Overt Liver Disease Research Articles

Prevalence of subclinical hypothyroidism and longitudinal thyroid-stimulating hormone changes in youth with metabolic dysfunction-associated steatotic liver disease: An observational study.

Studies on adults have shown an association between overt or subclinical hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). The goal of this study was to assess the relationship between thyroid-stimulating hormone (TSH) levels and the histological characteristics of MASLD in youth. This observational study used prospectively collected liver biopsy and clinical data from youth enrolled in 2 pediatric clinical trials in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). Thyroid assays were compared between youth with MASLD and population-based controls aged ≤18 years from the National Health and Nutrition Examination Survey. Individuals with overt hypothyroidism, abnormal antithyroid antibodies, or thyroid-related medications were excluded. Subclinical hypothyroidism was defined as TSH between 4.5 and 10.0uIU/L. Multinomial logistic regression was used to test the association between TSH and MASLD histological changes at baseline, adjusting for age, sex, race/ethnicity, and body mass index. Mixed-effect models, including treatment and time, were used for the longitudinal analysis. Mean TSH, total thyroxine (T4), total triiodothyronine (T3), and free T4 levels were higher ( p < 0.001) in the NASH CRN cohort (n = 218; 421 observations) than in the National Health and Nutrition Examination Survey cohort (n = 2198). TSH levels were positively associated with increased steatosis over time ( p = 0.03). Subclinical hypothyroidism was associated with borderline or definite metabolic-associated steatohepatitis on histology at baseline ( p = 0.03) and with changes in fibrosis over time ( p = 0.01). The association between TSH and steatosis severity in individuals with normal thyroid hormone concentrations suggests an independent role of TSH in MASLD.

Peripheral mucosal-associated invariant T (MAIT) cells are severely depleted in HIV-positive heavy alcohol users

Abstract MAIT cells are innate-like lymphocytes enriched in mucosal tissues, liver, and peripheral blood, contributing to protection against pathogens. Alcohol abuse and HIV infection independently reduce circulating MAIT cells. To assess their combined impact, we studied peripheral blood MAIT cells in heavy drinkers without overt liver disease (ALC), people with HIV (PWH) on ART, PWH on ART with heavy drinking (HIV-ALC), and healthy donors (HD). MAIT cell frequencies were significantly reduced in ALC (median 0.56, IQR 0.22-1.44; p=0.001), HIV (0.43, 0.20-0.97; p&amp;lt;0.001), and HIV-ALC (0.30, 0.14-0.74; p&amp;lt;0.001) vs HD (1.52, 0.74-2.71), accompanied by increased apoptotic MAIT cells. MAIT cells in HIV and HIV-ALC expressed elevated levels of activation markers (CD38, HLA-DR), with HIV-ALC also having higher CD69 levels than HIV and HD. Activated MAIT cells in HIV-ALC positively correlated with disease severity (prolonged prothrombin time, total bilirubin) and trended inversely with CD4% and CD4/CD8 ratio. However, no correlate was observed with cytokines linked to MAIT cell activation/function (IFN-α, IL-7, IL-12, IL-15, IL-17, IL-18, IL-23, IFN-γ, TNF-α). They also did not correlate with levels of blood biomarkers of gut injury/microbial translocation (TFF3, REG3α, LBP), monocyte/macrophage activation (sCD14, sCD163), and systemic inflammation (CRP). Conclusion: Peripheral blood MAIT cells in HIV-ALC were severely depleted, yet highly activated, and associated with disease severity.

Disrupted balance between pro-inflammatory lipid mediators and anti-inflammatory specialized pro-resolving mediators is linked to hyperinflammation in patients with alcoholic hepatitis.

Alcoholic hepatitis (AH) is characterized by intense systemic and liver inflammation, posing significant risks of health complications and mortality. While inflammation is a crucial defense mechanism against injury and infection, its timely resolution is essential to prevent tissue damage and restore tissue homeostasis. The resolution of inflammation is primarily governed by specialized pro-resolving mediators (SPMs), lipid metabolites derived from w-6 and w-3 poly-unsaturated fatty acids (PUFAs). Currently, the balance between pro-inflammatory lipid mediators (PLMs) and SPMs in the w-6 and w-3 PUFA metabolic pathways and the impact of alcohol abstinence on profiles of PLMs and SPMs in AH patients are not well studied. In this study, we used LC-MS/MS and ELISA to quantify levels of lipid mediators (LMs) and their precursors in the plasma samples from 58 AH patients, 29 heavy drinkers without overt liver diseases (HDCs), and 35 healthy controls (HCs). Subsequently, we assessed correlations of altered LMs with clinical parameters and inflammatory mediators. Furthermore, we conducted a longitudinal study to analyze the effects of alcohol abstinence on LMs over 6- and 12-month follow-ups. AH patients exhibited significantly higher plasma levels of w-6 PLMs (PGD2 and LTB4) and SPM RvE1 compared to HDCs or HCs. Conversely, the SPM LXA4 was significantly downregulated in AH patients. Some of these altered LMs were found to correlate with AH disease severity and various inflammatory cytokines. Particularly, the LTB4/LXA4 ratio was substantially elevated in AH patients relative to HDCs and HCs. This altered ratio displayed a positive correlation with the MELD score. Importantly, the majority of dysregulated LMs, particularly PLMs, were normalized following alcohol abstinence.

Association between non-alcoholic fatty liver disease and subclinical left ventricular dysfunction in the general population

Abstract Aims Emerging evidence suggests an association between non-alcoholic fatty liver disease (NAFLD) and heart failure (HF). We investigated the relationship between NAFLD and left ventricular (LV) functional remodelling in a general population sample without overt cardiac and liver disease. Methods and results We included 481 individuals without significant alcohol consumption who voluntarily underwent an extensive cardiovascular health check. The fatty liver index (FLI) was calculated for each participant, and NAFLD was defined as FLI ≥ 60. All participants underwent 2D transthoracic echocardiography; LV global longitudinal strain (LVGLS) was assessed with speckle-tracking analysis. Univariable and multivariable linear regression models were constructed to investigate the possible association between NAFLD and LVGLS. Seventy-one (14.8%) participants were diagnosed with NAFLD. Individuals with NAFLD exhibited larger LV size and LV mass index than those without NAFLD, although left atrial size and E/e′ ratio did not differ between groups. Left ventricular global longitudinal strain was significantly reduced in participants with vs. without NAFLD (17.1% ± 2.4% vs. 19.5% ± 3.1%, respectively; P &amp;lt; 0.001). The NAFLD group had a significantly higher frequency of abnormal LVGLS (&amp;lt;16%) than the non-NAFLD group (31.0% vs. 10.7%, respectively; P &amp;lt; 0.001). Multivariable linear regression analysis demonstrated that higher FLI score was significantly associated with impaired LVGLS independent of age, sex, conventional cardiovascular risk factors, and echocardiographic parameters (standardized β −0.11, P = 0.031). Conclusion In the general population without overt cardiac and liver disease, the presence of NAFLD was significantly associated with subclinical LV dysfunction, which may partly explain the elevated risk of HF in individuals with NAFLD.

Portal Systemic Encephalopathy without Significant Changes of Chronic Liver Disease: A Case Report

Introduction: Determining the etiology of an encephalopathy can be challenging for the neurologists, especially when the preliminary investigations do not indicate any significant biochemical or other systemic abnormality. Portosystemic shunts maybe easily missed and may present as recurrent encephalopathy with elevated serum ammonia or cerebrospinal glutamate levels. These shunts maybe easily identified in the presence of overt chronic liver disease, but maybe easily missed in patients with cryptogenic liver disease or in congenital abnormalities of the intrahepatic vascular system without an associated chronic liver disease. Materials and Methods: The triple-phase computed tomography (CT) or contrast magnetic resonance imaging can demonstrate the extent of portal vein thrombosis, map the extent of the portosystemic collateral, and aid in planning the treatment in patients with difficult anatomy of the portosystemic collaterals. Treatment regimens for patients with portosystemic shunts manifesting as hyperammonemic encephalopathy include restriction of oral protein intake, lactulose administration, oral nonabsorbable antibiotics, closure of the endovascular shunt, or finally, liver transplant. We present a case of a 55-year-old female with seizure disorder presenting with recurrent episodes of encephalopathy with elevated serum ammonia without the overt signs of chronic liver disease with identification of portosystemic shunting on a triple-phase CT of the abdomen. Conclusion: Specialized investigations to identify the presence of portosystemic collaterals should be conducted in patients with cryptogenic encephalopathy with elevated serum ammonia.

Liver stiffness not fatty liver disease is associated with atrial fibrillation: The Rotterdam study.

Fatty liver disease has become the most prevalent chronic liver disease globally and is linked to cardiovascular disease, including arrhythmias. However, there have been inconsistent reports on the association between fatty liver disease and atrial fibrillation, while the role of liver stiffness in this association remains unclear. Within the Rotterdam Study, a large prospective ongoing cohort, participants attending the abdominal ultrasound program between 2009-2014 were included. Exclusion criteria were no atrial fibrillation data or >20% missing data across analysis variables. Steatosis was assessed by ultrasound, liver stiffness by transient elastography and atrial fibrillation by 12-lead electrocardiograms. Incident atrial fibrillation was based on medical records and complete until 2014. Logistic and Cox-regression were used to quantify associations between fatty liver disease and atrial fibrillation. We included 5,825 participants (aged 69.5±9.1, 42.9% male), 35.7% had steatosis, liver stiffness measurement was available in 73.3%, and 7.0% had prevalent atrial fibrillation. Steatosis was not associated with prevalent atrial fibrillation in fully adjusted models (odds ratio [OR] 0.80; 95% CI 0.62-1.03), findings were consistent for non-alcoholic or metabolic dysfunction-associated fatty liver disease. Liver stiffness was significantly associated with prevalent atrial fibrillation (OR 1.09 per kPa, 95% CI 1.03-1.16); however, this was only persistent among those without steatosis (OR 1.18 per kPa, 95% CI 1.08-1.29). Lastly, no associations were found between steatosis (hazard ratio 0.88; 95% CI 0.59-1.33; follow-up 2.1 [1.1-3.2] years) and incident atrial fibrillation. Fatty liver disease was not associated with prevalent or incident atrial fibrillation, while liver stiffness was significantly associated with atrial fibrillation, especially among those without steatosis. This association might be driven by venous congestion instead of fibrogenesis, but this awaits further validation. We recommend assessing cardiovascular health in participants with high liver stiffness, especially in the absence of overt liver disease. NTR6831. There have been inconsistent reports about thepotential links between fatty liver disease and atrial fibrillation (an irregular and often very fast heart rhythm). Herein, we show that liver stiffness (which is a marker of liver fibrosis), but not fatty liver disease, was associated with a higher prevalence of atrial fibrillation. We hypothesis that atrial fibrillation, rather than fibrosis, may be the cause of increased liver stiffness in participants without overt liver disease.

Clinical Characteristics and Etiology of Chronic Liver Disease among Egyptian Patients in Nile Delta: A Clinical Study

Background: Chronic liver disease (CLD) is an extremely common clinical condition that causes significant morbidity and mortality and was responsible for 1.3 million deaths worldwide. There had been a 46% increase in CLD mortality in the world between 1980 and 2013 and most of this increase has been reported in low-income countries in Asia and Africa including Egypt. These countries are experiencing a demographic and epidemiologic transition in disease burden and Egypt is one of the epicenters of this change. Previously, CLD in Egypt was traditionally attributed to schistosomiasis mainly in the region of the Nile Delta until the mid-1980s.&#x0D; Aims: To capture the modes of clinical presentation and at which stage CLD patients seek clinical care, as well as the dramatic change in the etiological profile of CLD in this area of the Nile Delta&#x0D; Methods: 1013 newly diagnosed CLD patients were selected and identified from the Tanta Liver Center (TLC) across the middle of the Nile Delta. After informed or written consent, all consecutive patients (18 years and above) referred to TLC with suspected or overt chronic liver disease were subjected to full history taking, clinical examination searching for stigmata of chronic liver disease, and laboratory studies including urine, blood sugar, liver biochemical tests (bilirubin, ALT, AST&amp; serum albumin), prothrombin, viral markers (HCV Ab &amp; HBS Ag) and AFP. Imaging studies including the abdominal US for all patients and triphasic CT and liver biopsy in selected patients.&#x0D; Results: About 50% of our CLD patients present at a relatively advanced stage of decompensated cirrhosis (ascites in 39.2%, bleeding in 22.8%, and HCC in 9.3%).&#x0D; CLD patients of schistosomal etiology presented mainly with manifestations of portal hypertension (splenomegaly, UGI Bleed &amp; thrombocytopenia) that was significantly higher than the other 2 groups.&#x0D; The vast majority of our CLD patients (83.5%) have viral etiology, while only 11.1% have schistosomal etiology and the remaining 5.4% have non-identified etiology.&#x0D; Conclusion: based on the results of the present study, it is evident that HCV had replaced schistosomiasis as the predominant cause of CLD in Egypt particularly in the region of the Nile Delta. The late presentation of a good percentage of our CLD patients raises the importance of screening programs for CLD in this endemic area of the Nile Delta.

Liver Fibrosis in Primary Sjögren's Syndrome.

BackgroundPrimary Sjögren syndrome (pSS) is a systemic autoimmune epithelitis, potentially affecting salivary epithelium, biliary epithelium, and hepatocytes. Common immunological mechanisms might cause clinically silent liver inflammation, and combined with non-alcoholic fatty liver disease (NAFLD), liver fibrosis (LF) may occur. No studies have explored the occurrence of LF in the context of NAFLD among pSS patients.MethodsConsecutive pSS patients from the rheumatology outpatient clinic of the Department of Pathophysiology and individuals evaluated in the hepatology outpatient clinic for possible NAFLD serving as comparators underwent transient elastography (TE) to assess LF and liver steatosis (LS). All participants had no overt chronic liver disease. Clinical, demographic, and laboratory data were collected from all participants at the time of TE.ResultsFifty-two pSS patients and 198 comparators were included in the study. The median age (range) of pSS and comparators was 62.5 (30–81) and 55 (19–86) years, respectively. Both groups had similar prevalence regarding type 2 diabetes mellitus, hyperlipidemia, and similar body mass index (BMI). Patients with pSS had less frequently high LS (S2, S3) (27% vs. 62%, p < 0.001) and significant LF (F2–4) [2 (3.8%) vs. 34 (17.2%), p = 0.014] than comparators. Univariable analysis showed that advanced LF was significantly associated with older age, higher LS, greater BMI, and disease status (comparators than pSS); of these, only age was identified as an independent LF risk factor in the multivariable logistic regression analysis.ConclusionLiver fibrosis among pSS patients is most likely not attributed to the disease per se.

277-OR: Increased Liver Fat Is Associated with Severe Metabolic Perturbations in Men Born with a Low Birth Weight

Background: Ectopic fat deposition resulting from impaired subcutaneous adipose tissue expandability may take center stage in the pathophysiological events linking low birth weight (LBW) with increased risk of developing Type 2 diabetes (T2D) . However, the extent to which adult LBW subjects exhibit increased hepatic fat accumulation is controversial. Methods and Results: Using 1H MR spectroscopy, we found a significantly increased hepatic fat content (P=0.014) in 26 early middle-aged and non-obese LBW males compared with 21 BMI- and age-matched normal birth weight (NBW) controls. Interestingly, 5 LBW (20%) versus no NBW subjects, had previously unrecognized overt nonalcoholic fatty liver disease (NAFLD) with a median hepatic fat content of 9.45%. The LBW w/NAFLD displayed widespread metabolic changes compared with both NBW and LBW w/o NAFLD subjects including hepatic insulin resistance (P=0.02) , increased fasting plasma triglycerides (TGs) (P=0.03) , cholesterol (P=0.05) , leptin, C-peptide and GLP-1 levels, as well as decreased adiponectin levels (P-range: 0.02-0.007) . Among 65 distinct metabolites and 279 lipids identified by untargeted serum metabolomic and lipidomic analyses, the levels of 7 metabolites including ornithine and citrulline, were different (P&amp;lt;0.05) between LBW w/NAFLD and NBW subjects, pointing towards increased urea cycling in the LBW w/NAFLD subjects. Moreover, the LBW w/NAFLD subjects displayed disproportionately increased levels of phosphatidylcholines and TGs (P&amp;lt;0.05) , with both lipid species qualitatively changed in the LBW w/NAFLD subjects consisting of an increased amount of long chain fatty acids as well as fewer double bonds. These structural lipid characteristics are known to be associated with T2D. Conclusion: The data support a role for ectopic fat deposition in the pathophysiological events and trajectories linking LBW with increased risk of developing T2D and associated cardiometabolic traits including dyslipidemia. Disclosure L.Elingaard-larsen: None. T.Hansen: None. C.Brøns: Stock/Shareholder; Novo Nordisk. A.A.Vaag: Stock/Shareholder; AstraZeneca. L.Justesen: None. S.O.Villumsen: None. A.B.Thuesen: None. J.Størling: None. L.M.Sparks: None. M.Kim: None. C.Legido-quigley: None. E.R.Danielsen: None. Funding Novo Nordisk Foundation (NNF15OC0016692) , Aase and Ejnar Danielsens Fond, Augustinus Foundation, Simon Spies Fonden, TrygFonden.

Liver Fibrosis Marker and Postoperative Mortality in Patients Without Overt Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) can progress to advanced fibrosis, which, in the nonsurgical population, is associated with poor hepatic and extrahepatic outcomes. Despite its high prevalence, NAFLD and related liver fibrosis may be overlooked during the preoperative evaluation, and the role of liver fibrosis as an independent risk factor for surgical-related mortality has yet to be tested. The aim of this study was to assess whether fibrosis-4 (FIB-4), which consists of age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelets, a validated marker of liver fibrosis, is associated with postoperative mortality in the general surgical population. A historical cohort of patients undergoing general anesthesia at an academic medical center between 2014 and 2018 was analyzed. Exclusion criteria included known liver disease, acute liver disease or hepatic failure, and alcohol use disorder. FIB-4 score was categorized into 3 validated predefined categories: FIB-4 ≤1.3, ruling out advanced fibrosis; >1.3 and <2.67, inconclusive; and ≥2.67, suggesting advanced fibrosis. The primary analytic method was propensity score matching (FIB-4 was dichotomized to indicate advanced fibrosis), and a secondary analysis included a multivariable logistic regression. Of 19,861 included subjects, 1995 (10%) had advanced fibrosis per FIB-4 criteria. Mortality occurred intraoperatively in 15 patients (0.1%), during hospitalization in 272 patients (1.4%), and within 30 days of surgery in 417 patients (2.1%). FIB-4 ≥2.67 was associated with increased intraoperative mortality (odds ratio [OR], 3.63; 95% confidence interval [CI], 1.25-10.58), mortality during hospitalization (OR, 3.14; 95% CI, 2.37-4.16), and within 30 days from surgery (OR, 2.46; 95% CI, 1.95-3.10), after adjusting for other risk factors. FIB-4 was related to increased mortality in a dose-dependent manner for the 3 FIB-4 categories ≤1.3 (reference), >1.3 and <2.67, and ≥2.67, respectively; during hospitalization (OR, 1.89; 95% CI, 1.34-2.65 and OR, 4.70; 95% CI, 3.27-6.76) and within 30 days from surgery (OR, 1.77; 95% CI, 1.36-2.31 and OR, 3.55; 95% CI, 2.65-4.77). In a 1:1 propensity-matched sample (N = 1994 per group), the differences in mortality remained. Comparing the FIB-4 ≥2.67 versus the FIB-4 <2.67 groups, respectively, mortality during hospitalization was 5.1% vs 2.2% (OR, 2.70; 95% CI, 1.81-4.02), and 30-day mortality was 6.6% vs 3.4% (OR, 2.26; 95% CI, 1.62-3.14). A simple liver fibrosis marker is strongly associated with perioperative mortality in a population without apparent liver disease, and may aid in future surgical risk stratification and preoperative optimization.

Development of Alcohol-Associated Hepatitis Is Associated With Specific Changes in Gut-Modified Bile Acids.

The perturbations in bile acids (BAs) in alcohol‐associated hepatitis (AH) and its relationship to disease severity is not well defined. The aims of this study were to define (1) the effects of heavy alcohol consumption on BAs and related microbiome, (2) the additional changes with AH, and (3) the relationship of these changes to disease severity. In this multicenter study, plasma and fecal BAs and related microbiome were interrogated in healthy individuals, heavy drinking controls (HDCs) without overt liver disease, and AH. Compared to healthy controls, HDCs had increased glycine‐conjugated 7α and 27α primary BAs and increased secondary BA glycocholenic sulfate (multiple‐comparison adjusted P < 0.05 for all). Plasma‐conjugated cholic and chenodeoxycholic acid increased in AH along with the secondary BAs ursodeoxycholic and lithocholic acid (P < 0.001 for all), whereas deoxycholic acid decreased; however fecal concentrations of both deoxycholic acid and lithocholic acid were decreased. Glycocholenic acid further increased significantly from HDCs to AH. HDCs and AH had distinct plasma and fecal BA profiles (area under the curve, 0.99 and 0.93, respectively). Plasma taurochenodeoxycholic acid and tauroursodeoxycholic acid were directly related to disease severity, whereas fecal ursodeoxycholic acid was inversely related. The fecal abundance of multiple taxa involved in formation of secondary BAs, especially deoxycholic acid (Clostridium cluster XIVa) was decreased in AH. Multiple genera containing taxa expressing 3α, 3β, 7α, and 7β epimerases were decreased with concordant changes in fecal BAs that required these functions for formation. Conclusion: There are distinct changes in BA‐transforming microbiota and corresponding BAs in AH that are related to disease severity.

Markers of Monocyte Activation, Inflammation, and Microbial Translocation Are Associated with Liver Fibrosis in Alcohol Use Disorder

Background: The association between markers of inflammation (interleukin (IL)-6 and IL-10), monocyte activation (sCD163 and sCD14), and microbial translocation (lipopolysaccharide (LPS) and LPS binding protein) and liver fibrosis in patients with alcohol use disorder (AUD) and no overt liver disease is not well established. Methods: We studied patients admitted for treatment of AUD at two hospitals in Barcelona. Advanced liver fibrosis (ALF) was defined as FIB-4 > 3.25. Results: A total of 353 participants (76.3% male) were included and 94 (26.5%) had ALF. In adjusted correlation analyses, sCD163, sCD14, IL-6, IL-10, and LPS binding protein levels directly correlated with FIB-4 values (adjusted correlation coefficients 0.214, 0.452, 0.317, 0.204, and 0.171, respectively). However, LPS levels were inversely associated with FIB-4 (−0.283). All plasma marker levels in the highest quartile, except LPS, were associated with ALF (sCD163, sCD14, IL-6, IL-10, and LPS binding protein: adjusted odds ratio (aOR) 11.49 (95% confidence interval 6.42–20.56), 1.87 (1.11–3.16), 2.99 (1.79–5.01), 1.84 (1.11–3.16), and 2.13 (1.30–3.50), respectively). Conversely, LPS levels in the lowest quartile were associated with ALF (aOR 2.58 (1.48–4.58), p < 0.01). Conclusion: In AUD patients, plasma levels of the markers of inflammation, monocyte activation, and microbial translocation are associated with ALF.

Intravenous Lipid Emulsions in the Prevention and Treatment of Liver Disease in Intestinal Failure.

The development of intestinal failure-associated liver disease (IFALD) in pediatric and adult patients on parenteral nutrition is usually multifactorial in nature due to nutritional and non-nutritional causes. The role of lipid therapy as a contributing cause is well-established with the pathophysiological pathways now better understood. The review focuses on risk factors for IFALD development, biological effects of lipids, lipid emulsions and the mechanisms of lipid toxicity observed in laboratory animals followed by a synopsis of clinical studies in pediatric and adult patients. The introduction of fish oil-based lipid emulsions that provide partial or complete lipid replacement therapy has resulted in resolution of IFALD that had been associated with soybean oil-based therapy. Based on case reports and cohort studies in pediatric and adult patients who were at risk or developed overt liver disease, we now have more evidence that an early switch to partial or complete fish oil–based lipid therapy should be implemented in order to successfully halt and reverse IFALD.

An elevated Fibrosis-4 score is associated with poor clinical outcomes in patients with sepsis: an observational cohort study.

So far, no study has investigated the association between subclinical hepatic fibrosis and sepsis, especially in terms of prognosis. The purpose of our study was to explore the association of liver fibrosis indexes with the outcomes of septic patients without overt chronic liver disease. We performed a cohort study using data extracted from the Medical Information Mart for Intensive Care III (version 1.4) database. External validation was obtained from the First Affiliated Hospital of Wenzhou Medical University, China. We calculated the Aspartate Aminotransferase-to-Platelet Ratio Index, the Fibrosis‑4 (FIB‑4) score, and the Nonalcoholic Fatty Liver Disease Fibrosis Score using the existing formulas. The primary outcome was 28‑day mortality. We assessed the associations of these 3 indexes with patient outcomes using logistic regression analysis. In the FIB‑4 sepsis cohort (n = 1560), there was a significant stepwise increase from quartile 1 to quartile 4 in the risk of 28‑day mortality (quartile 1: reference; quartile 2: odds ratio [OR], 1.57, P = 0.06, 95% CI, 0.98-2.515; quartile 3: OR, 2.363, P <0.001, 95% CI, 1.512-3.692; quartile 4: OR, 2.933, P <0.001, 95% CI, 1.895-4.538). The results of multivariable regression, Kaplan-Meier, and Cox regression analyses as well as external validation exhibited good consistency. The FIB‑4 index is associated with 28‑day, 90‑day, and in‑hospital mortality as well as with renal replacement therapy in septic patients without overt chronic liver disease. In other words, an advanced stage of subclinical hepatic fibrosis as represented by the FIB‑4 score indicates poor outcomes in patients with sepsis.

Abstract C090: Community-based screening for nonalcoholic fatty liver disease with transient elastography in Latinos without overt liver disease at high risk of hepatocellular carcinoma

Abstract Introduction: Non-alcoholic fatty liver disease (NAFLD) is a disease spectrum that progresses through stages of liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). NAFLD has more than doubled in incidence over the last decade alongside the obesity pandemic, and Latinos are at least twice as likely to be affected. The key clinical challenge is how to efficiently screen high-risk communities to identify individuals with severe steatosis and advanced fibrosis or cirrhosis who would benefit from lifestyle modifications, therapeutics, or cancer surveillance. A high proportion of patients with NAFLD are asymptomatic for long periods of time with normal laboratory tests, thus non-invasive procedures for early identification are needed. Transient elastography (TE) is a validated non-invasive diagnostic tool which can identify patients with liver disease. Methods: From March-June 2019, we recruited 76 Latino participants attending a community health screening event in Los Angeles to determine the prevalence of undiagnosed liver disease. We utilized TE performed with a FibroScan® (Echosens) to produce liver stiffness measurement (LSM, a measure of fibrosis in kPa) and a controlled attenuation parameter (CAP, a measure of steatosis in dB/m) on fasting participants, and we collected a self-administered questionnaire for basic characteristics and past medical history, offered in Spanish or English. Results: A total of 74 participants had a valid test with a minimum of ten LSMs with an interquartile range/median value less than 0.3. The mean age of participants was 50 years, and 65% were female. For metabolic risk factors, 78% were overweight or obese, with a mean BMI of 29.5 kg/m2, and the percentage of participants with diabetes or high blood pressure was 29% and 15%, respectively. A minority of participants (4%) reported drinking alcohol 2-3 times per week or more. As for prior liver disease, 16% of participants reported a prior diagnosis of chronic liver disease: NAFLD (N=11), hepatitis B virus (N=1), or cholestatic disease (N=1). In subsequent analyses, we excluded participants with known liver disease. The TE data generated show that steatosis was present in 66% of participants (4% mild, 13% moderate, 49% severe steatosis), with a mean CAP of 273.9 dB/m. The mean LSM in this population was 5.8 kPa, with 22% of participants having kPa measure equivalent to a moderate fibrosis grade (F2 or greater). In univariate analyses, LSM was positively associated with BMI (P= 0.008) and CAP (P&amp;lt;0.001); CAP was positive associated with age (P=0.004) and BMI (P&amp;lt;0.001). In multiple linear regression, CAP (P=0.015), but not BMI, was significantly associated with LSM; and BMI (P&amp;lt;0.001) and age (P&amp;lt;0.002) were both significantly associated with CAP. Conclusion: This study demonstrates the feasibility of using TE at a community-based health screening in a high-risk population. We detected a high rate of clinically significant fibrosis and steatosis suggesting a high prevalence of undiagnosed NAFLD among Latinos. Citation Format: Shehnaz Hussain, Jihane Benhammou. Community-based screening for nonalcoholic fatty liver disease with transient elastography in Latinos without overt liver disease at high risk of hepatocellular carcinoma [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C090.

Persistent Hyperactivation of Endothelial Cells in Patients with Alcoholic Hepatitis.

Alcoholic hepatitis (AH) is a severe inflammatory liver disease that develops in some heavy drinkers. AH patients have intense hepatic infiltration of leukocytes. Up-regulation of cell adhesion molecules (CAMs) upon endothelial cell (EC) activation plays an important role in leukocyte transendothelial migration. CAMs can shed from EC surface and accumulate in the blood, serving as soluble markers for EC activation. In this study, we examined the impact of heavy drinking on expression of soluble forms of EC activation markers (CD146, ICAM-1, VCAM-1, and VEGF-A) and the effect of alcohol abstinence on the reversal of these abnormalities in heavy drinkerswith and without AH. ELISA and multiplex immunoassays were used to measure soluble EC activationmarkers in plasma samples from 79 AH patients, 66 heavy drinkers without overt liver disease (HDC), and 44 healthy controls (HC) at baseline, 31 AH patients and 30 HDC at 6-month follow-up, and 18 AH patients and 25 HDC at 12-month follow-up. At baseline, the 4 soluble markers were significantly up-regulated in AH patients compared with HDC and HC, whereas only sVCAM-1 was elevated in HDC relative to HC. At follow-ups, plasma levels of CD146, VCAM-1, and VEGF-A remained higher in AH patients, even for those who stopped drinking. These dysregulated markers correlated with AH disease severity, clinical parameters, and several solubleinflammatory factors. The levels of soluble CD146, ICAM-1, VCAM-1, and VEGF-A were highly elevated in AH patients, and alcohol abstinence did not completely reverse these abnormalities.

Wilson disease: 30-year data on epidemiology, clinical presentation, treatment modalities and disease outcomes from two tertiary Greek centers

Wilson disease is a rare genetic disorder of copper metabolism with a wide range of clinical presentations. The aim of this study is to describe the 30-year clinical experience in the management of Wilson disease patients followed at two Greek referral centers. A retrospective chart review was performed to identify past and present Wilson disease patients diagnosed during the last 30 years. Sixty-three patients were included. The median age of diagnosis was 19 (3-59) years, while nine (14%) patients were older than 40 years old. Clinical presentation included asymptomatic liver disease (57.1%), neurological disease (20.6%), overt liver disease (12.7%), acute liver failure (6.3%) and other (3.2%). Kayser-Fleischer rings were detected in 27/62 with a higher frequency in neurologic patients (P < 0.001). Ceruloplasmin values were low in 55/63 with significantly lower values in patients with neurological disease (P = 0.048) and in cirrhotic patients (P = 0.017). Increased 24-hour urine copper was measured in 59/63 patients. D-penicillamine was administered in 56/63 patients (88.8%), followed by trientine (6/63, 9.5%), while one patient needed liver transplantation at baseline. At least one treatment switch was performed in 18 patients. By the end of follow-up, all non-cirrhotic patients (25/25) were stable, 3/23 (13%) cirrhotic developed decompensated liver disease, two developed HCC, three received a liver transplant and two died. Five out of 13 neurologic patients had persisting symptoms despite treatment. Wilson disease presents with a wide spectrum of clinical manifestations and should be investigated even in older patients, as early diagnosis, close follow-up and treatment monitoring usually provide favorable outcomes.

Significance of Markers of Monocyte Activation (CD163 and sCD14) and Inflammation (IL-6) in Patients Admitted for Alcohol Use Disorder Treatment.

Monocyte activation and inflammation are prominent features of alcohol-related liver disease; however, they have not been thoroughly assessed in patients with alcohol use disorder (AUD) without overt liver disease. This study aimed to analyze associations among clinical and laboratory variables and markers of monocyte activation (CD163 and sCD14), and inflammation (interleukin [IL]-6) among AUD patients. We analyzed the aforementioned associations in the highest quartile in 289 patients (77.5% male; median age, 50years) consecutively admitted for alcohol detoxification in 2 tertiary hospitals in the Barcelona metropolitan area, Spain. Median alcohol intake was 142g/d; median glucose, albumin, creatinine, and bilirubin levels (mg/dl), 92, 40, 0.78, and 0.69, respectively; median AST, 41 U/l; median hemoglobin, median corpuscular volume, and platelet count, 14.1g/dl, 94.8fL, and 189×109 /l, respectively; median cholesterol, triglyceride, fibrinogen, and ferritin levels, 187mg/dl, 109.3mg/dl, 341mg/dl, and 177ng/ml, respectively. In addition, 36.7% patients had an erythrocyte sedimentation rate >20mm, 32.5% had a C-reactive protein (CRP) level of >5mg/l, and 10.9% were hepatitis C virus (HCV)-positive. Median CD163, sCD14, and IL-6 levels were 759, 1.68×106 , and 4.37pg/ml, respectively. On logistic regression analyses, glucose, AST, bilirubin, hemoglobin levels, and HCV infection (adjusted odds ratio [aORs]: 1.01, 1.02, 3.04, and 9.73, respectively) were associated with CD163. Glucose, AST, triglyceride, and CRP >5mg/l (aORs: 1.02, 1.01, 1.00, and 3.49, respectively) were associated with sCD14. Alcohol consumption upon admission, MCV, total cholesterol levels, and CRP >5mg/l (aORs: 0.99, 1.05, 0.99, and 2.56, respectively) were associated with IL-6. Monocyte activation and systemic inflammation are associated with higher glucose, liver enzyme, and lipid levels, HCV infections, and CRP of >5mg/l, thus potentially identifying patients with AUD at high risk of midterm poor outcomes.

Liver Biochemical Abnormalities in Adolescent Patients with Turner Syndrome

Objective:Elevated liver function tests (LFTs) are common in adult Turner syndrome (TS) patients. Data regarding children and adolescents are lacking. To investigate the prevalence of abnormal LFTs in children and adolescents with TS during several years of observation; to evaluate the potential impact of increased body mass index (BMI) and sex hormone replacement therapy (HRT) on LFTs.Methods:The analysis included 100 girls with TS, aged 4-16 years, all of whom were receiving recombinant human growth hormone therapy. A longitudinal study was conducted which included 81 patients.Results:Mean BMI-standard deviation (SD) score of the subjects was 0.63 (SD: 1.53). Forty-four were being treated with HRT. Elevated LFTs were found in 34% of the patients overall (32% not receiving HRT vs 36% on HRT). The relative risk of increased LFTs was not higher in obese vs normal weight [odds ratio (OR): 0.2; 95% confidence interval (CI): 0.1-0.36, p=0.38 vs OR: 0.16; 95% CI: 0.08-0.3, p=0.1]. HRT did not increase the risk of abnormal LFTs activity (OR: 0.8; 95% CI: 0.5-1.2, p=0.37 vs OR: 0.7; 95% CI: 0.4-1.1, p=0.27). During the follow-up period (mean±SD=4.31±0.82 years), no patient developed overt liver disease. There was no significant increase nor decrease of abnormal LFT frequency in the subsequent years of follow up.Conclusion:Constantly elevated LFTs in TS are common in children and adolescents with TS. However the causes and clinical significance remain unclear. This study suggests that obesity and HRT do not increase the risk of elevated LFTs.

Clinical Profile of Patients with Incidentally Detected Non-alcoholoic Fatty Liver Disease

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the commonest liver problem worldwide with disease spectrum ranging from steatosis to steatohepatitis, advanced fibrosis and cirrhosis.&#x0D; Objective: To delineate the clinical and biochemical profile of patients with incidentally detected NAFLD.&#x0D; Materials and Methods: In this observational study subjects without overt liver disease having sonological evidence of fatty liver underwent thorough physical examinations including anthropometric measurements and investigated for blood glucose level, lipid profile and liver function status. Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) ratio and BMI and diabetes (BARD) score were computed to assess hepatic fibrosis status non-invasively.&#x0D; Results: Out of 407 final participants, 213 were male and 194 were female. Mean age of the patients was 42.05±10.54 (range 21-71 years). Mean body mass index (BMI) of the subjects was 26.92±3.75Kg/m2. Visceral obesity as measured by abdominal circumference and waist-hip-ratio were found increased in 333(81.81%) and 336(82.5%) subjects respectively. Obesity (BMI &gt; 25 mg/m2), diabetes mellitus, hypertension, and metabolic syndrome (MS) were present in 68.8%, 48.2%, 36.4%, and 87.5% patients respectively. Cholesterol, high density lipoprotein, low density lipoprotein and triglyceride were found increased in 47.7% (n=194), 83.05% (n=338), 42.8%(n=174) and 80.59%(n= 328) NAFLD patients respectively. Elevated AST and ALT levels were found in 98 (24.1%) and 233 (57.0%) patients, respectively. AST/ALT ratio &gt;1 and BARD score &gt;2 were found in 27.5% (n=112) and 29.2% (n=119) patients respectively.&#x0D; Conclusion: In Bangladesh incidentally detected NAFLD patients are predominantly middle aged and obese. MS and hypertriglyceridaemia are highly prevalent among them. Around one fourth of them have evidence of advanced fibrosis non-invasively.&#x0D; Journal of Armed Forces Medical College Bangladesh Vol.14(1) 2018: 4-9