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Background and Aims: Despite the high prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD), the long-term incidence of cirrhosis or hepatocellular carcinoma (HCC) among adults with MAFLD is not well described. Using a national cohort of United States Veterans, we evaluated the overall incidence and predictors of cirrhosis and HCC among adults with noncirrhotic MAFLD., Methods: Data from the 2010 to 2022 Veterans Affairs database were used to identify adults with noncirrhotic MAFLD using established definitions. Five and 10-year incidence of cirrhosis and HCC were assessed and stratified by demographics and relevant clinical variables. Multivariate Cox proportional hazard models were utilized to determine predictors of cirrhosis and HCC., Results: Among 969,253 patients with noncirrhotic MAFLD (94.5% males, 70.2% non-Hispanic white, mean age of 62.7 ± 12.2 y), the 10-year incidence of cirrhosis and HCC was 3.70% (95% CI: 3.66-3.74) and 0.69% (95% CI: 0.67-0.70), respectively. When stratified by race/ethnicity, the 10-year incidence of cirrhosis was lowest among Asians (2.63%, 95% CI: 2.37-2.88) and highest among Hispanics (4.60%, 95% CI: 4.45-4.75), a pattern also observed with HCC. Significant disparities in risk of cirrhosis or HCC were observed when stratified by sex, substance use, and comorbidities. Risks of cirrhosis and HCC were highest in patients with baseline fibrosis-4 >2.67., Conclusion: This large study provides important epidemiological data describing the natural history of adults with MAFLD. Disparities in risk of cirrhosis and HCC were observed by demographic and clinical characteristics, emphasizing the importance of early identification of MAFLD with modifiable high-risk features to implement earlier interventions to improve long-term outcomes., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Backgrounds: The adverse effects of long-term use of proton pump inhibitors (PPIs) have led to growing concern. The association between PPIs use and the risks of nonalcoholic fatty liver disease (NAFLD) remains controversial., Goal: The aim of this study was to investigate the association between PPIs use and the risks of NAFLD among the general adult population in the United States., Study: We performed a cross-sectional study by extracting data from the National Health and Nutrition Examination Survey of 2017 to 2018. The association between PPIs use and NAFLD risks was analyzed by weighted multivariate logistic regression., Results: Among the 4238 participants included in this study, 2167 were diagnosed with NAFLD. In the multivariate logistic regression model, PPIs use was associated with increased risks of NAFLD [odds ratio (OR): 1.318, 95% CI: 1.044-1.663; P=0.020]. This association was nonsignificant in participants taking PPIs for ˂5 years (OR: 0.846, 95% CI: 0.579-1.238; P=0.390), whereas it remained significant in participants taking PPIs for more than 5 years (OR: 2.016, 95% CI: 1.366-2.975; P=0.031). Further analysis showed that the use of PPIs was positively associated with risks of severe hepatic steatosis (OR: 1.451, 95% CI: 1.034-2.036; P=0.031) but not with mild-to-moderate steatosis (OR: 1.242, 95% CI: 0.886-1.741; P=0.208)., Conclusions: This study indicated that taking PPIs was associated with increased risks of NAFLD, especially severe hepatic steatosis. Awareness should be raised regarding the potential risks of NAFLD when prescribing PPIs., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Goals: The main purpose of this study was to assess the recent trends in mortality and health care utilization of hepatocellular carcinoma (HCC) among Medicare population in the United States., Background: The incidence of HCC is increasing in the United States., Materials and Methods: Data were obtained for a sample of Medicare beneficiary from 2005 to 2014. Diagnosis of HCC and etiology of liver disease were based on ICD-9 codes. Temporal trends in HCC rates, clinical, demographical and utilization parameters were analyzed by joinpoint regression model., Results: Study cohort included 13,648 Medicare recipients with HCC (mean age: 70.0 y, 62.8% male and 76.0% white). Non-alcoholic fatty liver disease (NAFLD) was the most common cause of HCC in the inpatient (32.07%) and outpatient (20.22%) followed by hepatitis C virus (HCV) (19.2% and 9.75%, respectively). Between 2005 and 2014, HCC rate per 100,000 Medicare recipients increased from 46.3 to 62.8 [average annual percentage change (AAPC) =3.4%, P<0.001]. Rate of HCV-HCC increased from 6.18 to 16.54 (AAPC=11.8%, P<0.001) while the NAFLD-HCC increased from 9.32 to 13.61, P<0.001). Overall 1-year mortality decreased from 46.2% to 42.1% (AAPC=-1.7%, P=0.004). Total charges increased from $67,679 to $99,420 (AAPC=5.1%, P<0.001) for inpatients and from $11,933 to $32,084 (P<0.001) for outpatients. On comparison of patients with hepatitis B virus-HCC, those with NAFLD-HCC (odds ratio: 1.87, P<0.001) had higher risk of mortality. On comparison of patients with hepatitis B virus-HCC, those with HCV-HCC had higher charges (percent change: 24.33%, 95% confidence interval: 1.02%-53.02%, P=0.040)., Conclusions: Although HCC rates are increasing, the overall mortality is decreasing. NAFLD is the most important cause of HCC and an independent predictor of HCC in the outpatient setting for Medicare patients with HCC.

Background: The prevalence of NAFLD is rapidly increasing. NAFLD can progress to NASH, fibrosis, cirrhosis, and HCC, which will soon become the main causes of liver transplantation. To date, no effective drug for NASH has been approved by the Food and Drug Administration. This is partly due to the lack of reliable human in vitro models. Here, we present a novel human liver spheroid model that can be used to study the mechanisms underlying liver fibrosis formation and degradation., Methods and Results: Such spheroids, which contain hepatocytes, stellate cells, KC, and LSECs, spontaneously develop fibrosis that is exacerbated by treatment with free fatty acids. Conditioned medium from activated LSECs caused similar activation of fibrosis in spheroids containing primary human hepatocyte and NPCs, indicating the action of soluble mediators from the LSECs. Spheroids containing LSECs treated with free fatty acids produced tissue inhibitor of metalloproteinases inhibitor 1, a matrix metalloproteinases inhibitor important for fibrosis progression. Tissue inhibitor of metalloproteinases inhibitor 1 knockdown using siRNA led to a reduction in collagen and procollagen accumulation, which could be partially rescued using a potent matrix metalloproteinases inhibitor. Interestingly, tissue inhibitor of metalloproteinases inhibitor 1 was found to be expressed at higher levels, specifically in a subtype of endothelial cells in the pericentral region of human fibrotic livers, than in control livers., Conclusion: Potential anti-NASH drugs and compounds were evaluated for their efficacy in reducing collagen accumulation, and we found differences in specificity between spheroids with and without LSECs. This new human NASH model may reveal novel mechanisms for the regulation of liver fibrosis and provide a more appropriate model for screening drugs against NASH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: The high prevalence of obesity in the United States drives the burden of NASH, recently renamed as metabolic dysfunction-associated steatohepatitis (MASH). We assessed the most recent trends in liver transplantation in the United States., Methods: The Scientific Registry of Transplant Recipients (SRTR 2013-2022) was used to select adult (18 years or above) candidates who underwent liver transplant., Results: There were 116,292 candidates who underwent liver transplant with known etiology of chronic liver disease. In candidates without HCC, the most common etiology was alcohol-associated liver disease (ALD), increasing from 23% (2013) to 48% (2022), followed by NASH/MASH, which increased from 19% to 27%; the rates of viral hepatitis decreased (chronic hepatitis C: 28%-4%; chronic hepatitis B: 1.8%-1.1%) (all trend p<0.01). The proportion of HCC decreased from 25% (2013-2016) to 17% (2021-2022). Among HCC cohort, the proportion of chronic hepatitis C decreased from 60% (2013) to 27% (2022), NASH/MASH increased from 10% to 31%, alcohol-associated liver disease increased from 9% to 24% (trend p<0.0001), and chronic hepatitis B remained stable between 5% and 7% (trend p=0.62). The rapid increase in the proportion of NASH/MASH in HCC continued during the most recent study years [20% (2018), 28% (2020), 31% (2022)]; the trend remained significant after adjustment for age, sex, ethnicity, obesity, and type 2 diabetes., Conclusions: Liver transplant etiologies in the United States have changed over the last decade. Alcohol-associated liver disease and NASH/MASH remain the 2 most common indications for transplantation among those without HCC, and NASH/MASH is the most common in patients with HCC., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

NASH is the fastest-growing cause of liver cirrhosis and is the leading indication for liver transplantation (LT). However, significant racial and ethnic disparities in waitlist outcomes and LT allocation may unfairly disadvantage minorities. Our aim was to characterize racial and ethnic disparities in waitlist mortality and transplantation probability among patients with NASH. This is a retrospective analysis of the United Network for Organ Sharing registry data of LT candidates from January 1, 2000 to December 31, 2021. Outcomes analysis was performed using competing risk analysis with the Fine and Gray model. The multivariable adjustment was conducted, and mixed-effect regression was used to compare the model for end-stage liver disease scores at listing and removal. Of 18,562 patients with NASH cirrhosis, there were 14,834 non-Hispanic Whites, 349 African Americans, 2798 Hispanics, 312 Asians, and 269 of other races/ethnicities; African American (effect size: 2.307, 95% CI: 1.561-3.053, and p < 0.001) and Hispanic (effect size: 0.332, 95% CI: 0.028-0.637, p = 0.032) patients were found to have a significantly higher model for end-stage liver disease scores at the time of listing than non-Hispanic Whites. African Americans had a higher probability of receiving LT relative to non-Hispanic Whites (subdistribution HR: 1.211, 95% CI: 1.051-1.396, and p = 0.008). However, Hispanic race/ethnicity was associated with a lower transplantation probability (subdistribution HR: 0.793, 95% CI: 0.747-0.842, and p < 0.001) and increased waitlist mortality (subdistribution HR: 1.173, CI: 1.052-1.308, and p = 0.004) compared with non-Hispanic Whites. There are significant racial and ethnic disparities in waitlist outcomes of patients with NASH in the US. Hispanic patients are less likely to receive LT and more likely to die while on the waitlist compared with non-Hispanic Whites despite being listed with a lower model for end-stage liver disease scores., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background: We examined trends in NAFLD-related mortality in the United States from 1999 to 2022, focusing on sex, racial differences, and specific age groups., Methods: We analyzed age-adjusted mortality rates (AAMRs) for NAFLD-related deaths using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database and assessed differences between sex and racial groups., Results: Between 1999 and 2022, NAFLD-related mortality rose from an age-adjusted mortality rate (AAMR) of 0.2 to 1.7 per 100,000, with an average annual percent change (AAPC) of 10.0% (p < 0.001). In all, 85.4% of the cases were reported after 2008. Females (0.2-2 per 100,000, AAPC: 11.7%, p < 0.001) saw a steeper increase than males (0.2-1.3 per 100,000, AAPC: 9.3%, p < 0.001). White individuals' AAMR rose from 0.2 to 1.9 per 100,000 (AAPC: 10.8%, p < 0.001). Asian or Pacific Islanders (AAPI) increased from 0.2 in 2013 to 0.5 in 2022 (AAPC: 12.13%, p = 0.002), and American Indians or Alaska Natives (AI/AN) from 1 in 2013 to 2.2 in 2022 (AAPC: 7.9%, p = 0.001). African Americans (AA) showed an insignificant change (0.3-0.5 per 100,000, AAPC: 0.7%, p = 0.498). Regarding age, individuals 45-64 saw AAMR rise from 0.3 to 1.2 per 100,000 (AAPC: 6.5%, p < 0.001), and those 65+ from 0.2 to 6 per 100,000 (AAPC: 16.5%, p < 0.001). No change was observed in the 25-44 age group (AAMR: 0.2 per 100,000, AAPC: 0.0%, p = 0.008)., Conclusion: We report increased NAFLD-related mortality among both sexes and certain racial groups. The mortality rate increased for older populations, emphasizing the need for targeted public health measures and evidence-based interventions., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Nonalcoholic steatohepatitis (NASH) is an increasingly common etiology for liver-related hospitalizations in the United States. The aim of this study was to examine the differences of disease characteristics and outcomes between hospitalized Black and White patients with NASH., Materials and Methods: We used the National Inpatient Sample (NIS) to identify all adult hospitalizations with NASH (ICD-10 code: K75.81) from 2016 to 2018. We compared demographic and clinical characteristics between Black and White patients. Multivariable models were computed to compare all-cause mortality, length of stay (LOS), and total hospital costs between the groups., Results: There were 43,409 hospitalizations with NASH (41,143 White, 2266 Black). Black patients were less likely to have cirrhosis (33.6%) compared with Whites (56.4%), P <0.0001. Black patients were less likely to have esophageal variceal bleeding (1.2% vs. 3.5%), ascites (17.1% vs. 28.8%), and acute liver failure (16.2% vs. 28.9%) compared with Whites (all P <0.0001). These findings were consistent among patients with cirrhosis. Mortality was higher among Blacks compared with Whites (3.9% vs. 3.7%, adjusted odds ratio=1.34; 95% confidence interval: 1.05-1.71, P =0.018). Compared with Whites, Blacks had a longer LOS (6.3 vs. 5.6, P <0.001), and higher hospital costs ($18,602 vs. $17,467; P =0.03)., Conclusion: In this large population of inpatients with NASH, Black patients were less likely to have cirrhosis and liver disease-related complications, but had overall worse hospital mortality, longer LOS, and higher hospital costs. Further research is warranted to elaborate on factors that generate the health inequities in NASH outcomes between Black and White patients., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: We present findings from the inaugural American College of Sports Medicine (ACSM) International Multidisciplinary Roundtable, which was convened to evaluate the evidence for physical activity as a means of preventing or modifying the course of NAFLD., Approach and Results: A scoping review was conducted to map the scientific literature and identify key concepts, research gaps, and evidence available to inform clinical practice, policymaking, and research. The scientific evidence demonstrated regular physical activity is associated with decreased risk of NAFLD development. Low physical activity is associated with a greater risk for disease progression and extrahepatic cancer. During routine health care visits, all patients with NAFLD should be screened for and counseled about physical activity benefits, including reduction in liver fat and improvement in body composition, fitness, and quality of life. While most physical activity benefits occur without clinically significant weight loss, evidence remains limited regarding the association between physical activity and liver fibrosis. At least 150 min/wk of moderate or 75 min/wk of vigorous-intensity physical activity are recommended for all patients with NAFLD. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred., Conclusions: The panel found consistent and compelling evidence that regular physical activity plays an important role in preventing NAFLD and improving intermediate clinical outcomes. Health care, fitness, and public health professionals are strongly encouraged to disseminate the information in this report. Future research should prioritize determining optimal strategies for promoting physical activity among individuals at risk and in those already diagnosed with NAFLD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background and Aims: The American Gastroenterological Association (AGA) recently launched the Clinical Care Pathway for the Risk Stratification and Management of Patients with NAFLD to identify adults with significant fibrosis. We aimed to examine this pathway's performance in the US population., Approach and Results: Using the 2017-2018 National Health and Nutrition Examination Survey data, we identified participants aged ≥18 with available Fibrosis-4 (FIB-4) score and liver stiffness measurement (LSM) in the absence of other liver diseases. Based on the AGA clinical pathway, FIB-4 < 1.3 and LSM < 8 kilopascals (kPa) by vibration-controlled transient elastography (VCTE) are associated with low risk of significant fibrosis. Using these cutoffs, we examined the pathway performance using negative predictive value (NPV) and positive predictive value (PPV) and explored alternative risk-stratification strategies. There were 2322 participants with available data (projected to 94.2 million US adults). The NPV of LSM ≥ 8 kPa among those with FIB-4 < 1.3 was 90%, whereas the PPV among those with FIB-4 1.3-2.67 was 13%. As diabetes was a strong predictor of fibrosis, we propose a simple, alternative strategy to eliminate the indeterminate FIB-4 range and perform VCTE in those with FIB-4 ≥ 1.3 and diabetes. This strategy would decrease the number of VCTEs from 14.5 to 4.9 million and increase PPV from 13% to 33% without compromising the NPV among those who did not undergo VCTE., Conclusion: The implementation of the current AGA clinical pathway would lead to overutilization of VCTE. An alternative strategy using FIB-4 ≥ 1.3 and diabetes to select adults undergoing second-line testing will improve this pathway's performance and minimize unnecessary VCTEs., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Chronic liver diseases (CLDs) are associated with increased morbidity and mortality. Sarcopenia is an important complication of CLD that can be impacted by several modifiable risk factors. Our aim was to assess the associations between healthy living, sarcopenia, and long-term outcomes among patients with CLD. We used the Third National Health and Nutrition Examination Survey data with National Death Index-linked mortality files. We used the American Heart Association's Life's Simple 7 (LS7) metrics as surrogates of healthy living. The study included 12,032 subjects (34.9% CLDs [0.5% hepatitis B virus (HBV), 1.8% hepatitis C virus (HCV), 5.7% alcohol-associated liver disease (ALD), 26.9% nonalcoholic fatty liver disease (NAFLD)] and 65.1% controls). Prevalence of sarcopenia was higher among NAFLD than other CLDs and the controls (40.7% in NAFLD, 27.2% in ALD, 22.4% in HCV, 16.8% in HBV, and 18.5% in controls; p < 0.001). Among NAFLD and ALD, patients with sarcopenia were less likely to meet ideal LS7 metrics than those without sarcopenia. During 27 years of follow-up, among 4 patients with CLDs and the controls, all-cause cumulative mortality was highest among patients with HCV (35.2%), followed by ALD (34.7%) and NAFLD (29.6%). The presence of sarcopenia was associated with higher risk of all-cause mortality only among subjects with NAFLD (hazard ratio [HR] 1.24; 95% confidence interval [CI] 1.01-1.54; p = 0.04). Among subjects with NAFLD, presence of sarcopenia was associated with higher risk of cardiovascular-specific (HR 2.28 [1.71-3.05; p < 0.01]), cancer-specific (HR 1.90 [1.37-2.65]; p < 0.01), diabetes-specific (HR 6.42 [2.87-14.36]; p < 0.01), and liver-specific mortality (HR 2.49 [1.08-5.76]; p = 0.04). The multivariable model showed that component of LS7 metrics that provided the strongest protection against sarcopenia were ideal body mass index, ideal blood pressure, ideal physical activity, and ideal glycemic control among subjects with NAFLD subjects. Conclusions: Among subjects with NAFLD, sarcopenia is associated with a higher risk of all-cause mortality and liver mortality. Attainment of ideal LS7 metrics provides protection against sarcopenia in NAFLD., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background: Reliable, noninvasive tools to diagnose at-risk metabolic dysfunction-associated steatohepatitis (MASH) are urgently needed to improve management. We developed a risk stratification score incorporating proteomics-derived serum markers with clinical variables to identify high-risk patients with MASH (NAFLD activity score >4 and fibrosis score >2)., Methods: In this 3-phase proteomic study of biopsy-proven metabolic dysfunction-associated steatotic fatty liver disease, we first developed a multi-protein predictor for discriminating NAFLD activity score >4 based on SOMAscan proteomics quantifying 1305 serum proteins from 57 US patients. Four key predictor proteins were verified by ELISA in the expanded US cohort (N = 168) and enhanced by adding clinical variables to create the 9-feature MASH Dx score, which predicted MASH and also high-risk MASH (F2+). The MASH Dx score was validated in 2 independent, external cohorts from Germany (N = 139) and Brazil (N = 177)., Results: The discovery phase identified a 6-protein classifier that achieved an AUC of 0.93 for identifying MASH. Significant elevation of 4 proteins (THBS2, GDF15, SELE, and IGFBP7) was verified by ELISA in the expanded discovery and independently in the 2 external cohorts. MASH Dx score incorporated these proteins with established MASH risk factors (age, body mass index, ALT, diabetes, and hypertension) to achieve good discrimination between MASH and metabolic dysfunction-associated steatotic fatty liver disease without MASH (AUC: 0.87-discovery; 0.83-pooled external validation cohorts), with similar performance when evaluating high-risk MASH F2-4 (vs. MASH F0-1 and metabolic dysfunction-associated steatotic fatty liver disease without MASH)., Conclusions: The MASH Dx score offers the first reliable noninvasive approach combining novel, biologically plausible ELISA-based fibrosis markers and clinical parameters to detect high-risk MASH in patient cohorts from the United States, Brazil, and Europe., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

To reduce waitlist mortality, living donor liver transplantation (LDLT) has increased over the past decade in the United States, but not at a rate sufficient to completely mitigate organ shortage. As a result, there are ongoing efforts to expand the living liver donor pool. Simultaneously, the prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population has increased, which has significant implications on the pool of potential living liver donors. As such, a clinical assessment algorithm that exhaustively evaluates for NAFLD and fibrosis is critical to the safe expansion of LDLT. An ideal algorithm would employ safe and noninvasive methods, relying on liver biopsy only when necessary. While exclusion of NAFLD and fibrosis by noninvasive means is widely studied within the general population, there are no well-accepted guidelines for evaluation of living donors using these modalities. Here we review the current literature regarding noninvasive NALFD and fibrosis evaluation and propose a potential algorithm to apply these modalities for the selection of living liver donors., (© 2021 by the American Association for the Study of Liver Diseases.)

Background: Indications for use of statins are common among patients with nonalcoholic fatty liver disease (NAFLD). Epidemiologic studies have suggested a possible association between statins and decreased risk of malignancies. We hypothesized that statin use has a protective effect on cancer mortality in patients with NAFLD., Methods: Participants with NAFLD in 8 rounds of National Health and Nutrition Examination Survey (NHANES) were included in this study. Mortality data were obtained by linking the NHANES data to National Death Index. NAFLD was defined using the previously validated Hepatic Steatosis Index model., Results: A total of 10,821 participants with NAFLD were included and 23% were statin users (n=2523). Statin use was associated with a 43% lower risk of cancer mortality [hazard ratio (HR)=0.57, 95% confidence interval (CI): 0.43-0.75, P<0.001] in multivariable analysis. Statin use under 1 year did not show a significant effect on cancer mortality (HR=0.72, 95% CI: 0.46-1.12), while statin use for 1 to 5 years decreased cancer mortality by 35% (HR=0.65, 95% CI: 0.42-0.99, P=0.46), and statin use >5 years decreased cancer mortality by 56% (HR=0.44, 95% CI: 0.29-0.66, P<0.001). Statin use was associated with a significant decrease in the risk of cancer mortality in NAFLD patients with both low and high risk of liver fibrosis (HR=0.55, 95% CI: 0.38-0.81; and HR=0.53, 95% CI: 0.31-0.89, respectively)., Conclusion: Using a large US prospective cohort, we showed statin use is associated with a considerable decrease in cancer-related mortality among patients with NAFLD. These results are important for clinical decision making, as statin indications are prevalent among NAFLD patients, but many do not receive benefit in the event that the statin is discontinued due to liver test abnormalities., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

This cohort analysis investigated the prevalence of nonalcoholic fatty liver disease (NAFLD) and NAFLD with fibrosis at different stages, associated clinical characteristics, and comorbidities in the general United States population and a subpopulation with type 2 diabetes mellitus (T2DM), using the National Health and Nutrition Examination Survey (NHANES) database (2017-2018). Machine learning was explored to predict NAFLD identified by transient elastography (FibroScan ® ). Adults ≥20 years of age with valid transient elastography measurements were included; those with high alcohol consumption, viral hepatitis, or human immunodeficiency virus were excluded. Controlled attenuation parameter ≥302 dB/m using Youden's index defined NAFLD; vibration-controlled transient elastography liver stiffness cutoffs were ≤8.2, ≤9.7, ≤13.6, and >13.6 kPa for F0-F1, F2, F3, and F4, respectively. Predictive modeling, using six different machine-learning approaches with demographic and clinical data from NHANES, was applied. Age-adjusted prevalence of NAFLD and of NAFLD with F0-F1 and F2-F4 fibrosis was 25.3%, 18.9%, and 4.4%, respectively, in the overall population and 54.6%, 32.6%, and 18.3% in those with T2DM. The highest prevalence was among Mexican American participants. Test performance for all six machine-learning models was similar (area under the receiver operating characteristic curve, 0.79-0.84). Machine learning using logistic regression identified male sex, hemoglobin A1c, age, and body mass index among significant predictors of NAFLD (P ≤ 0.01). Conclusion: Data show a high prevalence of NAFLD with significant fibrosis (≥F2) in the general United States population, with greater prevalence in participants with T2DM. Using readily available, standard demographic and clinical data, machine-learning models could identify subjects with NAFLD across large data sets., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLc on behalf of the American Association for the Study of Liver Diseases.)

Studies have examined nonalcoholic fatty liver disease (NAFLD) prevalence and severity in Asians; however, this is not well understood in Asian Americans (both East and South Asian Americans) as few studies have analyzed this population. We aimed to describe characteristics, prevalence of NAFLD, and its severity in Asian Americans in the National Health and Nutrition Examination Surveys (NHANES) from 2017 to 2018. Respondents 18 years and older with interview, laboratory testing, and transient elastography data were included. Other causes of liver disease were excluded. Controlled attenuation parameter (CAP) cutoff ≥ 274 dB/m, as published in the literature, defined NAFLD. Sensitivity analysis for CAP cutoffs ≥ 248 and ≥302 dB/m were performed. We found that 450 out of 3639 respondents were Asian Americans, and prevalence using CAP ≥ 274 dB/m was 43.23%. Using sensitivity analysis cutoffs of CAP ≥ 248 dB/m and CAP ≥ 302 dB/m, the prevalence was 57.38% and 28.03%, respectively. Compared with non-Asian Americans with NAFLD, Asian Americans with NAFLD had significantly lower body mass index (BMI) and less prevalent smoking history. Comorbidities, such as prediabetes, diabetes, and hypertension, were not significantly different between Asian and non-Asian Americans with NAFLD. Compared to non-Asian Americans with NAFLD, Asian Americans with NAFLD exhibited higher aminotransferases and triglycerides. Fibrosis assessed by transient elastography was not significantly different between Asian and non-Asian Americans with NAFLD. Despite decreased prevalence of BMI ≥ 30 kg/m 2 , Asian Americans experienced similar NAFLD prevalence with increased hepatocellular injury and triglyceridemia compared to non-Asian Americans. Fibrosis stages were similar to non-Asian Americans., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Goals: We aimed to investigate the mortality and hospital utilization outcomes of hospitalized nonalcoholic steatohepatitis (NASH) patients with and without kidney failure in a nationwide cohort., Background: NASH is a common medical condition associated with significant morbidity and mortality. A paucity of data exists regarding the impact of kidney failure (defined as acute and chronic kidney failure) on outcomes of NASH hospitalizations., Materials and Methods: We conducted a retrospective cohort study using the 2016 Nationwide Inpatient Sample dataset of adult patients hospitalized for NASH, stratified for the presence of renal failure. The primary outcome was inpatient mortality, predictors were analyzed using multivariate logistic regression. Secondary outcomes were the length of stay and mean total hospitalization charges., Results: The overall sample included 7,135,090 patients. Among 6855 patients admitted for NASH, 598 or 8.7% had comorbid kidney failure. After multivariate regression analysis, NASH patients with renal failure had increased in-hospital mortality [odds ratio=28.72, 95% confidence interval (CI): 8.99-91.73], length of stay (β=3.02, 95% CI: 2.54-3.5), total hospital charges (β=$37,045, 95% CI: $31,756.18-$42,335.62). Positive predictors of mortality in the renal failure group were Charlson Comorbidity Index ≥3 [adjusted odds ratio (aOR)=3.46, 95% CI: 1.04-11.51], variceal bleeding (aOR=3.02, 95% CI: 1.06-8.61), and hepatic encephalopathy (aOR=26.38, 95% CI: 1.29-540.56). Predictors of decreased mortality were Medicaid (aOR=0.047, 95% CI: 0.28-0.79) and private insurance (aOR=0.56, 95% CI: 0.38-0.83)., Conclusions: The prevalence of renal failure in NASH hospitalizations is associated with markedly increased mortality, hospital costs, and length of stay. As a result, clinicians should be vigilant in treating kidney failure in this population., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

As the US population ages, more elderly patients may need liver transplantation. Our aim was to assess recent trends among elderly individuals requiring liver transplant in the United States. Scientific Registry of Transplant Recipients data (2002-2020) were used to select elderly (≥65 years) liver transplant candidates and assess on-list and posttransplant outcomes. During the study period, 31,209 liver transplant candidates ≥65 years were wait listed. Common etiologies included nonalcoholic steatohepatitis (NASH; 31%), hepatitis C (23%), and alcoholic liver disease (18%); 30% also had hepatocellular carcinoma (HCC). Over time, the proportion of patients ≥65 years among all adult liver transplant candidates increased from 9% (2002-2005) to 23% (2018-2020) (trend, p < 0.0001). The proportion of NASH among elderly candidates increased from 13% (2002-2005) to 39% (2018-2020). Of the elderly candidates, 54% eventually received transplants. In multivariate analysis, independent predictors of a higher chance of receiving a transplant for the elderly included more recent years of listing, male sex, higher Model for End-Stage Liver Disease (MELD) score, and HCC (all p < 0.01). Posttransplant mortality in elderly transplant recipients was higher than in younger patients but continued to decrease over time. In multivariate analysis, independent predictors of higher posttransplant mortality for elderly transplant recipients were earlier years of transplantation, older age, male sex, higher MELD score, history of diabetes, retransplantation, and having HCC (all p < 0.01). The proportion of elderly patients in need of liver transplantation in the United States is sharply increasing. NASH is the most common indication for liver transplantation among the elderly. The outcomes of these patients have been improving in the past 2 decades., (© 2022 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Objective: Few studies investigated the role of different predictors of advanced liver fibrosis in unselected populations. Here, we estimate the prevalence of steatosis and fibrosis in the general United States population by means of transient elastography and evaluate the impact of blood pressure (BP) and diabetes on disease severity., Methods: This is a cross-sectional study of United States adults participating in the 2017-2018 cycle of the National Health and Nutrition Examination Survey. Participants underwent a transient elastography examination, and liver steatosis and fibrosis were estimated through the controlled attenuation parameter (CAP) score and liver stiffness measurement (LSM), respectively., Results: Four thousand, three hundred and seventy-one participants had reliable transient elastography and BP readings. Steatosis (CAP ≥ 248 dB/m), advanced fibrosis (LSM ≥ 9.6 kPa) and cirrhosis (LSM ≥ 13 kPa) were present in 56.9, 5.5 and 2.9% of participants, respectively. After controlling for potential confounders, risk of steatosis increased proportionally going from participants with optimal (reference) to those with normal [odds ratio (OR) 1.24, 95% confidence interval (CI) 0.83-1.86], high normal (OR 1.41, 95% CI 1.01-1.97) and elevated BP (OR 1.64, 95% CI 1.21-2.21), whereas no significant association was found between BP status and liver fibrosis. Conversely, presence of diabetes increased the risk of both steatosis (OR 2.15, 95% CI 1.49-3.11) and advanced fibrosis (OR 2.25, 95% CI 1.36-3.72)., Conclusion: Liver steatosis and fibrosis are highly prevalent in the multiethnic United States adult population, raising concerns for future incidence of cirrhosis and its complications. BP status was associated with a progressively higher risk of steatosis, whereas obesity and diabetes were consistently associated with both steatosis and fibrosis., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: We assessed the burden of nonalcoholic fatty liver disease (NAFLD)-related acute on chronic liver failure (ACLF) among transplant candidates in the United States, along with waitlist outcomes for this population., Approach and Results: We analyzed the United Network for Organ Sharing registry from 2005 to 2017. Patients with ACLF were identified using the European Association for the Study of the Liver/Chronic Liver Failure criteria and categorized into NAFLD, alcohol-associated liver disease (ALD), and hepatitis C virus (HCV) infection. We used linear regression and Chow's test to determine significance in trends and evaluated waitlist outcomes using Fine and Gray's competing risks regression and Cox proportional hazards regression. Between 2005 and 2017, waitlist registrants for NAFLD-ACLF rose by 331.6% from 134 to 574 candidates (P < 0.001), representing the largest percentage increase in the study population. ALD-ACLF also increased by 206.3% (348-1,066 registrants; P < 0.001), whereas HCV-ACLF declined by 45.2% (P < 0.001). As of 2017, the NAFLD-ACLF population consisted primarily of persons aged ≥60 years (54.1%), and linear regression demonstrated a significant rise in the proportion of patients aged ≥65 in this group (β = 0.90; P = 0.011). Since 2014, NAFLD-ACLF grade 1 was associated with a greater risk of waitlist mortality relative to ALD-ACLF (subhazard ratio [SHR] = 1.24; 95% confidence interval [CI], 1.05-1.44) and HCV-ACLF (SHR = 1.35; 95% CI, 1.08-1.71), among patients aged ≥60 years. Mortality was similar among the three groups for patients with ACLF grade 2 or 3., Conclusions: NAFLD is the fastest rising etiology of cirrhosis associated with ACLF among patients listed in the United States. As the NAFLD population continues to grow and age, patients with NAFLD-ACLF will likely have the highest risk of waitlist mortality., (© 2020 by the American Association for the Study of Liver Diseases.)

Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. However, the natural history of NAFLD is incomplete. This is a retrospective cohort study of patients identified with NAFLD by diagnosis codes in a large, community-based health care delivery system. The objectives were (1) to follow patients from initial NAFLD presentation through progression to cirrhosis and/or decompensated cirrhosis to liver cancer, liver transplant, and death for up to 10 years; and (2) to conduct disease progression analysis restricted to patients with NAFLD identified as having diabetes at baseline. A total of 98,164 patients with full NAFLD and 26,488 with diabetes were divided into three baseline prevalent states: (1) no cirrhosis, (2) compensated cirrhosis, and (3) decompensated cirrhosis. In baseline patients without cirrhosis, annual rates of compensated cirrhosis, decompensated cirrhosis, and death were 0.28%, 0.31%, and 0.63% per year, respectively. With baseline compensated cirrhosis, the annual rates of decompensation and death were 2.4% and 6.7% per year. Finally, in those with decompensated cirrhosis at baseline, the death rate was 8.0% per year. In those without cirrhosis and with cirrhosis at baseline, the rates of liver cancer and death were increased approximately 2-fold in the diabetic subpopulation compared with the full NAFLD cohort. Age and comorbidities increased with increasing disease severity. Cox proportional hazards regression analysis showed that cirrhosis was strongly associated with death and liver cancer, and that diabetes was associated with a significant increase in the hazard of both liver cancer and death (2.56 [2.04-3.20] and 1.43 [1.35-1.52]), respectively. Conclusion: The findings of this community-based study further our understanding of the natural history of NAFLD and demonstrate that diabetes is a major factor in the progression of this disease., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

Population-based studies that estimate awareness of nonalcoholic fatty liver disease (NAFLD) in the United States are scant. We aimed to understand public awareness of NAFLD and its temporal trends. Our study included 11,700 adults (18+ years old) from five National Health and Nutrition Examination Surveys (2007-2016). NAFLD was determined by the improved Fatty Liver Index for the multiethnic U.S. population (US-FLI) in the absence of secondary causes of liver disease. Overall prevalence of NAFLD, hepatitis C virus, and hepatitis B virus were 36.6%, 1.02% and 0.35%, respectively. From 2007-2008 to 2015-2016, awareness of liver disease among adults with NAFLD improved from 4.4% to 6.3% (trend P = 0.026) but 4 to 10 times lower than awareness about viral hepatitis. In 2015-2016, among adults with NAFLD, awareness of liver disease was lower among young adults (aged 18-29 years) compared with those aged ≥ 30 years (0% vs. 6.9%) and lower among non-Hispanic Blacks compared with other races (0.7% vs. 6.6%) (all P < 0.001). In multivariable analysis, young adults (adjusted odds ratio [aOR] = 0.29; confidence interval [CI] 0.10-0.87) and non-Hispanic Blacks (aOR = 0.43; CI 0.20-0.96) were negatively associated with awareness of liver disease among adults with NAFLD, whereas diabetes (aOR = 2.22; CI 1.37-3.58), advanced fibrosis (aOR = 2.34; CI 1.17-4.68), and a higher number of health care visits (aOR = 1.33; CI 1.15-1.50) were positively associated with awareness of liver disease. Nearly 96% of adults with NAFLD in the United States were unaware they had liver disease, especially among young adults and non-Hispanic Blacks. Findings indicate efforts are needed to improve awareness of NAFLD., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

The American Heart Association (AHA) introduced Life's Simple 7 as a metric to define ideal cardiovascular health. We examined the association between cardiovascular health score (CHS) and prevalent nonalcoholic fatty liver disease (NAFLD) among Framingham Heart Study participants with varying genetic risk of NAFLD. Framingham Heart Study participants who underwent abdominal computed tomography scans were included (n = 2,773). We defined hepatic steatosis as the mean Hounsfield unit attenuation of the liver compared to a phantom control. We calculated CHS based on adherence to metrics from the AHA's Life's Simple 7 guidelines, including blood sugar, total cholesterol, blood pressure, body mass index (BMI), time spent on physical activity per week, and smoking status. We used multivariable-adjusted regression models to evaluate the association between CHS and hepatic steatosis, accounting for covariates and stratifying by NAFLD genetic risk. Overall, 12% of the sample achieved 0-1 goals and 25%, 27%, 21%, 13%, and 2.6% achieved 2, 3, 4, 5, or 6 goals, respectively. For each 1-unit increase in CHS, there was a decrease in the odds ratio (OR) of prevalent hepatic steatosis (OR, 0.54; 95% confidence interval, 0.49-0.59). Individually, BMI had the strongest association with NAFLD. Participants with high or intermediate genetic risk of NAFLD demonstrated higher relative decreases in hepatic steatosis with increased CHS compared to those at low genetic risk. Conclusion: Adhering to the AHA Life's Simple 7 metrics was associated with reduced odds of prevalent NAFLD, particularly for those at high genetic risk. Additional longitudinal studies are needed., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

Nonalcoholic fatty liver disease (NAFLD) is a global public health concern. Its natural history, the development of nonalcoholic steatohepatitis (NASH) and fibrosis, is highly variable, prone to endogenous (e.g., genetics, microbiota) and exogenous (e.g., nutrition, alcohol, physical activity) disease modifiers, and can fluctuate over time. The complexity of its pathophysiology is reflected by the multitude of pharmacological targets in development. NASH clinical trials have provided valuable insight that is applicable to future trial design. Endpoints for NASH have evolved over the past decade and will continue to be refined. Currently accepted endpoints for conditional approval include resolution of NASH without worsening of fibrosis and/or improvement in fibrosis without worsening of NASH by standardized evaluation of paired liver histology. In pediatric NASH, practical obstacles, pubertal hormonal changes, and stringent safety requirements mandate adaptations in trial design. In adult patients with NASH-related cirrhosis, clinical events (e.g. decompensation, hepatocellular carcinoma, transplantation, death) are more prevalent and thereby are viable primary endpoints. Consideration of the natural fluctuation of disease, the clinical implication of the chosen primary endpoint, and factors that may affect placebo response will facilitate an accurate determination of efficacy of emerging therapeutics for NASH. Conclusion: The June 2018 American Association for the Study of Liver Diseases and European Association for the Study of the Liver joint workshop on NAFLD endpoints summarized important findings from ongoing and completed trials, defined the scientific evidence supporting distinct endpoints, and provided guidance for future trial design., (© 2019 by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.)

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., (© 2019 by the American Association for the Study of Liver Diseases.)

Morbid obesity is considered a relative contraindication for liver transplantation (LT). We investigated if body mass index (BMI; lean versus obese) is a risk factor for post-LT graft and overall survival in nonalcoholic steatohepatitis (NASH) and non-NASH patients. Using the United Network for Organ Sharing (UNOS) database, LT recipients from January 2002 to June 2013 (age ≥18 years) with follow-up until 2017 were included. The association of BMI categories calculated at LT with graft and overall survival after LT were examined. After adjusting for confounders, all obesity cohorts (overweight and class 1, class 2, and class 3 obesity) among LT recipients for NASH had significantly reduced risk of graft and patient loss at 10 years of follow-up compared with the lean BMI cohort. In contrast, the non-NASH group of LT recipients had no increased risk for graft and patient loss for overweight, class 1, and class 2 obesity groups but had significantly increased risk for graft (P < 0.001) and patient loss (P = 0.005) in the class 3 obesity group. In this retrospective analysis of the UNOS database, adult recipients selected for first LT and NASH patients with the lowest BMI have the worse longterm graft and patient survival as opposed to non-NASH patients where the survival was worse with higher BMI., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Goals: The aim of this study was to understand the burden of nonalcoholic fatty liver disease (NAFLD) among hospitalized patients in the United States., Background: A major driver of the rapidly increasing US clinical and economic burden of NAFLD is attributed to inpatient health care resource utilization., Methods: We performed a cross-sectional study of the 2007 to 2014 Nationwide Inpatient Sample. A total of 481,122 hospitalizations in patients with NAFLD were identified using ICD-9 codes after excluding other etiologies of chronic liver disease. We analyzed survey-weighted annual trends in national estimates of hospitalizations in patients with NAFLD, stratified by metabolic comorbidities, cirrhosis, and other liver-related complications. Annual trends in total hospitalization charges were inflation adjusted to 2014 USD., Results: From 2007 to 2014, hospitalizations in patients with NAFLD increased by 83.4% (42,060 to 77,143, P<0.0001), and the proportion of total hospitalizations represented by patients with NAFLD increased by 104.4% (6.34 to 13.0 per 1000 hospitalizations). During this time, there was a 159% increase in total inpatient hospitalization charges in patients with NAFLD ($7.7 billion in 2007 to $19.9 billion in 2014, P<0.001). This increasing clinical and economic burden was observed across all metabolic comorbidities and liver complications evaluated among hospitalizations in patients with NAFLD., Conclusions: With the rising prevalence of NAFLD in the United States, the inpatient clinical and economic burden of NAFLD is also rapidly rising. In 2014, total estimated national hospitalization charges in patients with NAFLD reached nearly $20 billion, with metabolic comorbidities and liver-related complications being major contributors to this rising burden.

Acute-on-chronic liver failure (ACLF) is characterized by multiple organ failure (OF) with high short-term mortality. There is lack of population-based data on trends on etiology specific ACLF related burden. National Inpatient Sample (2006-2014) was queried using ICD-09 codes for admissions with cirrhosis and ACLF (≥2 extrahepatic OF). Of 1,928,764 admissions for cirrhosis between 2006 and 2014, 112,174 (5.9%) had ACLF (4.5%, 1.2%, and 0.2% with ACLF 1, 2, and 3, respectively). The brain was the most common OF in 11.9%, followed by respiratory failure in 7.7%, cardiac failure in 6.3%, and renal failure in 5.6%. ACLF increased by 24% between 2006 and 2014 with a 63% increase in 179,104 patients with nonalcoholic steatohepatitis (NASH) cirrhosis (3.5% to 5.7%); a 28% increase in patients with 429,306 alcoholic cirrhosis (5.6% to 7.2%); a 25% increase in patients with 1,091,053 with other etiologies (5.2% to 6.5%); and no significant change in 229,301 patients with viral hepatitis (VH) (4.0% to 4.1%). In-hospital mortality was higher among ACLF patients compared with patients without ACLF (44% versus 4.7%; P < 0.0001). Each NASH-related ACLF patient compared with other etiologies had a longer mean length of stay (14 versus 12 days), was associated with higher median total charges (US $151,196 versus US $134,597), and had more frequent use of dialysis (45% versus 36%) and longterm care (32% versus 26%; P < 0.0001 for all). Results remained similar in a subgroup analysis after including half of admissions with cryptogenic cirrhosis as NASH. In conclusion, NASH cirrhosis is the most rapidly growing indication for ACLF-related hospitalization and use of hospital resources. In the setting of improved treatment options for chronic hepatitis, the health care burden of chronic viral-related liver disease remains stable. Population-based strategies are needed to reduce the health care burden of cirrhosis, particularly related to NASH., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Nonalcoholic steatohepatitis (NASH) is one of the top 3 indications for liver transplantation (LT) in Western countries. It is unknown whether renal dysfunction at the time of LT has any effect on post-LT outcomes in recipients with NASH. From the United Network for Organ Sharing-Standard Transplant Analysis and Research data set, we identified 4088 NASH recipients who received deceased donor LT. We divided our recipients a priori into 3 categories: group 1 with estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m 2 at the time of LT and/or received dialysis within 2 weeks preceding LT (n = 937); group 2 with recipients who had eGFR ≥30 mL/minute/1.73 m 2 and who did not receive renal replacement therapy prior to LT (n = 2812); and group 3 with recipients who underwent simultaneous liver-kidney transplantation (n = 339). We examined the association of pretransplant renal dysfunction with death with a functioning graft, all-cause mortality, and graft loss using competing risk regression and Cox proportional hazards models. The mean ± standard deviation age of the cohort at baseline was 58 ± 8 years, 55% were male, 80% were Caucasian, and average exception Model for End-Stage Liver Disease score was 24 ± 9. The median follow-up period was 5 years (median, 1816 days; interquartile range, 1090-2723 days). Compared with group 1 recipients, group 2 recipients had 19% reduced trend for risk for death with a functioning graft (subhazard ratio [SHR], 0.81; 95% confidence interval [CI], 0.64-1.02) and similar risk for graft loss (SHR, 1.25; 95% CI, 0.59-2.62), whereas group 3 recipients had similar risk for death with a functioning graft (SHR, 1.23; 95% CI, 0.96-1.57) and graft loss (SHR, 0.18; 95% CI, 0.02-1.37) using an adjusted competing risk regression model. In conclusion, recipients with preserved renal function before LT showed a trend toward lower risk of death with a functioning graft compared with SLKT recipients and those with pretransplant severe renal dysfunction in patients with NASH., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

Nonalcoholic steatohepatitis (NASH) cirrhosis is the fastest growing indication for liver transplantation (LT) in the United States. We aimed to determine the temporal trend behind the rise in obesity and NASH-related additions to the LT waitlist in the United States and make projections for future NASH burden on the LT waitlist. We used data from the Organ Procurement and Transplantation Network database from 2000 to 2014 to obtain the number of NASH-related LT waitlist additions. The obese population in the United States from 2000 to 2014 was estimated using data from the U.S. Census Bureau and the National Health and Nutrition Examination Survey. Based on obesity trends, we established a time lag between obesity prevalence and NASH-related waitlist additions. We used data from the U.S. Census Bureau on population projections from 2016 to 2030 to forecast obesity estimates and NASH-related LT waitlist additions. From 2000 to 2014, the proportion of obese individuals significantly increased 44.9% and the number of NASH-related annual waitlist additions increased from 391 to 1,605. Increase in obesity prevalence was strongly associated with LT waitlist additions 9 years later in derivation and validation cohorts (R 2 = 0.9). Based on these data, annual NASH-related waitlist additions are anticipated to increase by 55.4% (1,354-2,104) between 2016 and 2030. There is significant regional variation in obesity rates and in the anticipated increase in NASH-related waitlist additions (P < 0.01). Conclusion: We project a marked increase in demand for LT for NASH given population obesity trends. Continued public health efforts to curb obesity prevalence are needed to reduce the projected future burden of NASH. (Hepatology 2017)., (Copyright © 2017 by the American Association for the Study of Liver Diseases.)

Nonalcoholic fatty liver disease is an increasingly prevalent condition, and its more severe progressive state, nonalcoholic steatohepatitis (NASH), is currently the second most common indication for wait-listed adults in the United States. The association of portal vein thrombosis (PVT) prior to or at transplant and poor graft and patient outcomes is not well established, particularly among NASH patients who inherently have an increased hypercoagulable profile. Using the United Network for Organ Sharing data set, we analyzed graft and patient outcomes of patients transplanted for the indication of NASH with and without PVT. Of 3689 NASH transplant recipients, the prevalence of PVT was 12% (450 with PVT and 3239 without PVT). NASH transplant recipients with PVT had inferior graft and patient survival compared with NASH transplant recipients without PVT, even after adjusting for recipient and donor demographic characteristics, body mass index, synthetic dysfunction, and presence of diabetes. In a multivariate Cox regression model, NASH transplant recipients with PVT had a 37% increased risk of graft failure (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.15-1.63; P < 0.001) and 31% increased risk of overall death (HR, 1.31; 95% CI, 1.09-1.58; P < 0.001) compared with NASH transplant recipients without PVT at transplant. This difference in graft and patient survival was most pronounced in the early posttransplant period. These results demonstrate that NASH patients with PVT have decreased graft and patient survival independent of recipient and donor factors., (Copyright © 2018 by the American Association for the Study of Liver Diseases.)

Goals: To analyze the frequency and trend of liver transplantation (LT) for nonalcoholic steatohepatitis (NASH) cirrhosis in young adults aged 18 to 40 years and to assess post-LT outcomes in this age group., Background: NASH is currently the fastest-growing indication for LT in US adults. It is believed that NASH is a rare indication for LT among young adults., Study: Using the United Network for Organ Sharing database, we performed a retrospective cohort analysis of all LTs in young adults between 2002 and 2012. Incidence rate ratio was calculated for each indication., Results: A total of 5157 young adults underwent LT over the study period-54% were male, 23% obese. Mean (±SD) age and body mass index were 31.6±6.7 years and 26.3±6.1 kg/m, respectively. The incidence of LTs performed for NASH cirrhosis increased from 0.53% in 2002 to 4.46% in 2012. NASH was the most rapidly growing indication for LT among all other etiologies with a 14% increment per year (incidence rate ratio, 1.14; 95% confidence interval, 1.09-1.20, P<0.001). The 5-year post-LT outcomes were comparable between NASH and non-NASH recipients, but graft survival was lower and retransplantation cumulative rates were higher in NASH recipients compared with those with other metabolic liver diseases (63.5% vs. 81.4%, P=0.003 and 12.7% vs. 4.2%, P=0.046, respectively)., Conclusions: NASH is the fastest-growing indication for LT among young US adults aged 18 to 40 years and now accounts for almost 5% of all LTs in this age group.

Goals/background: We aimed to assess temporal changes in the different types of liver disease (LD) cases and outcomes from emergency departments (EDs) across the United States., Study: We used data from the National Inpatient Survey database from 2005 to 2011. The International Classification of Diseases, Ninth Revision (ICD-9) clinical modification codes identified hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and other LDs including autoimmune hepatitis. We excluded cases without LD, nonhepatocellular carcinoma-related cancers, human immunodeficiency virus infection, or those with missing information. Logistic regression was used to estimate odds ratios with 95% confidence intervals. Controls were matched to cases without LD., Results: During the study period, 20,641,839 cases were seen in EDs. Of these, 1,080,008 cases were related to LD and were matched to controls without LD (N=19,557,585). The number of cases with LD increased from 123,873 (2005) to 188,501 (2011) (P<0.0001). Among cases with LD, diagnosis of HCV, HBV, and ALD remained stable during the study years (41.60% vs. 38.20%, 3.70% vs. 2.80%, and 41.4% vs. 38.5%, respectively), whereas NAFLD doubled [6.00% of all LD (2005) to 11.90% of all LD (2011) (P<0.0001)]. Diagnosis of LD in the ED independently predicted increased patient mortality [odds ratio, 1.20 (1.17 to 1.22)]., Conclusions: The number of LD cases presenting to EDs is increasing, and a diagnosis of LD is associated with a higher patient mortality for those admitted through the ED. There is a dramatic increase of NAFLD diagnoses in the ED.

Unlabelled: Nonalcoholic fatty liver disease (NAFLD) contributes to premature death along with obesity, diabetes, and cardiovascular disease (CVD). We examined whether hepatic steatosis (HS) on ultrasound and liver enzyme activities were associated with increased liver disease mortality in the U.S. National Health and Nutrition Examination Survey (NHANES), 1988-1994, with up to 23 years of linked-mortality data. Survey-linked National Death Index records were analyzed among 14,527 adult participants who were negative for viral hepatitis B and C and iron overload. HS on ultrasound was categorized as normal, mild, moderate, or severe. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) elevation was defined as the highest sex-specific decile. Cumulative mortality was 36.2% from all causes, including 16.3% from CVD, 10.8% from cancer, 5.4% from diabetes, and 1.1% from liver disease. Severe HS was associated with increased liver disease mortality in both age-adjusted (hazard ratio [HR]: 3.92; 95% confidence interval [CI]: 1.49-10.27; P for trend: 0.011) and multivariate-adjusted analyses (HR, 2.68; 95% CI: 1.02-7.03; P for trend: 0.072). HS was not independently associated with mortality from all causes, CVD, cancer, or diabetes. Higher liver disease mortality was found with elevated ALT (HR, 4.08; 95% CI: 1.99-8.33), AST (HR, 4.33; 95% CI: 2.18-8.59), and GGT (HR, 7.91; 95% CI: 3.06-20.46). GGT elevation was associated with increased overall mortality (HR, 1.45; 95% CI: 1.21-1.74). Liver enzymes were otherwise unrelated to overall or cause-specific mortality., Conclusions: In the U.S. population, severe hepatic steatosis on ultrasound and liver enzyme elevation were associated with increased liver disease mortality, but were not independently associated with mortality from all causes (except for GGT), CVD, cancer, or diabetes., (© 2015 by the American Association for the Study of Liver Diseases.)

Chronic liver disease (CLD) and cirrhosis are major sources of morbidity and mortality in the United States. Little is known about the epidemiology of these two diseases in ethnic minority populations in the United States. We examined the prevalence of CLD and cirrhosis by underlying etiologies among African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort. CLD and cirrhosis cases were identified using Medicare claims between 1999 and 2012 among the fee-for-service participants (n = 106,458). We used International Classification of Diseases Ninth Revision codes, body mass index, history of diabetes mellitus, and alcohol consumption from questionnaires to identify underlying etiologies. A total of 5,783 CLD (3,575 CLD without cirrhosis and 2,208 cirrhosis) cases were identified. The prevalence of CLD ranged from 3.9% in African Americans and Native Hawaiians to 4.1% in whites, 6.7% in Latinos, and 6.9% in Japanese. Nonalcoholic fatty liver disease (NAFLD) was the most common cause of CLD in all ethnic groups combined (52%), followed by alcoholic liver disease (21%). NAFLD was the most common cause of cirrhosis in the entire cohort. By ethnicity, NAFLD was the most common cause of cirrhosis in Japanese Americans, Native Hawaiians, and Latinos, accounting for 32% of cases. Alcoholic liver disease was the most common cause of cirrhosis in whites (38.2%), while hepatitis C virus was the most common cause in African Americans (29.8%)., Conclusions: We showed racial/ethnic variations in the prevalence of CLD and cirrhosis by underlying etiology; NAFLD was the most common cause of CLD and cirrhosis in the entire cohort, and the high prevalence of NAFLD among Japanese Americans and Native Hawaiians is a novel finding, warranting further studies to elucidate the causes. (Hepatology 2016;64:1969-1977)., Competing Interests: the authors disclose no conflicts, (© 2016 by the American Association for the Study of Liver Diseases.)

Portal vein thrombosis (PVT) is a common complication of cirrhosis sometimes implicated in hepatic decompensation. There are no consistent epidemiologic data to suggest an increased risk of thrombotic complications in nonalcoholic steatohepatitis (NASH); however, research suggests an increased risk of thrombosis. Our aim was to examine the independent association between NASH cirrhosis and PVT in patients who underwent liver transplantation (LT) in a cross-sectional study. Data on all LTs occurring in the United States between January 1, 2003 and December 31, 2012 were obtained from the United Network for Organ Sharing. Multivariable models were constructed to assess the statistical associations and risk factors for the development of PVT. A total of 33,368 patients underwent transplantation. Of these, 2096 (6.3%) had PVT. Of the patients with PVT, 12.0% had NASH. When we compared these patients to a composite of all other causes of cirrhosis, an increased prevalence of PVT was again found, with 10.1% having PVT at the time of transplantation versus 6.0% without NASH (P < 0.001). The strongest risk factor independently associated with a diagnosis of PVT in a multivariable analysis was NASH cirrhosis (odds ratio, 1.55; 95% confidence interval, 1.33-1.81; P < 0.001). NASH cirrhosis appears to predispose a patient to PVT independently of other risk factors. These epidemiological findings provide support for the idea that NASH is a prothrombotic state, and they should lead to more research in treatment and prevention in this population., (© 2015 American Association for the Study of Liver Diseases.)

Background and Aims: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD., Approach and Results: Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P < 0.001) and NASH (-13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End-Stage Liver Disease-Sodium score ≥30., Conclusions: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources., (© 2021 by the American Association for the Study of Liver Diseases.)

Metabolic-associated fatty liver disease (MAFLD) is a major cause of liver-related complications, including hepatocellular carcinoma (HCC). While MAFLD-related HCC is known to occur in the absence of cirrhosis, our understanding of MAFLD-related HCC in this setting is limited. Here, we characterize MAFLD-related HCC and the impact of cirrhosis and screening on survival. This was a multicenter, retrospective, cohort study of MAFLD-related HCC. MAFLD was defined based on the presence of race-adjusted overweight, diabetes, or both hypertension and dyslipidemia in the absence of excess alcohol use or other underlying cause of liver disease. The primary outcome of interest was overall survival, and the primary dependent variables were cirrhosis status and prior HCC screening. We used Kaplan-Meier methods to estimate overall survival and Cox proportional hazards models and random forest machine learning to determine factors associated with prognosis. This study included 1,382 patients from 11 centers in the United States and East/Southeast Asia. Cirrhosis was present in 62% of patients, but under half of these patients had undergone imaging within 12 months of HCC diagnosis. Patients with cirrhosis were more likely to have early stage disease but less often received curative therapy. After adjustment, cirrhosis was not associated with prognosis, but the presence of cancer-related symptoms at diagnosis was associated with poorer prognosis. Conclusion: Cirrhosis was not associated with overall survival in this cohort of MAFLD-related HCC, while diagnosis in the presence of symptoms was associated with poorer prognosis. The HCC surveillance rate in patients with MAFLD-related HCC was disappointingly low in a multicenter cohort., (© 2020 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.)

Understanding the burden of NAFLD among adolescents and young adults has become increasingly relevant. Our aim was to estimate the prevalence of NAFLD among adolescents and young adults in the United States. Data were obtained from National Health and Nutrition Examination Survey from 2007-2016. Adolescents and young adults aged 12 to 29 years were included. NAFLD was determined by the U.S. Fatty Liver Index in the absence of secondary causes of liver disease, and the differences in prevalence trends were analyzed based on age, gender, and race. Complete data were available for 4,654 adolescents and young adults (mean age 21 years; 50.9% male; 56.8% White, 20.9% Hispanic, and 13.3% Black). The overall prevalence of NAFLD among adolescents and young adults was 18.5%, ranging from 13.2% among early and middle adolescents (12-17 years) to 18.7% among late adolescents and young adults (18-24 years), to 24.0% among older young adults (25-30 years) (trend P < 0.001). The prevalence of NAFLD was higher for boys than for girls (aged 12-17: 15.1% vs. 11.3%; aged 18-24: 21.1% vs. 16.2%; aged 25-30: 28.7% vs. 19.2%, all P < 0.030). Among all age groups, Hispanics had a higher prevalence of NAFLD than Whites and Blacks (pairwise P < 0.001). Over the study time period, the prevalence of NAFLD among early and middle adolescents and young adults did not change (trend P > 0.80). In contrast, NAFLD prevalence among late adolescents increased (trend P = 0.018). In fact, White and Hispanic late adolescents were the drivers behind this increase in the prevalence of NAFLD. Conclusion: These data indicate an increasing trend in NAFLD prevalence among 18-24-year-olds. These data have important public health and policy implications., (© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) encompasses a range of conditions, from simple steatosis to nonalcoholic steatohepatitis. Studies in the United States have reported an increased mortality risk among individuals with NAFLD; therefore, the population attributable fractions (PAFs) for mortality were examined., Approach and Results: A total of 12,253 adult individuals with ultrasound assessment of NAFLD from the Third National Health and Nutrition Examination Survey and mortality follow-up through 2015 were included in the analysis. Cox proportional hazard regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for NAFLD in association with all-cause and cause-specific mortality. Overall, sex- and race/ethnicity-specific PAFs and 95% CIs were estimated. In the current study, presence of NAFLD was associated with a 20% increased risk of all-cause mortality (HR, 1.20; 95% CI, 1.08, 1.34). The overall PAF for all-cause mortality associated with NAFLD was 7.5% (95% CI, 3.0, 12.0). The PAF for diabetes-specific mortality was 38.0% (95% CI, 13.1, 63.0) overall, 40.8% (95% CI, 2.1, 79.6) in men, and 36.8% (95% CI, 6.6, 67.0) in women. The PAF for liver disease (LD)-specific mortality was notably higher in men (68.3%; 95% CI, 36.3, 100.0) than women (3.5%; 95% CI, -39.7, 46.8). In the race-specific analysis, the PAFs of NAFLD for all-cause mortality (9.3%; 95% CI, 4.0, 14.6) and diabetes-specific mortality (44.4%; 95% CI, 10.8, 78.0) were significantly greater than zero only for whites., Conclusions: In the United States, approximately 8% of all-cause mortality and more than one-third of LD- and diabetes-specific deaths are associated with NAFLD. With these high percentages, efforts are needed to reduce the burden of NAFLD in the United States., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Nonalcoholic fatty liver disease (NAFLD) comprises more than two thirds of patients with chronic liver disease in the United States. The effect of alcohol consumption on survival in patients with NAFLD is not clear. We gathered data on National Health and Nutrition Examination Survey participants from 1988 to 2010, and linked them to the National Death Index for follow-up of their survival. We diagnosed NAFLD based on a previously validated biochemical model (Hepatic Steatosis Index). We built multivariate Cox proportional hazards models to evaluate the effect of alcohol consumption on survival of patients with NAFLD. After excluding participants with significant alcohol use, viral hepatitis, or increased transferrin saturation, 4,568 participants with NAFLD were included in the analysis. In a Cox model adjusted for age, sex, and smoking history, drinking 0.5-1.5 drinks per day decreased the risk of overall mortality by 41% (hazard ratio [HR] = 0.59, 95% confidence interval [CI] 0.40-0.85, P = 0.005) compared with not drinking. Drinking ≥1.5 drinks per day showed a trend toward harm (HR = 1.16, 95% CI 0.99-1.36, P = 0.119). After further adjustment for race, physical activity, education level, diabetes, and fiber and polyunsaturated fatty acid intake, drinking 0.5-1.5 drinks per day continued to show a significant protective effect (HR = 0.64, 95% CI 0.42-0.97, P = 0.035), and drinking ≥1.5 drinks per day showed a significant harmful effect on mortality (HR = 1.45, 95% CI 1.01-2.10, P = 0.047). Among patients with NAFLD, modest alcohol consumption is associated with a significant decrease in all-cause mortality, whereas drinking ≥1.5 drinks per day is associated with an increase in mortality. These results help to inform the discussion of potential risks and benefits of alcohol use in patients with NAFLD., (© 2018 by the American Association for the Study of Liver Diseases.)

Nonalcoholic fatty liver disease (NAFLD) is a significant health burden in adolescents and young adults (AYAs) which has substantially risen in prevalence over the last decades. The occurrence of NAFLD parallels high rates of obesity and metabolic syndrome in this age group, with unhealthy lifestyle also playing an independent role. Genetic factors, sex, and ethnicity should be considered in a risk stratification model. NAFLD and nonalcoholic steatohepatitis (NASH) in AYAs often go unrecognized and, if untreated, can progress eventually to cirrhosis requiring liver transplantation (LT) before the age of 40. Recently, NASH has increased as an indication for LT in this age group. Important knowledge gaps include the feasibility of noninvasive diagnostic tests and imaging modalities as well as uncertainty about unique histological features and their predictive value. Future clinical trials focused on AYAs are needed to determine effectiveness of therapies. Tools for increasing awareness and prevention of NAFLD in AYAs are greatly needed. (Hepatology 2017;65:2100-2109)., (© 2017 by the American Association for the Study of Liver Diseases.)

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The health care burden resulting from the multidisciplinary management of this complex disease is unknown. We assessed the total health care cost and resource utilization associated with a new NAFLD diagnosis, compared with controls with similar comorbidities. We used OptumLabs Data Warehouse, a large national administrative claims database with longitudinal health data of over 100 million individuals enrolled in private and Medicare Advantage health plans. We identified 152,064 adults with a first claim for NAFLD between 2010 and 2014, of which 108,420 were matched 1:1 by age, sex, metabolic comorbidities, length of follow-up, year of diagnosis, race, geographic region, and insurance type to non-NAFLD contemporary controls from the OptumLabs Data Warehouse database. Median follow-up time was 2.6 (range 1-6.5) years. The final study cohort consisted of 216,840 people with median age 55 (range 18-86) years, 53% female, 78% white. The total annual cost of care per NAFLD patient with private insurance was $7,804 (interquartile range [IQR] $3,068-$18,688) for a new diagnosis and $3,789 (IQR $1,176-$10,539) for long-term management. These costs are significantly higher than the total annual costs of $2,298 (IQR $681-$6,580) per matched control with similar metabolic comorbidities but without NAFLD. The largest increases in health care utilization that may account for the increased costs in NAFLD compared with controls are represented by liver biopsies (relative risk [RR] = 55.00, 95% confidence interval [CI] 24.48-123.59), imaging (RR = 3.95, 95% CI 3.77-4.15), and hospitalizations (RR = 1.87, 95% CI 1.73-2.02). Conclusion: The costs associated with the care for NAFLD independent of its metabolic comorbidities are very high, especially at first diagnosis. Research efforts shouldfocus on identification of underlying determinants of use, sources of excess cost, and development of cost-effective diagnostic tests., (© 2018 by the American Association for the Study of Liver Diseases.)

Unlabelled: Hepatocellular carcinoma (HCC) is increasingly reported in patients with nonalcoholic fatty liver disease (NAFLD). Our aim was to assess the prevalence and mortality of patients with NAFLD-HCC. We examined Surveillance, Epidemiology and End Results (SEER) registries (2004-2009) with Medicare-linkage files for HCC, which was identified by the International Classification of Diseases for Oncology, third edition codes using topography and morphology codes 8170-8175. Medicare-linked data was used to identify NAFLD, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease (ALD), and other liver disease using International Classification of Diseases, Ninth Revision, Clinical Modification codes. NAFLD was also defined by clinical diagnosis (cryptogenic cirrhosis, obese-diabetics with cryptogenic liver disease). A logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HCC. In addition, adjusted hazard ratios for 1-year mortality were estimated by Cox's proportional hazard regression. A total of 4,929 HCC cases and 14,937 controls without HCC were included. Of the HCC cases, 54.9% were related to HCV, 16.4% to ALD, 14.1% to NAFLD, and 9.5% to HBV. Across the 6-year period (2004 to 2009), the number of NAFLD-HCC showed a 9% annual increase. NAFLD-HCC were older, had shorter survival time, more heart disease, and were more likely to die from their primary liver cancer (all P < 0.0001). Of those who received a transplant after HCC (n = 488), only 5% were related to NAFLD-HCC. In multivariate analysis, NAFLD increased the risk of 1-year mortality (OR, 1.21; 95% CI: 1.01-1.45). Additionally, older age, lower income, unstaged HCC increased risk of 1-year mortality while receiving a liver transplant (LT), and having localized tumor stage were protective (all P < 0.05)., Conclusions: NAFLD is becoming a major cause of HCC in the United States. NAFLD HCC is associated with shorter survival time, more advanced tumor stage, and lower possibility of receiving a LT., (© 2015 by the American Association for the Study of Liver Diseases.)

Unlabelled: Nonalcoholic steatohepatitis (NASH) is currently the third leading indication for liver transplantation (LT) in the U.S. and is predicted to become the leading indication for LT in the near future. The trends in NASH-related hepatocellular carcinoma (HCC) among LT recipients in the U.S. remain undefined. We performed a retrospective cohort study to evaluate trends in the etiology of HCC among adult LT recipients in the U.S. from 2002 to 2012, using national data from the United Network for Organ Sharing registry. From 2002-2012, there were 61,868 adults who underwent LT in the U.S., including 10,061 patients with HCC. The total number and proportion of HCC LT recipients demonstrated a significant increase following the implementation of the Model for Endstage Liver Disease (MELD) scoring system in 2002 (3.3%, n=143 in 2000 versus 12.2%, n=714 in 2005 versus 23.3%, n=1336 in 2012). The proportion of hepatitis C virus (HCV)-related HCC increased steadily from 2002 to 2012, and HCV remained the leading etiology of HCC throughout the MELD era (43.4% in 2002 versus 46.3% in 2007 versus 49.9% in 2012). NASH-related HCC also increased significantly, and NASH is the second leading etiology of HCC-related LT (8.3% in 2002 versus 10.3% in 2007 versus 13.5% in 2012). From 2002 to 2012, the number of patients undergoing LT for HCC secondary to NASH increased by nearly 4-fold, and the number of LT patients with HCC secondary to HCV increased by 2-fold., Conclusion: NASH is the second leading etiology of HCC leading to LT in the U.S. More important, NASH is currently the most rapidly growing indication for LT in patients with HCC in the U.S., (© 2014 by the American Association for the Study of Liver Diseases.)