Changes in mortality due to Chronic Liver Diseases (CLD) during the COVID-19 pandemic: Data from the United States' National Vital Statistics System.

INTRODUCTION: We assessed chronic liver disease (CLD)-related mortality in the U.S. using death data (2011-2021) obtained from National Vital Statistics System (NVSS). The average annual percentage change (AAPC) from the models selected by Joinpoint regression analysis over the pre-pandemic (2011-2019) and the 2019-2021 were reported because non-linear trend in death rates were observed over the 2011-2021. Liver-specific death was defined as an underlying cause of death and Chronic liver disease (CLD)-related death was defined as any cause of death. During the pre-pandemic, age-standardized HCC- and cirrhosis-specific death rates were annually increased by AAPC = +1.18% (95% confidence interval, 0.34% to 2.03%) and AAPC = +1.95% (1.56% to 2.35%). In contrast, during the 2019-2021, the AAPC in age-standardized cirrhosis-specific death rate (per 100,000) accelerated by up to AAPC +11.25% (15.23 in 2019 to 18.86 in 2021) whereas that in age-standardized HCC-specific death rate slowed to -0.39 (-1.32% to 0.54%) (3.86 in 2019 to 3.84 in 2021). Compared to HCC-specific deaths, cirrhosis-specific deaths were more likely to be non-Hispanic white (72.4% vs. 62.0%) and non-Hispanic American Indian and Alaska native (AIAN) (2.2% vs. 1.1%) and have NAFLD (45.3% vs. 12.5%) and ALD (27.6% vs. 22.0%). During the 2019-2021, the age-standardized HCV- and HBV-related death rate stabilized, whereas the age-standardized NAFLD- and ALD-related deaths rate increased to 20.16 in 2021 (AAPC = +12.13% [7.76% to 16.68%]) and to 14.95 in 2021 (AAPC = +18.30% [13.76% to 23.03%]), which were in contrast to much smaller incremental increases during the pre-pandemic (AAPC = +1.82% [1.29% to 2.35%] and AAPC = +4.54% [3.97% to 5.11%]), respectively). The most pronounced rise in the age-standardized NAFLD-related death rates during the pandemic was observed among AIAN (AAPC = +25.38%), followed by non-Hispanic White female (AAPC = +14.28%), whereas the age-standardized ALD-related death rates during the pandemic were highest among AIAN (AAPC = +40.65%), followed by non-Hispanic Black female (AAPC = +26.79%). CONCLUSIONS: COVID-19 pandemic had a major negative impact on cirrhosis-specific and CLD-related mortality in the U.S. with significant racial and gender disparities.

The burden of metabolic dysfunction-associated steatotic liver disease and viral hepatitis in Saudi Arabia.

BACKGROUND: Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is increasing. We assessed the burden and trends of MASLD and viral hepatitis in Saudi Arabia. METHODS: Prevalence, death, and disability data due to MASLD, hepatitis C virus (HCV), and hepatitis B virus (HBV) were obtained from 2019 Global Burden of Disease (GBD) database for Saudi Arabia. Time trends were assessed by annual percent change (APC) from joinpoint regression. RESULTS: From 2012 through 2019, MASLD prevalence in children and adults increased from 28.02% ( n = 8.34 million) to 33.11% ( n = 11.83 million); APC +2.43% (95% confidence interval: 2.33% to 2.54%). HBV prevalence decreased from 1.83% ( n = 0.54 million) to 1.53% ( n = 0.55 million); APC -1.74% (-2.66% to -0.81%). HCV prevalence stabilized from 0.72% ( n = 0.21 million) to 0.73% ( n = 0.26 million): APC +0.32% (-0.13% to 0.78%). Among adults (>20 years), MASLD prevalence increased from 40.64% to 43.95% (APC = +1.15%, 1.12% to 1.18%), HBV prevalence decreased from 2.67% to 2.05% (APC = -2.96%, -3.90% to -2.01%), and HCV leveled from 0.88% to 0.86% (APC = -0.30%, -0.75% to 0.16%). MASLD liver mortality rate from liver cancer and cirrhosis increased: APC of +1.15% (0.82% to 1.48%) from 1.31 to 1.43 (per 100,000). HBV and HCV liver mortality increased at slower rates (APC = +0.78%, 0.38% to 1.19%): 2.07 to 2.20 (per 100,000) and (APC = +0.55%, 0.09% to 0.89%): 6.32 to 6.61 (per 100,000), respectively. CONCLUSIONS: MASLD burden is increasing, while HBV and HCV burden is decreasing/remaining stable. Early prevention and diagnosis health policies for MASLD are needed.

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.

Nonalcoholic fatty liver disease (NAFLD) and associated mortality in individuals with type 2 diabetes, pre-diabetes, metabolically unhealthy, and metabolically healthy individuals in the United States.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) is high among subjects with type 2 diabetes (T2D). However, the prevalence and outcomes of NAFLD among individuals with pre-diabetes (PreD) and metabolically healthy and metabolically unhealthy individuals without T2D are not known. Our aim was to assess prevalence and mortality of NAFLD among these four groups. METHODS: The Third National Health and Nutrition Examination Survey (NHANES) III (1988-1994) with mortality data (follow up to 2019) via linkage to the National Death Index was utilized. NAFLD was defined by ultrasound and absence of other liver diseases and excess alcohol use. Pre-D was defined as fasting plasma glucose values of 100-125 mg/dL and/or HbA1c level between 5.7 %-6.4 % in the absence of established diagnosis of T2D. Metabolically healthy (MH) was defined if all of the following criteria were absent: waist circumference of ≥102 cm (men) or ≥ 88 cm (women) or BMI of ≥30; blood pressure (BP) ≥ 130/85 mmHg or using BP-lowering medication; triglyceride level ≥ 150 mg/dL or using lipid-lowering medication; lipoprotein cholesterol level of <40 mg/dL (men) or < 50 mg/dL (women); homeostasis model assessment of insulin resistance (HOMA-IR) score ≥ 2.5; C-reactive protein (CRP) level of >2 mg/L; Pre-D and T2D. Metabolically unhealthy (MU) individuals were defined as the presence of any component of metabolic syndrome but not having Pre-D and T2D. Competing risk analyses of cause-specific mortality were performed. FINDINGS: 11,231 adults (20-74y) were included: mean age 43.4 years; 43.9 % male; 75.4 % white, 10.8 % Black, and 5.4 % Mexican American, 18.9 % NAFLD, 7.8 % T2D; 24.7 % PreD; 44.3 % MU; and 23.3 % in MH individuals. In multivariable adjusted logistic model, as compared to MH individuals, the highest risk of having NAFLD were in T2D individuals (Odd Ratio [OR] = 10.88 [95 % confidence interval: 7.33-16.16]), followed by Pre-D (OR = 4.19 [3.02-5.81]), and MU (OR = 3.36 [2.39-4.71]). During a median follow up of 26.7 years (21.2-28.7 years), 3982 died. NAFLD subjects had significantly higher age-adjusted mortality than non-NAFLD (32.7 % vs. 28.7 %, p < .001). Among subjects with NAFLD, the highest age-standardized cumulative mortality was observed among those with T2D (41.3 %), followed by with Pre-D (35.1 %), MU subjects (30.0 %), and MH subjects (21.9 %) (pairwise p-values<.04 vs. MH). Multivariable adjusted cox models showed that NAFLD with T2D had a higher risk of all-causes and cardiac-specific deaths (Hazard Ratio [HR] = 4.71 [2.23-9.96] and HR = 20.01 [3.00-133.61]), followed by NAFLD with Pre-D (HR = 2.91 [1.41-6.02] and HR = 10.35 [1.57-68.08]) and metabolically unhealthy NAFLD (HR = 2.59 [1.26-5.33] and HR = 6.74 [0.99-46.03]) compared to metabolically healthy NAFLD. In addition to older age, independent predictors of mortality among NAFLD with T2D included high CRP, CVD, CKD, high FIB-4, and active smoking. Similarly, among NAFLD with PreD, high CRP, CKD, CVD, hypertension, and active smoking were associated with mortality. Finally, CVD and active smoking were predictors of mortality among metabolically unhealthy NAFLD, and active smoking was the only mortality risk among metabolically healthy NAFLD subjects. INTERPRETATION: Metabolic abnormality impacts both prevalence and outcomes of subjects with NAFLD.

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.

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.

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.

Vigorous physical activity provides protection against all-cause deaths among adults patients with nonalcoholic fatty liver disease (NAFLD).

BACKGROUND: Mortality benefits of vigorous leisure time physical activity (LTPA) among adults with NAFLD is not known. AIM: To investigate association between LTPA and reduction in all-cause mortality among adults with NAFLD. METHODS: We used NHANES (1999-2006) self-reported PA data for adults (≥40 years) with mortality follow-up through December 31, 2015. US-Fatty Liver Index in absence of secondary causes identified NAFLD. Moderate and vigorous LTPA were calculated by the 2018 PA Guidelines for Americans. RESULTS: NAFLD prevalence among 5211 adults (46.2% male; 75.8% white; mean age 53.2 years) was 32.7%. Adults with NAFLD were less likely to report the recommended minimal PA (≥ 150 min/week, 55.5% vs 64.8%) or highly active PA (≥300 min/week, 39.2% vs 48.5%) compared to adults without NAFLD. Over a median follow-up of 12.3 years, 355 deaths among adults with NAFLD and 510 deaths among adults without NAFLD were registered. In the metabolic comorbidities-adjusted model, adults with NAFLD who reported ≥50% of their total PA as vigorous activity had a 56% reduction in all-cause mortality risk (HR:0.44, 95%CI: 0.25-0.76) and cancer-specific mortality risk (HR: 0.21, 0.06-0.66) but not cardiac-specific mortality (p > 0.05) compared to adults with NAFLD who did not report any LTPA. This association remained significant even among adults with NAFLD who met the recommended minimal PA, among adults with NAFLD who reported any LTPA, and among adults with NAFLD who had metabolic abnormalities and in sensitivity analysis. CONCLUSIONS: Engaging in vigorous activity is beneficial for adults with NAFLD - especially those with metabolic abnormalities.

Sarcopenia, healthy living, and mortality in patients with chronic 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.

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.

The impact of hepatocellular carcinoma diagnosis on patients' health-related quality of life.

BACKGROUND: Patients with hepatocellular cancer (HCC) are known to have worse health-related quality of life (HRQL) than the general population. However, the change in HRQL from before the diagnosis to after diagnosis remains unknown and is difficult to estimate. We aimed to compare HCC cases with matched controls to evaluate the differences in change in HRQL from before to after HCC diagnosis. METHODS: We performed propensity score-matched analysis using the self-reported HRQL data from the Surveillance, Epidemiology, and End Results registries (SEER) data linked with Medicare Health Outcomes Survey (MHOS) data (1998-2014). Cases were selected as Medicare beneficiaries (aged ≥65 years) who were diagnosed with HCC between their baseline assessment and follow-up assessment. Matched controls were selected from the same data resource and the same time period to include subjects without cancer diagnosis by propensity scores. HRQL was assessed using the Medical Outcomes Study Short Form-36 (SF-36). RESULTS: The study included 62 subjects who developed HCC and 365 matched controls. Compared to their baseline HRQL scores, after diagnosis of HCC, subjects were more likely to report declines in scores related to the mental component of HRQL. When stratified by time since diagnosis, mental component remained significantly lower as the disease advanced. In contrast, only general health aspects of physical health worsened after HCC diagnosis. CONCLUSIONS: Diagnosis of HCC has a profound negative impact on patients' HRQL. Mental health component deteriorated significantly over time. The need of including mental health services within a multidisciplinary HCC care model is clearly evident.

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.

The Growing Burden of Disability Related to Chronic Liver Disease in the United States: Data From the Global Burden of Disease Study 2007-2017.

Chronic liver disease (CLD) causes significant morbidity and mortality in the United States with regional variations. Comparable and consistent state-level measures of CLD-related morbidity and disability among U.S. states have not been well studied. Our aim was to assess the CLD burden within the United States between 2007 and 2017 based on the most common causes of CLD: hepatitis B virus, hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). The Global Burden of Disease database was used for the years 2007-2017. International Classification of Diseases, Tenth Revision, codes were used to identify liver cancer (LC) and cirrhosis. Disability-adjusted life years (DALYs) were computed by the summation of years of life lost and years lived with disability. All rates reported here were age-standardized rates per 100,000 population. In 2017, there were 167,324 incident CLDs, 21% from LC and 79% from cirrhosis; this number was 30% higher than in 2007. The highest rate increases were seen in Kentucky, New York, and Pennsylvania. In 2017, there were 90,046 CLD-related deaths, which was 34% higher than in 2007. Highest rank increases were seen in Kentucky, Montana, and Washington. The rate of CLD incidence and death due to NAFLD was higher than other causes of CLD. In 2017, CLD caused 2.33 million DALYs, which was 27% higher than in 2007 and was mainly driven by HCV (37.2%), ALD (27.7%), and NAFLD (10.6%). California, Texas, and Florida had the highest DALYs; however, the highest CLD-DALY rates per 100,000 population were seen in New Mexico, District of Columbia, and Oklahoma. Conclusion: The CLD-related burden is increasing in the majority of U.S. states at an unprecedented rate. The impact of this burden on individual states is heterogeneous, and there are important disparities among states that merit further investigation.

Hospice care utilisation among elderly patients who died with hepatocellular carcinoma in the United States.

BACKGROUND & AIMS: The benefits of hospice care in Medicare recipients with hepatocellular carcinoma (HCC) have not been fully evaluated, which we aimed to study. METHODS: We used nationally representative samples of the Medicare beneficiaries in the USA (2011-2016) to assess the impact of hospice care on the outcomes of patients with HCC. Hospice care benefits on the survival time, length of stay (LOS), 30-day readmissions, and daily charges during the last year and month of life were assessed by logistic regression and generalised linear regression. RESULTS: Among 2,230 Medicare beneficiaries with HCC (mean age, 74.9 years; non-Hispanic White 79.1%; male 66.6%), median survival from HCC diagnosis was 68 days; 556 (24.9%) received hospice services; median hospice LOS was 12 days (4-35 days). Hospice users increased from 20.1% to 31.1% over time, driven by enrolment ≤15 days (45.1-59.2%, respectively). In the last year of life, hospice users (vs. no hospice care) had longer median survival time (76.5 vs. 66 days), lower in-hospital mortality (1.1% vs. 25.5%) and lower median daily charges ($951 vs. $1,004) despite more inpatient admissions and higher comorbid diseases. Hospice enrolment was associated with 48.6% reduction in daily charges (95% CI: -54.9% to -41.5%). Longer hospice LOS was associated with lower rates of healthcare utilisation. Patients with chronic liver disease were less likely to enrol in hospice care (odds ratio = 0.18, 95% CI: 0.14-0.24). CONCLUSIONS: Although hospice provides a significant decrease in healthcare utilisation and some benefit in survival, most care is given in the last 2 weeks of life. Efforts to encourage earlier use of hospice services must continue. LAY SUMMARY: The purpose of hospice care is to provide comfort and lessen suffering at the end of life. Hospice care allows one to die outside the hospital environment which is the wish of most people. However, we found that among persons aged 65 years and older who were diagnosed with liver cancer (which has a poor prognosis), only 25% were enrolled in hospice care and the majority used a hospice only in the last weeks of life. This is a disheartening finding as liver cancer patients with longer hospice enrolment had lower costs and improved survival. We suggest that healthcare practitioners consider discussion of palliative and hospice care routinely with patients suffering from liver cancer.

Performance of Noninvasive Liver Fibrosis Tests in Morbidly Obese Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in morbidly obese patients, and fibrosis is an independent predictor of mortality. Noninvasive tests (NITs) are being developed for the detection of advanced fibrosis (AF). PURPOSE: To assess the performance of three NITs (NAFLD fibrosis score, NFS, fibrosis-4 index, FIB-4, and aspartate aminotransferase-to-platelet ratio, APRI), in the identification of AF among morbidly obese patients. MATERIALS AND METHODS: Patients, who underwent bariatric surgery between 2004 and 2009 and had liver biopsy, were included. Fibrosis stages ≥ F2 and ≥ F3 were defined as significant and AF, respectively. Published and optimal thresholds (Youden index) for NFS, FIB-4 and APRI, sensitivity, specificity, positive and negative predictive values (PPV-NPV), and area under the receiver operator curves (AUROC) were evaluated. RESULTS: Among 584 patients (mean age 43.3 ± 11.3 years, 21.2% male, 75% white, mean BMI 45.5 ± 8.80), 31.7% had NASH. Stages distributions were F1 = 68.1%, F2 = 16.4%, F3 = 8%, and F4 = 3.2%. At published thresholds, all 3 NITs performed poorly for detection of AF, with AUROC < 0.62. Overall performance at optimal thresholds improved to 0.68, 0.72, and 0.74 for NFS, FIB-4, and APRI, respectively. At optimal thresholds, all tests had good NPV (94.4-95.9%) but low PPV (24.2-32.5%). Combinations of the tests did not improve their performance. CONCLUSIONS: NFS, FIB-4, and APRI fall short to detect advanced fibrosis but valuable for excluding advanced fibrosis. More research is needed to develop new NITs with high positive predictive value.

The Growing Burden of Disability Related to Nonalcoholic Fatty Liver Disease: Data From the Global Burden of Disease 2007-2017.

Chronic liver disease (CLD) is a growing cause of morbidity and mortality worldwide. The burden of CLD varies according to etiology and geographic location. We assessed the global burden of disability from the most important complications of CLD (cirrhosis and liver cancer [LC]) according to the most common etiologies between 2007 and 2017. We obtained years living with disability (YLD), years of life lost (YLL), and disability-adjusted life-years (DALYs) data from the Global Burden of Disease 2017 study. Between 2007 and 2017, LC DALYs decreased by 4.52% and cirrhosis DALYs decreased by 10.58%. Nevertheless, in 2017, CLD caused 62.16 million DALYs (33.4% LC and 66.5% cirrhosis), of which 96.8% came from YLL (34.1% LC and 65.9% cirrhosis) and 3.2% from YLD (11.6% LC and 88.4% cirrhosis). In 2017, Asia accounted for 66% of all DALYs globally. Central Asia, Africa regions, Southeast Asia, and Eastern Europe had the highest liver-related DALYs (≥1,000 per 100,000), whereas the lowest rates (≤500 per 100,000) were seen in high-income regions, such as Asia Pacific, North America, Western Europe, and Australasia. In 2007, hepatitis B virus caused the majority (47.5%) of liver-related DALYs, followed by hepatitis C virus (23.7%), alcoholic liver disease (14.2%), and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) (6.4%). In 2017, these rates shifted to 45.7%, 24.1%, 4.8%, and 7.1%, respectively. Between 2007 and 2017, cirrhosis-related DALYs due to NAFLD/NASH increased by 23.4%, whereas the increment was 37.5% for LC-related DALYs due to NAFLD/NASH. Conclusion: DALYs due to viral hepatitis still account for the largest proportion of CLD-related DALYs. Although DALYs from all other liver diseases have remained stable in the last decade, DALYs related to NAFLD/NASH are growing. National, regional, and global policies are needed to address the disability burden of NAFLD across the world.

Contribution of sarcopenia and physical inactivity to mortality in people with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Physical inactivity and sedentary lifestyle have contributed to the epidemic of obesity and non-alcoholic fatty liver disease (NAFLD). We assessed the association between physical activity, NAFLD, and sarcopenia, and their contributions to mortality. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 with Linked Mortality file (through 2015) was utilised. NAFLD was determined by the US Fatty Liver Index in the absence of secondary causes of liver disease. Sarcopenia was defined using appendicular lean mass divided by body mass index by the Foundation for the National Institutes of Health criteria. Activity level was determined using standard self-reports. Publicly available imputed dual-energy X-ray absorptiometry data sets were used. RESULTS: Of 4,611 NHANES participants (48.2% males; 72.5% White; mean age 45.9 years), NAFLD was present in 1,351 (29.3%), of whom 17.7% had sarcopenia. Of the NAFLD group, 46.3% was inactive, whilst intermediate and ideal physical activity rates were observed in 14.2% and 39.5%, respectively. Sarcopenia was significantly and inversely related to higher physical activity level, both amongst NAFLD (odds ratio [OR] = 0.45 [95% CI 0.30-0.69]) and non-NAFLD (OR = 0.51 [0.35-0.75]) groups. During a median follow-up of 13.5 years, a total of 586 subjects died, of whom 251 had NAFLD. Amongst those who died with NAFLD, 33.0% had sarcopenia and 54.3% were inactive. Compared with NAFLD without sarcopenia, NAFLD with sarcopenia was associated with a higher risk of all-cause (hazard ratio [HR] = 1.78 [1.16-2.73]), cardiac-specific (HR = 3.19 [1.17-8.74]), and cancer-specific mortality (HR = 2.12 [1.08-4.15]). CONCLUSIONS: Inactivity is associated with presence of sarcopenia, whilst sarcopenia is associated with increased mortality amongst NAFLD patients. Sarcopenia should be a part of clinical assessment of patients with NAFLD. Treatment of NAFLD should include optimal management of sarcopenia. LAY SUMMARY: Nonalcoholic fatty liver disease (NAFLD) and sarcopenia have similar pathophysiological profiles. Our data show that sarcopenia is associated with inactivity in subjects with NAFLD. The presence of sarcopenia in patients with NAFLD poses increased risk for all-cause and cardiac-specific mortality.