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.

Association of food insecurity with MASLD prevalence and liver-related mortality.

BACKGROUND & AIMS: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing. This study explores the association of food insecurity with MASLD prevalence and liver-related mortality (LRM) across the globe. METHODS: The study combines United Nations' country-level food security data with the MASLD data from the Global Burden of Disease study 2021. Mixed-effects linear regression models, accounting for country-level random effects, were used to assess associations of food security indicators with MASLD prevalence and LRM. The analyses were performed according to each country's socio-demographic index (SDI) status. RESULTS: In 2021, the median MASLD prevalence and liver-related mortality (MASLD-LRM) across 204 countries was 21.77% (14.14%-48.18%) and 2.92 per 100,000 (0.42-10.79) with the highest MASLD prevalence located in North Africa & Middle East (41.70%) and the lowest prevalence in high-income countries (17.31%). After adjustments for age, gender and SDI, higher MASLD prevalence was associated with increasing rates of obesity, type 2 diabetes and low physical activity (p <0.001). When analyses were performed based on SDI status, divergent patterns of MASLD prevalence were observed. In high SDI countries (socioeconomically more developed), MASLD prevalence was significantly higher in those in the top tertile of food insecurity compared to the bottom tertile (mean, 26.73% vs. 18.87%, p = 0.0001). In contrast, in low SDI countries (socioeconomically less developed), the opposite was true (19.45% vs. 24.96%, p = 0.0008). MASLD-LRM was associated with older age, obesity, and metabolic risks (p <0.001). CONCLUSIONS: MASLD prevalence and MASLD-LRM exhibit significant geographical variability, which is influenced by clinicodemographic factors, and food insecurity. Targeted public health strategies which consider the socio-economic realities of each region are essential for mitigating the global burden of MASLD. IMPACT AND IMPLICATIONS: Metabolic dysfunction-associated steatotic liver disease (MASLD) burden varies by region, influenced by food insecurity and healthcare access. In high socio-demographic index (SDI) countries, higher MASLD prevalence is linked to the consumption of low-quality, ultra-processed foods. Public health policies should focus on improving food quality, reducing unhealthy food consumption, and enhancing healthcare access. Conversely, in low SDI countries, while food insecurity can lead to outright deficiencies, the observed lower MASLD prevalence may also be partly attributable to underdiagnosis. In this context, limited healthcare access may have contributed to underestimation of the prevalence of MASLD. Therefore, country-specific policies should address both the issues related to poverty, as well as improving access to diagnostic modalities and healthcare infrastructure to ensure more accurate estimates of cases of MASLD in the specific country. Promoting physical activity is crucial in both high and low SDI countries to manage metabolic conditions associated with MASLD.

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.

The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review.

BACKGROUND AND AIMS: NAFLD is a leading cause of liver-related morbidity and mortality. We assessed the global and regional prevalence, incidence, and mortality of NAFLD using an in-depth meta-analytic approach. APPROACH AND RESULTS: PubMed and Ovid MEDLINE were searched for NAFLD population-based studies from 1990 to 2019 survey year (last published 2022) per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Meta-analysis was conducted using random-effects models. Bias risk assessment was per Joanna Briggs Institute. Of 2585 studies reviewed, 92 studies (N=9,361,716) met eligibility criteria. Across the study period (1990-2019), meta-analytic pooling of NAFLD prevalence estimates and ultrasound-defined NAFLD yielded an overall global prevalence of 30.05% (95% CI: 27.88%-32.32%) and 30.69% (28.4-33.09), respectively. Global NAFLD prevalence increased by +50.4% from 25.26% (21.59-29.33) in 1990-2006 to 38.00% (33.71-42.49) in 2016-2019 ( p <0.001); ultrasound-defined NAFLD prevalence increased by +38.7% from 25.16% (19.46-31.87) in 1990-2006 to 34.59% (29.05-40.57) ( p =0.029). The highest NAFLD prevalence was in Latin America 44.37% (30.66%-59.00%), then Middle East and North Africa (MENA) (36.53%, 28.63%-45.22%), South Asia (33.83%, 22.91%-46.79%), South-East Asia (33.07%, 18.99%-51.03%), North America (31.20%, 25.86%-37.08%), East Asia (29.71%, 25.96%-33.76%), Asia Pacific 28.02% (24.69%-31.60%), Western Europe 25.10% (20.55%-30.28%). Among the NAFLD cohort diagnosed without a liver biopsy, pooled mortality rate per 1000 PY was 12.60 (6.68-23.67) for all-cause mortality; 4.20 (1.34-7.05) for cardiac-specific mortality; 2.83 (0.78-4.88) for extrahepatic cancer-specific mortality; and 0.92 (0.00-2.21) for liver-specific mortality. CONCLUSIONS: NAFLD global prevalence is 30% and increasing which requires urgent and comprehensive strategies to raise awareness and address all aspects of NAFLD on local, regional, and global levels.

Pharmaco-Economic Assessment of Screening Strategies for High-Risk MASLD in Primary Care.

BACKGROUND AND AIMS: Several scientific associations recommend a sequential combination of non-invasive tests (NITs) to identify high-risk MASLD patients but their cost-effectiveness is unknown. METHODS: A cost-utility model was developed to assess the incremental cost-effectiveness ratio (ICER) of recommended screening strategies for patients with clinically suspected MASLD, specifically those with type 2 diabetes (T2D) and obesity with multiple cardiometabolic risk factors which will be initiated in primary care. Six screening strategies were assessed, using either vibration-controlled transient elastography (VCTE) or the enhanced liver fibrosis (ELF) test as a second-line test following an initial Fibrosis-4 (FIB-4) assessment as the first line NIT. The model included treatment effects of resmetirom for metabolic dysfunction-associated steatohepatitis (MASH) patients with F2 or F3 fibrosis. RESULTS: All screening strategies for high-risk MASLD in US incurred additional costs compared to no screening, ranging from $13 587 to $14 730 per patient with T2D and $14 274 to $15 661 per patient with obesity. However, screening reduced long-term costs, ranging from $22 150 to $22 279 per patient with T2D and $13 704 to $13 705 per patient with obesity, compared to $24 221 and $14 956 for no screening, respectively. ICERs ranged from $26 913 to $27 884 per QALY for T2D patients and $23 265 to $24 992 per QALY for patients with obesity. While ICERs were influenced by VCTE availability, they remained cost-effective when using ELF as the second-line test. Our findings remain robust across a range of key parameters. CONCLUSIONS: Screening for high-risk MASLD is cost-effective according to recent guidelines. Implementing these screening strategies in primary care should be considered.

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.

Nonalcoholic Fatty Liver Disease Is Independently Associated With Higher All-Cause and Cause-Specific Mortality.

BACKGROUND & AIMS: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing globally. We assessed independent associations of NAFLD with all-cause and cause-specific mortality in older community-dwelling adults in the United States. METHODS: Data from the Rancho Bernardo Study cohort, who participated in the research from 1992 to 1996 with mortality data (followed up to July 2019), were analyzed. NAFLD was determined by the improved Fatty Liver Index for the multiethnic US population in the absence of secondary causes of liver disease. Hazard ratios (HRs), 95% CIs, and population-attributable fractions of risk factors on mortality were calculated. Competing-risk analyses of cause-specific mortality were performed. RESULTS: Of the 1523 eligible participants (mean age, 71.8 y; 39.9% male; 99.3% non-Hispanic White; and 10.7% obese), 404 (26.4%) had NAFLD. During 23,311 person-years of follow-up evaluation (mean, 15.22 y; SD, 8.41 y), among NAFLD and non-NAFLD, there were 296 and 717 deaths from all causes, 113 and 263 cardiac deaths, 62 and 112 cancer deaths, and 6 and 2 liver deaths, respectively. NAFLD had a 26% higher all-cause mortality (HR, 1.26; 95% CI, 1.08-1.47) and a 33% (HR, 1.33; 95% CI, 1.04-1.70) and 55% (HR, 1.55; 95% CI, 1.11-2.15) higher cardiac and cancer mortality, respectively, than non-NAFLD. Population-attributable fractions showed 13.9% of deaths, 6.2% of cardiac deaths, and 12.1% of cancer deaths were attributable to NAFLD after adjustments of risk factors (sedentary lifestyle, obesity, hypertension, hyperlipidemia, diabetes). CONCLUSIONS: NAFLD is associated independently with all-cause, cardiac, and cancer mortality. Efforts must continue to raise awareness about NAFLD and develop care pathways and public health efforts to reduce NAFLD burden and associated mortality.

Sarcopenia Among Patients With Nonalcoholic Fatty Liver Disease (NAFLD) Is Associated With Advanced Fibrosis.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) and sarcopenia can be associated with advanced liver disease. Our aim was to assess the association between sarcopenia and the risk of fibrosis among patients with NAFLD. METHODS: We used the National Health and Nutrition Examination Survey (2017-2018). NAFLD was defined by transient elastography without other causes of liver disease or excessive alcohol use. Significant fibrosis (SF) and advanced fibrosis (AF) were defined by liver stiffness greater than 8.0 kPa and greater than 13.1 kPa, respectively. Sarcopenia was defined using the Foundation for the National Institutes of Health definition. RESULTS: Of the total cohort (N = 2422), 18.9% had sarcopenia, 9.8% had obese sarcopenia, 43.6% had NAFLD, 7.0% had SF, and 2.0% had AF. Moreover, 50.1% had neither sarcopenia nor NAFLD, 6.3% had sarcopenia without NAFLD, 31.1% had NAFLD without sarcopenia, and 12.5% had NAFLD with sarcopenia. Compared with individuals without NAFLD or sarcopenia, individuals with sarcopenic NAFLD had higher rates of SF (18.3% vs 3.2%) and AF (7.1% vs 0.2%). In the absence of sarcopenia, compared with individuals without NAFLD, individuals with NAFLD have a significantly increased risk of SF (odds ratio, 2.18; 95% CI, 0.92-5.19). In the presence of sarcopenia, NAFLD was associated with an increased risk of SF (odds ratio, 11.27; 95% CI, 2.79-45.56). This increase was independent of metabolic components. The proportion of SF that is attributable to the interaction of NAFLD and sarcopenia was 55% (attributable proportion, 0.55; 95% CI, 0.36-0.74). Increased leisure time physical activity was associated with a lower risk of sarcopenia. CONCLUSIONS: Patients with sarcopenic NAFLD are at risk for SF and AF. Increased physical activity and a healthy diet targeted to improve sarcopenic NAFLD could reduce the risk of significant fibrosis.

Are there outcome differences between NAFLD and metabolic-associated fatty liver disease?

BACKGROUND: Given the association of NAFLD with metabolic risks, a name change to MAFLD is proposed. We compared the long-term outcomes of NAFLD and MAFLD. METHODS: We included patients with fatty liver disease (FLD) from NHANES III and NHANES 2017-2018 (FLD defined as moderate to severe hepatic steatosis by ultrasound for NHANES III and as having a controlled attenuation parameter ≥285 dB/m for NHANES 2017-2018). NAFLD was defined as FLD without other liver diseases and excess alcohol use. Metabolic-associated fatty liver disease (MAFLD) was defined as FLD and metabolic dysfunction per criteria. All NHANES III participants had linked mortality data through December 31, 2015. RESULTS: NHANES III participants (n = 12,878): mean age 43.1 years old; 49.5% male; 20.3% with FLD, 16.5% with NAFLD, and 18.1% with MAFLD. NHANES 2017-2018 participants (n = 4328): mean age 48.0 years old; 49.1% male; 36.8% with FLD, 34.2% with NAFLD, and 36.3% with MAFLD. Excellent concordance was noted between MAFLD and NAFLD diagnosis in both data sets (kappa coefficient = 0.83-0.94). Except for components of each definition (e.g., alcohol use for MAFLD), no other major differences in clinical characteristics were noted. During up to 27 years of follow-up (median of 22.8 years), no differences in cumulative all-cause and cause-specific mortality were noted. In addition to the stage of fibrosis, insulin resistance was a predictor of liver mortality in NAFLD, and alcohol-associated liver disease (ALD) was a predictor of mortality in MAFLD. CONCLUSIONS: MAFLD and NAFLD have similar clinical profiles and long-term outcomes. The increased liver-related mortality among NAFLD is driven by insulin resistance, and among MAFLD is primarily driven by ALD.

Global burden of NAFLD and chronic liver disease among adolescents and young adults.

BACKGROUND AND AIM: The causes of chronic liver disease (CLD) among adults have changed. Data are lacking on trends among youth. We determined the trends and changes in the global burden of CLD among adolescents and young adults using Global Burden of Disease (GBD) data (2009-2019). APPROACH AND RESULTS: The GBD study estimation methods were used to assess CLD prevalence, incidence, and deaths (21 GBD regions). Annual percent change (APC) calculation by joinpoint regression modeling. Age groups were 15-19, 20-24, and 25-29 years old. Globally in 2019, the 15-29 group accounted for 17.2% (0.29 billion) of CLD prevalent cases, 11.2% (n = 232,072) CLD incident cases, and 3.8% (n = 55,515) CLD deaths. Between 2009 and 2019, CLD prevalence rate increased annually among 25-29 (APC = +0.41%, p < 0.001); remained stable among 20-24 (APC = +0.02%, p = 0.582); and decreased among 15-19 (APC = -2.13%, p < 0.001). CLD prevalence increases were driven by the proportion with NAFLD (15-19: 40.8% to 52.9%, p < 0.001); 20-24: 57.6% to 62.7%, p < 0.001); and 25-29: 66.9% to 70.1%, p < 0.001); the proportion with HBV decreased across all age groups. NAFLD prevalence worsening trend (APC ≥ 0%) was global. Overall CLD death rate decreased annually in all age groups, driven by the decrease in the proportion with HBV [aged 15-19 (from 5.90% to 5.20%, p < 0.001); aged 20-24 (from 18.62% to 16.37%, p < 0.001); and aged 25-29 (from 28.69% to 25.28%, p < 0.001)]; from 2015 to 2019, CLD death rate for HCV (APC = +1.46%) and NAFLD (APC = +2.26%) increased. CONCLUSIONS: Over the past decade, the causes of CLD among 15-29-year-olds have shifted: viral hepatitis remains the most common cause of CLD deaths, but the global burden of HBV incidence is decreasing, whereas NAFLD is the main driver for increased CLD incidence.

Non-alcoholic fatty liver disease is associated with greater risk of 30-day hospital readmission in the United States (U.S.).

INTRODUCTION AND OBJECTIVES: Data about 30-day readmission for patients with chronic liver disease (CLD) and their contribution to CLD healthcare burden are sparse. Patterns, diagnoses, timing and predictors of 30-day readmissions for CLD from 2010-2017 were assessed. MATERIALS AND METHODS: Nationwide Readmission Database (NRD) is an all-payer, all-ages, longitudinal administrative database, representing 35 million discharges in the US population yearly. We identified unique patients discharged with CLD including hepatitis B (HBV) and C (HCV), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) from 2010 through 2017. Survey-weight adjusted multivariable analyses were used. RESULTS: From 2010 to 2017, the 30-day readmission rate for CLD decreased from 18.4% to 17.8% (p=.008), while increasing for NAFLD from 17.0% to 19. 9% (p<.001). Of 125,019 patients discharged with CLD (mean age 57.4 years, male 59.0%) in 2017, the most common liver disease was HCV (29.2%), followed by ALD (23.5%), NAFLD (17.5%), and HBV (4.3%). Readmission rates were 20.5% for ALD, 19.9% for NAFLD, 16.8% for HCV and 16.7% for HBV. Compared to other liver diseases, patients with NAFLD had significantly higher risk of 30-day readmission in clinical comorbidities adjusted model (Hazard ratio [HR]=1.08 [95% confidence interval 1.03-1.13]). In addition to ascites, hepatic encephalopathy, higher number of coexisting comorbidities, comorbidities associated with higher risk of 30-day readmission included cirrhosis for NALFD and HCV; acute kidney injury for NAFLD, HCV and ALD; HCC for HCV, and peritonitis for ALD. Cirrhosis and cirrhosis-related complications were the most common reasons for 30-day readmission, followed by sepsis. However, a large proportion of patients (43.7% for NAFLD; 28.4% for HCV, 39.0% for HBV, and 29.1% for ALD) were readmitted for extrahepatic reasons. Approximately 20% of those discharged with CLD were readmitted within 30 days but the majority of readmissions occurred within 15 days of discharge (62.8% for NAFLD, 63.7% for HCV, 74.3% for HBV, and 72.9% for ALD). Among readmitted patients, patients with NAFLD or HCV readmitted ≤30-day had significantly higher costs and risk of in-hospital mortality (NAFLD +5.69% change [95% confidence interval, 2.54%-8.93%] and odds ratio (OR)=1.58 [1.28-1.95]; HCV +9.85% change [95%CI:6.96%-12.82%] and OR=1.31, 1.08-1.59). CONCLUSIONS: Early readmissions for CLD are prevalent causing economic and clinical burden to the US healthcare system, especially NAFLD readmissions. Closer surveillance and attention to both liver and extrahepatic medical conditions immediately after CLD discharge is encouraged.

Evidence for an association of serum microanalytes and myofascial pain syndrome.

BACKGROUND: Myofascial Pain Syndrome (MPS) is a common pain disorder. Diagnostic criteria include physical findings which are often unreliable or not universally accepted. A precise biosignature may improve diagnosis and treatment effectiveness. The purpose of this study was to assess whether microanalytic assays significantly correlate with characteristic clinical findings in people with MPS. METHODS: This descriptive, prospective study included 38 participants (25 women) with greater than 3 months of myofascial pain in the upper trapezius. Assessments were performed at a university laboratory. The main outcome measures were the Beighton Index, shoulder range of motion, strength asymmetries and microanalytes: DHEA, Kynurenine, VEGF, interleukins (IL-1b, IL-2, IL-4, IL-5, IL-7, IL-8, IL-13), growth factors (IGF-1, IGF2, G-CSF, GM-CSF), MCP-1, MIP-1b, BDNF, Dopamine, Noradrenaline, NPY, and Acetylcholine. Mann-Whitney test and Spearman's multivariate correlation were applied for all variables. The Spearman's analysis results were used to generate a standard correlation matrix and heat map matrix. RESULTS: Mean age of participants was 32 years (20-61). Eight (21%) had widespread pain (Widespread Pain Index ≥ 7). Thirteen (34%) had MPS for 1-3 years, 14 (37%) 3-10 years, and 11 (29%) for > 10 years. The following showed strong correlations: IL1b,2,4,5,7,8; GM-CSF and IL 2,4,5,7; between DHEA and BDNF and between BDNF and Kynurenine, NPY and acetylcholine. The heat map analysis demonstrated strong correlations between the Beighton Index and IL 5,7, GM-CSF, DHEA. Asymmetries of shoulder and cervical spine motion and strength associated with select microanalytes. CONCLUSION: Cytokine levels significantly correlate with selected clinical assessments. This indirectly suggests possible biological relevance for understanding MPS. Correlations among some cytokine clusters; and DHEA, BDNF kynurenine, NPY, and acetylcholine may act together in MPS. These findings should be further investigated for confirmation that link these microanalytes with select clinical findings in people with MPS.

Prevalence of High and Moderate Risk Nonalcoholic Fatty Liver Disease Among Adults in the United States, 1999-2016.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) subjects with fibrosis stage ≥2 are at high risk for mortality. We aimed to provide national estimates and temporal trends for NAFLD, based on different fibrosis severity. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) (1999-2016) and NHANES III (1988-1994) were utilized. NAFLD was determined by ultrasound showing moderate to severe steatosis. For those without ultrasound, NAFLD was determined by the U.S. Fatty Liver Index score of ≥30. Hepatic fibrosis was assessed using Fibrosis-4 (FIB-4) score (FIB-4 <1.3 = low risk; FIB-4 1.3-2.67 = moderate risk; and FIB-4 >2.67 = high risk). Annual percent change (APC) was calculated by using the joinpoint regression model. RESULTS: From NHANES III, 10,854 individuals were included (mean age 43.5 years; 47.5% male; 75.7% non-Hispanic White) and 37.7% had NAFLD. Among them, based on FIB-4, 80% had low-risk, 18.6% had moderate-risk, and 1.4% had high-risk NAFLD. NAFLD with moderate or high risk was more likely to have hypertension, hyperlipidemia, diabetes, cardiovascular disease, and metabolic syndrome than was low-risk NAFLD (all P < .02). NAFLD prevalence increased from 29.5% in 1999-2000 to 40.3% in 2015-2016 (APC, 2.78%; P < .02), moderate-risk NAFLD increased from 6.26% to 14.17% (APC, 5.34%; P < .02), and high-risk NAFLD increased from 0.49% to 1.15% (APC, 9.72%; P < .02). Independent predictors of advanced fibrosis were age (OR, 1.11; 95% CI, 1.06-1.17; P = .001) and diabetes (OR, 2.28; 95% CI, 1.03-5.05; P = .04). Compared with low-risk NAFLD, high-risk NAFLD was associated with significantly increased all-cause (HR, 1.53; 95% CI, 1.09-2.15; P = .01), cardiovascular disease-specific (HR, 1.99; 95% CI, 1.22-3.24, P < .01) and liver-specific (HR, 4.57; 95% CI, 1.03-28.79; P = .04) mortality. CONCLUSIONS: The prevalence of moderate- or high-risk NAFLD is increasing and is associated with increased all-cause, liver-related, and cardiovascular mortality.

The impact of fatigue on mortality of patients with non-alcoholic fatty liver disease: Data from National Health and nutrition examination survey 2005-2010 and 2017-2018.

OBJECTIVE: Fatigue among patients with NAFLD may negatively impact their health-related quality of life and clinical outcomes (mortality). We determined fatigue prevalence and its association with all-cause mortality among patients with NAFLD. DESIGN: NHANES 2005-2010 and 2017-2018 data were used with linked mortality data. NAFLD was defined by fatty liver index for NHANES 2005-2010 and by transient elastography for NHANES 2017-2018. Fatigue was assessed by Patient Health Questionnaire. RESULTS: NHANES 2005-2010 cohort (n = 5429, mean age 47.1 years, 49.7% male, 69.9% white), 37.6% had NAFLD. Compared to non-NAFLD controls, fatigue was more common in NAFLD (8.35% vs 6.0%, p = .002). Among NHANES 2017-2018 cohort (n = 3830, mean age 48.3 years, 48.6% male, 62.3% white), 36.9% had NAFLD. Compared to non-NAFLD controls, fatigue was more common among NAFLD (8.7% vs 6.2%). NAFLD had more sleep disturbance (34.0% vs 26.7%), cardiovascular disease (CVD) (10.7% vs. 6.3%), significant hepatic fibrosis (liver stiffness>8.0 kPa, 17.9% vs 3.5%) and advanced hepatic fibrosis (>13.1 kPa, 5.4% vs 0.9%; all p < .003). The presence of depression (OR: 11.52, 95% CI: 4.45-29.80, p < .0001), CVD (OR: 3.41, 95% CI: 1.02-11.34, p = .0462) and sleep disturbance (OR: 2.00, 95% CI: 1.00-3.98, p = .0491) was independently associated with fatigue; good sleep quality (OR: 0.58, 95% CI: 0.35-0.96, p = .0366) had an inverse association. By multivariable Cox model, NAFLD adults with fatigue experienced 2.3-fold higher mortality than NAFLD without fatigue (HR: 2.31, 95% CI: 1.37-3.89, p = .002). CONCLUSIONS: Fatigue among those with NAFLD is associated with increased risk for mortality and is mainly driven by depression, sleep disturbance and CVD. These findings have important clinical implications.

Causes of death in patients with Non-alcoholic Fatty Liver Disease (NAFLD), alcoholic liver disease and chronic viral Hepatitis B and C.

INTRODUCTION AND OBJECTIVES: Cause of mortality in patients with chronic liver diseases (CLDs) may differ based on underlying etiology of liver disease. Our aim was to assess different causes of death in patients with the most common types of CLD using a national database from the United States. MATERIALS AND METHODS: Death data from 2008 and 2018 from the National Vital Statistics System (NVSS) by the National Center for Health Statistics (NCHS) were used. The rank of cause-of-death for each etiology of CLDs was assessed. Causes of death were classified by the ICD-10 codes. Liver-related deaths included liver cancer, cirrhosis and CLDs. RESULTS: Among a total of 2,826,531 deaths in 2018, there were 85,807 (3.04%) with underlying CLD (mean age at death 63.0 years, 63.8% male, 70.8% white). Liver-related mortality was the leading cause of death for all types of CLD [45.8% in non-alcoholic fatty liver disease (NAFLD), 53.0% in chronic hepatitis C (CHC), 57.8% in chronic hepatitis B (CHB), 81.8% in alcoholic liver disease (ALD)]. This was followed by death from cardiac causes (NAFLD 10.3%, CHC 9.1%, CHB 4.6%, ALD 4.2%) and extrahepatic cancer (NAFLD 7.0%, CHC 11.9%, CHB 14.9%, ALD 2.1%). Although liver cancer was the leading cause of cancer death, lung, colorectal and pancreatic cancer were also common causes of cancer death. CONCLUSIONS: Among deceased patients with CLD, underlying liver disease was the leading cause of death. Among solid cancers, liver cancer was the leading cause of cancer-related mortality.

Burden of non-alcoholic fatty liver disease in Asia, the Middle East and North Africa: Data from Global Burden of Disease 2009-2019.

BACKGROUND & AIM: Non-alcoholic fatty liver disease (NAFLD) has become a major cause of chronic liver disease (CLD) worldwide. Our aim was to assess the burden of liver complications (LC, cirrhosis and liver cancer) related to NAFLD (LC-NAFLD) between 2009-2019 in Asia and the Middle East and North Africa (MENA) region. METHODS: We used Global Burden of Disease data to assess incidence, mortality, and disability-adjusted life years (DALYs) for LC-NAFLD from Asia and the MENA region. Annual % change (APC) in rates were computed using a joinpoint regression model. Associations of LC-NAFLD with low physical activity, diet and metabolic risks were determined by partial Spearman correlation coefficients (ρ). RESULTS: Globally in 2019, there were 170,000 incident cases of LC-NAFLD, accounting for 6.6% of LC incident cases from all CLDs. There were 168,969 deaths related to LC-NAFLD, accounting for 8.6% of LC deaths from all CLDs. Asia accounted for 48.3% of the global incidence of LC-NAFLD and for 46.2% of deaths attributable to LC-NAFLD, while MENA accounted for 8.9% and 8.6%, respectively. There were 2.08 million DALYs in Asia and 340,000 DALYs in MENA. From 2009 to 2019, regions in Asia and MENA experienced a rise in DALYs attributable to LC-NAFLD (compared to LC from other CLDs), ranging from South Asia (APC = +2.12% vs. -0.94%) to high-income Asia Pacific (APC = -0.07%, p = 0.646 vs. -0.97%). In Asia, NAFLD-related DALYs were significantly correlated with dietary risks (95% CI 0.280-0.763, p = 0.004), metabolic risks (0.341-0.790, p <0.001) and tobacco use (0.134-0.691, p = 0.007). In MENA, low physical activity (0.557-0.918, p <0.001), metabolic risks (0.432-0.888, p = 0.001), and dietary risks (0.315-0.855, p = 0.001) correlated with DALYs. CONCLUSIONS: NAFLD is posing a substantial burden in Asia and MENA. About half of the global burden of LC-NAFLD is accounted for by these regions. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) has emerged as one of the most common causes of chronic liver disease worldwide. We used Global Burden of Disease data to assess the incidence, mortality, and disability-adjusted life years attributable to NAFLD-related liver complications in Asia, the Middle East and North Africa. NAFLD is poised to contribute to a substantial liver disease burden in these regions. Regional and global policies are needed to address the increasing burden of complications of NAFLD.

Changes in the Global Burden of Chronic Liver Diseases From 2012 to 2017: The Growing Impact of NAFLD.

BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and alcohol-associated liver disease (ALD) are main causes of chronic liver disease. We assessed the global incidence, mortality, and disability-adjusted life-years (DALYs) related to chronic liver disease (primary liver cancer [LC] and cirrhosis). APPROACH AND RESULTS: We obtained data from the 2017 Global Burden of Disease study. In 2017, there were 2.14 million liver-related deaths (2.06-2.30 million), representing an 11.4% increase since 2012 (16.0% increase in LC deaths; 8.7% increase in cirrhosis deaths). LC and cirrhosis accounted for 38.3% and 61.7%, respectively, of liver deaths (LC and cirrhosis deaths were related to HBV [39% and 29%], HCV [29% and 26%], ALD [16% and 25%], and NAFLD [8% and 9%]). Between 2012 and 2017, age-standardized incidence rate, age-standardized death rate (ASDR), and age-standardized DALY rate increased for LC from 11.1 to 11.8, 10.1 to 10.2, and 250.4 to 253.6 per 100,000, respectively. Although age-standardized incidence rate for cirrhosis increased from 66.0 to 66.3, ASDR and age-standardized DALY rate decreased from 17.1 to 16.5 and 532.9 to 510.7, respectively. The largest increase in ASDR for LC occurred in Eastern Europe (annual percent change [APC] = 2.18% [0.89%-3.49%]), whereas the largest decrease occurred in high-income Asia Pacific (APC = -2.88% [-3.58 to -2.18%]). ASDR for LC-NAFLD and ALD increased annually by 1.42% (1.00%-1.83%) and 0.53% (0.08-0.89), respectively, whereas there were no increases for HBV (P = 0.224) and HCV (P = 0.054). ASDR for cirrhosis-NAFLD increased (APC = 0.29% [0.01%-0.59%]) but decreased for ALD (APC = -0.44% [-0.78% to -0.40%]), HCV (APC = -0.50% [-0.81% to -0.18%]), and HBV (APC = -1.43% [-1.71% to -0.40%]). CONCLUSIONS: From 2012 to 2017, the global burden of LC and cirrhosis has increased. Viral hepatitis remains the most common cause of liver deaths, and NAFLD is the most rapidly growing contributor to liver mortality and morbidity.

Among Medicare Patients With Hepatocellular Carcinoma, Non-alcoholic Fatty Liver Disease is the Most Common Etiology and Cause of Mortality.

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.