Alcoholic liver disease presents at advanced stage and progresses faster compared to non-alcoholic fatty liver diseas.

BACKGROUND AND OBJECTIVE: Steatohepatitis is a common cause of liver disease due to alcohol (ALD) or non-alcoholic fatty liver disease (NAFLD). We performed this study to compare natural history of ALD and NAFLD. MATERIAL AND METHODS: Retrospective analysis of ALD or NAFLD patients managed at our center (2007-2011). ALD diagnosed by excluding other liver diseases (except HCV) and alcohol abuse of > 40 g/d in women and > 60 g/d in men for > 5 years. NAFLD diagnosed by excluding other liver diseases and a history of alcohol use of < 10 g/d. Cirrhosis was diagnosed using biopsy for uncertain clinical diagnosis. RESULTS: Compared to patients with NAFLD (n = 365; mean age 50 yrs; 43% males; 53% diabetic), ALD patients (n = 206; mean age 51 yrs; 68% males; 24% diabetic) presented more often with cirrhosis or complications(46vs. 12%; P< 0.0001) with a higher MELD score (13 ± 7 vs. 8 ± 8; P<0.0001). On logistic regression, ALD diagnosis was associated with presence of cirrhosis by over 4-fold (4.1 [1.8-9.1]) even after excluding 23 patients with concomitant HCV. Over median follow up of about 3 and 4 yrs among ALD and NAFLD patients respectively, ALD patients more frequently developed cirrhosis or its complications including HCC with worse transplant free survival (90 vs. 95%; P = 0.038). CONCLUSIONS: Compared to NAFLD, ALD patients present at an advanced stage of liver disease with a faster progression on follow-up. Prospective multicenter studies are needed to identify potential barriers to early referral of ALD patients as basis for development of strategies to improve outcome of patients with ALD.

Impact of metabolic syndrome on the hospitalization rate of Crohn's disease patients seen at a tertiary care center: a retrospective cohort study.

BACKGROUND/AIMS: Recent studies suggest that markers of mesenteric inflammation, such as increased adipose tissue, may be associated with poor outcomes in Crohn's disease (CD). This study's hypothesis is that CD patients with metabolic syndrome (MetS) have more CD-related hospitalizations than CD patients without MetS. METHODS: We conducted a retrospective cohort study of CD patients seen from 2000 to 2012 at our tertiary care center. We analyzed crude and age-, sex- and duration of CD-adjusted incidence rate ratio (IRR) of CD-related hospitalization of those with MetS versus those without MetS. We also investigated possible associations between individual component conditions of MetS and rate of CD-related hospitalization. RESULTS: A total of 868 CD patients were included. There were 37 (4%) patients with MetS at initial observation. After multi-variable adjustment, patients with MetS had a CD-related hospitalization rate twice that of those who did not have MetS. High triglycerides (TG), low high density lipoprotein (HDL) cholesterol and diabetes mellitus (DM) were associated with increased risk of CD-related hospitalization. CONCLUSIONS: CD patients with MetS have a higher rate of CD-related hospitalization compared to those without MetS. Hypertriglyceridemia, low HDL cholesterol and DM may be good markers of local and systemic inflammation as seen in CD.

Autoimmune Markers Do Not Impact Clinical Presentation or Natural History of Steatohepatitis-Related Liver Disease.

BACKGROUND AND AIM: Autoimmune (AI) markers are reported in patients with steatohepatitis-related liver disease. However, their clinical significance is unclear. METHODS: Charts of patients due to alcoholic liver disease (ALD) or nonalcoholic fatty liver disease (NAFLD) were stratified for antinuclear antigen (ANA > 1:80), antismooth muscle antibody (ASMA > 1:40), or antimitochondrial antibody (AMA > 1:20). Study outcomes were patient survival and complications of liver disease. RESULTS: Of 607 patients (401 NAFLD), information about AI markers was available for 398 (mean age 50 ± 15 year; 52% males; median body mass index (BMI) 38; 44% diabetic; 62% nonalcoholic steatohepatitis (NASH) as type of steatohepatitis; median MELD score 9). A total of 78 (19.6%) patients were positive for AI markers without differences for ALD versus NAFLD, cirrhosis versus no cirrhosis, and NASH versus no NASH. There were no differences for age, gender, BMI, cirrhosis at presentation, MELD score, endoscopic findings, and histology based on AI markers. Serum ALT was higher among patients with AI markers (65 ± 46 vs. 59 ± 66 IU/l; P = 0.048). Data remained unchanged on analyzing NAFLD patients. None of the 11 ANA-positive patients (1:640 in 4) showed findings of AI hepatitis. Biopsy in three AMA-positive patients showed mild bile duct damage in one patient. On median follow-up of about 3 years, there were no differences in liver disease outcomes (ascites, encephalopathy, variceal bleeding), hepatocellular carcinoma, transplantation, and survival. CONCLUSIONS: Autoimmune markers are frequently present in steatohepatitis-related liver disease patients. Their presence is an epiphenomenon without histological changes of autoimmune hepatitis. Further, their presence does not impact clinical presentation and follow-up outcomes.

Tatsuji Inouye: the mind's eye.

INTRODUCTION: The name Tatsuji Inouye is relatively unknown in the West. This prominent Japanese scientist was one of the first to thoroughly study the visual cortex and to map its gyri. Inouye was also a caring physician who wanted only the best for his patients. CONCLUSIONS: In the present review, we discuss the life of Tatsuji Inouye and his significant contributions to our current understanding of the visual cortex.

Cholecystectomy does not worsen progression or outcomes in non-alcoholic fatty liver disease.

BACKGROUND: Cholecystectomy is a frequently performed surgical procedure for symptomatic cholelithiasis, which is reported to be more common in patients with non-alcoholic steatohepatitis (NASH), given the common risk factors. However, the data remains unclear on the association of cholecystectomy with NASH. We performed a retrospective study to examine the association of cholecystectomy and NASH. METHODS: Medical charts of patients with steatohepatitis related liver disease at a tertiary care center from 2004 to 2011 were stratified by cholecystectomy and defined by its history and/or absence of gallbladder on ultrasonography. Logistic regression model was built for predictors of cholecystectomy. Patients with NASH were stratified based on timing of cholecystectomy. The diagnosis of NASH and timing of cholecystectomy were compared based on baseline characteristics and outcomes (liver disease complications and survival) on follow up. Kaplan-Meier curves were generated for the two group comparisons. Chi-square and unpaired t-tests were used for comparing outcomes on follow up. P value <0.05 was considered significant. RESULTS: Analysis of 584 patients [379 non-alcoholic fatty liver disease (NAFLD)] showed that patients with cholecystectomy (N=191) were more likely to be female (57% vs. 44%), diabetic (53% vs. 37%), have liver biopsy (43% vs. 25%) and diagnosis of NAFLD (80% vs. 58%) P<0.001 for all. NAFLD diagnosis was associated with 2.79 folds odds of cholecystectomy. Among 379 (192 cholecystectomy) NAFLD patients, cirrhosis and female gender were associated with over 2 and 1.5 folds of cholecystectomy. Of 141 patients with data on timing of cholecystectomy, 55 (39%) with cholecystectomy at or after NAFLD diagnosis vs. 86 with cholecystectomy within median of 6 years prior to NAFLD diagnosis were similar on all characteristics except on model for end-stage liver disease (MELD) score (9.2±8.4 vs. 6.4±7.1, P=0.045). Of 28 with available histology data, there were no differences on histology based on timing of cholecystectomy. On a median follow up of 5 years, timing of cholecystectomy did not impact on development of cirrhosis (74% vs. 67%, P=0.45), ascites (31% vs. 38%, P=0.76), variceal bleeding (11% vs. 16%, P=0.44), hepatic encephalopathy (22% vs. 29%, P=0.74), hepatocellular carcinoma (HCC) (15% vs. 9%, P=0.59), and patient survival (95% vs. 98%, P=0.3). CONCLUSIONS: Cholecystectomy is associated with NAFLD diagnosis. We did not find cause and effect of cholecystectomy in the development of severity of NAFLD. Prospective studies are suggested to examine the role of cholecystectomy and bile acids in the pathogenesis of NAFLD.

Elevated expression of isopeptide bond cross-links contributes to fibrosis in scleroderma and the healing wounds of tight skin mice.

Scleroderma is a chronic disease characterized by excessive tissue fibrosis. Recent studies indicate that cultured dermal fibroblasts isolated from patients produce excessive amounts of collagen and other extracellular matrix components. In this study, we investigated the mechanism(s) of abnormal extracellular matrix accumulation in the scleroderma biopsies and the healing wounds of Tsk1/+ mice. Full-thickness excisional wounds were made in Tsk1/+ and wild-type mice and were subsequently harvested at days 7, 10, and 14 postinjury. The levels of pro-fibrotic cytokine, transforming growth factor were elevated in the wounds of Tsk1/+ mice. Interestingly, the levels of matrix metalloproteinase were significantly reduced in the granulation tissue of Tsk1/+ mice in comparison with wild-type. Furthermore, immunohistochemical analysis of the wounds indicated that the levels of gamma-glutamyl-epsilon-lysine cross-links were elevated in the granulation tissue of Tsk1/+ mice as well as the fibrotic lesions of scleroderma specimens. Collectively, these findings indicate that elevated collagen synthesis and decreased matrix metalloproteinase levels, in combination with increased isopeptide bond cross-links, contribute to abnormal collagen synthesis and assembly in granulation tissue of Tsk1/+ mice and the fibrotic lesions of scleroderma patients.

Biomarkers of Renal Injury in Cirrhosis: Association with Acute Kidney Injury and Recovery after Liver Transplantation.

BACKGROUND: To define urine or serum biomarkers in predicting renal function recovery after liver transplantation (LT). METHODS: Adults listed for LT (February 2011-July 2014) and with modified diet for renal disease-6 (MDRD-6) <60 mL/min provided urine/blood samples at baseline and serially until LT for biomarkers in serum (pg/mL) and urine (pg/mg creatinine). RESULTS: Of 271 LT listed patients (mean age 57 years, 63% males, median listing MELD 17.5), 1 year acute kidney injury (AKI) probability was 49%, with odds of 1.3-, 3.0-, 4.6-, and 8.5-fold times for listing MELD 16-20, 21-25, 26-30, and >30, compared to MELD <16. Thirty-seven people died over 1 year from the time of listing, with twofold increased odds with AKI. Among 67 patients with MDRD <60, only urinary epidermal growth factor was different comparing AKI (increase in serum creatinine ≥0.3 mg/dL from baseline within past 3 months) vs. no AKI (2,254 vs. 4,253, p = 0.003). Differences between acute tubular necrosis (ATN) and hepatorenal syndrome could not be ascertained for a small sample of 3 patients with ATN. Analyzing 15 of 43 receiving LT and MDRD-6 <30 prior to LT, biomarkers were not different comparing 5 patients recovering renal function (MDRD-6 >50 mL/min) at 6 months vs. 10 without recovery. CONCLUSIONS: AKI is common among LT listed patients, with a negative impact on transplant-free survival. Serum and urine biomarkers are not associated with the recovery of renal function after LT. Multicenter studies are suggested to (a) develop strategies to reduce the development of AKI and (b) derive novel biomarkers for use in accurately predicting renal recovery after LT.

Rates of hospitalization among African American and Caucasian American patients with Crohn's disease seen at a tertiary care center.

BACKGROUND: There is equivocal evidence regarding differences in the clinical course and outcomes of Crohn's disease (CD) among African Americans compared with Caucasian Americans. We sought to analyze whether African Americans with CD are more likely to be hospitalized for CD-related complications when compared with Caucasian Americans with CD. METHODS: We conducted a retrospective cohort study including 909 African Americans and Caucasian Americans with CD who were seen at our tertiary care Inflammatory Bowel Disease (IBD) referral center between 2000 and 2013. We calculated the rate of hospitalization for CD-related complications among African Americans and Caucasian Americans separately. Zero-inflated Poisson regression models with robust variance estimates were used to estimate crude and multivariable adjusted rate ratios (RR) for CD-related hospitalizations. Multivariable adjusted models included adjustment for age, sex, duration of CD, smoking and CD therapy. RESULTS: The cumulative rate of CD-related hospital admissions was higher among African American patients compared with Caucasian American patients (395.6/1000 person-years in African Americans vs. 230.4/1000 person-years in Caucasian Americans). Unadjusted and multivariable adjusted rate ratios for CD-related hospitalization comparing African Americans and Caucasian Americans were 1.59 (95% confidence interval [95%CI]: 1.10-2.29; P=0.01) and 1.44 (95%CI: 1.02-2.03; P=0.04), respectively. CONCLUSIONS: African Americans with CD followed at a tertiary IBD-referral center had a higher rate for CD-related hospitalizations compared with Caucasian Americans. Future studies should examine whether socioeconomic status and biologic markers of disease status could explain the higher risk observed among African Americans.

Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases.

BACKGROUND AND AIMS: Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease. Diabetes mellitus (DM) is a common comorbidity among NAFLD patients. We performed this study with the specific aim to examine the impact of DM on progression of alcoholic liver disease (ALD) liver and NAFLD. METHODS: Medical charts of 480 patients with ALD or NAFLD (2004-2011) managed at a tertiary center were retrospectively reviewed. NAFLD was diagnosed based on exclusion of other causes of liver disease and alcohol use of <10 g/d. ALD was diagnosed based on alcohol use of >40 g/d in women or >60 g/d in men for >5 years. RESULTS: Of 480 patients (307 NAFLD), 200 diabetics differed from nondiabetics for: age (52±11 vs. 49±11 years; p=0.004); male gender (48% vs. 57%; p=0.03); metabolic syndrome (49% vs. 30%; p=0.0002); NAFLD (80% vs. 56%; p<0.0001); cirrhosis (70% vs. 59%; p=0.005); and hepatocellular carcinoma (HCC; 8% vs. 3%; p=0.009). Over a 3 year median follow-up period, diabetics relative to nondiabetics had a higher probability to develop cirrhosis (60% vs. 41%; p=0.022) and HCC (27% vs. 10%; p=0.045). There was a trend for increased development of hepatic encephalopathy in diabetics compared to nondiabetics (55% vs. 39%; p=0.053), and there was no difference between the two groups in survival or other liver disease complications. CONCLUSIONS: DM increased risk for cirrhosis and HCC among patients with ALD and NAFLD. Prospective studies with longer follow-up periods are needed to examine the impact of DM on survival and the role of aggressive HCC screening in diabetic cirrhotics.

A case of sclerosing mesenteritis with spontaneous resolution with steroid therapy.

We present the case of a 59-year-old male who presented with sudden onset of severe epigastric pain and laboratory studies consistent with acute pancreatitis. Imaging showed a dramatic interval increase in mesenteric edema with a normal pancreas, and a diagnosis of acute-onset sclerosing mesenteritis was made. Corticosteroids were initiated, and the patient demonstrated a dramatic improvement in symptoms and laboratory abnormalities overnight. Subsequent imaging after 4 and 8 months revealed continued improvement of mesenteric abnormalities consistent with consolidative sclerosing mesenteritis with a radiographic picture more typical of this unusual disorder. The abrupt onset of symptoms with acute dramatic development of mesenteric edema and dramatic resolution of symptoms has not been previously described.