitis C,genotype 1,received treatment with peg-interferon plus ribavirin.Genotyping of rs12979860 was performed on peripheral blood DNA.Histopathological assessment of necroinflammatory grade and fibrosis stage were scored using the METAVIR system on a liver biopsy sample before treatment.Serum viral load,aminotransferase activity,and insulin level were measured.Insulin resistance index,body mass index,waist/hip ratio,percentage of body fat and fibrosis progression rate were calculated.Applied dose of interferon and ribavirin,platelet and neutrophil count and hemoglobin level were measured.RESULTS:A sustained virological response(SVR) was significantly associated with IL28B polymorphism(CC vs TT allele:odds ratio(OR),25;CC vs CT allele:OR,5.4),inflammation activity(G 1 vs G 1:OR,3.9),fibrosis(F 1 vs F 1:OR,5.9),platelet count( 200 × 10 9 /L vs 200 × 10 9 /L:OR,4.7;OR in patients with genotype CT:12.8),fatty liver(absence vs presence of steatosis:OR,4.8),insulin resistance index( 2.5 vs 2.5:OR,3.9),and baseline HCV viral load( 10 6 IU/mL vs 10 6 IU/mL:OR,3.0).There was no association with age,sex,aminotransferases activity,body mass index,waist/hip ratio,or percentage body fat.There was borderline significance(P = 0.064) of increased fibrosis in patients with the TT allele,and no differences in the insulin resistance index between groups of patients with CC,CT and TT alleles(P = 0.12).Spearman's rank correlation coefficient between insulin resistance and stage of fibrosis and body mass index was r = 0.618 and r = 0.605,respectively(P 0.001).Significant differences were found in the insulin resistance index(P = 0.01) between patients with and without steatosis.Patients with the CT allele and absence of a SVR had a higher incidence of requiring threshold dose reduction of interferon(P = 0.07).CONCLUSION:IL28B variation is the strongest host factor not related to insulin resistance that determines outcome of antiviral therapy.Baseline platelet count predicts the outcome of antiviral therapy in CT allele patients.     

Yi-Qi-Zeng-Min-Tang, a Chinese medicine, ameliorates insulin resistance in type 2 diabetic rats

AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic rats.METHODS:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabe...     

Low incidence of spontaneous bacterial peritonitis in asymptomatic cirrhotic outpatients

AIM: To compare the incidence of spontaneous bacterial peritonitis in cirrhotic outpatients and inpatients undergoing therapeutic paracentesisMETHODS: From January 1 to May 31, 2004, 1041 patients from 70 different hospitals underwent 2123 therapeutic abdominal paracentesis (AP) performed as a outpatient procedure in 355 and as inpatient procedure in 686 cases respectively. The following parameters were compared prospectively between outpatients and inpatients: spontaneous bacterial peritonitis (SBP) prevalence, age, gender, cause of cirrhosis, symptoms, score and grade according to Child-Pugh classification, cirrhosis complications, antibiotics treatment, serum creatinine, platelet count and ascitic protein concentration.RESULTS: SBP was observed in 91 patients. In the whole population the SBP prevalence was 8.7% (95%CI: 7.2-10.6) it was 11.7% (95%CI: 9.5-14.3) in inpatients and 3.1% (95%CI: 1.7-5.5) in outpatients (P < 0.00001). SBP prevalence was 8.3% (95%CI: 4.3-15.6) in symptomatic outpatients vs 1.2% (95%CI: 0.4-3.4) in asymptomatic outpatients (P < 0.002). Patients undergoing outpatient AP were significantly different from those undergoing inpatient AP; they were older (61.1 ± 11.1 years vs 59.4 ± 11.7 years; P = 0.028), cause of cirrhosis was less often alcohol (83 .7 vs 88.2%; P < 0.001), Child-Pugh score was lower (8.9 vs 10.1; P < 0.001) and more often B than C (63.7% vs 38%; P < 0.001). In addition, in outpatients the platelet count was higher (161 ± 93 Giga/L vs 143 ± 89 Giga/L; P = 0.003), serum total bilirubin concentration was lower (38.2 ± 60.7 μmol/L vs 96.3 ± 143.3 μmol/L; P < 0.0001), and ascitic protein concentration higher (17.9 ± 10.7 g/L vs 14.5 ± 10.9 g/L; P < 0.001) than in inpatients.CONCLUSION: In asymptomatic cirrhotic outpatients, the incidence of spontaneous bacterial peritonitis is low thus exploratory paracentesis could be avoided in these patients without significant risk.     

Effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing gastrectomy

AIM: To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy.METHODS: Within 24 h of intensive care unit management, patients with gastric cancer were enrolled after written informed consent and randomized to the intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or the conventional insulin therapy (CIT) group to keep levels less than 10 mmol/L. Resting energy expenditure (REE), respiratory quotient (RQ), resting energy expenditure per kilogram (REE/kg), and the lipid oxidation rate were monitored by the indirect calorimeter of calcium citrate malate nutrition metabolism investigation system. The changes in body composition were analyzed by multi-frequency bioimpedance analysis. Blood fasting glucose and insulin concentration were measured for assessment of Homeostasis model assessment of insulin resistance.RESULTS: Sixty patients were enrolled. Compared with preoperative baseline, postoperative REE increased by over 22.15% and 11.07%; REE/kg rose up to 27.22 ± 1.33 kcal/kg and 24.72 ± 1.43 kcal/kg; RQ decreased to 0.759 ± 0.034 and 0.791 ± 0.037; the lipid oxidation ratio was up to 78.25% ± 17.74% and 67.13% ± 12.76% supported by parenteral nutrition solutions from 37.56% ± 11.64% at the baseline; the level of Ln-HOMA-IR went up dramatically (P < 0.05, respectively) on postoperative days 1 and 3 in the IIT group. Meanwhile the concentration of total protein, albumin and triglyceride declined significantly on postoperative days 1 and 3 compared with pre-operative levels (P < 0.05, respectively). Compared with the CIT group, IIT reduced the REE/kg level (27.22 ± 1.33 kcal/kg vs 29.97 ± 1.47 kcal/kg, P = 0.008; 24.72 ± 1.43 kcal/kg vs 25.66 ± 1.63 kcal/kg, P = 0.013); and decreased the Ln-HOMA-IR score (P = 0.019, 0.028) on postoperative days 1 and 3; IIT decreased the level of CRP on postoperative days 1 and 3 (P = 0.017, 0.006); the total protein and albumin concentrations in the IIT group were greater than those in the CIT group (P = 0.023, 0.009). Postoperative values of internal cell fluid (ICF), fat mass, protein mass (PM), muscle mass, free fat mass and body weight decreased obviously on postoperative 7th day compared with the preoperative baseline in the CIT group (P < 0.05, respectively). IIT reduced markedly consumption of fat mass, PM and ICF compared with CIT (P = 0.009 to 0.026).CONCLUSION: There were some benefits of IIT in decreasing the perioperative insulin resistance state, reducing energy expenditure and consumption of proteins and lipids tissue in patients undergoing gastrectomy.     

Prevalence of functional dyspepsia and its subgroups in patients with eating disorders

AIM: To study the prevalence of functional dyspepsia (FD) (Rome III criteria) across eating disorders (ED), obese patients, constitutional thinner and healthy volunteers.METHODS: Twenty patients affected by anorexia nervosa, 6 affected by bulimia nervosa, 10 affected by ED not otherwise specified according to diagnostic and statistical manual of mental disorders, 4th edition, nine constitutional thinner subjects and, thirty-two obese patients were recruited from an outpatients clinic devoted to eating behavior disorders. Twenty-two healthy volunteers matched for age and gender were enrolled as healthy controls. All participants underwent a careful clinical examination. Demographic and anthropometric characteristics were obtained from a structured questionnaires. The presence of FD and, its subgroups, epigastric pain syndrome and postprandial distress syndrome (PDS) were diagnosed according to Rome III criteria. The intensity-frequency score of broader dyspeptic symptoms such as early satiety, epigastric fullness, epigastric pain, epigastric burning, epigastric pressure, belching, nausea and vomiting were studied by a standardized questionnaire (0-6). Analysis of variance and post-hoc Sheffè tests were used for comparisons.RESULTS: 90% of patients affected by anorexia nervosa, 83.3% of patients affected by bulimia nervosa, 90% of patients affected by ED not otherwise specified, 55.6% of constitutionally thin subjects and 18.2% healthy volunteers met the Postprandial Distress Syndrome Criteria (χ², P < 0.001). Only one bulimic patient met the epigastric pain syndrome diagnosis. Postprandial fullness intensity-frequency score was significantly higher in anorexia nervosa, bulimia nervosa and ED not otherwise specified groups compared to the score calculated in the constitutional thinner group (4.15 ± 2.08 vs 1.44 ± 2.35, P = 0.003; 5.00 ± 2.45 vs 1.44 ± 2.35, P = 0.003; 4.10 ± 2.23 vs 1.44 ± 2.35, P = 0.002, respectively), the obese group (4.15 ± 2.08 vs 0.00 ± 0.00, P < 0.001; 5.00 ± 2.45 vs 0.00 ± 0.00, P < 0.001; 4.10 ± 2.23 vs 0.00 ± 0.00, P < 0.001, respectively) and healthy volunteers (4.15 ± 2.08 vs 0.36 ± 0.79, P < 0.001; 5.00 ± 2.45 vs 0.36 ± 0.79, P < 0.001; 4.10 ± 2.23 vs 0.36 ± 0.79, P < 0.001, respectively). Early satiety intensity-frequency score was prominent in anorectic patients compared to bulimic patients (3.85 ± 2.23 vs 1.17 ± 1.83, P = 0.015), obese patients (3.85 ± 2.23 vs 0.00 ± 0.00, P < 0.001) and healthy volunteers (3.85 ± 2.23 vs 0.05 ± 0.21, P < 0.001). Nausea and epigastric pressure were increased in bulimic and ED not otherwise specified patients. Specifically, nausea intensity-frequency-score was significantly higher in bulimia nervosa and ED not otherwise specified patients compared to anorectic patients (3.17 ± 2.56 vs 0.89 ± 1.66, P = 0.04; 2.70 ± 2.91 vs 0.89 ± 1.66, P = 0.05, respectively), constitutional thinner subjects (3.17 ± 2.56 vs 0.00 ± 0.00, P = 0.004; 2.70 ± 2.91 vs 0.00 ± 0.00, P = 0.005, respectively), obese patients (3.17 ± 2.56 vs 0.00 ± 0.00, P < 0.001; 3.17 ± 2.56 vs 0.00 ± 0.00, P < 0.001 respectively) and, healthy volunteers (3.17 ± 2.56 vs 0.17 ± 0.71, P = 0.002; 3.17 ± 2.56 vs 0.17 ± 0.71, P = 0.001, respectively). Epigastric pressure intensity-frequency score was significantly higher in bulimic and ED not otherwise specified patients compared to constitutional thin subjects (4.67 ± 2.42 vs 1.22 ± 1.72, P = 0.03; 4.20 ± 2.21 vs 1.22 ± 1.72, P = 0.03, respectively), obese patients (4.67 ± 2.42 vs 0.75 ± 1.32, P = 0.001; 4.20 ± 2.21 vs 0.75 ± 1.32, P < 0.001, respectively) and, healthy volunteers (4.67 ± 2.42 vs 0.67 ± 1.46, P = 0.001; 4.20 ± 2.21 vs 0.67 ± 1.46, P = 0.001, respectively). Vomiting was referred in 100% of bulimia nervosa patients, in 20% of ED not otherwise specified patients, in 15% of anorexia nervosa patients, in 22% of constitutional thinner subjects, and, in 5.6% healthy volunteers (χ², P < 0.001).CONCLUSION: PDS is common in eating disorders. Is it mandatory in outpatient gastroenterological clinics to investigate eating disorders in patients with PDS?     

Health-related quality of life of 256 recipients after liver transplantation

AIM:To investigate health-related quality of life(HRQoL) and psychological outcomes in 256 adults who had undergone liver transplantation(LT).METHODS:A stratified random sampling method was used in this follow-up multicenter study to select a representative sample of recipients undergoing either living donor liver transplantation(LDLT) or deceased donor liver transplantation(DDLT).HRQoL was measured by using the Chinese version of Medical Outcome Study Short Form-36(SF-36),and psychological outcomes by using the beck anxiety inventory(BAI) and the self-rating depression scale(SDS).Clinical and demographic data were collected from the records of the Chinese Liver Transplant Registry and via questionnaires.RESULTS:A total of 256 patients were sampled,including 66(25.8%) receiving LDLT and 190(74.2%) undergoing DDLT;15(5.9%) recipients had anxiety and four(1.6%) developed severe depression after the operation.Compared with LDLT recipients,DDLT patients had higher scores in general health(60.33 ± 16.97 vs 66.86 ± 18.42,P = 0.012),role-physical(63.64 ± 42.55 vs 74.47 ± 36.46,P = 0.048),roleemotional(61.11 ± 44.37 vs 78.95 ± 34.31,P = 0.001),social functioning(78.60 ± 22.76 vs 88.16 ± 21.85,P = 0.003),vitality(70.30 ± 15.76 vs 75.95 ± 16.40,P = 0.016),mental health(65.88 ± 12.94 vs 71.85 ± 15.45,P = 0.005),physical component summary scale(PCS,60.07 ± 7.36 vs 62.58 ± 6.88,P = 0.013) and mental component summary scale(MCS,52.65 ± 7.66 vs 55.95 ± 10.14,P = 0.016).Recipients 45 years old at the time of transplant scored higher in vitality(77.33 ± 15.64 vs 72.52 ± 16.66,P = 0.020),mental health(73.64 ± 15.06 vs 68.00 ± 14.65,P = 0.003) and MCS(56.61 ± 10.00 vs 54.05 ± 9.30,P = 0.037) than those aged ≤ 45 years.MCS was poorer in recipients with than in those without complications(52.92 ± 12.21 vs 56.06 ± 8.16,P = 0.017).Regarding MCS(55.10 ± 9.66 vs 50.0 ± 10.0,P 0.05) and PCS(61.93 ± 7.08 vs 50.0 ± 10.0,P 0.05),recipients scored better than the Sichuan general and had improved overall QoL compared to patients with chronic diseases.MCS and PCS significantly correlated with scores of the BAI(P 0.001) and the SDS(P 0.001).CONCLUSION:Age 45 years at time of transplant,DDLT,full-time working,no complications,anxiety and depression were possible factors influencing postoperative HRQoL in liver recipients.     

Clinical course of sub-centimeter-sized nodules detected during surveillance for hepatocellular carcinoma

AIM: To evaluate the outcome of sub-centimeter-sized nodules (SCSNs) detected during surveillance for hepatocellular carcinoma (HCC) in patients at risk.METHODS: We retrospectively analyzed a total of 142 patients with liver cirrhosis or chronic hepatitis B or C without a prior history of HCC in whom a SCSN was detected during HCC surveillance. We calculated the rate of HCC development from SCSNs in the study population and analyzed the differences in the baseline clinical characteristics and imaging features between the patients with SCSNs that eventually developed into HCC and patients with SCSNs that did not develop into HCC.RESULTS: During 667 person-years of follow-up, HCC developed in 33 patients. The calculated HCC development rate was 4.9% per year. The cumulative one-, two-, three- and five-year HCC development rates were 5.6%, 10.6%, 14.1% and 20.4%, respectively. Upon baseline comparison, the HCC group was older (54.4 ± 8.3 years vs 48.9 ± 9.4 years; P = 0.003) and had lower albumin levels (3.56 ± 0.58 g/dL vs 3.84 ± 0.55 g/dL; P = 0.012) and higher baseline alpha-fetoprotein (AFP) levels (8.5 ng/mL vs 5.4 ng/mL; P = 0.035) compared to the non-HCC group. Nodule pattern and initial radiologic diagnosis also differed between the two groups. Multivariate analysis revealed that age [P = 0.012, odds ratio (OR) =1.075, 95% confidence interval (CI) =1.016-1.137], sex (P = 0.009, OR = 3.969, 95% CI: 1.403-11.226), and baseline AFP level (P = 0.024, OR = 1.039, 95% CI: 1.005-1.073) were independent risk factors for developing HCC.CONCLUSION: The overall risk of HCC development in patients with SCSNs is similar to that in liver cirrhosis patients. Patients with these risk factors need to be closely monitored during follow-up.     

Serum zonulin levels in patients with liver cirrhosis: Prognostic implications

BACKGROUND Increased gut permeability and bacterial translocation play an important role in liver cirrhosis. Zonulin is a recently recognized protein involved in the disintegration of the intestinal barrier.AIM To investigate possible differences in serum zonulin levels among patients with different cirrhosis stages and their potential prognostic implications.METHODS Consecutive cirrhotic patients who attended our liver clinic were included in the study. Serum zonulin levels, clinical, radiological and biochemical data were collected at baseline. Patients who accepted participation in a regular surveillance program were followed-up for at least 12 mo.RESULTS We enrolled 116 cirrhotics [mean Child-Turcotte-Pugh(CTP) score: 6.2 ± 1.6;model for end-stage liver disease score: 11 ± 3.9]. The causes of cirrhosis were viral hepatitis(39%), alcohol(30%), non-alcoholic fatty liver disease(17%), and other(14%). At baseline, 53% had decompensated cirrhosis, 48% had ascites, and 32% had history of hepatic encephalopathy. Mean zonulin levels were significantly higher in patients with CTP-B class than CTP-A class(4.2 ± 2.4 ng/dL vs 3.5 ± 0.9 ng/dL, P = 0.038), with than without ascites(P = 0.006), and with than without history of encephalopathy(P = 0.011). Baseline serum zonulin levels were independently associated with the probability of decompensation at 1 year(P = 0.039), with an area under the receiving operating characteristic of 0.723 for predicting hepatic decompensation. Higher CTP score(P = 0.021) and portal vein diameter(P = 0.022) were independent predictors of mortality.CONCLUSION Serum zonulin levels are higher in patients with more advanced chronic liver disease and have significant prognostic value in identifying patients who will develop decompensation.     

Antiviral drug resistance increases hepatocellular carcinoma: A prospective decompensated cirrhosis cohort study

AIM:To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients.METHODS:Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort.With two years of follow-up,198patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed.RESULTS:Among the antiviral treatment patients,162had a complete virological response(CVR),and 36 were drug-resistant(DR).The two-year cumulative incidence of hepatocellular carcinoma(HCC)in the DR patients(30.6%)was significantly higher than that in both the CVR patients(4.3%)and the control group(10.3%)(P<0.001).Among the DR patients in particular,the incidence of HCC was 55.6%(5/9)in those who failed rescue therapy,which was extremely high.The rtA181T mutation was closely associated with rescue therapy failure(P=0.006).The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline(8.9±2.3 vs 6.0±1.3,P=0.043).CONCLUSION:This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients,especially in those who failed rescue therapy.     

Clinical efficacy of antiviral therapy in patients with hepatitis B-related cirrhosis after transjugular intrahepatic portosystemic shunt

BACKGROUNDAs a country with a high burden of hepatitis B, China has about 86 million cases of hepatitis B virus infection, ranking the first in the world. Currently, there are about 390000 deaths due to hepatitis B-related complications such as liver cirrhosis and liver cancer every year. Consequently, how to control portal hypertension, improve liver functional reserve, and reduce the incidence of hepatic failure and liver cancer in such patients is the focus of current clinical attention. Previous clinical study in our center suggested that at 24 mo after transjugular intrahepatic portosystemic shunt (TIPS), the liver functional reserve of patients with hepatitis B cirrhosis was better than that of patients with alcohol-induced and immune cirrhosis, which may be related to the effective etiological treatment.AIMTo investigate the clinical efficacy of three first-line antiviral drugs recommended by the guidelines of prevention and treatment for chronic hepatitis B in China (2019) in the treatment of patients with hepatitis B-related cirrhosis who had received a TIPS.METHODSThe clinical data of 137 patients with hepatitis B-related cirrhosis with portal hypertension after receiving TIPS at our centre between March 2016 and December 2020 were analysed retrospectively. According to different anti-viral drugs, the patients were divided into entecavir (ETV) (n = 70), tenofovir alafenamide fumarate (TAF) (n = 32), and tenofovir disoproxil fumarate (TDF) (n = 35) groups. The cumulative incidence of hepatic encephalopathy and hepatocellular carcinoma, survival, and changes in hepatic reserve function and glomerular filtration rate in patients treated with different antiviral drugs within 24 mo after surgery were investigated.RESULTSAt 24 mo after surgery, the Child–Pugh score in the TAF group (6.97 ± 0.86) was lower than that in the TDF (7.49 ± 0.82; t = -2.52, P = 0.014) and ETV groups (7.64 ± 1.17; t = -2.92, P = 0.004). The model for end-stage liver disease score in the TAF group at 24 mo after surgery was 9.72 ± 1.5, which was lower than that in the TDF (10.74 ± 2.33; t = -2.09, P = 0.040) and ETV groups (10.97 ± 2.17; t = -2.93, P = 0.004). At 24 mo after surgery, the estimated glomerular filtration rate (eGFR) in the TAF group (104.41 ± 12.54) was higher than that in the TDF (93.54 ± 8.97) and ETV groups (89.96 ± 9.86) (F = 21.57, P < 0.001).CONCLUSIONAt 24 mo after surgery, compared with TDF and ETV, TAF has significant advantages in the improvement of liver functional reserve and eGFR.     

Fluctuations in butyrate-producing bacteria in ulcerative colitis patients of North India

AIM: To study the interplay between butyrate concentration and butyrate-producing bacteria in fecal samples of ulcerative colitis (UC) patients vs control individuals. METHODS: Fecal samples were collected from 14 control individuals (hemorrhoid patients only) and 26 UC patients (severe: n = 12, moderate: n = 6, remission: n = 8), recruited by the gastroenterologist at the Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India. Disease activity in UC patients was determined by clinical colitis activity index. We employed fluorescent in situ hybridization in combination with flow cytometry to enumerate the clostridium cluster population targeted by 16S rRNA gene probe. Major butyrate-producing species within this cluster were quantified to see if any change existed in control vs UC patients with different disease activity. This observed change was further validated by quantitative polymerase chain reaction. In addition to this,we carried out gas chromatography to evaluate the changes in concentration of major short chain fatty acids (SCFAs), namely acetate, n -butyrate, iso -butyrate, in the above samples. Student t test and Graph pad prism-6 were used to compare the data statistically. RESULTS: There was a significant decrease of Clostridium coccoides (control, 25.69% ± 1.62% vs severe, 9.8% ± 2.4%, P = 0.0001) and Clostridium leptum clusters (control, 13.74% ± 1.05% vs severe, 6.2% ± 1.8%, P = 0.0001) in fecal samples of UC patients. Furthermore, we demonstrated that some butyrateproducing members of the clostridial cluster, like Fecalibacterium prausnitzii (control, 11.66% ± 1.55% vs severe, 6.01% ± 1.6%, P = 0.0001) and Roseburia intestinalis (control, 14.48% ± 1.52% vs severe, 9% ± 1.83%, P = 0.02) were differentially present in patients with different disease activity. In addition, we also demonstrated decreased concentrations of fecal SCFAs, especially of n -butyrate (control, 24.32 ± 1.86 mmol/μL vs severe, 12.74 ± 2.75 mmol/μL, P = 0.003), iso -butyrate (con     

Outcomes of autologous bone marrow mononuclear cell transplantation in decompensated liver cirrhosis

AIM: To determine the long-term efficacy of autologous bone marrow mononuclear cells (BM-MNCs) transplantation in terms of improving liver function and reducing complications in patients with decompensated cirrhosis.METHODS: A total of 47 inpatients with decompensated liver cirrhosis were enrolled in this trial, including 32 patients undergoing a single BM-MNCs transplantation plus routine medical treatment, and 15 patients receiving medical treatment only as controls. Forty-three of 47 patients were infected with hepatitis B virus. Bone marrow of 80-100 mL was obtained from each patient and the BM-MNCs suspension was transfused into the liver via the hepatic artery. The efficacy of BM-MNCs transplantation was monitored during a 24-mo follow-up period.RESULTS: Liver function parameters in the two groups were observed at 1 mo after BM-MNCs transfusion. Prealbumin level was 118.3 ± 25.3 mg/L vs 101.4 ± 28.7 mg/L (P = 0.047); albumin level was 33.5 ± 3.6 g/L vs 30.3 ± 2.2 g/L (P = 0.002); total bilirubin 36.9 ± 9.7 mmol/L vs 45.6 ± 19.9 mmol/L (P = 0.048); prothrombin time 14.4 ± 2.3 s vs 15.9 ± 2.8 s (P = 0.046); prothrombin activity 84.3% ± 14.3% vs 74.4% ± 17.8% (P = 0.046); fibrinogen 2.28 ± 0.53 g/L vs 1.89 ± 0.44 g/L (P = 0.017); and platelet count 74.5 ± 15.7 × 10⁹/L vs 63.3 ± 15.7 × 10⁹/L (P = 0.027) in the treatment group and control group, respectively. Differences were statistically significant. The efficacy of BM-MNCs transplantation lasted 3-12 mo as compared with the control group. Serious complications such as hepatic encephalopathy and spontaneous bacterial peritonitis were also significantly reduced in BM-MNCs transfused patients compared with the controls. However, these improvements disappeared 24 mo after transplantation.CONCLUSION: BM-MNCs transplantation is safe and effective in patients with decompensated cirrhosis. It also decreases the incidence of serious complications.     

Colchicine reduces procollagen III and increases pseudocholinesterase in chronic liver disease

AIM: To test whether colchicine would be an effective antifibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon.METHODS: Seventy-four patients (46 males, 28 females) aged 40-66 years (mean 53 ± 13 years) participated in the study. The patients were affected by chronic liver diseases with cirrhosis which was proven histologically (n = 58); by chronic active hepatitis C (n = 4), chronic active hepatitis B (n = 2), and chronic persistent hepatitis C (n = 6). In the four patients lacking histology, cirrhosis was diagnosed from anamnesis, serum laboratory tests, esophageal varices and ascites. Patients were assigned to colchicine (1 mg/d) or standard treatment as control in a randomized, double-blind trial, and followed for 4.4 years with clinical and laboratory evaluation.RESULTS: Survival at the end of the study was 94.6% in the colchicine group and 78.4% in the control group (P = 0.001). Serum N-terminal peptide of type III procollagen levels fell from 34.0 to 18.3 ng/mL (P = 0.0001), and pseudocholinesterase levels rose from 4.900 to 5.610 mU/mL (P = 0.0001) in the colchicine group, while no significant change was seen in controls. Best results were obtained in patients with chronic hepatitis C and in alcoholic cirrhotics.CONCLUSION: Colchicine is an effective and safe antifibrotic drug for long-term treatment of chronic liver disease in which fibrosis progresses towards cirrhosis.     

High level of serum cholesteryl ester transfer protein in active hepatitis C virus infection

AIM: To determine the significance of cholesteryl ester transfer protein(CETP) in lipoprotein abnormalities in chronic hepatitis C virus(HCV) infection.METHODS: We evaluated the significance of the serum concentration of CETP in 110 Japanese patients with chronic HCV infection. Fifty-five patients had active HCV infection, and HCV eradication had been achieved in 55. The role of CETP in serum lipoprotein abnormalities, specifically, in triglyceride(TG) concentrations in the four major classes of lipoproteins, was investigated using Pearson correlations in conjunction with multiple regression analysis and compared them between those with active HCV infection and those in whom eradication had been achieved. RESULTS: The serum CETP levels of patients with active HCV infection were significantly higher than those of patients in whom HCV eradication was achieved(mean ± SD, 2.84 ± 0.69 μg/m L vs 2.40 ± 1.00 μg/m L, P = 0.008). In multiple regression analysis, HCV infection status(active or eradicated) was an independent factor significantly associated with the serum CETP level. TG concentrations in low-density lipoprotein(mean ± SD, 36.25 ± 15.28 μg/m L vs 28.14 ± 9.94 μg/m L, P = 0.001) and high-density lipoprotein(HDL)(mean ± SD, 25.9 ± 7.34 μg/m L vs 17.17 ± 4.82 μg/m L, P 0.001) were significantly higher in patientswith active HCV infection than in those in whom HCV eradication was achieved. The CETP level was strongly correlated with HDL-TG in patients with active HCV infection(R = 0.557, P 0.001), whereas CETP was not correlated with HDL-TG in patients in whom HCV eradication was achieved(R =-0.079, P = 0.56). CONCLUSION: Our results indicate that CETP plays a role in abnormalities of lipoprotein metabolism in patients with chronic HCV infection.