Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats

Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptosis in rats with pre-existing nonalcoholic steatohepatitis (NASH). This study investigated whether moderate alcohol intake alters SIRT1 activity, adiponectin/Adiponectin receptor (AdipoR)-related signaling and lipid metabolism in a pre-existing NASH status. Sprague-Dawley rats were fed with a high-fat diet (71% energy from fat) for 6 weeks to induce NASH then subsequently divided into 2 sub-groups: fed either a modified high-fat diet (HFD, 55% energy from fat) or a modified high-fat alcoholic diet (HFA, 55% energy from fat and 16% energy from ethanol) for an additional 4 weeks. We observed in comparison to HFD group, HFA increased hepatic nuclear SIRT1 protein but decreased its deacetylase activity. SREBP-1c protein expression and FAS mRNA levels were significantly upregulated, while DGAT1/2 and CPT-I mRNA levels were downregulated in the livers of HFA compared to HFD. Although hepatic AdipoR1 decreased, HFA did not alter AdipoR2 and their downstream signaling. There were no significant changes in plasma adiponectin and free fatty acids (FFA), as well as adiponectin expression in adipose tissue between the two groups. The present study indicates that suppression in SIRT1 deacetylase activity contributes to alcohol-exacerbated hepatic inflammation and apoptosis in rats with pre-existing NASH. In addition, moderate alcohol intake did not modulate adiponectin/AdipoR signaling axis in this model.     

Detection of carcinogenic etheno-DNA adducts in children and adolescents with non-alcoholic steatohepatitis (NASH)

Background

Carcinogenic exocyclic-DNA adducts like 1,N⁶-etheno-2''-deoxyadenosine (εdA) are formed through reactive intermediates of 4-hydroxynonenal (4-HNE) or other lipid peroxidation (LPO) products with the DNA bases A, C, methyl-C and G. High levels of hepatic etheno-DNA adducts have been detected in cancer prone liver diseases including alcoholic liver disease (ALD). In ALD εdA levels correlated significantly with cytochrome P-450 2E1 (CYP2E1) expression which is also induced in non-alcoholic steatohepatitis (NASH). We investigated the occurrence of εdA adducts in children with NASH as a DNA damage marker.

Methods

Liver biopsies from 21 children/adolescents with histologically proven NASH were analysed for hepatic fat content, inflammation, and fibrosis. εdA levels in DNA, CYP2E1-expression and protein bound 4-hydroxynonenal (HNE) were semi-quantitatively evaluated by immunohistochemistry.

Results

Among 21 NASH children, εdA levels in the liver were high in 3, moderate in 5, weak in 9 and not elevated in 4 patients. There was a positive correlation between CYP2E1 and protein-bound 4-HNE (r=0.60; P=0.008) and a trend for a positive relationship for CYP2E1 vs. staining intensity of εdA (r=0.45; P=0.06). Inflammatory activity and fibrosis correlated significantly (r=0.49, P=0.023).

Conclusions

Our results demonstrate for the first time the presence of elevated carcinogenic etheno-DNA lesions (εdA) in the majority (17/21) of liver biopsies from young NASH patients. Our data suggest that LPO-derived etheno-adducts are implicated in NASH. Whether these adducts may serve as predictive risk markers in NASH children to develop hepatocellular cancer later in life remains to be investigated.     

Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Steatohepatitis and Orthotopic Liver Transplantation

Obesity, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are becoming increasingly common medical problems in the developed world, often in the setting of the metabolic or insulin resistance syndrome (IRS). It is predicted that by the year 2025 > 25 million Americans may have NASH-related liver disease. NASH and NAFLD also affect the donor population. The use of steatotic donor livers for liver transplantation (LT) is associated with an increased risk of primary nonfunction (PNF) in the allograft. There is particular reluctance to use steatotic livers for living donor LT. There is indirect evidence to suggest that patients undergoing LT for cirrhosis resulting from NASH may have poorer outcome, despite careful selection of LT candidates. Indeed it is likely that many potential LT candidates with NASH are excluded from LT due to co-morbid conditions related to IRS. The post-LT patient is at risk of several components of IRS, such as diabetes mellitus, hypertension, hyperlipidaemia and obesity and there is increasing recognition of de novo and recurrent NAFLD and NASH after LT. Thus NAFLD and NASH affect all aspects of LT including donors, patients in evaluation and the LT recipient.     

Prevalence of NASH/NAFLD in people with obesity who are currently classified as metabolically healthy

BackgroundWhile metabolic health in obesity may confer a protective status, recent studies indicate that nonalcoholic fatty liver disease (NAFLD) or even nonalcoholic steatohepatitis (NASH) may exist in this category of individuals. Although cardiovascular and diabetic risks have been well described, the risk of NAFLD and NASH among this population requires further investigation.ObjectiveOur goal was to compare the prevalence of steatosis, NAFLD, and NASH between individuals with metabolically healthy obesity (MHO) and individuals with metabolically abnormal obesity (MAO) and to identify preoperative risk factors for these conditions in a prospective cohort with morbid obesity scheduled for bariatric surgery.SettingsTertiary referral university hospital in France.MethodsThe prospective cohort included 837 bariatric patients who also had an intraoperative liver biopsy between 2002 and 2015. Obese individuals fulfilling none of the criteria in the strict definition of metabolic syndrome were considered metabolically healthy. Preoperative blood samples and liver pathology examinations were reviewed. Steatosis, NAFLD, and NASH were carefully identified allowing comparison of prevalence and risk factors between the 2 cohorts.ResultsIn total, 149 patients (17.8%) had MHO and the remaining 688 (82.2%) had MAO. The cohort with MHO was significantly younger, had a significantly lower glycosylated hemoglobin, a lower homeostasis model assessment of insulin resistance, and increased C-reactive protein. In individuals with MHO, 44 patients (29.5%) had at least moderate steatosis (>33% macrovesicular steatosis) and 5.4% had NASH. Using logistic regression, waist circumference was positively associated with NASH, whereas body mass index and alanine aminotransferase were significantly associated with severe steatosis (>66%).ConclusionOur study indicates that obese individuals without metabolic syndrome may develop subclinical liver involvement. Therefore, the occurrence of NAFLD and NASH in this population needs further investigation.     

Prevalence and predictors of asymptomatic liver disease in patients undergoing gastric bypass surgery

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of fatty liver disease that is increasingly recognized. There are limited data on the prevalence of NASH and the role of risk factors for NASH among the morbidly obese. HYPOTHESIS: The prevalence of asymptomatic NASH among morbidly obese patients undergoing gastric bypass surgery is high, and there are identifiable risk factors for NASH. DESIGN: Prospective case study. SETTING: University hospital. PATIENTS: Forty-eight consecutive patients undergoing gastric bypass surgery who had a concurrent open liver biopsy. Exclusion criteria included current consumption of more than 2 alcohol beverages monthly and known cirrhosis. A hepatopathologist blinded to clinical data reviewed biopsy specimens. MAIN OUTCOME MEASURES: The presence of NASH or severe fibrosis, preoperative body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters), fasting triglyceride level, and presence of type 2 diabetes mellitus (DM). RESULTS: Patients (mean +/- SD age, 42 +/- 10 years; 33 women) had an initial mean BMI of 59.9 +/- 12. Thirty-one patients (65%) had moderate to severe steatosis. Only 6 (12%) had advanced fibrosis. Sixteen (33%) had evidence of NASH. There was no difference in mean age, sex, BMI, or fasting triglyceride level between patients with and without NASH or advanced fibrosis. The odds of NASH were 128 times greater (95% confidence interval [CI], 5.2-3137.0) and the odds of severe fibrosis 75 times greater (95% CI, 4.5-1247.0) in patients with DM than in those without DM. Preoperative BMI was not independently associated with NASH (odds ratio, 1.01; 95% CI, 0.9-1.1) or severe fibrosis (odds ratio, 0.9; 95% CI, 0.86-1.02) after adjustment for DM. CONCLUSIONS: Moderate to severe hepatic steatosis and NASH are common among individuals undergoing gastric bypass procedures. Diabetes mellitus but not BMI is associated with NASH and advanced hepatic fibrosis in these patients.     

Accuracy of non-invasive liver stiffness measurement and steatosis quantification in patients with severe and morbid obesity

BackgroundVibration controlled transient elastography (VCTE) and controlled attenuation parameter (CAP™) have shown reliable performance predicting fibrosis and steatosis in normal- to overweight patients but have not been validated in severe to morbid obesity. This study aimed at determining the accuracy of VCTE, CAP™ and the composite score FibroScan-AST (FAST) in patients with a body mass index (BMI) of ≥35 kg/m².MethodsPatients scheduled for bariatric-metabolic surgery underwent preoperative VCTE/CAP™ measurement, and intraoperative liver biopsy. The feasibility and accuracy of VCTE, CAP™ and the composite score FAST were retrospectively analysed to evaluate fibrosis, steatosis and active fibrotic non-alcoholic steatohepatitis [NASH + non-alcoholic fatty liver disease (NAFLD) activity score ≥4 + fibrosis grade ≥2] using per protocol (PP) and intent to diagnose (ITD) calculation.ResultsIn total, 170 patients (median BMI 44.4 kg/m²) were included in the study. Liver biopsy showed NASH, simple steatosis, and normal livers in 60.6% (n=103), 28.8% (n=49), and 10.6% (n=18), respectively. VCTE and CAP™ delivered reliable results in 90.6% (n=154/170) and 90.5% (n=134/148). The AUC (PP) of VCTE, CAP™, and FAST were 0.687 (≥F2), 0.786 (≥F3), 0.703 (≥S2), 0.738 (S3), and 0.780 (active fibrotic NASH). The AUC increased to 0.742 (≥F2), 0.842 (≥F3), 0.712 (≥S2), 0.780 (S3), and 0.836 (active fibrotic NASH) in patients below the median BMI of 44.4 kg/m².ConclusionsVCTE, CAP™ and FAST show acceptable accuracy for the detection of fibrosis, steatosis and NASH in a real-life cohort of patients with obesity. Accuracy improves in patients with a BMI <44.4 kg/m².     

Are there Predictive Factors of Severe Liver Fibrosis in Morbidly Obese Patients with Non-alcoholic Steatohepatitis?

Background: Non-alcoholic steatohepatitis (NASH) is a clinicopathological entity characterized by the presence of steatosis and lobular and/or portal inflammation with or without fibrosis. Patients with non-alcoholic fatty liver and fibrosis on liver biopsy have increased liver-related deaths. Methods: 181 wedge liver biopsies, taken at the time of bariatric surgery from patients with a mean body mass index (BMI) of 47, were studied. In all cases, the liver biopsy was performed without knowledge of the patient's clinical and biochemical data, which were then examined with univariate and multivariate analysis. Results: Diagnosis of NASH was established in 105 patients (91%); 74 patients (70%) showed mild steatosis, 20 (19%) had moderate inflammation and fibrosis, and 11 (10%) had steatosis with severe fibrosis. None of the liver biopsies showed cirrhosis. Age was the only independent predictor of moderate and severe fibrosis (p=0.001). Conclusions: Since only age was a predictor of moderate or severe fibrosis, and no clinical or biochemical abnormalities detected slowly progressive hepatic fibrosis, liver biopsy is the only means of detecting progression to more advanced liver disease in a NASH patient.     

非酒精性脂肪肝与骨密度关联研究的相关进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是非常常见的与代谢综合征的临床特征密切相关的病理状态,其特点在于肝内三酰甘油的堆积及肝脏病变持续进展。在全球,非酒精性脂肪肝的患病率越来越高,特别是在发展中国家,日渐成为危害公众健康的问题。过去认为胰岛素抵抗和肥胖是非酒精性脂肪肝的主要危险因素,与肥胖有着平行关系,近期倾向于肝脏是涉及多器官及系统的复杂作用的中心,包括骨骼及骨骼肌系统。多个横断面研究也发现,胰岛素抵抗、肥胖除了与NAFLD密切相关外,同时也与骨密度间存在着关联,并且不少研究发现NAFLD患者骨密度及骨量较正常同龄人减少,但具体机制仍未清楚。目前认为导致骨质疏松症骨密度的恶化是与年龄相关的过程,另外,NAFLD的患病率也随着年龄增长而增加,两者均有年龄相关性。但NAFLD与骨密度间是否存在关联,目前尚存在争议,笔者就NAFLD对骨密度的影响及相互关系结合国内外的研究进展进行综述。     

Cadmium Exposure and Liver Disease among US Adults

Background

Effects of chronic cadmium exposure on liver disease and liver-related mortality are unknown. We evaluated the association of creatinine-corrected urinary cadmium levels with hepatic necroinflammation, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver-related mortality, and liver cancer mortality in the US general population.

Methods

We analyzed the relationship of individuals in the top quartile for urinary cadmium measured in 12,732 adults who participated in the Third National Health and Nutrition Examination Survey in 1988–1994 (NHANES III), and hepatic necroinflammation, NAFLD, and NASH. Associations between cadmium, liver-related mortality, and liver cancer mortality were evaluated in the NHANES III mortality follow-up study.

Results

The cutoffs for highest quartile of urinary cadmium per gram of urinary creatinine were 0.65 and 0.83 μg/g for men and women, respectively (P?<?0.001). After multivariate adjustment for other factors including smoking, the odds ratios [95 % confidence intervals (CI)] for hepatic necroinflammation, NAFLD, and NASH associated with being in the top quartile of cadmium levels by gender, were 2.21 (95 % CI, 1.64–3.00), 1.30 (95 % CI, 1.01–1.68) and 1.95 (95 % CI, 1.11–3.41) for men and 1.26 (95 % CI, 1.01–1.57), 1.11 (95 % CI, 0.88–1.41) and 1.34 (95 % CI, 0.72–2.50) for women, respectively. The hazard ratios for liver-related mortality and liver cancer mortality for both genders were 3.42 (95 % CI, 1.12–10.47) and 1.25 (95 % CI, 0.37–4.27).

Conclusions

Environmental cadmium exposure was associated with hepatic necroinflammation, NAFLD, and NASH in men, and hepatic necroinflammation in women. Individuals in the top quartile of creatinine-corrected urinary cadmium had over a threefold increased risk of liver disease mortality but not in liver cancer related mortality.     

Non-alcoholic Steatohepatitis (NASH) and Hepatocellular Carcinoma

Non-alcoholic fatty liver disease (NAFLD) is characterized by an excessive accumulation of fatty acids and triglycerides within the cytoplasm of the hepatocytes of non-alcohol users. The natural history varies according to the initial histological diagnosis. A current consideration is that cryptogenic cirrhosis may be representative of a late stage of non-alcoholic steatohepatitis (NASH), which has lost its features of necroinflammatory activity and steatosis in up to 80% of patients. Since NASH is able to progress to cirrhosis, hepatocellular carcinoma (HCC) development may be an end-stage of this disease. We report below two clinical cases of patients diagnosed with NASH who developed HCC. The relationship between NAFLD and HCC is reviewed.     

A clinical and biochemical profile of biopsy-proven non-alcoholic Fatty liver disease subjects

Objective: To describe clinical and biochemical features of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD). Study Design: Case-series. Place and Duration of Study: Medical Unit of Rawalpindi Medical College, Rawalpindi, from July 2005 to July 2006. Patients and Methods: Fifty patients of either and of all ages were included, who had ultrasound evidence of fatty liver, deranged liver enzymes, and negative history of alcohol uptake. Serological/biochemical tests/markers of other liver diseases were negative. Each subject underwent liver biopsy reported by a single histopathologist. Clinical (symptoms, hypertension, hepatomegaly, and obesity) and biochemical evaluation (for diabetes, lipid abnormalities, and aspartate to alanine aminotransferase ratio [AST/ALT]) of each subject was done. Chi-square and t-tests were used for p-value calculation for finding significant difference between fatty liver and non-alcoholic steato-hepatitis groups. Results: Thirty three (66%) patients were female and 34% were male. Mean age was 45.50 +/- 11.50 years. Histopathologically, 62% subjects had fatty liver alone, while 38% had nonalcoholic steatohepatitis (NASH). Fatigue (100%), hypertriglyceridemia (80%), hepatomegaly (72%), AST/ALT ratio < 1 (72%), and obesity/overweight (54%) were common NAFLD-related features. Except for hypertriglycedemia (p-value 0.008), no statistically significant association was noted between these features and histopathological subtypes of NAFLD. Conclusion: NAFLD-related clinical and biochemical features included fatigue, obesity, hepatomegaly, AST/ALT ratio<1, and hypertriglycedemia. Significant relationship existed between hypertriglyceridemia and NASH.     

Metabolic Syndrome Is Related to Nonalcoholic Steatohepatitis in Severely Obese Subjects

BACKGROUND: Metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD), ranging from simple steatosis to steatohepatitis (NASH), have become important health issues in obese subjects. In this study, we investigated the relationship between MetS and NASH in severely obese subjects. METHODS: A total of 111 non-alcoholic obese patients who underwent laparoscopic bariatric surgery (BMI 45.4 +/- 5.7 kg/m2) were enrolled from February to September 2004 in a referral center in North Taiwan. MetS and its individual components were defined using the American Heart Association/National Heart, Lung, and Blood Institute criteria. Based on liver biopsy during surgery, subjects were classified into either having NASH or not. The relationship among NASH, adiponectin, insulin resistance, MetS and its individual components was examined using a multivariate logistic regression analysis. RESULTS: The prevalence of NASH and MetS in these subjects was 79.3% and 68.5%, respectively. Using a multivariate logistic regression analysis with NASH as the outcome variable, odds ratio (OR) of NASH for subjects with MetS versus without MetS was 2.96 (95% CI = 1.14-7.68) adjusted for age, gender, and BMI. Also, high blood pressure (OR = 2.97, 1.31-6.73) and high fasting glucose (OR = 2.94, 1.13-7.67) were independently associated with NASH after adjustment for age, gender, and BMI. Insulin resistance measured as HOMA-IR and serum adiponectin level were not significantly different between the NASH and non-NASH group. CONCLUSION: MetS and NASH were common in severely obese Taiwanese adults. Presence of MetS, high blood pressure, and high fasting glucose was independently related to increased risk of NASH. The underlying mechanism deserves to be explored in the future.     

Visual Liver Score to Stratify Non-Alcoholic Steatohepatitis Risk and Determine Selective Intraoperative Liver Biopsy in Obesity

Background

Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are endemic in obesity. We aimed to evaluate the diagnostic accuracy and reproducibility of a simple intraoperative visual liver score to stratify the risk of NASH and NAFLD in obesity and determine the need for liver biopsy.

Methods

This is a prospective cohort study of obese adults undergoing bariatric surgery. The surgical team used a visual liver score to evaluate liver colour, size and surface. This was compared to histology from an intraoperative liver biopsy.

Results

There were 152 participants, age 44.6 ± 12 years, BMI 45 ± 8.3 kg/m². Prevalence of NAFLD was 70.4%, with 12.1% NASH and 26.4% borderline NASH. Single-visual components were less accurate than total composite score. Steatosis was most accurately identified (significant steatosis: AUROC 0.746, p < 0.05; severe steatosis: AUROC 0.855, p < 0.05). NASH was identified with moderate accuracy (AUROC 0.746, p = 0.001), with sensitivity 75% for a score ≥ 2. Stratification into low (≤ 1) and high-risk (≥ 4) scores accurately identified patients who should or should not have an intraoperative biopsy. Most patients with a normal-appearing liver did not have disease (94.4%). The structured visual assessment was quick and interobserver agreement was reasonable (κ = 0.53, p < 0.05).

Conclusions

A simple, structured tool based on liver appearance can be a useful and reliable tool for NAFLD risk stratification and identification of patients who would most and least benefit from a biopsy. A normal liver appearance reliably excludes significant liver disease, avoiding the need for liver biopsy in patients otherwise at high clinical risk of NASH.

     

Hepatocellular Carcinoma Arising from Nonalcoholic Steatohepatitis: Report of Two Cases

Sporadic cases of hepatocellular carcinoma (HCC) originating from nonalcoholic steatohepatitis (NASH) have recently been reported. Thus, we investigated the prevalence of NASH in patients with HCC. A review of the clinical records of 481 patients who underwent liver resection for HCC in our department between January 1991 and December 2003 revealed only two (0.4%) patients with HCC associated with NASH. Both of these patients had noninsulin-dependent diabetes mellitus, and neither had a history of alcohol consumption or blood transfusion. All serologic markers for hepatitis B and C viruses were negative. Histological examination of the noncancerous hepatic tissue revealed NASH with moderate hepatic fibrosis in one patient and cirrhosis in the other. Thus, clinical follow-up and screening for HCC should be done for patients with hepatic fibrosis caused by NASH, even though this form of hepatitis is an uncommon cause of HCC.     

Lipopolysaccharide-Binding Protein Plasma Levels and Liver TNF-Alpha Gene Expression in Obese Patients: Evidence for the Potential Role of Endotoxin in the Pathogenesis of Non-Alcoholic Steatohepatitis

Background Some lines of evidence suggest that endotoxin may induce non-alcoholic steatohepatitis (NASH) in a background of fatty liver. However, a clear association between increased endotoxemia and development of steatohepatitis in obese patients has not been confirmed. We aim to assess the endotoxemic state of patients with non-alcoholic fatty liver disease (NAFLD) and its relationship with the liver expression of TNF-α and the presence of NASH. Methods Prospective study comprising 40 patients with morbid obesity who were diagnosed with NAFLD. Blood samples and liver biopsies were collected. Endotoxemia was assessed by the evaluation of circulating level of LPS-binding protein (LBP). Plasma levels of LBP and TNF-α were assessed by ELISA. The expression of TNF-α in liver tissue was evaluated by real-time PCR. Histological examination was performed to evaluate the presence of steatosis or NASH. Results Levels of LBP were increased in obese patients with NAFLD. In addition, plasma level of LBP was increased in patients with steatohepatitis (14.2 ± 3.9 μg/mL) when compared with patients with simple steatosis (11.5 ± 3.2 μg/mL), P = 0.041.The TNF-α mRNA expression in liver tissue was significantly higher in patients with NASH.This increment correlated with the rise in plasma levels of LBP (r = 0.412, P = 0.036). Conclusion NAFLD patients have elevated plasma levels of LBP and they are further increased in patients with NASH. This increase is related to a rise in TNF-α gene expression in the hepatic tissue which supports a role for endotoxemia in the development of steatohepatitis in obese patients.     

非酒精性脂肪性肝炎的诊断和治疗进展

非酒精性脂肪肝疾病(nonalcoholic fatty liver disease,NAFLD)以肝细胞中脂肪过多积累为标志,包括非酒精性脂肪肝(nonalcoholic fatty liver,NAFL)和非酒精性脂肪性肝炎(nonalcohol-ic steatohepatitis,NASH),其中NASH可能会...     

Implications of worse renal dysfunction and medical comorbidities in patients with NASH undergoing liver transplant evaluation: impact on MELD and more

Increasing numbers of patients with non-alcoholic steatohepatitis (NASH) are referred for liver transplant (LT). Our objective was to characterize patients with NASH among referred LT candidates (from 1998 to 2008), and we compared demographics, etiology of liver disease, diabetes, hypertension, smoking, obesity, cardiac disease, cancer, laboratory data, model for end-stage liver disease (MELD), and outcomes between NASH and non-NASH patients. Patients with NASH (n = 71) were compared to other chronic liver disease (n = 472). Patients with NASH were older (58.7 vs. 52.5 yr, p < 0.0001), Asian (53.5% vs. 34.7%, p = 0.03) and women (50.7% vs. 32.1%, p = 0.003). Patients with NASH had more diabetes, hypertension, obesity, cardiac disease, and smoking history (p < 0.05). Patients with NASH were equally likely to have liver cancer, but more likely to have non-liver cancers (20.8% vs. 4.4%, p = 0.008). There was no difference in MELD, but patients with NASH had lower protime/international normalized ratio (1.14 vs. 1.27, p = 0.04) and higher creatinine (1.26 vs. 0.98 mg/dL, p = 0.0018). Patients with NASH were equally likely to undergo evaluation, listing, and transplantation compared to non-NASH patients. While all patients with chronic liver disease can have renal dysfunction because of hepatorenal syndrome, patients with NASH have more renal dysfunction, perhaps related to diabetes, hypertension, and cardiovascular disease. Transplant centers should consider this carefully in selection of candidates for LT.     

Weight Loss and Non-alcoholic Fatty Liver Disease: Falls In Gamma-Glutamyl Transferase Concentrations are Associated with Histologic Improvement

Background: The ability for aminotransferase levels to track histological features of non-alcoholic fatty liver disease (NAFLD) with weight loss has not been examined. Methods: We examined the effect of weight loss following laparoscopic adjustable gastric banding surgery on the histological features of NAFLD and plasma aminotransferase concentrations (AST, ALT and GGT) in 60 (12M, 48F) selected severely obese patients. All 120 paired biopsies were deidentified and scored for lobular steatosis, fibrosis, inflammation, Mallory bodies and NASH. Results: 30 patients (50%) had baseline histological features of non-alcoholic steatohepatitis (NASH). Repeat biopsies were taken at 29.5±10 months after baseline. Mean weight loss was 31.5±18 kg. There were improvements in AST, ALT, GGT, lobular steatosis, inflammation and fibrosis between baseline and follow-up (P<0.001 for all). Only 6 (10%) of repeat biopsies showed NASH. No change in aminotransferase concentrations predicted the change in steatosis, but changes in AST and GGT predicted improved scores for inflammation, fibrosis, Mallory bodies and NASH. The lowering of GGT best predicted the improvements in inflammation, fibrosis and NASH. Conclusion: With weight loss, falls in GGT and, to a lesser extent, in AST, are predictive of improved lobular inflammation and fibrosis, key prognostic features of NAFLD.