Liver histology is associated with long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis.

BACKGROUND: Few studies have examined the risk of long-term clinical outcomes in patients with metabolic dysfunction-associated steatohepatitis in relation to liver histology. We aimed to study this using a real-world cohort. METHODS: Adults (N = 702) recorded on Vanderbilt University Medical Center's Synthetic Derivative database (1984-2021) with evidence of metabolic dysfunction-associated steatohepatitis on liver biopsy were followed from the first biopsy until the first clinical event or last database entry (median: 4.7 y). Risks of cirrhosis (N = 650), other noncirrhotic liver-related (N = 702) and cardiovascular-related outcomes (N = 660), and mortality due to liver, cardiovascular, or cancer events (N = 660) were determined as a function of baseline histology (fibrosis stage [F], lobular inflammation grade [LI], hepatocyte ballooning grade [HB], and steatosis score) adjusting for sex, age, diabetes, and weight-loss surgery. RESULTS: Cirrhosis risk was reduced for lower versus higher fibrosis stage (HR: F0-1 vs. F3: 0.22 [95% CI: 0.12-0.42]), LI1 versus LI2-3 (0.42 [0.19-0.97]), and HB1 versus HB2 (0.20 [0.08-0.50]). Lower fibrosis stage was associated with significantly lower risks of liver-related outcomes versus F4 cirrhosis (eg, F0-1: 0.12 [0.05-0.25]), whereas no differences were seen across baseline lobular inflammation, hepatocyte ballooning, and steatosis grades/scores. Lower versus higher lobular inflammation grade was associated with lower risks for liver-related outcomes in patients with weight-loss surgery. There was a trend for lower risks for cardiovascular-related and any long-term outcomes with lower versus higher fibrosis stage. CONCLUSIONS: Fibrosis stage and lobular inflammation and hepatocyte ballooning grades predict the risk of long-term outcomes, supporting the use of these histological features as potential surrogate markers of disease progression or clinical outcomes.

Development of a Primary Biliary Cholangitis-specific Version of Chronic Liver Disease Questionnaire: CLDQ-PBC.

BACKGROUND AND AIM: Primary biliary cholangitis (PBC) is a chronic liver disease leading to cirrhosis and impairment of patient-reported outcomes (PROs). We aimed to develop a PBC-specific version of the Chronic Liver Disease Questionnaire (CLDQ) instrument to assess health-related quality of life of patients with PBC. METHODS: From our Liver Database, we included patients with PBC who had CLDQ, clinico-laboratory data, and completed Short Form-36 (SF-36) and The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). The 29 items of CLDQ were subjected to item reduction, exploratory factor analysis, and fed into a standard instrument validation pipeline. RESULTS: Data were available for 108 PBC patients: 57±11 years, 7% male, 58% cirrhosis, 24% decompensated cirrhosis (Child's B and C). Of 29 CLDQ items, none met the exclusion criteria. Exploratory factor analysis (95% of variance) returned 7 factors. Based on evaluation of factor loadings and face validity, those factors yielded 7 domains (Diet, Emotion, Fatigue, Itch, Symptoms, Sleep, Worry). Good to excellent internal consistency (Cronbach's alpha 0.85-0.93) was observed for 5/7 domains. For the remaining two domains (Diet, Itch), additional items obtained from patients, experts and review of the literature were included. For 5 domains, known-groups validity tests discriminated between PBC patients with and without cirrhosis, advanced cirrhosis, depression (p<0.05 for 3-5 domains). The CLDQ-PBC domains were correlated with relevant domains of SF-36, CLDQ-PBC Fatigue correlated with Fatigue Scale of FACIT-F (rho=+0.85) and CLDQ-PBC Worry domain negatively correlated with alkaline phosphatase (rho=-0.38, p=0.0082). CONCLUSION: The CLDQ-PBC has been developed based on the original CLDQ. The new instrument has evidence for internal consistency and validity, and is being fully validated using an external cohort.

MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials.

Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.

Epidemiology of NAFLD - Focus on diabetes.

There is increasing appreciation of the complex interaction between nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D) and insulin resistance. Not only is the prevalence of NAFLD disease high among patients with T2D, the liver disease is also more progressive. Currently, the global prevalence of NAFLD in the general population (2016-2019) is 38 %. The prevalence of T2D among those with NAFLD is approximately 23 % while the prevalence of NAFLD among those with T2D can be as high as 70 %. The prevalence of nonalcoholic steatohepatitis (NASH) is approximately 7 % in the general population and 37 % among patients with T2D. Globally, the MENA and Latin America regions of the world appear to have the highest burden of both NAFLD and T2D. Compared to those with NAFLD but without T2D, those with NAFLD and T2D are at a much higher risk for disease progression to cirrhosis and for decompensated cirrhosis, hepatocellular carcinoma, and all-cause mortality. Given that highly effective new treatments are available for T2D, high risk NAFLD with T2D should be considered for these regimens. This requires implementation of risk stratification algorithms in the primary care and endocrinology practices to identify those patients at highest risk for adverse outcomes.

Assessment of fatigue and its impact in chronic liver disease.

Patient reported outcomes (PROs) such as health related quality of life (HRQL) are important outcome measures for patients with chronic liver diseases (CLDs). Presence of cirrhosis and advanced liver disease have been associated with worsened HRQL and fatigue. On the other hand, some patients with earlier stages of CLD such as primary biliary cholangitis (PBC), chronic hepatitis C viral infection (HCV) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), also experience fatigue causing PRO impairment. Treatment for some CLDs may improve HRQL and, sometimes, levels of fatigue. We aimed to provide an in-depth expert review of concepts related to fatigue and HRQL in patients with PBC, HCV and MASLD. As such, a panel of experts in fatigue and CLD reviewed and discussed the literature and collaborated to provide this expert review of fatigue in CLD. Herein, we review and report on the complexity of fatigue highlighting that fatigue is comprised of peripheral (neuromuscular failure, often in conjunction with sub-maximal cardiorespiratory function) and central (central nervous system dysfunction) causes. Fatigue and HRQL are measured using validated self-report instruments. Additionally, fatigue can be measured through objective tests (e.g. grip strength). Fatigue has deleterious effects on HRQL and one's ability to be physically active and socially engaged but does not always correlate with CLD severity. Treatments for HCV and MASLD can improve levels of fatigue and HRQL, but current treatments for PBC do not seem to affect levels of fatigue. We conclude that obtaining PRO data to include HRQL and fatigue are essential for determining the comprehensive burden of CLD and its potential treatments. IMPACT AND IMPLICATIONS: Fatigue is a complex phenomenon associated with both a peripheral cause (neuromuscular failure and sub-maximal cardiorespiratory function) and a central cause (central nervous system dysfunction). Although fatigue is common among patients with CLD, it does not always correlate with the severity of the liver disease, but fatigue is related with significant decreases in patients' health related quality of life (HRQL). Appreciating the impact of fatigue using validated self-report measurements is important to better understand the burden of CLD and the effectiveness of treatment.

Clinical and patient-reported outcomes in patients with chronic hepatitis B and C and non-alcoholic fatty liver disease from real-world practices in Saudi Arabia, Turkey and Egypt.

Patients with chronic liver disease (CLD) experience health-related quality of life (HRQoL) and patient-reported outcomes (PROs) impairments. We assessed and identified predictors of HRQoL and PROs in CLD patients from Saudi Arabia (SA), Turkey and Egypt. Patients enrolled in Global Liver Registry™ with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) were included. Clinical data and PRO questionnaires (FACIT-F, CLDQ and WPAI) were compared across countries. Linear regression identified PRO predictors. Of the 4014 included patients, 26.9% had CHB, 26.9% CHC and 46.1% NAFLD/NASH; 19.2% advanced fibrosis. Compared across countries, CHB patients were younger in Egypt (mean age [years] 41.2 ± 11.4 vs. 45.0 ± 10.3 SA, 46.1 ± 12.0 Turkey), most often employed in SA (64.8% vs. 53.2% Turkey) and had the lowest prevalence of obesity in Turkey (26.7% vs. 37.8% SA, 38.5% Egypt). In SA, CHB patients had lowest prevalence of fibrosis and comorbidities (all p < .01). There was a higher frequency of males with NAFLD/NASH in SA (70.0% vs. 49.6% Turkey, and 35.5% Egypt). Among NAFLD/NASH patients, CLDQ-NAFLD/NASH scores were highest in SA (mean total score: 5.3 ± 1.2 vs. 4.8 ± 1.2 Turkey, 4.1 ± 0.9 Egypt, p < .01). Independent predictors of worse PROs included younger age, female sex, advanced fibrosis, non-hepatic comorbidities and lack of regular exercise (all p < .05). Clinical presentation and PRO scores of CLD patients vary across SA, Turkey and Egypt. Impairment of HRQoL is associated with demographic factors, lack of regular exercise, advanced fibrosis and non-hepatic comorbidities.

The Global Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis Among Patients With Type 2 Diabetes.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction associated steatotic liver disease (MASLD), is closely associated with type 2 diabetes (T2D). Our aim was to estimate the most recent global prevalence of NAFLD/MASLD, nonalcoholic steatohepatitis (NASH), now known as metabolic dysfunction associated steatohepatitis (MASH), advanced fibrosis, and mortality among patients with T2D. METHODS: We systematically searched PubMed and Ovid MEDLINE for terms including NAFLD, NASH, and T2D published in 1990-2023 according to PRISMA. The meta-analysis was conducted using a random-effects model. Assessment of bias risk used the Joanna Briggs Institute appraisal tool. RESULTS: From 3134 studies included in the initial search, 123 studies (N = 2,224,144 patients with T2D) were eligible. Another 12 studies (N = 2733 T2D patients with liver biopsy) were eligible for histologic assessments. The global pooled prevalence of NAFLD/MASLD among patients with T2D was 65.33% (95% confidence interval, 62.35%-68.18%). This prevalence increased from 55.86% (42.38%-68.53%) in 1990-2004 to 68.81% (63.41%-73.74%) in 2016-2021 (P = .073). The highest NAFLD/MASLD prevalence among T2D patients was observed in Eastern Europe (80.62%, 75.72%-84.73%), followed by the Middle East (71.24%, 62.22%-78.84%), and was lowest in Africa (53.10%, 26.05%-78.44%). Among patients with liver biopsy data, the global pooled prevalence of NASH/MASH, significant fibrosis, and advanced fibrosis was 66.44% (56.61%-75.02%), 40.78% (24.24%-59.70%), and 15.49% (6.99%-30.99%), respectively. The pooled all-cause mortality was 16.79 per 1000 person-years (PY) (10.64-26.40), 4.19 per 1000 PY (1.34-7.05) for cardiac-specific mortality; 6.10 per 1000 PY (0.78-4.88) for extrahepatic cancer-specific mortality; and 2.15 per 1000 PY (0.00-2.21) for liver-specific mortality. CONCLUSIONS: The prevalence of NAFLD/MASLD among T2D is high and growing. The majority of NAFLD/MASLD patients with T2D have NASH/MASH, and a significant proportion have advanced fibrosis.

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.

Prevalence of metabolic dysfunction-associated steatotic liver disease in the Middle East and North Africa.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is common and closely associated with type 2 diabetes (T2D). We assessed the prevalence of NAFLD/MASLD in the general population and among patients with T2D in the Middle East and North Africa (MENA) region. METHODS: We searched PubMed and Embase for English-language articles published between 1990 and 2023 according to PRISMA. Each country's NAFLD/MASLD prevalence in the general population and in T2D patients was predicted by using a multivariable meta regression model. Input data were extracted from our systematic review, GBD and NCD Risk Factor Collaboration. Confidence intervals were constructed by using prediction intervals with the delta method. RESULTS: Meta-analytic pooling estimated the prevalence of NAFLD/MASLD as 39.43% in the general population and 68.71% among T2D patients. NAFLD/MASLD prevalence has increased from 35.42% (2008-2016) to 46.20% (2017-2020). Using GBD-2019 dataset, it was predicted that there are 141.51 million cases of NAFLD/MASLD in the MENA region. The highest number of NAFLD/MASLD cases were expected in Egypt (25.71 million), followed by Türkiye (23.33 million) and Iran (19.85 million). Estimated NAFLD prevalence exceeded 40% in 10 of 21 countries with the top countries being Kuwait (45.37%), Egypt (45.0%), Qatar (44.4%), and Jordan (43.3%). Furthermore, it was predicted that there are 24.96 million cases of NAFLD/MASLD with T2D in the MENA region. CONCLUSIONS: In the MENA region, prevalence of NAFLD/MASLD is very high and growing, necessitating an urgent need for regional public policy to deal with this growing burden.

Understanding the Burden of Nonalcoholic Fatty Liver Disease: Time for Action.

The prevalence of nonalcoholic fatty liver disease (NAFLD) in the United States is 38%, having increased by 50% within the past 3 decades. The estimated NAFLD prevalence among people with type 2 diabetes is 55-70%. The presence of type 2 diabetes is associated with a higher likelihood of progression of NAFLD to fibrosis development, liver transplant, and death. Cardiovascular disease is the main cause of mortality among people with NAFLD, and the risk of death is significantly higher in people with both NAFLD and type 2 diabetes. NAFLD carries high patient and economic burdens but low awareness among both the general public and health care providers. This article reviews the epidemiology of NAFLD and discusses the need for appropriate risk stratification, referral for specialty care, management of cardiometabolic risk factors, and treatment of the disease. The authors present a call to action to raise awareness of NAFLD and address its increasing burden in a systematic and efficient manner.

Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Concern remains regarding whether the evidence generated under the NAFLD definition can be used for MASLD. We compared the clinical profile and outcomes of NAFLD to MASLD using tertiary care- and population-based data. METHODS: Comparison data were obtained from our NAFLD database and the National Health and Nutrition Examination Survey (NHANES III). Clinical profiles and non-invasive tests (enhanced liver fibrosis [ELF] score, fibrosis-4 index [FIB-4] and vibration-controlled transient elastography) were compared. Mortality data were obtained from NHANES-National Death Index. All-cause mortality was assessed by Cox proportional hazards regression models and cause-specific mortality by competing risk analysis. RESULTS: There were 6,429 patients in the NAFLD database (age: 54 ± 12 years, 42% male, BMI 35.4 ± 8.3, waist circumference 112 ± 17 cm, 52% type 2 diabetes). Average scores for ELF, FIB-4 and liver stiffness were 9.6 ± 1.2, 1.69 ± 1.24,14.0 ± 11.8 kPa, respectively; 99% met MASLD criteria; 95% met MASLD on BMI only. Predictive accuracy of ELF and FIB-4 were identical between MASLD and NAFLD. We included 12,519 eligible participants from NHANES (age 43.00 years, 47.38% male, 22.70% obese, 7.28% type 2 diabetes, 82.51% ≥1 cardiometabolic criteria). Among the NHANES study population, there was excellent concordance between MASLD and NAFLD diagnoses: Cohen's kappa coefficient: 0.968 (95% CI 0.962-0.973) with 5.29% of NAFLD cases not meeting MASLD criteria. After a median follow-up of 22.83 years, there were no mortality differences between MASLD and NAFLD diagnoses (p values ≥0.05). CONCLUSIONS: NAFLD and MASLD are similar except individuals with MASLD seem to be older with slightly higher mortality risk, likely owing to cardiometabolic risk factors. Clinical profiles and non-invasive test thresholds were also identical. These data provide evidence that NAFLD and MASLD terminologies can be used interchangeably. For the small proportion of patients with NAFLD who do not meet MASLD criteria, further consideration is needed. IMPACT AND IMPLICATIONS: In June 2023, new terminology (MASLD) was adopted to replace the term NAFLD as a means to better describe what the liver disease is rather than what it is not, as well as to potentially reduce stigma. Given that MASLD requires at least one cardiometabolic risk factor, questions were raised as to whether this change in the definition would nullify the similarities between NAFLD and MASLD and require new evidence to be generated for MASLD. We used our NAFLD database and a US population-based database to show that the vast majority of patients with NAFLD fulfill criteria for MASLD. Non-invasive tests performed similarly in both groups. Mortality risk was slightly higher in those with MASLD, which is attributed to the presence of cardiometabolic risks. These results provide evidence that data generated in the past three decades for NAFLD can be used interchangeably for MASLD.

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.

Recompensation in cirrhosis: unravelling the evolving natural history of nonalcoholic fatty liver disease.

Recompensation has gained increasing attention in the field of cirrhosis, particularly in chronic liver disease with a definite aetiology. The current global prevalence of obesity and nonalcoholic fatty liver disease (NAFLD) is increasing, but there is currently a lack of a clear definition for recompensation in NAFLD-related cirrhosis. Here, we provide an up-to-date perspective on the natural history of NAFLD, emphasizing the reversible nature of the disease, summarizing possible mechanisms underlying recompensation in NAFLD, discussing challenges that need to be addressed and outlining future research directions in the field. Recompensation is a promising goal in patients with NAFLD-related cirrhosis, and further studies are needed to explore its underlying mechanisms and uncover its clinical features.

The impact of hepatitis B and C positive serologies on the outcomes of non-hepatic solid organ transplantation in the United States.

Chronic viral hepatitis B (HBV) and C (HCV) infection could negatively affect outcomes of non-hepatic solid organ transplantations due to the risk of viral reactivation in the presence of immunosuppression. This study aimed to determine post-transplant outcomes in patients with HBV or HCV positivity receiving non-hepatic solid-state organ transplant. Data was collected from the Scientific Registry of Transplant Recipients (SRTR) 2006-2021 for patients (≥18) who received a lung, heart, or kidney single organ transplant in the U.S. Hepatitis C positivity (HCV+) was determined as positive HCV Ab and hepatitis B positivity (HBV+) as positive HBsAg. We included N = 30,872 lung, N = 36,990 heart and N = 280,162 kidney transplant recipients. The prevalence of HBV+ was 1.3% in lung, 1.5% in heart and 1.7% in kidney patients, HCV+ was 2.2%, 2.2% and 5.0%, respectively. Post-transplant survival of patients with vs. without HBV+ was similar in all solid organ transplants (all p > .05). Similarly, there was no difference in post-transplant survival between lung transplant recipients with vs. without anti-HCV (all p > .05). Heart transplant recipients with HCV+ had higher crude post-transplant mortality (all p < .01). Similarly, there was higher post-transplant mortality in kidney transplant recipients with HCV+ (1-year: 6% vs. 3%; 5-year: 21% vs. 13%; 10-year: 47% vs. 31%; all p < .0001). In multivariate analysis controlling for confounders, only the association of HCV+ with higher post-kidney transplant mortality remained significant: adjusted hazard ratio (aHR) (95% CI) = 1.16 (1.12-1.20), p < .0001. There was no association of viral hepatitis seropositivity with the risk of graft failure in all groups (p > .05). In most cases, the presence of HBV or HCV serologies is not associated with adverse post-transplant outcomes in non-hepatic solid organ transplants. However, kidney transplant recipients who are positive for HCV serology have an increased risk for post-transplant mortality.