Fatty liver index vs waist circumference for predicting non-alcoholic fatty liver disease

AIM: To determine the discriminatory performance of fatty liver index (FLI) for non-alcoholic fatty liver disease (NAFLD).METHODS: The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from body mass index, waist circumference (WC), triglyceride, and gamma glutamyl transferase data. Logistic regression analysis was conducted to determine the association between FLI and NAFLD. The discriminatory performance of FLI in the diagnosis of NAFLD was evaluated by receiver operating characteristic analysis. Area under the curves (AUCs) and related confidence intervals were estimated. Optimal cutoff points of FLI in the diagnosis of NAFLD were determined based on the maximum values of Youden’s index.RESULTS: The mean age of men and women in the study population were 44.8 ± 16.8 and 43.78 ± 15.43, respectively (P = 0.0216). The prevalence of NAFLD was 40.1% in men and 44.2% in women (P < 0.0017). FLI was strongly associated with NAFLD, so that even a one unit increase in FLI increased the chance of developing NAFLD by 5.8% (OR = 1.058, 95%CI: 1.054-1.063, P < 0.0001). Although FLI showed good performance in the diagnosis of NAFLD (AUC = 0.8656 (95%CI: 0.8548-0.8764), there was no significant difference with regards to WC (AUC = 0.8533, 95%CI: 0.8419-0.8646). The performance of FLI was not significantly different between men (AUC = 0.8648, 95%CI: 0.8505-0.8791) and women (AUC = 0.8682, 95%CI: 0.8513-0.8851). The highest performance with regards to age was related to the 18-39 age group (AUC = 0.8930, 95%CI: 0.8766-0.9093). The optimal cutoff points of FLI were 46.9 in men (sensitivity = 0.8242, specificity = 0.7687, Youden’s index = 0.5929) and 53.8 in women (sensitivity = 0.8233, specificity = 0.7655, Youden’s index = 0.5888).CONCLUSION: Although FLI had acceptable discriminatory power in the diagnosis of NAFLD, WC was a simpler and more accessible index with a similar performance.

Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification

AIM:To compare noninvasive methods presently used for steatosis detection and quantification in nonalcoholic fatty liver disease(NAFLD).METHODS:Cross-sectional study of subjects from the general population,a subgroup from the First Israeli National Health Survey,without excessive alcohol consumption or viral hepatitis.All subjects underwent anthropometric measurements and fasting blood tests.Evaluation of liver fat was performed using four noninvasive methods:the SteatoTest;the fatty liver index(FLI);regular abdominal ultrasound(AUS);and the hepatorenal ultrasound index(HRI).Two of the noninvasive methods have been validated vs liver biopsy and were considered as the reference methods:the HRI,the ratio between the median brightness level of the liver and right kidney cortex;and the SteatoTest,a biochemical surrogate marker of liver steatosis.The FLI is calculated by an algorithm based on triglycerides,body mass index,γ-glutamyl-transpeptidase and waist circumference,that has been validated only vs AUS.FLI < 30 rules out and FLI ≥ 60 rules in fatty liver.RESULTS:Three hundred and thirty-eight volunteers met the inclusion and exclusion criteria and had valid tests.The prevalence rate of NAFLD was 31.1% according to AUS.The FLI was very strongly correlated with SteatoTest(r = 0.91,P < 0.001) and to a lesser but significant degree with HRI(r = 0.55,P < 0.001).HRI and SteatoTest were significantly correlated(r = 0.52,P < 0.001).The κ between diagnosis of fatty liver by SteatoTest(≥ S2) and by FLI(≥ 60) was 0.74,which represented good agreement.The sensitivity of FLI vs SteatoTest was 85.5%,specificity 92.6%,positive predictive value(PPV) 74.7%,and negative predictive value(NPV) 96.1%.Most subjects(84.2%) with FLI < 60 had S0 and none had S3-S4.The κ between diagnosis of fatty liver by HRI(≥ 1.5) and by FLI(≥ 60) was 0.43,which represented only moderate agreement.The sensitivity of FLI vs HRI was 56.3%,specificity 86.5%,PPV 57.0%,and NPV 86.1%.The diagnostic accuracy of FLI for steatosis > 5%,as predicted by SteatoTest,yielded an area under the receiver operating characteristic curve(AUROC) of 0.97(95% CI:0.95-0.98).The diagnostic accuracy of FLI for steatosis> 5%,as predicted by HRI,yielded an AUROC of 0.82(95% CI:0.77-0.87).The κ between diagnosis of fatty liver by AUS and by FLI(≥ 60) was 0.48 for the entire sample.However,after exclusion of all subjects with an intermediate FLI score of 30-60,the κ between diagnosis of fatty liver by AUS and by FLI either ≥ 60 or < 30 was 0.65,representing good agreement.Excluding all the subjects with an intermediate FLI score,the sensitivity of FLI was 80.3% and the specificity 87.3%.Only 8.5% of those with FLI < 30 had fatty liver on AUS,but 27.8% of those with FLI ≥ 60 had normal liver on AUS.CONCLUSION:FLI has striking agreement with SteatoTest and moderate agreements with AUS or HRI.However,if intermediate values are excluded FLI has high diagnostic value vs AUS.

Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus infection.Methods:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),respectively.In addition,the HSI was less predictive for Fibroscan®-defined fatty liver.Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and FLI.Conclusions:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty liver.In addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

Impact of national Human Development Index on liver cancer outcomes: Transition from 2008 to 2018

BACKGROUND Liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide.Socioeconomic development,indicated by the Human Development Index(HDI),is closely interconnected with public health.But the manner in which social development and medical advances influenced liver cancer patients in the past decade is still unknown.AIM To investigate the influence of HDI on clinical outcomes for patients with existing liver cancer from 2008 to 2018.METHODS The HDI values were obtained from the United Nations Development Programme,the age-standardized incidence and mortality rates of liver cancer were obtained from the GLOBOCAN database to calculate the mortality-toincidence ratio,and the estimated 5-year net survival of patients with liver cancer was provided by the CONCORD-3 program.We then explored the association of mortality-to-incidence ratio and survival with HDI,with a focus on geographic variability across countries as well as temporal heterogeneity over the past decade.RESULTS From 2008 to 2018,the epidemiology of liver cancer had changed across countries.Liver cancer mortality-to-incidence ratios were negatively correlated and showed good fit with a modified“dose-to-inhibition response”pattern with HDI(r=-0.548,P<0.0001 for 2018;r=-0.617,P<0.0001 for 2008).Cancer survival was positively associated with HDI(r=0.408,P<0.01)and negatively associated with mortality-to-incidence ratio(r=-0.346,P<0.05),solidly confirming the interrelation among liver cancer outcome indicators and socioeconomic factors.Notably,in the past decade,the HDI values in most countries have increased alongside a decreasing tendency of liver cancer mortality-to-incidence ratios(P<0.0001),and survival outcomes have simultaneously improved(P<0.001),with significant disparities across countries.CONCLUSION Socioeconomic factors have a significant influence on cancer outcomes.HDI values have increased along with improved cancer outcomes,with significant disparities among countries.

Role of cystatin C and renal resistive index in assessment of renal function in patients with liver cirrhosis

AIM:To evaluate the clinical significance of cystatin C and renal resistive index for the determination of renal function in patients with liver cirrhosis.METHODS:We conducted a study of 63 patients with liver cirrhosis.A control group comprised of 30 age and gender-matched healthy persons.Serum cystatin C was determined in all study subjects and renal Doppler ultrasonography was made.Estimated glomerular filtration rate from serum creatinine(GFRCr)and cystatin C(GFRCys)was calculated.RESULTS:We confirmed significant differences in val-ues of cystatin C between patients with different stages of liver cirrhosis according to Child-Pugh(P=0.01),and a significant correlation with model of end stage liver disease(MELD)score(rs=0.527,P<0.001).More patients with decreased glomerular filtration rate were identified based on GFRCys than on GFRCr(P<0.001).Significantly higher renal resistive index was noted in Child-Pugh C than in A(P<0.001)and B stage(P=0.001).Also,a significant correlation between renal resistive index and MELD score was observed(rs=0.607,P<0.001).Renal resistive index correlated significantly with cystatin C(rs=0.283,P=0.028)and showed a negative correlation with GFRCys(rs=-0.31,P=0.016).CONCLUSION:Cystatin C may be a more reliable marker for assessment of liver insufficiency.Additionally,cystatin C and renal resistive index represent sensitive indicators of renal dysfunction in patients with liver cirrhosis.

Benefit of laparoscopic liver resection in high body mass index patients

AIM: To explore the impact of body mass index(BMI) on surgical outcomes in patients undergoing laparoscopic liver resection(LLR).METHODS: From January 2010 to February 2015, sixty-eight patients who underwent primary partial liver resection in our institute were retrospectively reviewed. Surgical outcomes of LLR were compared with those of open liver resection(OLR). In addition, we analyzed associations with BMI and surgical outcomes.RESULTS: Among 68 patients, thirty-nine patients underwent LLR and 29 were performed OLR. Significant difference in operation time, blood loss, and postoperative hospital stay was observed. There were no signi ficant di fferences in mortali ty and morbidity in two groups. Twenty-two patients(32.4%) were classified as obese(BMI ≥ 25). A statistically significant correlation was observed between BMI and operation time, between BMI and blood loss in OLR, but not in LLR. The operation time and blood loss of OLR were significantly higher than that of LLR in obese patients. Open liver resection and BMI were independent predictors for prolonged operation time and increased blood loss in multivariate analysis.CONCLUSION: The present study demonstrated that BMI had influenced to surgical outcomes of OLR. LLR was less influenced by BMI and had great benefit in obese patients.

Body mass index and its effects on liver fat content in overweight and obese young adults by proton magnetic resonance spectroscopy technique

AIM To assess the association between liver fat content(LFC) and weight status in young adults using proton magnetic resonance spectroscopy(1H MRS) technique.METHODSSeventy-eight healthy young adults, between 19-30 years of age participated in this study. This group was then separated into a control of 39 subjects and an overweight/obese group(OW/OB group) consisting of 39 subjects. Blood biochemical quantity and 1 H MRS was performed for LFC assessment.RESULTS LFC was found to be almost three times higher in OW/OB group when compared to the control group. A 48.7% incidence of non-alcoholic fatty liver disease in the OW/OB group was found. Blood biochemical measurements showed statistically higher low-density lipoproteins and triglyceride, lower highdensity lipoproteins, and increased glycosylated hemoglobin and fasting glucose in the OW/OB group. Body mass index was a significant independent predictor for LFC after adjusting for age and sex(multiple linear regression; β = 0.459, P <0.001).CONCLUSION Due to the prevalence of high LFC in the OW/OB group, it can be proposed that weight gain and obesity are sensitive indicators of high hepatic fat content.

A new index for non-invasive assessment of liver fibrosis

AIM:To construct and evaluate a new non-invasive fibrosis index for assessment of the stage of liver f ibrosis. METHODS:A new f ibrosis index (Fibro-Stiffness index) was developed in 165 of 285 patients with chronic hepatitis C, and was validated in the other 120 patients where liver biopsy was performed. Its usefulness was compared with liver stiffness (LS) measured by FibroScan, the aminotransferase-to-platelet ratio index, the Forns index and the FibroIndex. RESULTS: The Fibro-Stiffness index consists of LS,platelet count and prothrombin time. The values of the Fibro-Stiffness index differed signif icantly between neighboring f ibrosis stages except F0-F1. The area under the receiver operating characteristics curves of the Fibro-Stiffness index for prediction of F≥2 (0.90), F≥ 3 (0.90) and F= 4(0.92) in the estimation group and those for F≥ 3 (0.93) and F =4 (0.97) in the validation group were the highest among the 5 methods examined. The accuracy of the Fibro-Stiffness index had highest values for F≥2, F≥3 and F=4 in both the estimation and validation groups. The diagnostic performance for F= 4 was improved by a combination of the Fibro-Stiffness index with serum hyaluronic acid level. CONCLUSION: The Fibro-Stiffness index was constructed and validated. It showed superior diagnostic performance to other indices for F ≥ 2,3 and 4.

Comparison of Entropy vs. Bispectral Index Anesthetic Depth Monitoring during Isoflurane Anesthesia in Living Donor Liver Transplantation: Observational Study

Liver transplantation (LT) recipients are known to require less anesthetic agents. Providing minimally required anesthetics while avoiding awareness is especially important in LT recipients because it would help manage perioperative hemodynamic instability with less vasopressor and fast track recovery. This study aims to compare state entropy (SE) against bispectral index (BIS) during isoflurane anesthesia in LT. We adjusted anesthesia to BIS values 40 - 60, and compared it with concomitant SE values. BIS, SE values, and anesthetic requirements according to liver failure severity, etiology and LT stages were analyzed. For BIS-SE differences, SE value that is different from the concomitant BIS by more than 15 was defined as a significant disagreement. Mann Whitney, Kruskal Wallis test and a Poisson exact test were used for analysis. The BIS-SE pair sets of 2895 from 38 patients were analyzed. BIS, SE values and anesthetic requirements were significantly lower in MELD ≥ 20 (p < 0.001 in all) and in alcoholic etiology (p < 0.001 in all). For BIS-SE differences, 320 disagreement data pairs were seen at a rate of 1.33 times/hr (95% CI = [1.19, 1.48], p < 0.001). A significant disagreement was delineated in MELD score ≥ 20 (3.04 times/hr, CI = [2.64, 3.49], p < 0.001), alcoholic etiology (3.19 times/hr, [2.67, 3.78], p < 0.001) and postreperfusion stage (1.63 times/hr, [1.43, 1.85], p < 0.001). In these significant BIS-SE differences, 95.9% (307/320 disagreement data pairs) showed higher BIS than SE. In conclusion, in high MELD and alcoholic etiology, anesthetic requirements were significantly less, and BIS and SE showed great discrepancy with lower SE values. Therefore, when SE monitoring is used during LT, anesthesiologists may need to consider that in high MELD and alcoholic etiology, SE tends to show lower values than the concomitant BIS values that are within optimal anesthetic depth ranges.

Impact of body mass index on outcomes of 48281 patients undergoing first time cadaveric liver transplantation

AIM: To investigate possible disparities in perioperative morbidity and mortality among different body mass index(BMI) groups and to simulate the impact that these differences might have had on the cohort of patients undergoing cadaveric liver transplantation(LT).METHODS: All adult recipients undergoing first time LT for benign conditions and receiving a whole graft from brain-dead donors were selected from the united network of organ sharing registry. From January 1994 to June 2013, 48281 patients satisfied the inclusion criteria and were stratified by their BMI. The hypothesis that abnormal BMIs were independent predictors of inferior outcomes was tested with univariate and multivariate regression analyses.RESULTS: In comparison to normal weight recipients, underweight and morbidly obese recipients had increased 90-d mortality(adjusted OR = 1.737; 95%CI: 1.185-2.548, P = 0.005)(adjusted OR = 1.956; 95%CI: 1.473-2.597, P = 0.000) respectively and inferior patients' survivals(adjusted HR = 1.265; 95%CI: 1.096-1.461, P = 0.000)(adjusted HR = 1.157; 95%CI: 1.031-1.299, P = 0.013) respectively. Overall, patients' 5-year survival were 73.9% for normal-weight, 71.1% for underweight, 74.0% for overweight, 74.4% for class Ⅰ obese, 75.0% for class Ⅱ obese and 71.5% for class Ⅲ obese recipients. Analysis of hypothetical exclusion of underweight and morbidly obese patients from the pool of potential LT candidates would have improved the overall survival of the entire cohort by2.7%(95%CI: 2.5%-3.6%).CONCLUSION: Selected morbidly obese patients undergoing LT for benign conditions had 5-year survival rates clinically comparable to normal weight recipients. Impact analysis showed that exclusion of high-risk recipients(underweight and morbid obese patients) would not significantly improve the overall survival of the entire cohort of patients requiring LT.

A Review on the Role of Low Glycemic Index Foods for Glycemic Control in Chronic Liver Disease

Liver is an essential organ that maintains fasting and postprandial blood glucose response via various metabolic pathways. The liver function gradually deteriorates in chronic liver disease (CLD) due to inflammation and destruction of liver parenchyma. The development of glucose intolerance and hepatogenous diabetes (HD) in patients with CLD is an inevitable event. Diabetes and CLD can coexist, and function synergistically to cause unfavorable clinical consequences, including poor treatment outcomes and frequent hospitalization. The complications associated with liver disease (malnutrition, hypoglycemia, acute kidney injury, lactic acidosis, etc.) and lack of guidelines limit pharmacological management of HD. Dietary recommendations by The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines (2019), suggested weight reducing hypocaloric diet along with adequate branched-chain amino acid (BCAA) and micronutrient consumption to improve steatosis and insulin sensitivity in patients with CLD. Dietary glycemic index controls prognosis of obesity, non-alcoholic fatty liver disease (NAFLD) and diabetes. The importance of low GI diet in reducing fasting blood glucose, hepatic glucose influx and fat accumulation, thereby improving weight loss and NAFLD score, is being published in patients with diabetes or liver disease. Several countries have already incorporated GI into their national health policies, for identification of the nutrient value, resulting in establishment of worldwide GI and glycemic load tables for specific food items. However, the apparent complexity of GI and lack of low GI meal choices need to be resolved in order to enhance patient’s quality of life, health and well-being. Low GI nutritional supplements, comprising of balanced proportion of carbohydrate, protein, BCAAs, fibers and micronutrients, may reduce the complexity related to dietary management of HD. The review summarizes the importance of nutritional management in HD with focus on low GI diet in people with CLD.

Triglyceride and Glucose Index (TyG) is a Reliable Biomarker to Predict Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease worldwide. There is no specific biomarker for the diagnosis of NAFLD. Trigly-ceride and glucose index (TyG) may predict the subsequent occurrence of NAFLD in later life. This cross sectional study was aimed to evaluate the effectiveness of triglyceride and glucose index (TyG) as a possible biomarker of NAFLD. The study was conducted at the Department of Laboratory Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from March 2019 to February 2020. A total of 124 subjects were taken as study population following selection criteria. Among them 62 were diagnosed patients of NAFLD and 62 were healthy subjects as control group. Fasting plasma glucose was measured by glucose oxidase method and serum triglyceride was measured by enzymatic-colorimetric method, while TyG index was calculated accordingly. The mean age was 39.5 ± 11.27 years in NAFLD patients and 37.10 ± 12.28 years in control subjects with male female ratio 1:1.7 and 1:1.8 respectively. Major portion of NAFLD patients (62.9%) were overweight (BMI ≥ 25). The mean fasting plasma glucose level was 5.73 ± 1.47 mmol/L in NAFLD patients and 5.27 ± 0.69 mmol/L in control group (p < 0.027). The mean serum triglyceride level was 237.19 ± 96.47 mg/dl in NAFLD patients and 117.32 ± 53.07 mg/dl in control group (p < 0.001). The triglyceride and glucose index (TyG) was 9.36 ± 0.47 in NAFLD group and 8.53 ± 0.42 in control group. TyG index was significantly higher in NAFLD patients in comparison to control group (p < 0.001). In ROC analysis, cut off value of TyG index was 8.85 with sensitivity 93.5% and specificity 79%. As a fast and effective method, TyG index can be used as a diagnostic tool to predict NAFLD.

Ursodeoxycholic acid as a means of preventing atherosclerosis,steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUND Atherosclerotic cardiovascular disease(ASCVD)is the leading cause of mortality in patients with nonalcoholic fatty liver disease(NAFLD).Weight loss is a key factor for successful NAFLD and CVD therapy.Ursodeoxycholic acid(UDCA),which is one of the first-line therapeutic agents for treatment of NAFLD,is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIM To evaluate the effects of 6 mo of UDCA treatment on hepatic function tests,lipid profile,hepatic steatosis and fibrosis,atherogenesis,and ASCVD risk in men and women with NAFLD,as well as to assess the impact of>5%weight reduction on these parameters.METHODS An open-label,multicenter,international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise.The efficacy criteria were liver enzymes,lipid profile,fatty liver index(FLI),noninvasive liver fibrosis tests(nonalcoholic fatty liver disease fibrosis score and liver fibrosis index),carotid intima-media thickness(CIMT),and ASCVD risk score.To test statistical hypotheses,the Wilcoxon test,paired t-test,Fisher’s exact test,and Pearson's chi-squared test were used.RESULTS The alanine aminotransferase(ALT)level changed by-14.1 U/L(-31.0;-5.3)from baseline to 3 mo and by-6.5 U/L(-14.0;0.1)from 3 to 6 mo.The magnitude of ALT,aspartate transaminase,and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo(P<0.001,P<0.01,P<0.001,respectively).At 6 mo,in the total sample,we observed a statistically significant decrease in body weight and levels of FLI:84.9±10.4 vs 72.3±17.6,P<0.001,total cholesterol:6.03±1.36 vs 5.76±1.21,Р<0.001,lowdensity lipoprotein:3.86±1.01 vs 3.66±0.91,Р<0.001,and triglyceride:3.18(2.00;4.29)vs 2.04(1.40;3.16),Р<0.001.No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found.The CIMT decreased significantly in the total sample(0.985±0.243 vs 0.968±0.237,P=0.013),whereas the highdensity lipoprotein(Р=0.036)and 10-year ASCVD risk(Р=0.003)improved significantly only in women.Fifty-four patients(31%)achieved>5%weight loss.At the end of the study,the FLI decreased significantly in patients with(88.3±10.2 vs 71.4±19.6,P<0.001)and without>5%weight loss(83.5±10.3 vs 72.8±16.7,P<0.001).The changes in ALT,aspartate transaminase,glutamyltransferase,total cholesterol,and low-density lipoprotein levels were similar between the subgroups.CONCLUSION UDCA normalizes liver enzymes greatly within the first 3 mo of treatment,improves lipid profile and hepatic steatosis independent of weight loss,and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.

Helicobacter pylori infection is not associated with nonalcoholic fatty liver disease

AIM: To determine whether Helicobacter pylori (H. pylori) infection confers a higher risk of Nonalcoholic fatty liver disease (NAFLD).METHODS: Healthy people who underwent health screening were analyzed retrospectively. Inclusion criteria were age ≥ 20 years, history of H. pylori infection, and recorded insulin level. Participants were classified as H. pylori positive or negative according to 13C urea breath tests. NAFLD was defined using the hepatic steatosis index (HSI) and NAFLD liver fat score (NAFLD-LFS). Those with an HSI > 36 or NAFLD-LFS > -0.640 were considered to have NAFLD. Multivariable logistic regression was performed to identify risk factors for NAFLD.RESULTS: Three thousand six hundred and sixty-three people were analyzed and 1636 (44.7%) were H. pylori positive. H. pylori infection was associated with older age, male gender, hypertension, higher body mass index, and a dyslipidemic profile. HSI differed significantly between H. pylori positive and negative subjects (median 33.2, interquartile range (IQR) 30.0-36.2 for H. pylori-positive vs median 32.6, IQR 29.8-36.0 for negative participants, P = 0.005), but NAFLD-LSF did not [median -1.7, IQR -2.4 - -0.7 vs median -1.8, IQR -2.4-(-0.7), respectively, P = 0.122]. The percentage of people with NAFLD did not differ between infected and uninfected groups: HIS, 26.9% vs 27.1%, P = 0.173; NAFLD-LFS, 23.5% vs 23.1%, P = 0.778. H. pylori infection was not a risk factor, but C-reactive protein concentration and smoking were significant risk factors for NAFLD.CONCLUSION: H. pylori infection is not a risk factor for NAFLD as indicated by HSI or NAFLD-LFS. Prospective, large-scale studies involving liver biopsies should be considered.

Wilson disease developing osteoarthritic pain in severe acute liver failure: A case report

BACKGROUND Wilson disease (WD) is a rare copper metabolism disorder with symptoms including hepatic disorders, neuropsychiatric abnormalities, Kayser-Fleischer rings, and hemolysis in association with acute liver failure (ALF). Osteoarthritis is a rare manifestation of WD. We experienced a case of WD with arthritic pain in the knee and liver cirrhosis. Here, we report the clinical course in a WD patient with arthritic pain and liver cirrhosis receiving combination therapy with Zn and a chelator and discuss the cause of arthritic pain. CASE SUMMARY We present an 11-year-old boy who developed osteoarthritis symptoms and ALF, with a New Wilson Index Score (NWIS) of 12. He was diagnosed with WD with decreased serum ceruloplasmin and copper levels, increased urinary copper excretion, and ATP7B gene mutations detected on gene analysis. There was improvement in the liver cirrhosis, leading to almost normal liver function and liver imaging, one year after receiving combination therapy with Zn and a chelator. Moreover, his arthritic pain transiently deteriorated but eventually improved with a decrease in the blood alkaline phosphatase levels following treatment. CONCLUSION Patients with WD who develop ALF with an NWIS > 11 may survive after treatment with Zn and chelators, without liver transplantation, when they present with mild hyperbilirubinemia and stage ≤ II hepatic encephalopathy. Osteoarthritis symptoms may improve with long-term Zn and chelator therapy without correlation of liver function in WD.

Factors associated with long-term survival after liver transplantation:A retrospective cohort study

AIM To identify predictive factors associated with long-term patient and graft survival(> 15 years) in liver transplant recipients.METHODS Medical charts of all de novo adult liver transplant recipients(n = 140) who were transplanted in Hamburg between 1997 and 1999 were retrospectively reviewed.In total,155 transplantations were identified in this time period(15 re-transplantations).Twenty-six orthotopic liver transplant(OLT) recipients were early lost to followup due to moving to other places within 1 year after transplantation.All remaining 114 patients were included in the analysis.The following recipient factors were analysed:Age,sex,underlying liver disease,pre-OLT body mass index(BMI),and levels of alanine aminotransferase(ALT),bilirubin,creatinine and gammaglutamyltransferase(gamma-GT),as well as warm and cold ischemia times.Furthermore,the following donor factors were assessed:Age,BMI,cold ischemia time and warm ischemia time.All surviving patients were followed until December 2014.We divided patients into groups according to their underlying diagnosis:(1) hepatocellularcarcinoma(n = 5,4%);(2) alcohol toxic liver disease(n = 25,22.0%);(3) primary sclerosing cholangitis(n = 6,5%);(4) autoimmune liver diseases(n = 7,6%);(5) hepatitis C virus cirrhosis(n = 15,13%);(6) hepatitis B virus cirrhosis(n = 21,19%);and(7) other(n = 35,31%).The group "other" included rare diagnoses,such as acute liver failure,unknown liver failure,stenosis and thrombosis of the arteria hepatica,polycystic liver disease,Morbus Osler and Caroli disease.RESULTS The majority of patients were male(n = 70,61%).Age and BMI at the time point of transplantation ranged from 16 years to 69 years(median:53 years) and from 15 kg/m^2 to 33 kg/m^2(median:24),respectively.Sixty-six OLT recipients(58%) experienced a follow-up of 15 years after transplantation.Recipient's age(P = 0.009) and BMI(P = 0.029) were identified as risk factors for death by χ~2-test.Kaplan-Meier analysis confirmed BMI or age above the median as predictors of decreased long-term survival(P = 0.008 and P = 0.020).Hepatitis B as underlying disease showed a trend for improved long-term survival(P = 0.049,χ~2-test,P = 0.055;Kaplan-Meier analysis,Log rank).Pre-transplant bilirubin,creatinine,ALT and gamma-GT levels were not associated with survival in these patients of the pre-era of the model of end stage liver disease.CONCLUSION The recipients' age and BMI were predictors of longterm survival after OLT,as well as hepatitis B as underlying disease.In contrast,donors' age and BMI were not associated with decreased survival.These findings indicate that recipient factors especially have a high impact on long-term outcome after liver transplantation.

Hepatitis C virus clearance and less liver damage in patients with high cholesterol, low-density lipoprotein cholesterol and APOE ε4 allele

BACKGROUND Cholesterol is related to improvements in the rate of sustained virological response and a robust immune response against the hepatitis C virus(HCV).APOE gene polymorphisms regulate cholesterol levels modifying the course of the HCV infection.The relationship between cholesterol,APOE alleles,and the outcome of HCV infection has not been evaluated in the admixed population of Mexico.AIM To investigate the role of APOE-ε2,-ε3,and-ε4 alleles and the metabolic profile in the outcome of HCV infection.METHODS A total of 299 treatment-na?ve HCV patients were included in this retrospective study.Patients were stratified in chronic hepatitis C(CHC)(n=206)and spontaneous clearance(SC)(n=93).A clinical record was registered.Biochemical tests were assessed by dry chemistry assay.APOE genotypes were determined using a Real-Time polymerase chain reaction assay.RESULTS Total cholesterol,low-density lipoprotein cholesterol(LDL-c),triglycerides,and hypercholesterolemia were higher in SC than CHC patients as well as the frequency of the APOEε4 allele(12.4%vs 7.3%).SC patients were overweight(54.8%).Theε4 allele was associated with SC(OR=0.55,95%CI:0.31-0.98,P=0.042)and mild fibrosis(F1-F2)in CHC patients(OR 0.091,95%CI 0.01-0.75,P=0.020).LDL-c≥101.5 mg/dL(OR=0.20,95%CI:0.10-0.41,P<0.001)and BMI≥26.6 kg/m2(OR=0.37,95%CI:0.18-0.76,P<0.001)were associated with SC status;while ALT≥50.5 IU/L was negatively associated(OR=5.67,95%CI:2.69-11.97,P<0.001).CONCLUSION In SC patients,the APOEε4 allele and LDL-c conferred a protective effect in the course of the HCV infection in the context of excess body weight.

Risk assessment of alcohol and obesity on liver enzymes (transaminases, cholestatic)

Background: This study was designed to investigate the BMI and alcohol consumption effects on hepatic enzymes. The degree of alteration among moderate drinkers is still unclear. Objective: To determine causes of liver failure due to alcohol and obesity. We observed the association between moderate alcohol consumption, body mass index (BMI;in kg/m2) and transaminase, cholestatic enzymes. Design: Serum alanine aminotransferase (ALT), alkaline phosphate (ALP), aspartate aminotransferase (AST), and gammaglutamyltransferase (GGT) were examined in 995 healthy persons. In this study 400 persons were reported as abstainers and 595 participants involved as a moderate drinkers. The study population was further split into according to BMI as follows: <19 (underweight), ≥19 and <25 (normal weight), ≥25 and <30 (over- weight), and ≥30 (obese). Results: Serum ALT (P < 0.002), GGT (P < 0.001) and ALP (P < 0.001) but not AST (P < 0.883) activities in moderate drinkers were higher than those in abstainers. Mean ALT activity is higher in obese and over weight in alcohol consumers and abstainers as compared to mean AST activity in the same groups. ALP activity was increased with BMI in moderate drinkers. In abstainers activity of ALP shows weak relation in order to BMI. Conclusion: The result of moderate alcohol use raises activity of hepatic enzymes with increasing BMI. Most participants with alcohol consumption have an AST/ALT ratio above 1.

急性胰腺炎患者血清CXC趋化因子配体10和CC类趋化因子22水平与疾病严重程度关系及临床诊断价值研究

目的:分析急性胰腺炎患者血清CXC趋化因子配体10(CXCL10)和CC类趋化因子22(CCL22)水平与疾病严重程度的关系及临床诊断价值。方法:选取急性胰腺炎患者102例,分为轻症组(轻症急性胰腺炎患者,47例)、中度重症组(中度重症急性胰腺炎患者,31例)和重症组(重症急性胰腺炎患者,24例)。选择52例体检健康者为健康组。采用全自动生化分析仪检测受试者肝功能指标[丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)]、肾功能指标[肌酐(Scr)、血尿素氮(BUN)]以及淀粉酶(AMY)水平。采用酶联免疫吸附法检测血清中CXCL10、CCL22水平。采用急性胰腺炎严重程度床边指数(BISAP)评分评估急性胰腺炎患者疾病严重程度。采用Logistic回归分析中度重症和重症急性胰腺炎发生的影响因素。采用Pearson法分析急性胰腺炎患者血清CXCL10、CCL22水平及BISAP评分间的相关性。采用受试者工作特征(ROC)曲线评价血清CXCL10、CCL22水平诊断中度重症和重症急性胰腺炎的价值。结果:与健康组比较,轻症组ALT、Scr、BUN、AMY水平升高,中度重症组和重症组ALT、AST、Scr、BUN、AMY水平升高(均P<0.05)。与轻症组比较,中度重症组BUN水平升高,重症组ALT、AST、Scr、BUN水平升高(均P<0.05)。与中度重症组比较,重症组BUN水平升高(P<0.05)。四组血清CXCL10、CCL22水平及BISAP评分依次升高(均P<0.05)。急性胰腺炎患者血清CXCL10和CCL22水平呈正相关(P<0.05);血清CXCL10、CCL22水平与BISAP评分呈正相关(均P<0.05)。血清CXCL10、CCL22、BISAP评分是中度重症和重症急性胰腺炎发生的独立危险因素(均P<0.05)。血清CXCL10、CCL22对中度重症和重症急性胰腺炎均有一定诊断价值,且两项联合诊断价值更高(均P<0.05)。结论:急性胰腺炎患者血清CXCL10、CCL22水平呈高表达,且随疾病严重程度的加重而升高,两者联合诊断中度重症和重症急性胰腺炎的价值较高。

Evaluation of the updated definition of early allograft dysfunction in donation after brain death and donation after cardiac death liver allografts

BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation after brain death(DBD) and donation after cardiac death(DCD) allograft recipients.METHODS:We reviewed our prospectively entered database for all DBD(n=377) and DCD(n=38) liver transplantations between January 1,2006 and October 30,2011.The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups.RESULTS:EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients,but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD(11.5%) compared with those without EAD(16.7%)(P=0.664) or in the rate of death in recipients with EAD(3.8%) compared with those without EAD(8.3%)(P=0.565).The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7(P=0.022).CONCLUSIONS:The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts.On initial assessment,it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts,however a study with a larger sample size of DCD allografts is needed to confirm these findings.The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure.An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.