A global action agenda for turning the tide on fatty liver disease.

BACKGROUND AND AIMS: Fatty liver disease is a major public health threat due to its very high prevalence and related morbidity and mortality. Focused and dedicated interventions are urgently needed to target disease prevention, treatment, and care. APPROACH AND RESULTS: We developed an aligned, prioritized action agenda for the global fatty liver disease community of practice. Following a Delphi methodology over 2 rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the action priorities using Qualtrics XM, indicating agreement using a 4-point Likert-scale and providing written feedback. Priorities were revised between rounds, and in R2, panelists also ranked the priorities within 6 domains: epidemiology, treatment and care, models of care, education and awareness, patient and community perspectives, and leadership and public health policy. The consensus fatty liver disease action agenda encompasses 29 priorities. In R2, the mean percentage of "agree" responses was 82.4%, with all individual priorities having at least a super-majority of agreement (> 66.7% "agree"). The highest-ranked action priorities included collaboration between liver specialists and primary care doctors on early diagnosis, action to address the needs of people living with multiple morbidities, and the incorporation of fatty liver disease into relevant non-communicable disease strategies and guidance. CONCLUSIONS: This consensus-driven multidisciplinary fatty liver disease action agenda developed by care providers, clinical researchers, and public health and policy experts provides a path to reduce the prevalence of fatty liver disease and improve health outcomes. To implement this agenda, concerted efforts will be needed at the global, regional, and national levels.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

Food Insecurity, Low Household Income, and Low Education Level Increase the Risk of Having Metabolic Dysfunction-Associated Fatty Liver Disease Among Adolescents in the United States.

INTRODUCTION: In the United States, 10.2% households (HH) report child food insecurity. We assessed associations between metabolic dysfunction-associated fatty liver disease (MASLD) and food insecurity among the adolescents in the United States. METHODS: This cross-sectional study was performed using data from the National Health and Nutrition Examination Survey 2017-2018. Food insecurity was assessed by the US Department of Agriculture Child Food Security Survey Module. MASLD was defined by transient elastography. RESULTS: Among 771 adolescents (aged 12-18 years) (mean age 14.7 years; 52.5% male; 50.9% White, 12.7% Black, 24.4% Hispanic, and 12.1% other), 9.8% reported food insecurity; MASLD prevalence of 10.12% (95% confidence interval [CI] 7.13%-13.20%) affecting 4.27 million adolescents; and nonalcoholic fatty liver disease prevalence of 10.77% (95% CI 7.76-13.78) affecting 4.52 million adolescents. There was near-perfect concordance between MASLD and nonalcoholic fatty liver disease (Cohen's κ coefficient of 0.971, 95% CI 0.946-0.996). The prevalence of MASLD was greater among food-insecure adolescents vs food-secure ones (17.4% vs 9.4%) and adolescents living with a low HH income vs those with a higher HH income (15.0% vs 7.2%) and living with a head of HH with a lower education level vs one with a higher education level (18.0% vs 8.2%) ( P < 0.05). The fully adjusted model showed that compared with adolescents living in a higher HH income, food-insecure adolescents living in low income HH had a 3-fold greater risk (odds ratio [OR] 3.25, 1.31-8.08) of having MASLD, while food-secure adolescents living in low-income HH had no increased risk (OR 1.58, 0.85-2.93, P = 0.139). The fully adjusted odds of having MASLD was elevated by +163% with the presence of HTN (OR 2.63, 1.02-6.78), +241% with being Hispanic (OR 3.41, 1.36-8.56), and +138% with being male (OR 2.38, 1.20-4.75). In addition, a 1-unit increase in BMI was associated with 25% increase in the odds of having MASLD (OR 1.25, 1.17-1.33) among US adolescents. DISCUSSION: Food insecurity is associated with MASLD among US low-income adolescents especially Hispanic male individuals with obesity and hypertension. Policies addressing inequities are needed.

Intermittent fasting-the future treatment in NASH patients?

NASH is one of the leading causes of chronic liver disease with the potential of evolving towards end-stage liver disease and HCC, even in the absence of cirrhosis. Apart from becoming an increasingly prevalent indication for liver transplantation in cirrhotic and HCC patients, its burden on the healthcare system is also exerted by the increased number of noncirrhotic NASH patients. Intermittent fasting has recently gained more interest in the scientific community as a possible treatment approach for different components of metabolic syndrome. Basic science and clinical studies have shown that apart from inducing body weight loss, improving cardiometabolic parameters, namely blood pressure, cholesterol, and triglyceride levels; insulin and glucose metabolism; intermittent fasting can reduce inflammatory markers, endoplasmic reticulum stress, oxidative stress, autophagy, and endothelial dysfunction, as well as modulate gut microbiota. This review aims to further explore the main NASH pathogenetic metabolic drivers on which intermittent fasting can act upon and improve the prognosis of the disease, and summarize the current clinical evidence.

The global fatty liver disease Sustainable Development Goal country score for 195 countries and territories.

BACKGROUND AND AIMS: Fatty liver disease is highly prevalent, resulting in overarching wellbeing and economic costs. Addressing it requires comprehensive and coordinated multisectoral action. We developed a fatty liver disease Sustainable Development Goal (SDG) country score to provide insights into country-level preparedness to address fatty liver disease through a whole-of-society lens. APPROACH AND RESULTS: We developed 2 fatty liver disease-SDG score sets. The first included 6 indicators (child wasting, child overweight, noncommunicable disease mortality, a universal health coverage service coverage index, health worker density, and education attainment), covering 195 countries and territories between 1990 and 2017. The second included the aforementioned indicators plus an urban green space indicator, covering 60 countries and territories for which 2017 data were available. To develop the fatty liver disease-SDG score, indicators were categorized as "positive" or "negative" and scaled from 0 to 100. Higher scores indicate better preparedness levels. Fatty liver disease-SDG scores varied between countries and territories (n = 195), from 14.6 (95% uncertainty interval: 8.9 to 19.4) in Niger to 93.5 (91.6 to 95.3) in Japan; 18 countries and territories scored > 85. Regionally, the high-income super-region had the highest score at 88.8 (87.3 to 90.1) in 2017, whereas south Asia had the lowest score at 44.1 (42.4 to 45.8). Between 1990 and 2017, the fatty liver disease-SDG score increased in all super-regions, with the greatest increase in south Asia, but decreased in 8 countries and territories. CONCLUSIONS: The fatty liver disease-SDG score provides a strategic advocacy tool at the national and global levels for the liver health field and noncommunicable disease advocates, highlighting the multisectoral collaborations needed to address fatty liver disease, and noncommunicable diseases overall.

American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Practical Lifestyle Management of Nonalcoholic Fatty Liver Disease for Busy Clinicians.

Weight loss achieved through a combination of healthy eating patterns that encompass the principles of the Mediterranean diet and regular physical activity is the most evidence-based treatment for nonalcoholic fatty liver disease. Although other types of diets have demonstrated efficacy in liver fat reduction, the Mediterranean diet confers additional cardiometabolic benefits. Macronutrient composition, food choices, and timing of eating can be tailored to individual preferences, culture, and financial circumstances; however, recommended healthy eating patterns are characterized by minimally processed or unprocessed foods (vegetables, legumes, nuts and seeds, fruits, whole grains, and unprocessed meats and fish) that are low in sugar, refined carbohydrates, and saturated fat and high in fiber, polyphenols, vitamins, minerals, and healthy fats. Physical activity can independently improve steatosis, prevent fibrosis and cirrhosis, and reduce mortality.

The association between liver fibrosis score and incident dementia: A nationwide retrospective cohort study.

BACKGROUND: We assessed the relationship of liver fibrosis score with incident dementia in a large, national sample. METHODS: For this retrospective cohort study, data of dementia-free individuals aged 40-69 years were derived from electronic records of the largest healthcare provider in Israel. The association between liver fibrosis score (FIB-4), assessed from routine laboratory measurements, and incident dementia was explored through multivariate cox regression models. RESULTS: Of the total sample (N = 826,578, mean age 55 ± 8 years at baseline), 636,967 (77%) had no fibrosis, 180,114 (21.8%) had inconclusive fibrosis status and 9497 (1.2%) had high risk for advanced fibrosis. Over a median follow-up of 17 years, 41,089 dementia cases were recorded. Inconclusive liver fibrosis and advanced fibrosis were associated with increased dementia risk (HR = 1.09, 95%CI: 1.07-1.11 and HR = 1.18, 95%CI: 1.10-1.27, respectively). This association remained robust through seven sensitivity analyses. CONCLUSIONS: Liver fibrosis assessed through a serum-based algorithm may serve as a risk factor for dementia in the general population. HIGHLIGHTS: Liver fibrosis may predict dementia diagnosis in the general population. Inconclusive liver fibrosis was associated with 9% increased dementia risk. Advanced liver fibrosis was associated with 18% increased dementia risk. Findings remained robust in sensitivity analyses and after adjustments.

A global research priority agenda to advance public health responses to fatty liver disease.

BACKGROUND & AIMS: An estimated 38% of adults worldwide have non-alcoholic fatty liver disease (NAFLD). From individual impacts to widespread public health and economic consequences, the implications of this disease are profound. This study aimed to develop an aligned, prioritised fatty liver disease research agenda for the global health community. METHODS: Nine co-chairs drafted initial research priorities, subsequently reviewed by 40 core authors and debated during a three-day in-person meeting. Following a Delphi methodology, over two rounds, a large panel (R1 n = 344, R2 n = 288) reviewed the priorities, via Qualtrics XM, indicating agreement using a four-point Likert-scale and providing written feedback. The core group revised the draft priorities between rounds. In R2, panellists also ranked the priorities within six domains: epidemiology, models of care, treatment and care, education and awareness, patient and community perspectives, and leadership and public health policy. RESULTS: The consensus-built fatty liver disease research agenda encompasses 28 priorities. The mean percentage of 'agree' responses increased from 78.3 in R1 to 81.1 in R2. Five priorities received unanimous combined agreement ('agree' + 'somewhat agree'); the remaining 23 priorities had >90% combined agreement. While all but one of the priorities exhibited at least a super-majority of agreement (>66.7% 'agree'), 13 priorities had <80% 'agree', with greater reliance on 'somewhat agree' to achieve >90% combined agreement. CONCLUSIONS: Adopting this multidisciplinary consensus-built research priorities agenda can deliver a step-change in addressing fatty liver disease, mitigating against its individual and societal harms and proactively altering its natural history through prevention, identification, treatment, and care. This agenda should catalyse the global health community's efforts to advance and accelerate responses to this widespread and fast-growing public health threat. IMPACT AND IMPLICATIONS: An estimated 38% of adults and 13% of children and adolescents worldwide have fatty liver disease, making it the most prevalent liver disease in history. Despite substantial scientific progress in the past three decades, the burden continues to grow, with an urgent need to advance understanding of how to prevent, manage, and treat the disease. Through a global consensus process, a multidisciplinary group agreed on 28 research priorities covering a broad range of themes, from disease burden, treatment, and health system responses to awareness and policy. The findings have relevance for clinical and non-clinical researchers as well as funders working on fatty liver disease and non-communicable diseases more broadly, setting out a prioritised, ranked research agenda for turning the tide on this fast-growing public health threat.

Current therapies and new developments in NASH.

Non-alcoholic steatohepatitis is becoming the most important aetiology for advanced liver disease. There has been important progress in the field in recent years and the complexity of the pathophysiology of NASH is better understood. Multiple non-invasive circulating and imaging biomarkers have been tested. The importance of lifestyle has been recognised and several drugs are being tested in clinical trials. This review addresses the challenges that healthcare professionals face in the management of NASH patients.

The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge?

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, yet largely underappreciated liver condition which is closely associated with obesity and metabolic disease. Despite affecting an estimated 1 in 4 adults globally, NAFLD is largely absent on national and global health agendas. METHODS: We collected data from 102 countries, accounting for 86% of the world population, on NAFLD policies, guidelines, civil society engagement, clinical management, and epidemiologic data. A preparedness index was developed by coding questions into 6 domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) and categorising the responses as high, medium, and low; a multiple correspondence analysis was then applied. RESULTS: The highest scoring countries were India (42.7) and the United Kingdom (40.0), with 32 countries (31%) scoring zero out of 100. For 5 of the domains a minority of countries were categorised as high-level while the majority were categorised as low-level. No country had a national or sub-national strategy for NAFLD and <2% of the different strategies for related conditions included any mention of NAFLD. National NAFLD clinical guidelines were present in only 32 countries. CONCLUSIONS: Although NAFLD is a pressing public health problem, no country was found to be well prepared to address it. There is a pressing need for strategies to address NAFLD at national and global levels. LAY SUMMARY: Around a third of the countries scored a zero on the NAFLD policy preparedness index, with no country scoring over 50/100. Although NAFLD is a pressing public health problem, a comprehensive public health response is lacking in all 102 countries. Policies and strategies to address NAFLD at the national and global levels are urgently needed.

Effects of personalized diets by prediction of glycemic responses on glycemic control and metabolic health in newly diagnosed T2DM: a randomized dietary intervention pilot trial.

BACKGROUND: Dietary modifications are crucial for managing newly diagnosed type 2 diabetes mellitus (T2DM) and preventing its health complications, but many patients fail to achieve clinical goals with diet alone. We sought to evaluate the clinical effects of a personalized postprandial-targeting (PPT) diet on glycemic control and metabolic health in individuals with newly diagnosed T2DM as compared to the commonly recommended Mediterranean-style (MED) diet. METHODS: We enrolled 23 adults with newly diagnosed T2DM (aged 53.5 ± 8.9 years, 48% males) for a randomized crossover trial of two 2-week-long dietary interventions. Participants were blinded to their assignment to one of the two sequence groups: either PPT-MED or MED-PPT diets. The PPT diet relies on a machine learning algorithm that integrates clinical and microbiome features to predict personal postprandial glucose responses (PPGR). We further evaluated the long-term effects of PPT diet on glycemic control and metabolic health by an additional 6-month PPT intervention (n = 16). Participants were connected to continuous glucose monitoring (CGM) throughout the study and self-recorded dietary intake using a smartphone application. RESULTS: In the crossover intervention, the PPT diet lead to significant lower levels of CGM-based measures as compared to the MED diet, including average PPGR (mean difference between diets, - 19.8 ± 16.3 mg/dl × h, p < 0.001), mean glucose (mean difference between diets, - 7.8 ± 5.5 mg/dl, p < 0.001), and daily time of glucose levels > 140 mg/dl (mean difference between diets, - 2.42 ± 1.7 h/day, p < 0.001). Blood fructosamine also decreased significantly more during PPT compared to MED intervention (mean change difference between diets, - 16.4 ± 37 µmol/dl, p < 0.0001). At the end of 6 months, the PPT intervention leads to significant improvements in multiple metabolic health parameters, among them HbA1c (mean ± SD, - 0.39 ± 0.48%, p < 0.001), fasting glucose (- 16.4 ± 24.2 mg/dl, p = 0.02) and triglycerides (- 49 ± 46 mg/dl, p < 0.001). Importantly, 61% of the participants exhibited diabetes remission, as measured by HbA1c < 6.5%. Finally, some clinical improvements were significantly associated with gut microbiome changes per person. CONCLUSION: In this crossover trial in subjects with newly diagnosed T2DM, a PPT diet improved CGM-based glycemic measures significantly more than a Mediterranean-style MED diet. Additional 6-month PPT intervention further improved glycemic control and metabolic health parameters, supporting the clinical efficacy of this approach. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT01892956.

Administrative Coding in Electronic Health Care Record-Based Research of NAFLD: An Expert Panel Consensus Statement.

BACKGROUND AND AIMS: Electronic health record (EHR)-based research allows the capture of large amounts of data, which is necessary in NAFLD, where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Diseases (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues. APPROACH AND RESULTS: Researchers with an interest in EHR-based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR-based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research. CONCLUSIONS: This expert panel consensus statement can help harmonize and improve generalizability of EHR-based NAFLD research.

One size does not fit all; practical, personal tailoring of the diet to NAFLD patients.

Different dietary regimens for weight loss have developed over the years. Since the most evidenced treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction, it is not surprising that more diets targeting obesity are also utilized for NAFLD treatment. However, beyond the desired weight loss effects, one should not ignore the dietary composition of each diet, which may not necessarily be healthy or safe over the long term for hepatic and extrahepatic outcomes, especially cardiometabolic outcomes. Some of these diets are rich in saturated fat and red meat, are very strict, and require close medical supervision. Some may also be very difficult to adhere to for long periods, thus reducing the patient's motivation. The evidence for a direct benefit to NAFLD by restrictive diets such as very-low-carb, ketogenic, very-low-calorie diets, and intermittent fasting is scarce, and the long-term safety has not been tested. Nowadays, the approach is that the diet should be tailored to the patient's cultural and personal preferences. There is strong evidence for the independent protective association of NAFLD with a diet based on healthy eating patterns of minimally-processed foods, low in sugar and saturated fat, high in polyphenols, and healthy types of fats. This leads to the conclusion that a Mediterranean diet should serve as a basis that can be restructured into other kinds of diets. This review will elaborate on the different diets and their role in NAFLD. It will provide a practical guide to tailor the diet to the patients without compromising its composition and safety.

Management of NAFLD in primary care settings.

Non-alcoholic fatty liver disease (NAFLD) affects at least 25% of the general population and is an increasingly important cause of cirrhosis and hepatocellular carcinoma. Although it is the research focus of the hepatology field, it is clear that primary care physicians are seeing the majority of NAFLD patients and are in a pivotal position to provide quality care. In this article, we review the role of primary care in the management of NAFLD. NAFLD is common in patients with diabetes, obesity and other metabolic risk factors. Abdominal ultrasonography is the most commonly used method to diagnose fatty liver. Simple fibrosis scores have high negative predictive values in excluding advanced liver fibrosis and future liver-related events and can be used in primary care as initial evaluation. An abnormal result should be followed by subsequent workup or specialist referral. Primary care is the ideal setting to institute multidisciplinary care, especially the involvement of dietitians and physical activity trainers in lifestyle intervention, as well as initiating the discussion of bariatric surgery in patients with severe obesity. Although specific drug treatment for steatohepatitis would require a more precise diagnosis, metabolic drugs that improve both steatohepatitis and cardiovascular outcomes (e.g. glucagon-like peptide-1 receptor agonists) may be considered in patients with NAFLD.

Stratifying individuals into non-alcoholic fatty liver disease risk levels using time series machine learning models.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the population worldwide, and its prevalence is anticipated to increase globally. While most NAFLD patients are asymptomatic, NAFLD may progress to fibrosis, cirrhosis, cardiovascular disease, and diabetes. Research reports, with daunting results, show the challenge that NAFLD's burden causes to global population health. The current process for identifying fibrosis risk levels is inefficient, expensive, does not cover all potential populations, and does not identify the risk in time. Instead of invasive liver biopsies, we implemented a non-invasive fibrosis assessment process calculated from clinical data (accessed via EMRs/EHRs). We stratified patients' risks for fibrosis from 2007 to 2017 by modeling the risk in 5579 individuals. The process involved time-series machine learning models (Hidden Markov Models and Group-Based Trajectory Models) profiled fibrosis risk by modeling patients' latent medical status resulted in three groups. The high-risk group had abnormal lab test values and a higher prevalence of chronic conditions. This study can help overcome the inefficient, traditional process of detecting fibrosis via biopsies (that are also medically unfeasible due to their invasive nature, the medical resources involved, and costs) at early stages. Thus longitudinal risk assessment may be used to make population-specific medical recommendations targeting early detection of high risk patients, to avoid the development of fibrosis disease and its complications as well as decrease healthcare costs.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Dietary Treatment for NAFLD: New Clinical and Epidemiological Evidence and Updated Recommendations.

The key factor in preventing and treating nonalcoholic fatty liver disease (NAFLD) is a holistic lifestyle modification approach, encompassing diet based on healthy eating patterns of unprocessed foods, exercise, balanced drinking, and smoking habits. The Mediterranean diet and other healthy dietary patterns can reduce liver fat and may be related with lower disease progression. The type of diet should be tailored to the patient's cultural and personal preferences. Changing dietary composition without reducing caloric intake may offer an additional and sometimes more feasible alternative, so that the nutritional treatment incorporates, but is not focused on, weight reduction goals. The growing global consumption of ultra-processed foods, which is the polar opposite of the Mediterranean diet and its concept of home-based cooking, poses a great challenge in the prevention of NAFLD and probably hepatocellular carcinoma.This review will cover the most updated clinical and epidemiological evidence for lifestyle treatment in NAFLD and provide practical treatment tools.

Diet Associations With Nonalcoholic Fatty Liver Disease in an Ethnically Diverse Population: The Multiethnic Cohort.

BACKGROUND AND AIMS: Epidemiological data on dietary risk factors for nonalcoholic fatty liver disease (NAFLD) from population-based studies, particularly in an ethnically diverse population, are scarce. We examined dietary factors in relation to NAFLD risk in African Americans, Japanese Americans, Latinos, native Hawaiians, and whites in the Multiethnic Cohort (MEC). APPROACH AND RESULTS: A nested case-control analysis was conducted within the MEC, a large prospective study with >215,000 older adult participants in Hawaii and California. NAFLD was identified using Medicare claims data, and controls were selected among participants without liver disease and individually matched to cases by birth year, sex, ethnicity, and length of Medicare enrollment. Diet was assessed at baseline through a validated quantitative food frequency questionnaire. Diet-NAFLD associations were quantified by odds ratios and 95% confidence intervals using multivariable conditional logistic regression. The study consisted of 2,974 NAFLD cases (518 with cirrhosis, 2,456 without cirrhosis) and 29,474 matched controls. Red meat (P trend = 0.010), processed red meat (P trend = 0.004), poultry (P trend = 0.005), and cholesterol (P trend = 0.005) intakes were positively associated with NAFLD, while dietary fiber intake (P trend = 0.003) was inversely associated with risk. Stronger associations were observed between red meat and cholesterol and NAFLD with cirrhosis than without cirrhosis (P heterogeneity ≤0.014). CONCLUSIONS: Dietary factors are independently associated with NAFLD and NAFLD-related cirrhosis in a multiethnic population. Decreasing the consumption of cholesterol, red and processed meat, and poultry and increasing consumption of fiber may reduce the risk for NAFLD and related advanced liver disease.