Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial

AIM:To evaluate the effect of resistance training(RT)on non alcoholic liver disease(NAFLD)patients.METHODS:A randomized clinical trial enrolling NAFLD patients without secondary liver disease(e.g.,without hepatitis B virus,hepatitis C virus or excessive alcohol consumption).Patients were randomly allocated either to RT,three times weekly,for 3 mo or a control arm consisting of home stretching.The RT included leg press,chest press,seated rowing,latissimus pull down etc.with 8-12 repetitions,3 sets for each exercise,for a total duration of 40 min.Hepatic ultrasound,fasting blood tests,anthropometrics and body composition by dual energy X-ray absorptiometry were assessed.At baseline and follow-up,patients filled out a detailed semi-quantitative food frequency questionnaire reporting their habitual nutritional intake.Steatosis was quantified by the hepatorenal-ultrasound index(HRI)representing the ratio between the brightness level of the liver and the right kidney.The HRI has been previously demonstrated to be highly reproducible and was validated against liver biopsy and proton magnetic resonance spectroscopy.RESULTS:Eighty two patients with primary NAFLD were randomized to receive 3 mo of either RT or stretching.After dropout or exclusion from analysis because of protocol violation(weight change>3 kg),thirty three patients in the RT arm and 31 in the stretching arm completed the study per protocol.All baseline characteristics were similar for the two treatment groups with respect to demographics,anthropometrics and body composition,blood tests and liver steatosis on imaging.HRI score was reduced significantly in the RT arm as compared to the stretching arm(-0.25±0.37 vs-0.05±0.28,P=0.017).The RT arm had a significantly higher reduction in total,trunk and android fat with increase in lean body mass.There was no correlation between the reduction in HRI in the RT arm and weight change during the study,but it was positively correlated with the change in trunk fat(r=0.37,P=0.048).The RT arm had a significant reduction in serum ferritin and total cholesterol.There was no significant difference between arms in dietary changes and these did not correlate with HRI change.CONCLUSION:Three months RT improves hepatic fat content accompanied by favorable changes in body composition and ferritin.RT may serve as a complement to treatment of NAFLD.

Trans-arterial chemo-embolization is safe and effective for very elderly patients with hepatocellular carcinoma

AIM: To assess the safety and efficacy of trans-arterial chemo-embolization (TACE) in very elderly patients. METHODS: A prospective cohort study, from 2001 to 2010, compared clinical outcomes following TACE between patients ≥ 75 years old and younger patients (aged between 65 and 75 years and younger than 65 years) with hepatocellular carcinoma (HCC), diagnosed according to the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases criteria. The decision that patients were not candidates for curative therapy was made by a multidisciplinary HCC team. Data collected included demographics, co-morbidities, liver disease etiology, liver disease severity and the number of procedures. The primary outcome was mortality; secondary outcomes included post-embolization syndrome (nausea, fever, abdominal right upper quadrant pain, increase in liver enzymes with no evidence of sepsis and with a clinical course limited to 3-4 d post procedure) and 30-d complications. Additionally, changes in liver enzyme measurements were assessed [alanine and aspartate aminotransferase (ALT and AST), gamma-glutamyl transpeptidase and alkaline phosphatase] in the week following TACE. Analysis employed both univariate and multivariate methods (Cox regression models). RESULTS: Of 102 patients who underwent TACE as sole treatment, 10 patients (9.8%) were > 80 years old at diagnosis; 13 (12.7%) were between 75 and 80 years, 45 (44.1%) were between 65 and 75 years and 34 (33.3%) were younger than 65 years. Survival analysis demonstrated similar survival patterns between the elderly patients and younger patients. Age was also not associated with the adverse event rate. Survival rates at 1, 2 and 3 years from diagnosis were 74%, 37% and 31% among patients < 65 years; 83%, 66% and 48% among patients aged 65 to 75 years; and 86%, 41% and 23% among patients ≥ 75 years. There were no differences between the age groups in the pre-procedural care, including preventive treatment for contrast nephropathy and prophylactic antibiotics. Multivariate survival analysis, controlling for disease stage at diagnosis with the Barcelona Clinic Liver Cancer score, number of TACE procedures, sex and alphafetoprotein level at the time of diagnosis, found no significant difference in the mortality hazard for elderly vs younger patients, and there were no differences in post-procedural complications. Serum creatinine levels did not change after 55% of the procedures, in all age groups. In 42% of all procedures, serum creatinine levels increased by no more than 25% above the baseline levels prior to TACE. Overall, there were 69 post-embolization events (23%). Hepatocellular enzymes often increased following TACE, with no association with prognosis. In 40% of the procedures, ALT and AST levels rose by at least 100%. The increases in hepatocellular enzymes occurred similarly in all age groups. CONCLUSION: TACE is safe and effective in very elderly patients with HCC, and is not associated with decreased survival or increased complication rates.

Toll-like receptors in inflammatory bowel disease-stepping into uncharted territory

Ulcerative colitis and Crohn's disease are chronic relapsing-remitting inflammatory processes of the intestinal tract. The etiology of these diseases is currently unknown. However, inflammation is hypothesized to result from inappropriate activation of mucosal immunity by luminal antigens in genetically susceptible individuals. Toll-like receptors (TLRs) are a family of transmembrane proteins that act as microbial pattern recognition receptors. They are crucial initiators of innate immune responses. The role of TLRs in the pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. In this review, we aim to analyze the available data connecting individual TLRs to intestinal inflammation and IBD.

Treatment of hepatocellular carcinoma: Steps forward but still a long way to go

Hepatocellular carcinoma(HCC) is the fifth most common malignancy and the third cause of tumor associated deaths worldwide. HCC incidence rates are increasing in many parts of the world including developing and developed countries. Potentially curative treatments for HCC are resection and liver transplantation, but these are only suitable for patients with small tumors, meeting strict pre-defined criteria, or well-compensated liver disease. Early diagnosis of HCCcan be achieved by surveillance of at-risk populations. For patients with non-resectable disease treatments modalities include loco-ablative and systemic therapies. In this review we focus on treatment options in HCC and their allocation. Although significant research is in progress, to this date, the results are unsatisfactory with limited long-term survival. In the fight against this deadly disease, there is still a long way to go.

Hepatocellular carcinoma in the post-hepatitis C virus era: Should we change the paradigm?

Hepatocellular carcinoma (HCC) is a common and deadly malignancy. The disease usually develops on a background of chronic liver disease. Until recently, the most common etiology was infection with the hepatitis C virus (HCV). The advent of direct-acting antiviral (DAA) therapies has been a major breakthrough in HCV treatment. Sustained virologic response can now be achieved in almost all treated patients, even in patients with a high risk for the development of HCC, such as the elderly or those with significant fibrosis. Early reports raised concerns of a high risk for HCC occurrence after DAA therapy both in patients with previous resection of tumors and those without previous tumors. As the World Health Organization’s goals for eradication of HCV are being endorsed worldwide, the elimination of HCV seems feasible. Simultaneous to the decrease in the burden of cirrhosis from HCV, non-alcoholic fatty liver disease (NAFLD) incidence has been increasing dramatically including significant increased incidence of cirrhosis and HCC in these patients. Surprisingly, a substantial proportion of patients with NAFLD were shown to develop HCC even in the absence of cirrhosis. Furthermore, HCC treatment and potential complications are known to be influenced by liver steatosis. These changes in etiology and epidemiology of HCC suggest the beginning of a new era: The post–HCV era. Changes may eventually undermine current practices of early detection, surveillance and management of HCC. We focused on the risk of HCC occurrence and recurrence in the post–HCV era, the surveillance needed after DAA therapy and current studies in HCC patients with NAFLD.

Oral immune regulation using colitis extracted proteins for treatment of Crohn's disease: Results of a phase Ⅰ clinical trial

AIM: To evaluate safety and possible efficacy of induction of oral immune regulation using colitis extracted proteins(CEP) in Crohn's disease (CD) subjects.METHODS: Ten CDs were treated orally with autologous CEP thrice weekly for 16 wk. Subjects were monitored for CDAI and IBDQ. Immune modulatory effect was assessed by T-lymphocyte FACS analysis, CEP-specific IFNγ ELISPOT assay and cytokine levels.RESULTS: Induction of oral immune regulation significantly ameliorated disease activity. All (10/10) subjects had clinical response (CDAI≤70) and 7/10 achieved clinical remission (CDAI≤150). Significant increase in mean IBDQ score was noted (134±9vs 164±12). No treatment-related adverse events were noted. High levels of CEP-specific IFNγ spot forming colonies were detected in five subjects prior to treatment and in all five, a marked decrease was observed. The CD4+/CDS+ lymphocyte ratio and peripheral NKT cell numbers increased significantly, in 7/10 and in 5/10 subjects, respectively. Significant increase in serum IL-10 and IL-4 levels was observed in 7/10 subjects during treatment period.CONCLUSION: Immune regulation via oral administration of CEP is a safe and possibly effective treatment for subjects with moderate CD and may provide means of antigen-specific immune modulation.

Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients

AIM To describe the relationships between non-alcoholic fatty-liver disease(NAFLD) patient's disease consequences and treatment perceptions, self-efficacy, and healthy lifestyle maintenance. METHODS A cross-sectional study among 146 ultrasound diagnosed NAFLD patients who visited the fatty liver clinic at the TelAviv Medical Center. Eighty-seven of these individuals, participated in a clinical trial of physical activity and underwent fasting blood tests, analyzed at the same lab. Exclusion criteria included positivity for serum HBsA g or anti-HCV antibodies; fatty liver suspected to be secondary to hepatotoxic drugs; excessive alcohol consumption(≥ 30 g/d in men or ≥ 20 g/d in women) and positive markers of genetic or immune-mediated liver diseases. Patients were asked to complete a selfreport structured questionnaire, assembled by the Israeli Center for Disease Control. Nutrition habits were measured using six yes/no questions(0 = no, 1 = yes) adopted from the national survey questionnaire. Participants in the clinical trial completed a detailed semi-quantitative food frequency questionnaire(FFQ) reporting their habitual nutritional intake during the past year. Self-efficacy was assessed by the Self-Efficacy Scale questionnaire, emotional representation, degree of illness understanding, timeline perception, treatment perception and symptoms were measured by the Brief Illness Perception questionnaire. Illness consequences were measured by the Personal Models of Diabetes Interview questionnaire. A path analysis was performed to describe the interrelationships between the patients' illness perceptions, and assess the extent to which the data fit a prediction of nutritional habits.RESULTS The study sample included 54.1% men, with a mean age of 47.76 ± 11.68 years(range: 20-60) and mean body mass index of 31.56 ± 4.6. The average perceived nutrition habits score was 4.73 ± 1.45 on a scale between 0-6, where 6 represents the healthiest eating habits. Most of the study participants(57.2%) did not feel they fully understood what NAFLD is. Better nutritional habits were positively predicted by the degree of illness understanding(β = 0.26; P = 0.002) and selfefficacy(β = 0.25; P = 0.003). Perceptions of more severe illness consequences were related with higher emotional representation(β = 0.55; P < 0.001), which was related with lower self-efficacy(β =-0.17; P = 0.034). The perception of treatment effectiveness was positively related with self-efficacy(β = 0.32; P < 0.001). In accordance with the correlation between self-efficacy and the perceived nutrition habits score, self-efficacy was also correlated with nutrient intake evaluated by the FFQ; negatively with saturated fat(percent of saturated fat calories from total calories)(r =-0.28, P = 0.010) and positively with fiber(r = 0.22, P = 0.047) and vitamin C intake(r = 0.34, P = 0.002). In a sub analysis of the clinical trial participants, objectively measured compliance to physical activity regimen was positively correlated with the self-efficacy level(r = 0.34, P = 0.046). CONCLUSION Self-efficacy and illness understanding are major determinants of lifestyle-modification among NAFLD patients. This information can assist clinicians in improving compliance with lifestyle changes among these patients.

Longitudinal decrease in platelet counts as a surrogate marker of liver fibrosis

BACKGROUND Liver cirrhosis is a significant source of morbidity and mortality worldwide.The disease is usually indolent and asymptomatic early in its course while many cirrhotic patients are diagnosed late when severe complications occur.A major challenge is to diagnose advanced fibrosis as early as possible,using simple and non-invasive diagnostics tools.Thrombocytopenia represents advanced fibrosis and portal hypertension(HTN)and most non-invasive scores that predict liver fibrosis incorporate platelets as a strong risk factor.However,little is known about the association between longitudinal changes in platelet counts(PTC),when still within the normal range,and the risk of cirrhosis.AIM To explore whether platelet counts trajectories over time,can predict advanced liver fibrosis across the different etiologies of liver diseases.METHODS A nested case-control study utilizing a large computerized database.Cirrhosis cases(n=5258)were compared to controls(n=15744)matched for age and sex at a ratio of 1:3.All participants had multiple laboratory measurements prior to enrollment.We calculated the trends of PTC,liver enzymes,bilirubin,international normalized ratio,albumin and fibrosis scores(fibrosis-4 and aspartate transaminase-to-platelet ratio index)throughout the preceding 20 years prior to cirrhosis diagnosis compared to healthy controls.The association between PTC,cirrhosis complications and fibrosis scores prior to cirrhosis diagnosis was investigated.RESULTS The mean age in both groups was 56(SD 15.8).Cirrhotic patients were more likely to be smokers,diabetic with chronic kidney disease and had a higher prevalence of HTN.The leading cirrhosis etiologies were viral,alcoholic and fatty liver disease.The mean PTC decreased from 240000/μL to 190000/μL up to 15 years prior to cirrhosis diagnosis compared to controls who’s PTC remained stable around the values of 240000/μL.This trend was consistent regardless of sex,cirrhosis etiology and was more pronounced in patients who developed varices and ascites.Compared to controls whose values remained in the normal range,in the cirrhosis group aspartate aminotransferase and alanine aminotransferase,increased from 40 U/L to 75 U/L and FIB-4 increased gradually from 1.3 to 3 prior to cirrhosis diagnosis.In multivariable regression analysis,a decrease of 50 units in PTC was associated with 1.3 times odds of cirrhosis(95%CI 1.25-1.35).CONCLUSION In the preceding years before the diagnosis of cirrhosis,there is a progressive decline in PTC,within the normal range,matched to a gradual increase in fibrosis scores.

Older age, longer procedures and tandem endoscopic-ultrasound as risk factors for post-endoscopic retrograde cholangiopancreatography bacteremia

BACKGROUND Clinically significant post-endoscopic retrograde cholangiopancreatography(ERCP) bacteremia(PEB) occurs in up to 5% of cases, while antibiotic prophylaxis is recommended only when an ERCP is unlikely to achieve complete biliary drainage. However, the current recommendations may not cover all potential risk factors for PEB.AIM To identify novel risk factors for PEB and evaluate appropriateness of antibiotic prophylaxis.METHODS A retrospective study of 1082 ERCP procedures performed between January 2012-December 2013 in a single tertiary medical center. Data collection included: Demographic and clinical characteristics such as pre and post procedure antibiotic treatment and bacterial blood cultures. Exclusion criteria were:(1) Age < 18 years;(2) Positive bacterial blood culture before ERCP;(3) Scheduled antibiotic treatment prior to ERCP;(4) Hospitalization longer than 14 d before ERCP;and(5) missing critical data. Stepwise Logistic Regression analysis and Decision Tree algorithms were used for prediction modeling of PEB.RESULTS A total of 626 ERCPs performed in 434 patients were included. Mean age 66.49 ± 15.4 years and 46.5% were males. PEB prevalence was 3.7%. Antibiotic prophylaxis was administrated in 139/626(22.2%) cases but was indicated according to the guidelines only in 44/626(7%) cases. In all the PEB cases, prophylaxis was deemed not indicated. A stepwise logistic regression [receiver operating characteristic(ROC), 0.766], identified 3 variables as independent risk factors for PEB: Age at ERCP ≥ 75 years(OR, 3.780, 95%CI: 1.519-9.408, P = 0.004);Tandem EUS/ERCP with fine needle aspiration(FNA)(OR, 14.528, 95%CI: 3.571-59.095, P < 0.001);ERCP duration longer than 60 min(OR, 5.396, 95%CI: 1.86-15.656, P = 0.002). In a decision tree model(ROC, 0.778) the probability for PEB without any risk factors was 1% regardless of prophylaxis administration.CONCLUSION The prevalence of PEB in our study is similar to previous reports, despite the fact that antibiotic prophylaxis was administrated more readily than recommended. ERCP duration longer than 60 min, tandem EUS-ERCP with FNA and age above 75 years are significant risk factors for PEB. These factors should be further evaluated as indications for prophylactic antibiotic treatment before ERCP.

Clinical management of acute liver failure: Results of an international multi-center survey

AIM To assess the practice of caring for acute liver failure(ALF) patients in varying geographic locations and medical centers.METHODS Members of the European Acute Liver Failure Consortium completed an 88-item questionnaire detailing management of ALF. Responses from 22 transplantation centers in 11 countries were analyzed,treating between 300 and 500 ALF cases and performing over 100 liver transplants(LT) for ALF annually. The questions pertained to details of the institution and their clinical activity,standards of care,referral and admission,wardbased care versus intensive care unit(ICU) as well as questions regarding liver transplantation- including criteria,limitations,and perceived performance. Clinical data was also collected from 13 centres over a 3 mo period. RESULTS The interval between referral and admission of ALF patients to specialized units was usually less than 24 h and once admitted,treatment was provided by a multidisciplinary team. Principles of care of patients with ALF were similar among centers,particularly in relation to recognition of severity and care of the more critically ill. Centers exhibited similarities in thresholds for ICU admission and management of severe hepatic encephalopathy. Over 80% of centers administered n-acetyl-cysteine to ICU patients for non-paracetamolrelated ALF. There was significant divergence in the use of prophylactic antibiotics and anti-fungals,lactulose,nutritional support and imaging investigations in admitted patients and in the monitoring and treatment of intra-cranial pressure(ICP). ICP monitoring was employed in 12 centers,with the most common indications being papilledema and renal failure. Most patients listed for transplantation underwent surgery within an average waiting time of 1-2 d. Over a period of 3 mo clinical data from 85 ALF patients was collected. Overall patient survival at 90-d was 76%. Thirty six percent of patients underwent emergency LT,with a 90% post transplant survival to hospital discharge,42% survived with medical management alone. CONCLUSION Alongside similarities in principles of care of ALF patients,major areas of divergence were present in key areas of diagnosis,monitoring,treatment and decision to transplant.

A prospective study assessing the efficacy of abdominal computed tomography scan without bowel preparation in diagnosing intestinal wall and luminal lesions in patients presenting to the emergency room with abdominal complaints

AIM: To evaluate the positive predictive value of abdominal non-prepared computed tomography (CT) for diagnosing intestinal lumen or wall lesions in patients presenting to the emergency room (ER) with abdominal complaints.METHODS: For 1-year we prospectively evaluated all ER patients hospitalized after abdominal CT scan detected either intraluminal or intestinal wall lesions. These patients underwent colonoscopy serving as gold standard. Patients with prior abdominal pathology or CT findings of appendicitis or diverticulitis were excluded.RESULTS: Five hundred and sixty-eight abdominopelvic CT scans were performed in the ER, 96 had positive colonic findings. Sixty-two patients were excluded, 46 because of diverticulitis or appendicitis, 16 because of prior abdominal pathology. Of the remaining 34 patients, 14 did not undergo colonoscopy during hospitalization.Twenty eligible patients were included in the study. The positive predictive value of the CT scans performed in the ER was calculated to be 45% (95% CI 25-67).CONCLUSION: CT findings correlated with colonoscopic findings only in approximately half of the cases. Relying on non-prepared CT scan findings in planning patient management and colonoscopy may lead to unnecessary diagnostic work-ups.

Non-alcoholic fatty liver disease is not associated with a lower health perception

AIM: To examine the association between nonalcoholic fatty liver disease(NAFLD) and general health perception.METHODS: This cross sectional and prospective follow-up study was performed on a cohort of a subsample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index.RESULTS: Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213(32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association(OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception(OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception(compared to "else") increased among men(OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity(OR = 1.01, 95%CI: 1.00-1.01, P < 0.001, per every minute/week) and decreased with increasing level of BMI(OR = 0.91, 95%CI: 0.84-0.99, P = 0.028, per every kg/m^2) and older age(OR = 0.96, 95%CI: 0.93-0.99, P = 0.033, per one year). Current smoking was not associated with health perception(OR = 1.31, 95%CI: 0.54-3.16, P = 0.552). Newly diagnosed(naive) and previously diagnosed(at the first survey, not naive) NAFLD patients did not differ in their self-health perception. The presence of NAFLD at the first survey as compared to normal liver did not predict health perception deterioration at the 7 years follow-up. In terms of health-services utilization, subjects diagnosed with NAFLD had a similar number of physician's visits(general physicians and specialty consultants) as in the normal liver group. Parameters in the fatigue impact scale were equivalent between the NAFLD and the normal liver groups.CONCLUSION: Fatty liver without clinically significant liver disease does not have independent impact on selfhealth perception.

Analysis of aggressiveness factors in hepatocellular carcinoma patients undergoing transarterial chemoembolization

AIM To investigate novel predictors of survival in hepatocellular carcinoma(HCC) patients following transarterial chemoembolization(TACE).METHODS One hundred sixty seven patients with un-resectable HCC were retrospectively analyzed to identify factors that might contribute to their HCC biology and aggressiveness. We correlated routine laboratory results(total bilirubin, AST, ALKP, GGTP, albumin etc.) to maximum tumor diameter, number of tumor nodules, portal vein thrombosis and blood alpha-fetoprotein levels. These 4 parameters were previously combined to form an aggressiveness index(AgI). We used The Wilcoxon ranksum(Mann-Whitney), to test the correlation between the AgI categories and liver function parameters. The Cox proportional hazards model was applied to evaluate the categories of AgI associated with overall survival. RESULTS The AgI was strongly correlated with survival in this novel patient population. Three year survival probability for AgI > or < 4 was 42.4% vs 61.8%; P < 0.0863 respectively. Several factors independently correlated with AgI using univariate multiple logistic regression of AgI with 8 laboratory parameters. Lower albumin levels had an OR of 2.56(95%CI: 1.120-5.863 P < 0.026), elevated Alkaline phosphatase and gamma glutamyl transpeptidase(GGTP) had ORs of 1.01(95%CI: 1.003-1.026, P < 0.017) and 0.99(95%CI: 0.99-1.00, P < 0.053) respectively. In a Cox proportional hazard model combining mortality for AgI score and liver function parameters, only GGTP levels and the AgI were independently associated with survival. An AgI > 4 had HR for mortality of 2.18(95%CI: 1.108-4.310, P < 0.024). GGTP's single unit change had a HR for mortality of 1.003(95%CI: 1.001-1.006, P < 0.016). These were considered in the final multivariate model with the total cohort. An AgI > 4 had a HR for mortality of 2.26(95%CI: 1.184-4.327, P < 0.016). GGTP had a HR of 1.003(95%CI: 1.001-1.004, P < 0.001).CONCLUSION Our study validates the AgI in a new population with un-resectable HCC patients undergoing TACE. The analysis establishes a correlation between GGTP and the AgI.

Predictors for advanced fibrosis in morbidly obese nonalcoholic fatty liver patients

AIM To investigate predictors for fibrosis specifically in a high risk population of morbidly obese patients, including detailed evaluation of lifestyle. METHODS We conducted a cross-sectional study among morbidly obese patients attending the bariatric clinic at the TelAviv Medical Center between the years 2013-2014 with body mass index(BMI) above 40 or above 35 with co-morbidity. Patients with serum hepatitis B surface antigen or anti-hepatitis C virus antibodies, genetic liver diseases, autoimmune disease or high alcohol intake(≥ 30 g/d in men or ≥ 20 g/d in women) were excluded from the study. Liver fibrosis was estimated by transient elastography(Fibro Scan?), using the ‘‘XL'' probe. We collected data on age and gender, education, smoking status and amount, medical history, nutrition and lifestyle habits. All these data were collected using structured and validated questionnaires. Fasting blood test were available for a subsample. RESULTS Fibroscan was performed on a total of 91 patients, of which 77 had a valid examination according to the accepted criteria. Of those, 21% had significant fibrosis(F2) and 39% had advanced or severe fibrosis(F3 or F4). In multivariate analysis, male gender and BMI had a positive association with advanced fibrosis; the OR for fibrosis F ≥ 2 was 7.93(95%CI: 2.36-26.64, P = 0.001) for male gender and 1.33(1.11-1.60 kg/m2, P = 0.002) for BMI. The OR for fibrosis F ≥ 3 was 2.92(1.08-7.91, P = 0.035) for male gender and 1.17(1.03-1.33, P = 0.018) for BMI. Subjects were categorized to subgroups based on the combination of male gender and BMI of 40 and above. A significant dose response association with stiffness level was noted across these categories, with the highest stiffness among men with a higher BMI(P = 0.001). In addition, a significant positive correlation between pack-years cigarette smoking and liver stiffness was demonstrated among men(r = 0.54, P = 0.012).CONCLUSION In the morbidly obese population, a higher BMI, male gender and degree of smoking in men bears a greater risk for advanced nonalcoholic fatty liver disease.

Emergency department targeted screening for hepatitis C does not improve linkage to care

BACKGROUND Hepatitis C virus(HCV)infection is a leading cause of chronic liver disease worldwide.New treatments for HCV revolutionized management and prompted the world health organization to set the goal of viral elimination by 2030.These developments strengthen the need for HCV screening in order to identify asymptomatic carriers prior to development of chronic liver disease and its complications.Different screening strategies have been attempted,most targeting high-risk populations.Previous studies focusing on patients arriving at emergency departments showed a higher prevalence of HCV compared to the general population.AIM To identify previously undiagnosed HCV carriers among high risk emergency room attendees and link them to care for anti-viral treatment.METHODS In this single center prospective study,persons visiting the emergency department in an urban hospital were screened by a risk factor-specific questionnaire.The risk factors screened for were exposure to blood products or organ transplantation before 1992;origins from countries with high prevalence of HCV;intravenous drug use;human immunodeficiency virus carriers;men who have sex with men;those born to HCV-infected mothers;prior prison time;and chronic kidney disease.Those with at least one risk factor were tested for HCV by serum for HCV antibodies,a novel oral test from saliva(OraQuick®)or both.RESULTS Five hundred and forty-one participants had at least one risk factor and were tested for HCV.Eighty four percent of all study participants had only one risk factor.Eighty five percent of participants underwent OraQuick®testing,34%were tested for serum anti-HCV antibodies,and 25%had both tests.3.1%of patients(17/541)had a positive result,compared to local population incidence of 1.96%.Of these,82%were people who inject drugs(current or former),and 64%served time in prison.One patient had a negative HCV-RNA,and two patients died from non-HCV related reasons.On review of past medical records,12 patients were found to have been previously diagnosed with HCV but were unaware of their carrier state.At 1-year follow-up none of the remaining 14 patients had completed HCV-RNA testing,visited a hepatology clinic or received anti-viral treatment.CONCLUSION Targeted high-risk screening in the emergency department identified undiagnosed and untreated HCV carriers,but did not improve treatment rates.Other strategies need to be developed to improve linkage to care in high risk populations.

Nat Cell Biol:研究发现人肝细胞抵抗HCV感染的代谢过程

病毒感染是二十一世纪面临的主要医学挑战之一，从影响全球3％人口的丙肝病毒（HCV）流行病到最近爆发的西尼罗河病毒、寨卡病毒和埃博拉病毒感染。病毒缺乏进行自我复制所需的基础代谢机制。为了解决这个问题，它们劫持它们的宿主的代谢机制以便完成它们的生命周期和进行增殖。然而，科学家们仍然并没有很好地理解病毒与它们感染的有机体之间在代谢上的相互作用。这主要是因为人基因与代谢过程之间存在复杂的相互作用。