Search

BackgroundOne challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease.AimTo derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes.MethodsWe used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic fibrosis (> 8 kPa). Possible predictors included data from the EHR for age, gender, diabetes, hypertension, FIB-4, body mass index (BMI), LDL, HDL, and triglycerides.ResultsOf 344 patients (56.4% women), 34 had any hepatic fibrosis, and 15 significant hepatic fibrosis. Three variables (BMI, FIB-4, diabetes) were identified from both approaches. When we used variable cut-offs defined by Youden's index, the final model predicting any hepatic fibrosis had an AUC of 0.75 (95% CI 0.67-0.84), NPV of 91.5% and PPV of 40.0%. The final model with variable categories based on standard clinical thresholds (i.e., BMI ≥ 30 kg/m2; FIB-4 ≥ 1.45) had lower discriminatory ability (AUC 0.65), but higher PPV (50.0%) and similar NPV (91.3%). We observed similar findings for predicting significant hepatic fibrosis.ConclusionsOur results demonstrate that standard thresholds for clinical risk factors/biomarkers may need to be modified for greater discriminatory ability among populations with high prevalence of obesity and diabetes.

Background & aimsA recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population.MethodsWe conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 dB/m was used to define NAFLD, whereas MAFLD was defined as controlled attenuation parameter median ≥290 dB/m and either body mass index ≥25 kg/m2 or diabetes, or 2 or more of the following: hypertension, high triglycerides, low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol.ResultsThe mean age of participants was 50.9 years, 55.4% were women, 42.8% were white, and 43.8% were Black. The prevalence of NAFLD was 40.6% (82/202). All 82 patients with NAFLD had a body mass index ≥25 kg/m2, and therefore met our criteria for MAFLD (ie, 100% concordance). Compared with patients with no metabolic trait, patients with ≥3 traits had a 48-fold (adjusted odds ratio, 47.6; 95% confidence interval, 11.3-200) higher risk of NAFLD/MAFLD. Overall, 19 participants (9.4% of the total, 15.9% of those with NAFLD) had at least moderate fibrosis.ConclusionsNAFLD was present in 40% of Veterans registered in primary care; 9.4% of veterans had at least moderate hepatic fibrosis, with most having concurrent NAFLD. There was perfect concordance between NAFLD and the alternative MAFLD definition.

BackgroundDiet is associated with metabolic (dysfunction)-associated fatty liver disease (MAFLD), but the dietary composition associated with MAFLD risk has not been well-examined.AimThe purpose of this study was to assess the association of two healthy eating indices with the presence and severity of MAFLD in a sample of Veterans in a primary care setting.MethodsThis was a single center cross-sectional study using a random stratified sample of Veterans enrolled in primary care. Participants underwent a Fibroscan and completed an interviewer-administered Diet History Questionnaire II from which we calculated the Healthy Eating Index-2015 and Alternate Mediterranean Diet Score. We used multivariable logistic regression models to assess associations of dietary quality with MAFLD.ResultsWe analyzed data from 187 participants, 53.5% of whom were female. On average, participants were 50.2 years of age (SD, 12.3 years) with an average BMI of 31.7 kg/m2. MAFLD was detected in 78 (42%) and at least moderate fibrosis in 12 (6%) participants. We found that the Alternate Mediterranean Diet Score was inversely associated with MAFLD (adjusted OR = 0.85, 95%CI 0.72-1.00), but controlling for BMI and total energy intake attenuated the association (adjusted OR = 0.92, 95%CI 0.74-1.15). We found no statistically significant associations between the Healthy Eating Index-2015 and MAFLD or advanced fibrosis.DiscussionWe found that the Alternate Mediterranean Diet Score was significantly associated with lower MAFLD risk in Veterans; however, the association was mediated by BMI and total energy intake. A Mediterranean-style diet could potentially help reduce the risk of MAFLD, particularly if it helps control total energy intake and weight.

Liver cancer epidemiology is changing due to increasing alcohol consumption, rising prevalence of obesity, and advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) treatment. However, the impact of these changes on global liver cancer burden remains unclear. We estimated global and regional temporal trends in the burden of liver cancer and the contributions of various liver disease etiologies using the methodology framework of the Global Burden of Disease study. Between 2010 and 2019, there was a 25% increase in liver cancer deaths. Age-standardized death rates (ASDRs) increased only in the Americas and remained stable or fell in all other regions. Between 2010 and 2019, non-alcoholic steatohepatitis (NASH) and alcohol had the fastest growing ASDRs, while HCV and HBV declined. Urgent measures are required at a global level to tackle underlying metabolic risk factors and slow the growing burden of NASH-associated liver cancer, especially in the Americas.

Find AGA's NASH Clinical Care Pathway App for iOS and Android mobile devices at nash.gastro.org. Scan this QR code to be taken directly to the website.Nonalcoholic fatty liver disease (NAFLD) is becoming increasingly common, currently affecting approximately 37% of US adults. NAFLD is most often managed in primary care or endocrine clinics, where clinicians must determine which patients might benefit from secondary care to address hepatic manifestations, comorbid metabolic traits, and cardiovascular risks of the disease. Because NAFLD is largely asymptomatic, and because optimal timing of treatment depends on accurate staging of fibrosis risk, screening at the primary care level is critical, together with consistent, timely, evidence-based, widely accessible, and testable management processes. To achieve these goals, the American Gastroenterological Association assembled a multidisciplinary panel of experts to develop a Clinical Care Pathway providing explicit guidance on the screening, diagnosis, and treatment of NAFLD. This article describes the NAFLD Clinical Care Pathway they developed and provides a rationale supporting proposed steps to assist clinicians in diagnosing and managing NAFLD with clinically significant fibrosis (stage F2-F4) based on the best available evidence. This Pathway is intended to be applicable in any setting where care for patients with NAFLD is provided, including primary care, endocrine, obesity medicine, and gastroenterology practices.

One quarter of the global population is estimated to have nonalcoholic fatty liver disease (NAFLD). The incidence of nonalcoholic steatohepatitis (NASH) is projected to increase by up to 56% in the next 10 years. NAFLD is already the fastest growing cause of hepatocellular carcinoma (HCC) in the USA, France and the UK. Globally, the prevalence of NAFLD-related HCC is likely to increase concomitantly with the growing obesity epidemic. The estimated annual incidence of HCC ranges from 0.5% to 2.6% among patients with NASH cirrhosis. The incidence of HCC among patients with non-cirrhotic NAFLD is lower, approximately 0.1 to 1.3 per 1,000 patient-years. Although the incidence of NAFLD-related HCC is lower than that of HCC of other aetiologies such as hepatitis C, more people have NAFLD than other liver diseases. Urgent measures that increase global awareness and tackle the metabolic risk factors are necessary to reduce the impending burden of NAFLD-related HCC. Emerging evidence indicates that reduced immune surveillance, increased gut inflammation and gut dysbiosis are potential key steps in tumorigenesis. In this Review, we discuss the global epidemiology, projections and risk factors for NAFLD-related HCC, and propose preventive strategies to tackle this growing problem.

Nonalcoholic fatty liver disease (NAFLD) is a leading etiology for chronic liver disease with an immense public health impact and affects >25% of the US and global population. Up to 1 in 4 NAFLD patients may have nonalcoholic steatohepatitis (NASH). NASH is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Recent data confirm that HCC represents the fifth most common cancer and is the second leading cause of cancer-related death worldwide, and NAFLD has been identified as a rapidly emerging risk factor for this malignancy. NAFLD-associated liver complications are projected to become the leading indication for liver transplantation in the next decade. Despite evidence that NAFLD-associated HCC may arise in the absence of cirrhosis, is often diagnosed at advanced stages, and is associated with lower receipt of curative therapy and with poorer survival, current society guidelines provide limited guidance/recommendations addressing HCC surveillance in patients with NAFLD outside the context of established cirrhosis. Limited data are presently available to guide clinicians with respect to which patients with NAFLD should undergo HCC surveillance, optimal screening tools, frequency of monitoring, and the influence of coexisting host- and disease-related risk factors. Herein we present an evidence-based review addressing HCC risk in patients with NAFLD and provide Best Practice Advice statements to address key issues in clinical management.

Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.

Background: Early detection of hepatocellular carcinoma (HCC) is crucial for improving patient outcomes, but we lack robust clinical biomarkers. This study aimed to identify a metabolite and/or lipid panel for early HCC detection. Methods: We developed a high-resolution liquid chromatography mass spectrometry (LC-MS)-based profiling platform and evaluated differences in the global metabolome and lipidome between 28 pre-diagnostic serum samples from patients with cirrhosis who subsequently developed HCC (cases) and 30 samples from patients with cirrhosis and no HCC (controls). We linked differentially expressed metabolites and lipids to their associated genes, proteins, and transcriptomic signatures in publicly available datasets. We used machine learning models to identify a minimal panel to distinguish between cases and controls. Results: Among cases compared with controls, 124 metabolites and 246 lipids were upregulated, while 208 metabolites and 73 lipids were downregulated. The top upregulated metabolites were glycoursodeoxycholic acid, 5-methyltetrahydrofolic acid, octanoyl-coenzyme A, and glycocholic acid. Elevated lipids comprised glycerol lipids, cardiolipin, and phosphatidylethanolamine, whereas suppressed lipids included oxidized phosphatidylcholine and lysophospholipids. There was an overlap between differentially expressed metabolites and lipids and previously published transcriptomic signatures, illustrating an association with liver disease severity. A panel of 12 metabolites that distinguished between cases and controls with an area under the receiver operating curve of 0.98 for the support vector machine (interquartile range, 0.9– 1). Conclusion: Using prediagnostic serum samples, we identified a promising metabolites panel that accurately identifies patients with cirrhosis who progressed to HCC. Further validation of this panel is required. [ABSTRACT FROM AUTHOR]

Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed. Integrative molecular HCC subtyping incorporating unsupervised clustering of five data platforms identified three subtypes, one of which was associated with poorer prognosis in three HCC cohorts. Integrated analyses enabled development of a p53 target gene expression signature correlating with poor survival. Potential therapeutic targets for which inhibitors exist include WNT signaling, MDM4, MET, VEGFA, MCL1, IDH1, TERT, and immune checkpoint proteins CTLA-4, PD-1, and PD-L1.