Risk Of Advanced Liver Disease Research Articles

Referral to hepatology is lower in patients with excessive alcohol use who have mental health disorders despite a high fibrosis-4 index.

Alcohol use disorder (AUD) is a multifaceted disease, and integration of AUD treatment between mental health and hepatology is necessary to improve outcomes. We aimed to ascertain whether patients with excessive alcohol use (EAU) and high FIB-4, which is a non-invasive method to identify advanced liver disease, are appropriately referred to hepatology and detect which clinical barriers, if any, might pertain. Records of patients with excessive alcohol use between 2013 and 2023 were extracted from a large public system. Demographics, alcohol-related hospitalizations, mental health conditions, Charlson comorbidity index (CCI) and referral patterns were evaluated. Comparisons were made between those referred to hepatology versus not. 1131 subjects showed evidence of EAU but on further review, 189 were in alcohol-remission. The remaining 942 (636 men, age 55.7 ± 14.5 years, 548 white, 363 black, 19 Hispanic) subjects with CCI 2.61 ± 2.23 were further analyzed for FIB-4 score and referral patterns. 316 patients had active EAU and a high FIB-4, of whom only 116 (37%) were referred to hepatology. Patients with alcohol-related mental health concerns and admitted for trauma were less likely to be referred. Logistic regression showed referral was higher with alcohol-related liver hospitalizations (OR: 9.25, 95% CI: 4.90-17.47, p < 0.001), higher CCI (OR: 6.23, 95% CI: 3.00-12.94, p < 0.0001) and lower with mental health admissions (OR: 0.36, 95% CI: 0.15-0.48, p < 0.001) or mental health diagnoses (OR: 0.36, 95% CI: 0.15-0.82, p = 0.02) and increasing age (OR: 0.95, 95% CI: 0.92-0.97, p < 0.001). In a large public health system, almost 63% of patients with EAU and FIB-4 >2.67 are not referred to hepatology for evaluation. Patients not referred were more likely to have alcohol-related mental-health hospitalizations and mental health diagnoses, while those with liver-related hospitalizations and comorbidities were more likely to be referred. Greater education of mental health providers and for teams taking care of inpatients admitted with alcohol-related mental health concerns would better integrate care and improve outcomes for patients with higher risk for advanced liver disease.

Metabolic syndrome is associated with significant hepatic fibrosis and steatosis in patients with nonalcoholic steatohepatitis

Background and aimsNonalcoholic steatohepatitis (NASH), an inflammatory form of non-alcoholic fatty liver disease, can progress to advanced liver fibrosis, cirrhosis, and liver cancer. Metabolic syndrome (MetS) parallels the prevalence of non-alcoholic fatty liver disease/NASH and increases patients’ risk of advanced liver disease. This study aimed to determine whether MetS was associated with the histological progression of NASH. MethodsPatients with liver biopsy-proven NASH were retrospectively screened and categorized into two groups for each histological feature: with (<2 points) or without (≥2 points) significant hepatic steatosis/inflammation/fibrosis. Multivariable logistic regression was used to explore the association between MetS and histological features. ResultsIn total, 386 patients with a median age of 33.0 years were enrolled; among them, 35.2% were female, and 41.2% had MetS. The proportion of significant hepatic fibrosis and steatosis in those with MetS was significantly higher than in those without MetS (p < 0.05). Multivariable logistic regression analyses showed that MetS remained significantly associated with significant hepatic fibrosis (adjusted odds ratio: 1.852, 95% confidence interval: 1.042–3.292, p = 0.036), and severe hepatic steatosis (adjusted odds ratio: 2.008, 95% confidence interval: 1.030–3.914, p = 0.041). ConclusionMetS was associated with significant hepatic fibrosis and steatosis in patients with NASH. Our results suggest that NASH patients with MetS should be closely monitored and given targeted intervention and treatment, which may help to prevent disease progression and mitigate the growing burden of NASH.

The interplay of metabolic dysfunction-associated fatty liver disease and viral hepatitis on liver disease severity: A large community-based study in a viral endemic area.

The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its interplay with hepatitis B virus (HBV) and hepatitis C virus (HCV) in terms of liver disease severity is elusive. A mass surveillance program was conducted in a viral hepatitis endemic area. The objective was to identify MAFLD/non-MAFLD subjects with advanced liver disease. Two thousand two hundred and forty-two (41.7%) of the 5378 subjects were identified as having MAFLD, and 375 (7.0%) had advanced liver disease. The proportions of anti-HCV and HBsAg seropositivity were 19.3% and 9.7%, respectively. The proportions of advanced fibrosis in subjects with non-viral hepatitis (NBNC), HBV and HCV infection were 2.8%, 5.7% and 23.4%, respectively. Subjects with MAFLD had a significantly higher proportion of advanced fibrosis (8.7% vs 5.7%, P<0.001). Factors associated with advanced fibrosis included age (odds ratio [OR]/95% confidence interval [CI]: 4.8/3.7-6.0, P<0.001), male sex (OR/CI: 1.3/1.0-1.7, P=0.019), anti-HCV seropositivity (OR/CI: 5.9/4.6-7.5, P=0.019), MAFLD-lean metabolic dysregulation (MS) (OR/CI: 2.6/1.3-5.2, P=0.005; compared with the non-MAFLD group) and MAFLD-diabetes (OR/CI: 1.5/1.1-2.1, P=0.008; compared with the non-MAFLD group). MAFLD did not aggravate liver disease severity in patients with viral hepatitis. However, among NBNC subjects, factors associated with advanced liver disease included MAFLD-lean MS group (OR/CI: 9.1/2.4-34.6, P=0.001; compared with non-MAFLD group) and MAFLD-DM group (OR/CI: 2.0/1.2-3.2, P=0.004; compared with non-MAFLD group). MAFLD patients with diabetes and metabolic dysregulation had a higher risk of advanced liver disease. The effect was more significant in non-viral hepatitis subjects in a community level.

National study of NAFLD management identifies variation in delivery of care in the UK between 2019 to 2022

Non-alcoholic fatty liver disease (NAFLD) is associated with liver and cardiovascular morbidity and mortality. Recently published NAFLD Quality Standards include 11 key performance indicators (KPIs) of good clinical care. This national study, endorsed by British Association for the Study of the Liver (BASL) and British Society of Gastroenterology (BSG), aimed to benchmark NAFLD care in UK hospitals against these KPIs. This study included all new patients with NAFLD reviewed in the outpatient clinic in the months of March 2019 and March 2022. Participating UK hospitals self-registered for the study through BASL/BSG. KPI outcomes were compared using Fisher's exact or Chi-square tests. Data from 776 patients with NAFLD attending 34 hospitals (England [25], Scotland [four], Wales [three], Northern Ireland [two]) were collected. A total of 85.3% of hospitals reported established local liver disease assessment pathways, yet only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment documented at the point of referral to secondary care. In secondary care, 79.1% of patients had fibrosis assessment. Assessment of cardiometabolic risk factors including obesity, type 2 diabetes, hypertension, and smoking were conducted in 73.2%, 33.0%, 19.3%, and 54.9% of all patients, respectively. There was limited documentation of diet (35.7%) and exercise advice (55.1%). Excluding those on statins, only 9.1% of patients with NAFLD at increased cardiovascular risk (T2DM and/or QRISK-3 >10%) had documented discussion of statin treatment. Significant KPI improvements from 2019 to 2022 were evident in use of non-invasive fibrosis assessment before secondary care referral, statin recommendations, and diet and exercise recommendations. This national study identified substantial variation in NAFLD management in the UK with clear areas for improvement, particularly fibrosis risk assessment before secondary care referral and management of associated cardiometabolic risk factors. This study identified significant variation in the management of NAFLD in the UK. Only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment performed to identify those at greater risk of advanced liver disease before specialist referral. Greater emphasis is needed on the management of associated cardiometabolic risk factors in individuals with NAFLD. Hospitals with multidisciplinary NAFLD service provision had higher rates of fibrosis evaluation and assessment and management of cardiometabolic risk than hospitals without multidisciplinary services. Further work is needed to align guideline recommendations and real-world practice in NAFLD care.

Metabolic-Associated Fatty Liver Disease (MAFLD) is associated with immune activation, increased epicardial fat volume, and steatohepatitis among people with HIV in a Thai cohort.

A change in terminology from fatty liver disease to metabolic-associated fatty liver disease (MAFLD), along with modified diagnostic criteria, was proposed in 2020, and data regarding MAFLD burden in people living with HIV are limited. We investigated associations between MAFLD and immune activation, cardiovascular disease (CVD) risks including epicardial fat volume, and steatohepatitis in an Asian cohort. We evaluated CVD risk (epicardial fat tissue, coronary artery calcium [CAC] score, and 10-year atherosclerotic CVD [ASCVD] score) in people living with HIV aged >50 years. Individuals with excessive alcohol consumption and viral hepatitis infections were excluded. MAFLD diagnosis was based on 2020 International Consensus criteria. Non-alcoholic steatohepatitis (NASH) with significant activity and liver fibrosis was defined as FibroScan-aspartate aminotransferase (FAST) score ≥0.67 and >0.35. Multivariate logistic regression models were used to investigate factors associated with MAFLD and NASH with significant activity and liver fibrosis. The median age was 54 years (interquartile range [IQR] 52-60) and current CD4 count was 613 (IQR 467-804) cells/mm3 . A total of 37% were female, and most (98%) people living with HIV were virally suppressed. The prevalence of MAFLD and non-alcoholic fatty liver disease was 35% and 38%, respectively. In multivariate analyses, higher body mass index, albumin, epicardial fat volume, and liver stiffness were significantly associated with MAFLD. A higher CD4/CD8 ratio was associated with a lower risk of MAFLD. People with HIV with MAFLD had higher odds of having NASH with significant activity and liver fibrosis (adjusted odds ratio 3.3; 95% confidence interval 1.6-6.6), and similar associations were also observed among different MAFLD categories. The complex relationship between MAFLD and immune activation, steatohepatitis, and epicardial fat tissue suggests an increased risk of advanced liver disease and CVDs beyond the traditional risk factors in people living with HIV with fatty liver disease.

Heterogeneous liver on research ultrasound identifies children with cystic fibrosis at high risk of advanced liver disease

BackgroundThis study examines whether heterogeneous (HTG) pattern on liver ultrasound (US) identifies children at risk for advanced cystic fibrosis liver disease (aCFLD). MethodsProspective 6-year multicenter case-controlled cohort study. Children with pancreatic insufficient cystic fibrosis (CF) aged 3–12 years without known cirrhosis underwent screening US. Participants with HTG were matched (by age, Pseudomonas infection status and center) 1:2 with participants with normal (NL) US pattern. Clinical status and laboratory data were obtained annually and US bi-annually for 6 years. Primary endpoint was development of nodular (NOD) US pattern consistent with aCFLD. Results722 participants underwent screening US, with 65 HTG and 592 NL. Final cohort included 55 HTG and 116 NL with ≥ 1 follow-up US. ALT, AST, GGTP, FIB-4, GPR and APRI were higher, and platelets were lower in HTG compared to NL. HTG had a 9.5-fold increased incidence (95% confidence interval [CI]:3.4, 26.7, p<0.0001, 32.7% vs 3.4%) of NOD versus NL. HTG had a sensitivity of 82% and specificity of 75% for subsequent NOD. Negative predictive value of a NL US for subsequent NOD was 96%. Multivariate logistic prediction model that included baseline US, age, and log(GPR) improved the C-index to 0.90 compared to only baseline US (C-index 0.78). Based on survival analysis, 50% of HTG develop NOD after 8 years. ConclusionsResearch US finding of HTG identifies children with CF with a 30–50% risk for aCFLD. A score based on US pattern, age and GPR may refine the identification of individuals at high risk for aCFLD. Clinical Trial RegistrationProspective Study of Ultrasound to Predict Hepatic Cirrhosis in CF: NCT 01,144,507 (observational study, no consort checklist)

Cleaning up alpha-1 antitrypsin deficiency related liver disease.

Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic disorders arising due to mutations in alpha-1 antitrypsin (AAT) gene affecting primarily the lung and the liver. This review summarizes the pathophysiology and clinical manifestation of different AATD genotypes and discusses the recent therapeutic developments. The focus is on the severe, rare homozygous Pi∗ZZ and the common heterozygous Pi∗MZ genotype. Pi∗ZZ individuals harbor an up to 20 times higher risk of liver fibrosis and cirrhosis than noncarriers and liver transplantation is currently the only available therapeutic option. AATD constitutes a proteotoxic disorder arising from hepatic AAT accumulation and the currently most promising data come from a phase 2, open-label trial of fazirsiran, a hepatocyte-targeted siRNA. Pi∗MZ subjects display an increased risk of advanced liver disease and at the latter stage, a faster deterioration than individuals without AAT mutation. Although the fazirsiran data offer a glimpse of hope to AATD patients, a consensus on appropriate study endpoint, a careful patient selection as well as monitoring of long-term safety will be essential for an approval.

S1412 Non-Invasive NAFLD Screening in the Primary Care Setting of a Safety Net Hospital System

Introduction: Nonalcoholic fatty liver disease (NAFLD) is one of the most common etiologies of cirrhosis and fastest growing indications for liver transplantation in Western countries. Currently, there is no universal recommendation for NAFLD screening in the primary care setting. Clinical data analysis can be used to identify patients at risk for developing NAFLD with advanced liver disease so that these patients can be referred for liver elastography for further risk stratification. Methods: 2528 patients from the Highland primary care clinic in Oakland California from 2020 to 2022 were evaluated using the Epic Software electronic medical record system. The inclusion criteria included patients at Alameda Health System (AHS) Highland Hospital Adult Medicine with a hemoglobin A1c ≥ 6.5%, BMI ≥ 30, age ≥ 50, with aspartate aminotransferase (AST) ≥ 15 U/L, alanine transaminase (ALT) ≥ 15 U/L, albumin < 3.5 mg/dL, and platelets (PLT) < 160 per microliter that, at a minimum, corresponds to a NAFLD Fibrosis Score (NFS) of 0.7 (Fibrosis stage 3-4). The exclusion criteria included a history of viral or autoimmune hepatitis, clinically significant alcohol use, or previously diagnosed cirrhosis from an etiology other than NAFLD. Results: The percentage of patients with NAFLD who were at risk for advanced liver disease increased from 16.79% [Confidence Interval (CI) 0.61; 16.2-17.4] in 2020-2021 to 18.55% [CI 0.57; 17.9-19.2] in 2021-2022. The percentage was highest in Black patients (42.3%, p < 0.01) and female patients (57.0%, p < 0.01), and lowest in Asian patients (8.2%, p < 0.01) (Figure). The percentage of Black, White, Asian, and male patients was relatively unchanged from 2020 to 2022, while the percentage in Hispanic patients increased from 11.9% to 12.7%, and the percentage of women increased from 57.0% to 60.1% (Figure). Conclusion: NAFLD with advanced liver disease is closely associated with diabetes and obesity. The United States Preventive Services Task Force currently does not recommend screening for NAFLD. However, non-invasive criterion-based screenings are feasible and effective at identifying patients with risk factors for developing NAFLD with advanced liver disease. Furthermore, screenings should be implemented in the primary care setting using criterion targeted clinical data, to identify patients who will benefit from liver elastography, so that early interventions can be performed to prevent cirrhosis and cardiovascular related complications.Figure 1: . (F1). Demographic trends for NAFLD in AHS county hospital primary care setting in Oakland California from 2020 to 2022.

Superinfection of other hepatitis viruses on top of chronic hepatitis B: The more, the worse

Superinfection of other hepatitis viruses on top of chronic hepatitis B: The more, the worse

Heterogeneous Liver on Research Ultrasound Identifies Children with Cystic Fibrosis at High Risk of Advanced Liver Disease: Interim Results of a Prospective Observational Case-Controlled Study

To assess if a heterogeneous pattern on research liver ultrasound examination can identify children at risk for advanced cystic fibrosis (CF) liver disease. Planned 4-year interim analysis of a 9-year multicenter, case-controlled cohort study (Prospective Study of Ultrasound to Predict Hepatic Cirrhosis in CF). Children with pancreatic insufficient CF aged 3-12years without known cirrhosis, Burkholderia species infection, or short bowel syndrome underwent a screening research ultrasound examination. Participants with a heterogeneous liver ultrasound pattern were matched (by age, Pseudomonas infection status, and center) 1:2 with participants with a normal pattern. Clinical status and laboratory data were obtained annually and research ultrasound examinations biannually. The primary end point was the development of a nodular research ultrasound pattern, a surrogate for advanced CF liver disease. There were 722 participants who underwent screening research ultrasound examination, of which 65 were heterogeneous liver ultrasound pattern and 592 normal liver ultrasound pattern. The final cohort included 55 participants with a heterogeneous liver ultrasound pattern and 116 participants with a normal liver ultrasound pattern. All participants with at least 1 follow-up research ultrasound were included. There were no differences in age or sex between groups at entry. Alanine aminotransferase (42±22 U/L vs 32±19 U/L; P=.0033), gamma glutamyl transpeptidase (36±34 U/L vs 15±8 U/L; P<.001), and aspartate aminotransferase to platelet ratio index (0.7±0.5 vs 0.4±0.2; P<.0001) were higher in participants with a heterogeneous liver ultrasound pattern compared with participants with a normal liver ultrasound pattern. Participants with a heterogeneous liver ultrasound pattern had a 9.1-fold increased incidence (95% CI, 2.7-30.8; P=.0004) of nodular pattern vs a normal liver ultrasound pattern (23% in heterogeneous liver ultrasound pattern vs 2.6% in normal liver ultrasound pattern). Research liver ultrasound examinations can identify children with CF at increased risk for developing advanced CF liver disease.

Study of viral markers, clinical and biochemical profile of viral hepatitis in patients of alcoholic liver disease

Background: There is a significant worldwide burden of Alcoholic Liver Disease (ALD). Both alcohol abuse and infection with hepatitis viruses can lead to liver disease. Alcohol and hepatitis viruses have synergistic effects in the development of liver disease. Thus, early detection of virus hepatitis and targeted interventions can improve prognosis in ALD.Methods: This cross-sectional study was conducted among 180 patients coming to Baroda medical college and SSG hospital, Vadodara having alcoholic liver disease were studied and evaluated for markes of viral hepatitis and its clinical and biochemical profile in alcoholic liver disease.Results: our study we had taken 180 patients of alcoholic liver disease out of which male were 92% and female were 8%. Prevalence of viral hepatitis was 27.7% in ALD patients. Out of which hepatitis E was 13% followed by hepatitis A 11%, hepatitis B 4.44% and least was Hepatitis C 0.5%. In clinical profile fever was significantly higher in patients of viral hepatitis with ALD than patients without viral hepatitis. Bilirubin was not significant differ in both groups of patients but SGOT and SGPT had higher values in patients of viral hepatitis with ALD and thus ratio of SGOT/SGPT was also affected due to higher value of SGOT and SGPT.Conclusions: Alcohol consumption and hepatitis virus infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. Patients starting treatment for chronic viral hepatitis infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefit from additional support during antiviral therapy specially in chronic hepatitis.

What may GLP1 receptor agonists contribute to the treatment of patients with non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease (NAFLD) poses a challenge to health services both in developed and developing countries, with a significant increase in incidence and prevalence that is related to the currently increased prevalence of obesity. Besides an acknowledged higher risk for advanced liver disease (cirrhosis, hepatocellular carcinoma), morbidity and mortality from cardiovascular disease both increase in people with NAFLD. As a matter of fact, NAFLD is a cardiovascular risk factor.

360. Advanced Liver Disease in HIV/Hepatitis B Coinfected Patients: Associated with Race, Age, and Comorbidities

BackgroundHepatitis B virus (HBV) coinfection is common in people with HIV. Compared with HBV mono-infected individuals, those that are HIV/HBV coinfected show evidence of more rapid progression to advanced liver disease (ALD) and increased mortality rate. In this study, we identified characteristics in an HIV/HBV cohort associated with ALD.MethodsWe retrospectively examined an HIV/HBV coinfected cohort to determine the prevalence of ALD and its correlation with selected variables. Data were drawn from HIV and HBsAg+ patients at three HIV clinics in Houston, Dallas, and San Antonio, Texas. Those without chronic HBV were excluded. ALD was defined as cirrhosis, decompensation, and/or hepatocellular carcinoma, as determined by imaging. Variables included demographics, HIV risk factors, comorbidities, HBsAg loss, HepBeAg, CD4+ count, HBV DNA, and HIV RNA viral load. Bivariate analysis was performed using chi-square and student t-test as appropriate; a logistic regression model was used to identify independent associations among significant variables (STATA).ResultsWithin those with HIV/HBV coinfection (n = 501), 89 (18%) met the criteria for ALD (92% male, 47% Black, 33% White, 16% Hispanic, 73% >40 years old). Amongst these (n = 89), significant differences were observed with race (P = 0.039), age (P = 0.001), patients identified as MSM/Bisexuals (P = 0.047), diabetes mellitus (DM) (P = 0.01) and hepatitis C virus (HCV) coinfection (P ≤ 0.001). Compared with Whites, Blacks are less likely to have ALD (95% CI 0.27, 0.79, P = 0.004), and those age 40–49 (95% CI 1.28, 10.92, P = 0.016) and >50 (95% CI 1.63, 15.54, P = 0.005) were more likely. The multivariate logistic regression analysis showed patients that are White race, age >50, have DM, and those with HCV coinfection had increased risk for ALD (Table 1). No differences were seen with gender, insurance, alcohol use, HBsAg loss, HepBeAg status or baseline CD4+ count, HBV DNA, HIV RNA, and AIDS.ConclusionIncreased monitoring for the presence of ADL should be conducted in HIV/HBV coinfection. Particular attention and surveillance should be paid to those with the following risk factors: Whites, elder age (>50), and comorbidities of DM and HCV. These should be taken into consideration when approaching the development and treatment of ADL in HIV/HBV patients. Disclosures All authors: No reported disclosures.

Risks of Light and Moderate Alcohol Use in Fatty Liver Disease: Follow-Up of Population Cohorts.

The effects of alcohol use in nonalcoholic fatty liver disease are unclear. We investigated the impact of alcohol use in fatty liver disease on incident liver, cardiovascular, and malignant disease, as well as death. Our study comprised 8,345 persons with hepatic steatosis (fatty liver index >60) who participated in health-examination surveys (FINRISK 1992-2012 or Health 2000), with available data on baseline alcohol intake. Main exclusions were baseline clinical liver disease, viral hepatitis, ethanol intake >50g/day, and current abstainers. Data were linked with national registers for hospital admissions, malignancies, and death regarding liver, cardiovascular, and malignant disease, as well as all-cause death. Adjustment were for multiple confounders. Alcohol consumption showed a dose-dependent risk increase for incident advanced liver disease and malignancies. Consuming 10-19g/day of alcohol in general or 0-9g/day as nonwine beverages doubled the risk for advanced liver disease compared to lifetime abstainers. In contrast, alcohol intake up to 49g/day was associated with a 22%-40% reduction of incident cardiovascular disease (CVD). We observed a J-shaped association between alcohol intake and all-cause death with a maximal risk reduction of 21% (95% confidence interval, 5%-34%) at alcohol intake of 0-9g/day compared to lifetime abstainers. However, these benefits on CVD and mortality were only observed in never smokers. Alcohol intake >30g/day yielded increased risk estimates for mortality compared to lifetime abstainers. In a subpopulation with longitudinal data, alcohol intake remained stable over time in >80% of subjects. Even low alcohol intake in fatty liver disease is associated with increased risks for advanced liver disease and cancer. Low to moderate alcohol use is associated with reduced mortality and CVD risk but only among never smokers.

Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis

Introduction and objectivesNon-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. It is often related to metabolic syndrome, presenting an increased risk of advanced liver disease and cardiovascular-related death. In some etiologies of chronic liver disease, thrombocytopenia has been associated not only with advanced stages of fibrosis but also with autoimmune disease. In NAFLD, however, its prevalence and related factors are still unknown. The aim of this study is to evaluate the prevalence of thrombocytopenia in NAFLD patients without cirrhosis and to investigate its related risk factors. Patients and methodsThis was a retrospective study carried out in two tertiary hospitals in the South and Southeast regions of Brazil. Patients diagnosed with NAFLD by liver biopsy were included. Those with other causes of liver disease and/or cirrhosis were excluded. For analysis, patients were divided into two groups, with and without thrombocytopenia. Data was analyzed using a significance level of 5%. Results441 non-cirrhotic patients with NAFLD (evaluated by liver biopsy) were included in the study. The prevalence of thrombocytopenia was 3.2% (14/441 patients). In the comparative analysis between groups, thrombocytopenia was associated with male sex (p=0.007) and level of hemoglobin (p=0.023). ConclusionThrombocytopenia is an infrequent event in NAFLD patients without cirrhosis and is related with male sex and higher hemoglobin levels.

THU-293-Increased risk of advanced liver disease independently of classic metabolic risk factors or drug induced hepatotoxicity in patients with psoriasis

THU-293-Increased risk of advanced liver disease independently of classic metabolic risk factors or drug induced hepatotoxicity in patients with psoriasis

Significant Increase in Risk of Fibrosis or Cirrhosis at Time of HCV Diagnosis for Hispanics With Diabetes and Obesity Compared With Other Ethnic Groups

Advanced liver disease, which includes fibrosis and cirrhosis, has been reported to be more prevalent in Hispanics patients at the time of diagnosis of chronic hepatitis C virus (HCV) infection than non-Hispanic black or non-Hispanic white patients. We performed a propensity score-matched analysis to determine whether metabolic risk factors contribute to this disparity. We collected data from persons with 748 HCV infection (22% Hispanic, 53% non-Hispanic black, and 26% non-Hispanic white; 23% with advanced liver disease), born from 1945 through 1965, diagnosed at 6 health care systems in Texas. Advanced liver disease was defined as a FIB-4 index score above 3.25. We examined the association between advanced liver disease and race or ethnicity, metabolic risk (based on diabetes mellitus and body mass index [BMI]) and heavy alcohol use in propensity score-matched analyses. In propensity-score matched models, among those who were obese (BMI ≥30) with a diagnosis of diabetes, the adjusted odds ratio of advanced liver disease for Hispanics vs non-Hispanic black was 7.89 (95% CI, 3.66-17.01) and adjusted odds ratio = 12.49 (95% CI, 3.24-48.18) for Hispanic vs non-Hispanic white patients (both P < .001). HCV-infected Hispanics with obesity and diabetes have a far higher risk for advanced liver disease than other racial or ethnic groups. These findings highlight the need for HCV treatment and management of probable concurrent fatty liver disease. Even after we accounted for metabolic risk factors, Hispanics were still at higher risk for advanced liver disease, indicating the potential involvement of other factors such as genetic variants.

Neutralization of IL-15 abrogates experimental immune-mediated cholangitis in diet-induced obese mice

Obesity is a global epidemic affecting chronic inflammatory diseases. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that can occur as an extraintestinal manifestation of inflammatory bowel disease (IBD). Previously we reported that patients with PSC who are obese have a higher risk of advanced liver disease. Currently it is unknown how obesity accelerates or worsens PSC. We evaluated the progression of PSC in an antigen-driven cholangitis mouse model of diet-induced obesity. Obesity was induced in our murine model of immune-mediated cholangitis (OVAbil). OVAbil mice were fed standard chow or high-fat/sucrose diet for twelve weeks followed by induction of biliary inflammation by OVA-specific T cell transfer. Histopathological damage in portal tracts was scored and serum collected. Neutralizing antibodies against IL-15 were administered daily until study termination. Obese mice developed exacerbated liver inflammation and damage. Immune cell phenotyping in liver revealed greater numbers of neutrophils and CD8+ T cells in obese mice. Higher levels of cytokines and chemokines were found in obese mice with cholangitis. Immuno-neutralizing antibodies against IL-15 greatly attenuated cholangitis in obese mice. Obesity exacerbated experimental PSC in part by overproduction of IL-15. Timely targeting of IL-15 may slow the progression of PSC.

Prevalence of elevated liver enzymes in children with cystic fibrosis diagnosed by newborn screen

BackgroundPrevalence and risks for elevated liver enzymes have not been studied systematically in children with CF identified by newborn screen. Methods298 CF children identified by newborn screen since 1982. AST, ALT and GGT tested at annual visits. Percent of children with 1 or ≥2 values of elevated AST, ALT and GGT determined. Relationship of liver enzymes to clinical factors or subsequent liver disease was analyzed ResultsAt least one abnormal value for AST (63%), ALT (93%) and ALT ≥1.5× ULN (52%) occurred by 21years of age. Liver enzyme elevations were not correlated with CFTR mutation, meconium ileus or ethnicity. AST and GGT ≥1.5× ULN were associated with later advanced liver disease HR (CI) 6.53 (2.02–21.1) and 4.03 (1.15–13.45), respectively. ConclusionsElevated liver enzymes are common during childhood in CF patients identified by newborn screen. Elevated AST and GGT may be markers for risk of advanced liver disease.

Diagnosis of non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) increases risk of mortality from liver and cardiovascular disease (CVD) and is the major cause of hepatocellular carcinoma (HCC), which may develop without cirrhosis. NAFLD predicts type 2 diabetes, even independently of obesity. Globally, the prevalence of NAFLD averages 25% and is as common as the metabolic syndrome. The majority of patients with type 2 diabetes have NAFLD. The challenge for the diabetologist is to identify patients at risk of advanced liver disease and HCC. At a minimum, liver function tests (LFTs), despite being neither specific nor sensitive, should be performed in all patients with the metabolic syndrome or type 2 diabetes. Increases in LFTs, for which the updated reference values are lower (serum ALT ≈30U/l in men and ≈20U/l in women) than those hitherto used in many laboratories, should prompt assessment of fibrosis biomarkers and referral of individuals at risk to a NAFLD/hepatology clinic. Preferably, evaluation of NAFLD should be based on measurement of steatosis biomarkers or ultrasound if easily available. A large number of individuals carry the patatin-like phospholipase domain containing 3 (PNPLA3) I148M variant (30-50%) or the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant (11-15%). These variants increase the risk of advanced liver disease and HCC but not of diabetes or CVD. Genotyping of selected patients for these variants is recommended. Many patients have 'double trouble', i.e. carry both a genetic risk factor and have the metabolic syndrome. Excess use of alcohol could be a cause of 'triple trouble', but such patients would be classified as having alcoholic fatty liver disease. This review summarises a presentation given at the symposium 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by John Jones, DOI: 10.1007/s00125-016-3940-5 ) and a commentary by the Session Chair, Michael Roden (DOI: 10.1007/s00125-016-3911-x ).