Higher Prevalence Of Nonalcoholic Steatohepatitis Research Articles

1349-P: People with Type 2 Diabetes Have a High Prevalence of Nonalcoholic Steatohepatitis with Significant Fibrosis When Screened by NIS4 or Elastography

Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Diagnosis remains challenging as a liver biopsy is usually not feasible. NIS4 is a novel plasma diagnostic test combining the measurement of A1c and 3 biomarkers (miR-34a-5p, A2M, YKL-40) linked to NASH disease activity and higher cirrhosis risk. The aim of this study was to assess the prevalence of high-risk NASH (NASH with significant fibrosis [≥F2]) as estimated by NIS4 or elastography in the outpatient setting. A total 400 participants (age: 55±11 years; BMI: 31.6±6.6 kg/m2; T2DM: 32%; obese without T2DM [OB]: 33%), unaware of having NAFLD, were recruited from PCP and endocrine clinics and screened by: a) Elastography (Fibroscan®) for steatosis (controlled attenuation parameter or CAP ≥274 dB/m) and for fibrosis (liver stiffness measurement or LSM ≥7.0 kPa); and b) NIS4 for high-risk NASH (defined as a NIS4 >0.63; low-risk: <0.36). Among patients with T2DM or OB, 68% had steatosis compared to 35% without obesity or T2DM (CON) (p<0.01), while fibrosis (LSM≥7.0 kPa) was present in 14% of patients with T2DM (CON = 1%; p=0.02). High-risk NASH by NIS4 occurred frequently among patients with T2DM, either with (30%) or without (26%) obesity, and rare in those without T2DM (3%; p<0.001). NIS-4 correlated with steatosis (CAP) (r = 0.35) and fibrosis (LSM) (r = 0.32; both p<0.001). Patients with high-risk NASH by NIS4 compared to those with low-risk NASH, more often had steatosis (82% vs 46%), fibrosis (16% vs 4%), AST≥30 IU/L (41% vs. 8%) and ALT≥30 IU/L (36% vs. 15%), hepatic (HOMA-IR: 68% vs. 25%) and adipose tissue (adipo-IR: 80% vs 56%) insulin resistance (all p<0.01). NIS4 correlated with having metabolic syndrome (r=0.41; p<0.01) and was more often increased in people from endocrine vs. PCP clinics (34% vs. 9%; p<0.05). Conclusion: NASH with significant fibrosis is common in T2DM. Patients with elevated NIS4 often have NAFLD with fibrosis and an unfavorable cardiometabolic profile. Disclosure S.Kalavalapalli: None. T.R.Prezant: None. M.A.Connelly: Employee; LabCorp, Stock/Shareholder; LabCorp. D.Barb: None. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. E.Godinez leiva: None. R.Lomonaco: None. S.A.Marangi: None. E.Valdez saenz: None. A.Ortiz rocha: None. J.T.Budd: None. Y.Mohseni: None. K.Y.Chun: None. Funding National Institutes of Health (R01120331-01A1)

Predictors of Nonalcoholic Steatohepatitis Severity in Obese Patients Undergoing Bariatric Surgery: A Cross-Sectional Study

Background: Nonalcoholic steatohepatitis (NASH) currently affects 3–5% of the general population and 10–50% of patients with obesity. Our aim was to determine the predictors of severity of NASH in patients with obesity undergoing sleeve gastrectomy. Methods: We conducted a retrospective study in patients with obesity who underwent sleeve gastrectomy from 2013 to 2016. Liver biopsy at the time of the surgery showed a histological grade of NASH in all the patients. Patients were stratified into two groups, mild and moderate-severe (MS) NASH. Predictors were evaluated with multivariate logistic regression. Results: We included 193 patients. Of these, 139 had mild, 22 moderate, and 36 severe NASH. Majority of patients were female (54.8%) and the mean body mass index was 40.30 ± 2.19 kg/m2. In the adjusted regression model, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (prevalence ratios [PR]: 1.06, confidence interval [95% CI]: 1.02–1.10) and alanine aminotransferase (ALT) (PR: 1.01, 95% CI: 1.00–1.01) were factors associated with MS NASH. Conclusions: Despite the high prevalence of NASH in the obese population, most patients presented mild severity. A higher severity of NASH among patients with obesity can be predicted by clinical abnormalities such as higher HOMA-IR and ALT levels. Higher HOMA-IR levels are potential predictors of MS NASH regardless of insulin resistance status and in patients without metabolic syndrome.

Analysis of clinicopathological characteristics of non-alcoholic fatty liver disease

Objective: To investigate the clinical and pathologic characteristics of obese adults with nonalcoholic fatty liver disease (NAFLD) and to aid the diagnosis of nonalcoholic steatohepatitis (NASH). Methods: A total of 262 patients eligible for inclusion who received volume reduction metabolism surgery and liver biopsy in the First Affiliated Hospital of Nanjing Medical University from June 2018 to September 2019 were selected. HE staining, reticular fiber staining and Masson staining were performed. Statistical analysis was performed using SPSS 20.0. Results: The patients ranged in age from 18 to 66 years. Among the 262 cases, 65 cases (65/262, 24.8%) were male and 197 cases (197/262, 75.2%) were female. Sixty-one cases (61/262, 23.3%) were non-NAFLD, 201 cases (201/262, 76.7%) were NAFLD including 27 cases (27/201, 13.4%) of nonalcoholic fatty live (NAFL) and 174 cases (174/201, 86.6%) of NASH. The main lesions of NAFLD were in hepatic acinus zone 3. There were significant differences in age, alanine aminotransferase (ALT), glutamic oxaloacetic transaminase (AST), body mass index (BMI), fasting blood-glucose (FPG) and apolipoprotein A (APOA) levels among the non-NAFLD group, NAFL group and NASH group (P<0.05). Patients with BMI≥35 m/kg2 combined with type 2 diabetes had a higher prevalence of NASH. Multiple logistic regression showed that ALT and APOA were independent predictors of NASH (P<0.001, OR=1.05, 95%CI: 1.020-1.082; P=0.027, OR=0.916, 95%CI: 0.878-0.941). Total cholesterol (CHO) and high-density lipoprotein (HDL) were independent predictors of lobular inflammation (P=0.043, 95%CI: 0.010-0.634; P=0.024, 95%CI:-3.068--0.216). AST and HDL were independent predictors of fibrosis stage (P=0.029, 95%CI: 0.001-0.021; P<0.001, 95%CI:-2.670--0.645). Conclusions: Biochemical indicators of NAFLD are closely related to its pathology. The histological lesions of NAFLD are mainly present in hepatic acinar area 3. The diagnosis of NASH is supported by extensive steatosis and high levels of CHO, ALT, AST and BMI, low levels of HDL and ApoA in biochemical markers, but pathological examination is still the gold standard for it.

Effect of common genetic variants on the risk of cirrhosis in non-alcoholic fatty liver disease during 20 years of follow-up.

Several genotypes associate with a worse histopathological profile in patients with non-alcoholic fatty liver disease (NAFLD). Whether genotypes impact long-term outcomes is unclear. We investigated the importance of PNPLA3, TM6SF2, MBOAT7 and GCKR genotype for the development of severe outcomes in NAFLD. DNA samples were collected from 546 patients with NAFLD. Advanced fibrosis was diagnosed by liver biopsy or elastography. Non-alcoholic steatohepatitis (NASH) was histologically defined. Additionally, 5396 controls matched for age, sex and municipality were identified from population-based registers. Events of severe liver disease and all-cause mortality were collected from national registries. Hazard ratios (HRs) adjusted for age, sex, body mass index and type 2 diabetes were estimated with Cox regression. In NAFLD, the G/G genotype of PNPLA3 was associated with a higher prevalence of NASH at baseline (odds ratio [OR] 3.67, 95% CI=1.66-8.08), but not with advanced fibrosis (OR 1.81, 95% CI=0.79-4.14). After up to 40 years of follow-up, the PNPLA3 G/G genotype was associated with a higher rate of severe liver disease (adjusted hazard ratio [aHR] 2.27, 95% CI=1.15-4.47) compared with the C/C variant. NAFLD patients developed cirrhosis at a higher rate than controls (aHR 9.00, 95% CI=6.85-11.83). The PNPLA3 G/G genotype accentuated this rate (aHR 23.32, 95%=CI 9.14-59.47). Overall mortality was not affected by any genetic variant. The PNPLA3 G/G genotype is associated with an increased rate of cirrhosis in NAFLD. Our results suggest that assessment of the PNPLA3 genotype is of clinical relevance in patients with NAFLD to individualize monitoring and therapeutic strategies.

IS HOMEOSTASIS MODEL ASSESSMENT FOR INSULIN RESISTANCE >2.5 A DISTINGUISHED CRITERIA FOR METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE IDENTIFICATION?

Insulin resistance (IR), assessed by different criteria, is an important factor in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). More recently with the characterization of this metabolic dysfunction-associated fatty liver disease (MAFLD), one of the proposed criteria for this diagnosis has been the determination of the homeostasis model assessment-insulin resistance (HOMA-IR). The purpose of this study was to evaluate the relationship of HOMA-IR>2.5 with clinical, metabolic, biochemical and histological data obtained in non-diabetic patients diagnosed with NAFLD by liver biopsy. Cross-sectional, retrospective study was carried out with data from 174 adult individuals of both genders with non-diabetics NAFLD, without obvious signs of portal hypertension. The body mass index (BMI) was classified according to the World Health Organization (1998), and the metabolic syndrome by the criteria of NCEP-ATP-III. Biochemical tests were evaluated using an automated method and insulinemia through immunofluorometric assay. Histological findings were classified according to Kleiner et al. (2005). The mean age of the studied population was 53.6±11.2 years, with 60.3% being female. The average BMI was 30.3 kg/m2 and 75.9% of the patients had increased waist circumference. Among evaluated metabolic parameters, there was a higher prevalence of metabolic syndrome (MS) in patients with HOMA-IR>2.5, with no statistical difference in relation to BMI between studied groups. Values of liver enzymes and serum ferritin were significantly higher in patients with this marker of IR, who had a higher prevalence of non-alcoholic steatohepatitis (NASH) and advanced liver fibrosis. In the multivariate analysis, the clinical diagnosis of MS, hyperferritinemia and the presence of NASH in the liver biopsy were the factors independently associated with the presence of altered HOMA-IR. HOMA-IR values >2.5 identify patients with NAFLD with distinct clinical and metabolic characteristics and with a greater potential for disease progression, which validates this parameter in the identification of patients with MAFLD.

Lower serum copper concentrations are associated with higher prevalence of nonalcoholic steatohepatitis: a matched case–control study

Copper is an essential trace element involved in oxidative stress reactions and energy metabolism. While nonalcoholic fatty liver disease (NAFLD) is closely related to metabolic dysfunction, the role of copper in the development of simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) is still unclear. We aimed to compare serum copper levels between patients with simple steatosis and those with NASH. We studied 102 patients with biopsy-proven NASH (cases) and 102 NAFL controls, who were matched for age, sex, and residential city. Multivariable conditional logistic analysis was performed to explore associations between serum copper levels and the presence of NASH. Serum copper levels were significantly lower in patients with NASH than in those with matched NAFL controls (15.53 ± 2.41 μmol/l vs. 16.34 ± 3.23 μmol/l; P = 0.029). This intergroup difference in serum copper levels was more pronounced in men than in women. The per unit, per SD, and per doubling of serum copper levels were associated, respectively, with an approximately 20, 40, and 90% decrease in risk of having NASH, even after adjustment for potential confounding factors. Lower serum copper concentrations are significantly associated with higher prevalence of NASH among biopsied-proven NAFLD patients, particularly in men.

Living Donor Liver Transplant in Patients Aged 60 Years or Older: Experience from a Large Volume Centre in India

With ageing population and higher prevalence of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in older patients, more and more living donor liver transplants (LDLTs) are being considered in this group of patients as eligibility for deceased donor liver transplant is restricted to those aged 65 years and younger. However, the short- and long-term outcomes of this group have not been reported from India, which does not have a robust national health scheme. The aim of this study was to provide guidelines for transplant in this group. All patients aged 60 years and older (group 1) who underwent LDLT in our centre between January 2006 and December 2017 were studied. A propensity score-matched group in 1:2 ratio was created with comparable sex and Model for End-Stage Liver Disease score (group 2). The 2 groups were compared for duration of hospital stay, surgical complications, hospital mortality and 1-, 3- and 5-year survival. Group 1 consisted of 207 patients, and group 2 had 414 patients. The number of patients in group 1 gradually increased with time from 4 in 2006 to 33 in 2017 accounting for 15% of total cases. Group 1 had more patients with viral hepatitis, NASH and HCC, and they had a higher 30-day mortality due to cardiorespiratory complications. Although 1- and 3-year survival was similar, the 5-year survival was significantly lower in group 1. Five-year survival was lower in the elderly group due to cardiorespiratory complications and recurrence of HCC. Outcomes in the elderly group can be improved with better patient selection and preventing HCC recurrence.

Lower levels of plasma NT-proBNP are associated with higher prevalence of NASH in patients with biopsy-proven NAFLD

Background and aimsEmerging evidence suggests that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are decreased in patients with imaging-defined nonalcoholic fatty liver disease (NAFLD), but no data are currently available on the association between plasma NT-proBNP levels and the histological severity of NAFLD. Methods and resultsWe enrolled 351 (73.5% men) consecutive adult patients with biopsy-proven NAFLD without a prior history of cardiovascular disease (CVD). Plasma NT-proBNP levels were measured using a commercially available immunochemical system (VITROS® 5600, Johnson, New Jersey). Fifty-three percent of these subjects had nonalcoholic steatohepatitis (NASH). After stratification of patients by plasma NT-proBNP tertiles; compared to those in the 1st tertile (NT-proBNP ≤16 pg/ml), the odds ratio for NASH was 0.52 (95% CI 0.29–0.95) in patients in the 2nd tertile (NT-proBNP of 17–33 pg/ml) and 0.49 (95% CI 0.26–0.93) in those in the 3rd tertile (NT-proBNP ≥34 pg/ml) of plasma NT-proBNP levels, even after adjustment for age, sex, body mass index, homeostasis model assessment (HOMA)-estimated insulin resistance, pre-existing diabetes, hypertension, and dyslipidemia. ConclusionIn subjects with biopsy-proven NAFLD without known CVD, this cross-sectional study shows for the first time, that lower plasma NT-proBNP levels are strongly associated with a higher prevalence of NASH.

Presence of Serum Antinuclear Antibodies Does Not Impact Long-Term Outcomes in Nonalcoholic Fatty Liver Disease.

We investigated the longitudinal impact of antinuclear antibody (ANA) on clinical outcomes and survival in nonalcoholic fatty liver disease (NAFLD). ANA were found in 16.9% of 923 biopsy-proven NAFLD patients, but none of them had histologic autoimmune hepatitis (AIH) or developed AIH after a mean follow-up of 106±50 months. Although ANA-positive cases had a higher prevalence of nonalcoholic steatohepatitis at baseline, the occurrence of liver-related events, hepatocellula carcinoma, cardiovascular events, extrahepatic malignancy, and overall survival were similar to ANA-negative. Once AIH has been ruled out, the long-term outcomes and survival are unaffected by the presence of ANA in patients with NAFLD.

Features of the course of non-alcoholic fatty liver disease in HIV-infected individuals

This article reflects the course of non-alcoholic fatty liver disease (NAFLD) in HIV-infected individuals. It is noted that long-term antiretroviral therapy and the use of D-drugs can explain the high prevalence of steatosis in this category of patients. The results of experimental studies that demonstrate the direct effect of HIV on liver steatosis by infection of stellate liver cells, stimulation of abnormal expression of SREBP-1 and PPARγ are considered. The role of HIV-mediated microbial translocation as one of the triggers for the development of non-alcoholic steatohepatitis (NASH), which contributes to chronic inflammation due to an increase in the permeability of the intestinal barrier to bacterial products and endotoxins, is noted. Data are presented confirming the high prevalence of the abnormal distribution of fat and visceral obesity (components of lipodystrophy syndrome) in a cohort of HIV-infected individuals. There was a high prevalence of steatosis and steatohepatitis in HIV-infected patients with lipodystrophy as compared with HIV-infected patients without lipodystrophy. Data showing the high prevalence of NASH in HIV-infected individuals are presented. A high rate of progression of NAFLD in a cohort of HIV-infected individuals was observed, regardless of the presence/absence of a combined viral infection (chronic hepatitis C). It has been established that the classic risk factors for NAFLD (high body mass index, dyslipidemia, metabolic syndrome) can contribute to the rapid progression of the disease in people living with HIV, compared with representatives of the general population.

C-peptide is associated with NAFLD inflammatory and fibrotic progression in type 2 diabetes.

A higher prevalence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis was observed in type 2 diabetes. We aim to investigate whether C-peptide is associated with nonalcoholic fatty liver disease (NAFLD) progression in type 2 diabetic adults. A total of 4937 diabetic participants were enrolled from China in 2018. Liver steatosis was detected by ultrasound. Subjects with NAFLD were categorized into simple NAFLD and probable NASH by the concurrent presence of metabolic syndrome. NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. Individuals with a longer history of type 2 diabetes had a lower C-peptide level and a lower prevalence of probable NASH but a higher prevalence of advanced fibrosis. C-peptide was positively associated with simple NAFLD and probable NASH, with odds ratios (ORs) of 4.55 [95% confidence interval (CI) 3.16, 6.55] and 5.28 (95% CI 3.94, 7.09), respectively, comparing quartile 4 with quartile 1 (both p for trend <0.001). However, C-peptide quartiles were negatively associated with the probable presence of advanced fibrosis (Q4 vs. Q1, OR 0.59, 95% CI 0.36, 0.97, p for trend <0.05). A 1-SD increment of ln(C-peptide) was also significantly associated with inflammatory and fibrotic progression (OR 1.34, 95% CI 1.27, 1.41; OR 0.88, 95% CI 0.79, 0.98, respectively). Significant but opposite associations between C-peptide and inflammatory and fibrotic progression of NAFLD were observed. Understanding islet hormone changes during type 2 diabetes and differentiating the stage of NAFLD may help to personalize treatment strategies for NAFLD patients with type 2 diabetes.

1565-P: Gender Differences in Clinical Predictors of Nonalcoholic Steatohepatitis in Type 2 Diabetes

Introduction: Nonalcoholic steatohepatitis (NASH) associated with type 2 diabetes (T2D) increases the risk for cardiovascular disease, cirrhosis and hepatocellular carcinoma. Several clinical predictors of NASH are known but gender differences in subjects with T2D are unknown. Aims: To determine gender differences in clinical predictors of NASH in Asian Indians with T2D. Methods: This one-year prospective study was conducted after institutional approval and informed consent. Recruited participants had no history of liver disease, hepatotoxic drugs or alcohol intake. Transient elastography by FibroScan, validated for diagnosis of fibrosis by liver stiffness measurement (LSM), was used in this study. NASH was diagnosed when LSM was ≥7 kPa. Results are tabulated below. Conclusions: In subjects with T2D, women had significantly higher prevalence of NASH (34.7%) compared to men (26.3%), with a 50% higher risk. Obesity, hypertriglyceridemia and hypoalbuminemia were strong predictors of NASH in both genders. Systolic hypertension doubled the risk in women but was not significant in men, while hyperglycemia was a significant predictor in men but not in women. Raised Waist/Height Ratio conferred much higher risk of NASH in women compared to men, while the high risk due to raised BMI and waist circumference was similar in both genders. Predictors of NASH are crucial targets for intervention but vary by gender. Disclosure S. Panicker: Speaker's Bureau; Self; Abbott, AstraZeneca, Biocon, Dr. Reddys Laboratories, Eli Lilly and Company, Intas Pharmaceuticals Ltd., Johnson &amp; Johnson, Novartis AG, Novo Nordisk A/S, Sanofi India Pvt Ltd; Speaker's Burea; Self; SUN Pharma Self.J.W. Stephens: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, NAPP Pharmaceuticals Limited.

High prevalence of nonalcoholic steatohepatitis and abnormal liver stiffness in a young and obese Mexican population.

ObjectiveTo identify nonalcoholic steatohepatitis (NASH) and liver stiffness in Mexican subjects with different body mass index (BMI).MethodsA cross-sectional study was conducted in 505 adults. Risk for NASH was defined as the presence of one or more of the following biochemical and metabolic parameters (BMPs): fasting glucose ≥100 mg/dl, triglycerides (TG) ≥150 mg/dl, homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.5, aspartate aminotransferase (AST) >54 IU/L and alanine aminotransferase (ALT) >42 IU/L. Body mass index measurement and nutritional assessment were performed by standard procedures. Liver fibrosis stage was determined by liver stiffness measurement using transitional elastography (TE) or by liver biopsy (LB).ResultsRisk for NASH was 57% (290/505). Most BMPs values incremented by BMI category. Among 171 at-risk patients, 106 subjects were evaluated by TE and 65 subjects by LB. Abnormal liver stiffness (≥6.0 kPa) was prevalent in 54% (57/106) of the cases, whereas by LB, 91% (59/65) of patients with obesity had NASH and liver fibrosis. Furthermore, liver fibrosis was prevalent in 46% (6/13) in normal weight individuals, whereas 4.6% (3/65) of patients with a BMI ≥ 35 kg/m2 showed no histopathological abnormalities. Overall, 67.8% (116/171) of the patients had abnormal liver stiffness or NASH. The normal weight patients with liver damage consumed relatively a higher fat-rich diet compared to the other groups whereas the remaining subgroups shared a similar dietary pattern.ConclusionYoung patients with overweight and obesity showed a high prevalence of altered BMPs related to abnormal liver stiffness assessed by TE and NASH by LB. Early diagnostic strategies are required to detect the risk for NASH and avoid further liver damage in populations with a rising prevalence of obesity by defining the risk factors involved in the onset and progression of NASH.

Prevalence of nonalcoholic steatohepatitis in Japanese patients with morbid obesity undergoing bariatric surgery.

Patients with morbid obesity selected for bariatric surgery have a high prevalence of nonalcoholic steatohepatitis (NASH); however, the incidence is varied and depends on race. The prevalence of NASH in obese Japanese patients is unknown. We evaluated the prevalence of NASH in a prospective cohort of Japanese patients with morbid obesity. From October 2009 to July 2011, consecutive patients requiring bariatric surgery underwent a liver biopsy during the operation. The indications for bariatric surgery followed the guidelines of the Asia-Pacific Metabolic and Bariatric Surgery Society. One hundred two patients (55 males and 47 females, age 42.7 ± 10.7 years) were analyzed. The mean body mass index was 42.1 ± 8.2 kg/m(2). Among the 102 patients, 84 patients (82.4%) had nonalcoholic fatty liver disease and 79 patients (77.5%) had NASH. The grading and staging of NASH by Brunt's classification were as follows: grade 0 steatosis, one patient; grade 1 steatosis, 35 patients; grade 2 steatosis, 32 patients; grade 3 steatosis, 11 patients; stage 1 fibrosis, 25 patients; stage 2 fibrosis, 38 patients; stage 3 fibrosis, 16 patients, stage 4 fibrosis, no patients. The body weight, waist-hip ratio, visceral fat area, and aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, fasting plasma glucose, fasting plasma insulin, C peptide, hemoglobin A1c, and homeostasis model assessment insulin resistance levels were significantly elevated in the NASH group in comparison with the non-NASH group. The platelet count was significantly decreased in the NASH group. The waist-hip ratio and the alanine aminotransferase, fasting plasma glucose, and homeostasis model assessment insulin resistance levels were found to be independent predictors of NASH in a multivariate analysis. The prevalence of NASH was 77.5% in this prospective Japanese cohort. The prevalence of NASH in Japanese morbidly obese patients was extremely high, and early intervention should be undertaken.

The Higher Prevalence of Non-Alcoholic versus Alcoholic Steatohepatitis in Alcoholics.

The aim of this study was to evaluate the prevalence of alcoholic (ASH) and non-alcoholic steatohepatitis (NASH) in alcoholics by non-invasive biochemical markers: AshTest and NashTest. The tested group consisted of 142 alcoholic patients. All biochemical markers were assessed using the recommended methods. The highest values of AshTest and NashTest were observed in the highest H3 score and N2 score, respectively. The distribution of AshTest scores was the following: H0 - 94.1%, H1 - 5.2%, H2 - 0%, and H3 - 0.7%, while for NashTest was: N0 - 56.6%, N1 - 38.2% and N2 - 5.1%. In summary, alcoholic steatohepatitis was present only in 5.9% of alcoholics and non-alcoholic steatohepatitis in 43.3% of patients. Co-occurrence of ASH and NASH was observed in 3.7% of patients. The BMI, mean glucose, and triglyceride levels were significantly different between NashTest scores, but not between AshTest scores. These results may evidence that non-alcoholic steatohepatitis is associated with metabolic risk factors such as diabetes mellitus, dyslipidemia, and obesity. The MCV value and AST/ALT ratio were higher in alcoholic steatohepatitis than in non-alcoholic steatohepatitis. In conclusion, the prevalence of non-alcoholic steatohepatitis in alcoholics is higher than of alcoholic steatohepatitis, as estimated by non-invasive tests. Co-occurrence of alcoholic steatohepatitis and non-alcoholic steatohepatitis in alcoholic patients is low and the high prevalence of non-alcoholic steatohepatitis is related with high occurrence of metabolic risk factors.

Risk of obstructive sleep apnea with daytime sleepiness is associated with liver damage in non-morbidly obese patients with nonalcoholic fatty liver disease.

BackgroundA high prevalence of obstructive sleep apnea syndrome (OSAS) has been reported in severely obese patients with nonalcoholic fatty liver disease (NAFLD), but few studies have evaluated OSAS in non-morbidly obese NAFLD patients.AimsTo determine the prevalence of risk for OSAS with or without daytime sleepiness in non-morbidly obese patients with NAFLD and evaluate the association with the severity of liver damage.MethodsWe considered 159 consecutive patients with histological NAFLD and body mass index (BMI) <35 Kg/m2, and 80 controls without ultrasonographic steatosis matched for age, sex, and BMI. OSAS risk was determined by positivity for Berlin questionnaire (BQ), and daytime sleepiness by the Sleepness Epworth Scale (ESS). Liver damage was evaluated according to the NAFLD activity score.ResultsIn NAFLD patients, BQ alone was positive in 39 (25%), ESS in 8 (5%), and both in 13 (8%, OSAS with sleepines); p = ns vs. controls without steatosis. In NAFLD patients at risk for OSAS with (but not in those without) sleepiness, we observed a higher prevalence of nonalcoholic steatohepatitis (NASH; 11/13, 85% vs. 72/146, 49%; p = 0.018), and of clinically significant fibrosis (stage>1; 9/13, 69% vs. 39/146, 27%; p = 0.003). At multivariate logistic regression analysis, OSAS with sleepiness was strongly associated with NASH and fibrosis>1 independently of known clinical risk factors such as age, gender, BMI, diabetes, and ALT levels (OR 7.1, 95% c.i. 1.7–51, p = 0.005 and OR 14.0, 95% c.i. 3.5–70, p = 0.0002, respectively).ConclusionsA proportion of NAFLD patients without severe obesity is at risk for OSAS with daytime sleepiness, which is associated with the severity of liver damage independently of body mass and other cofactors.

NONALCOHOLIC FATTY LIVER DISEASE IN SEVERE OBESE PATIENTS, SUBJECTED TO BARIATRIC SURGERY

Nonalcoholic fatty liver disease encompasses a spectrum of histopathological changes that range from simple steatosis to nonalcoholic steatohepatitis. Works suggest that iron (Fe) deposits in the liver are involved in the physiopathology of nonalcoholic steatohepatitis. The aim of this study was to determine the prevalence of simple steatosis and nonalcoholic steatohepatitis in patients with morbid obesity, subjected to bariatric surgery and to establish a correlation of the anatomopathological findings with the presence of liver fibrosis. A total of 250 liver biopsies were conducted in the transoperation of the surgeries. Steatosis was present in 226 (90.4%) of the samples, 76 (30.4%) being classified as mild; 71 (28.4%) as moderate and 79 (31.6%) as intense. Nonalcoholic steatohepatitis was diagnosed in 176 (70.4%) cases, where 120 (48.4%) were mild; 50 (20%) were moderate, and 6 (2.4%) cases were intense. Fibrosis was referred to in 108 (43.2%) biopsies, 95 of which (38%) were mild; 2 (0.8%) were moderate; 7 (2.8%) were intense, and cirrhosis was diagnosed in 4 (1.6%) cases. There was a correlation between the degree of steatosis and the level of inflammatory activity (rs = 0.460; P<0.001) and between the degree of this activity and the degree of fibrosis (rs = 0.583; P<0.001). Only 13 (5.2%) samples showed Fe deposits. There is a high prevalence of nonalcoholic steatohepatitis in these patients and a positive correlation of the degrees of nonalcoholic steatohepatitis with the intensity of fibrosis. The low prevalence of Fe deposits found makes it questionable that the presence of this ion has any participation in the physiopathogeny of nonalcoholic fatty liver disease.

Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients

The characteristics of nonalcoholic fatty liver disease (NAFLD) in elderly patients are unknown. Therefore, we aimed to examine the differences between elderly and nonelderly patients with NAFLD and to identify determinants of nonalcoholic steatohepatitis (NASH) and advanced fibrosis (bridging fibrosis or cirrhosis) in elderly patients. This is a cross-sectional analysis of adult participants who were prospectively enrolled in the NASH Clinical Research Network studies. Participants were included based on availability of the centrally reviewed liver histology data within 1 year of enrollment, resulting in 61 elderly (age ≥65 years) and 735 nonelderly (18-64 years) participants. The main outcomes were the presence of NASH and advanced fibrosis. Compared to nonelderly patients with NAFLD, elderly patients had a higher prevalence of NASH (56% versus 72%, P = 0.02), and advanced fibrosis (25% versus 44%, P = 0.002). Compared to nonelderly patients with NASH, elderly patients with NASH had higher rates of advanced fibrosis (35% versus 52%, P = 0.03), as well as other features of severe liver disease including the presence of ballooning degeneration, acidophil bodies, megamitochondria, and Mallory-Denk bodies (P ≤ 0.05 for each). In multiple logistic regression analyses, independent determinants of NASH in elderly patients included higher aspartate aminotransferase (AST) (odds ratio [OR] = 1.12, P = 0.007) and lower platelets (OR = 0.98, P = 0.02); and independent determinants of advanced fibrosis included higher AST (OR = 1.08, P = 0.007), lower alanine aminotransferase value (OR = 0.91, P = 0.002), and an increased odds of having low high-density lipoprotein (OR = 8.35, P = 0.02). Elderly patients are more likely to have NASH and advanced fibrosis than nonelderly patients with NAFLD. Liver biopsy may be considered in elderly patients and treatment should be initiated in those with NASH and advanced fibrosis.

1363 CHARACTERIZATION OF THE GUT MICROBIOTA BY QUANTITATIVE METAGENOMICS: A PROMISING TOOL FOR RISK STRATIFICATION IN NAFLD PATIENTS

patients with nonalcoholic fatty liver disease (NAFLD), an emerging liver disease associated with obesity and the metabolic syndrome, and it has been postulated that intermittent hypoxia is a cofactor of liver damage progression. Few studies have evaluated the relationship between NAFLD and OSAS in non severely obese patients, and none analyzed liver damage by histology, the gold standard for prognostic assessment. Aim of this study was to determine the risk of OSAS in patients with NAFLD without severe obesity and to evaluate the association with liver damage. Methods: 85 consecutive patients with histologically proven NAFLD and body mass index (BMI) <35kg/m. The risk of OSAS was assessed by the Berlin Questionnaire (BQ) and Sleepness Epworth Scale (ESS). Liver damage was evaluated according to Kleiner score. Results: BQ was positive in 28 (35%), ESS in 11 (13%), and both in 9 (11%) of patients. In patients at high risk of OSAS (as identified by positivity of both BQ and ESS) we observed: a. a higher prevalence of nonalcoholic steatohepatitis (NASH, the progressive form of NAFLD: 8/9, 89% vs. 22/55, 40%, p = 0.009), b. higher severity of NAFLD activity score, reflecting histological liver damage (p =0.002), and c. of hepatic fibrosis (p = 0.015). Vice versa, a higher prevalence of BQ and ESS positivity was observed in patients with than in those without NASH (8/31, 21% vs. 1/45 2%, p = 0.009). At multivariate logistic regression analysis, BQ and ESS positivity was a risk factor of NASH independently of known clinical confounders, such as BMI and glucose levels (OR 7.46, 95% confidence interval 1.2–146, p = 0.03). Conclusions: A high proportion of NAFLD patients without severe obesity is at risk of OSAS. High risk of OSAS, as detected by BQ and ESS combined positivity, is independently associated with NASH. Although the association between OSAS and NASH awaits confirmation by polysomnography, data suggest that OSAS may be involved in the pathogenesis of liver disease progression in NAFLD patients without severe obesity, with potential therapeutic implications.

Nonalcoholic Steatohepatitis (NASH) Does Not Increase Complications After Laparoscopic Bariatric Surgery

Advanced liver disease is associated with increased risk for postoperative complications. It is not well known whether the presence of nonalcoholic steatohepatitis (NASH) in morbidly obese patients contributes to the rate of postoperative complications. The main objective was to study the association between NASH and postoperative complications in bariatric patients. A total of 340 contemporary sequential patients who underwent laparoscopic bariatric operations and who had intraoperative liver biopsies were studied. The rates of severe postoperative complications were compared across three patient groups-those with (1) no liver disease or with simple steatosis, (2) mild nonalcoholic NASH [steatosis with necroinflammation and mild fibrosis (stage 0-1)], and (3) advanced NASH [steatosis, necroinflammation, and more advanced fibrosis (stage ≥ 2)]. Of 340 patients, 141 (42%) had no NASH, and 151 (44%) and 48 (14%) had mild and advanced NASH, respectively. Superobesity (P = 0.037), diabetes (P < 0.001), and cerebrovascular disease (P = 0.013) had highest frequencies in patients with advanced NASH. Hypertension was highly prevalent in cohort (57%) but similarly distributed across three groups. Forty-five patients experienced at least one complication (pulmonary 4, cardiovascular 8, surgical 16, and acute kidney injury 21). The complications rate did not differ significantly across NASH categories. Median hospital stay was 3days (IQR 2, 3), and it was not associated with NASH severity. There were no 30-day postoperative deaths. Despite the high prevalence of NASH among morbidly obese surgical patients, this condition was not associated with increased risk for postoperative complications. Postoperative acute kidney injury was the most frequent single complications.