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.

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.

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.

How to Identify Advanced Nonalcoholic Fatty Liver Disease in the Primary Care Setting.

Nonalcoholic fatty liver disease (NAFLD) affects 30 to 40% of the population globally and is increasingly considered the most common liver disease. Patients with type 2 diabetes, obesity, and cardiovascular diseases are at especially increased risk for NAFLD. Although most patients with NAFLD do not have progressive liver disease, some patients progress to cirrhosis, liver cancer, and liver mortality. Given the sheer number of patients with NAFLD, the burden of disease is enormous. Despite this large and increasing burden, identification of NAFLD patients at risk for progressive liver disease in the primary care and diabetology practice settings remains highly suboptimal. In this review, our aim is to summarize a stepwise approach to risk stratify patients with NAFLD which should help practitioners in their management of patients with NAFLD.

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.

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.

The impact of variants and vaccination on the mortality and resource utilization of hospitalized patients with COVID-19.

BACKGROUND: COVID-19 outcomes among hospitalized patients may have changed due to new variants, therapies and vaccine availability. We assessed outcomes of adults hospitalized with COVID-19 from March 2020-February 2022. METHODS: Data were retrieved from electronic health medical records of adult COVID-19 patients hospitalized in a large community health system. Duration was split into March 2020-June 2021 (pre-Delta period), July-November 2021 (Delta period), and December 2021-February 2022 (Omicron period). RESULTS: Of included patients (n = 9582), 75% were admitted during pre-Delta, 9% during Delta, 16% during Omicron period. The COVID-positive inpatients were oldest during Omicron period but had lowest rates of COVID pneumonia and resource utilization (p < 0.0001); 46% were vaccinated during Delta and 61% during Omicron period (p < 0.0001). After adjustment for demographics and comorbidities, vaccination was associated with lower inpatient mortality (OR = 0.47 (0.34-0.65), p < 0.0001). The Omicron period was independently associated with lower risk of inpatient mortality (OR = 0.61 (0.45-0.82), p = 0.0010). Vaccination and Omicron period admission were also independently associated with lower healthcare resource utilization (p < 0.05). Magnitudes of associations varied between age groups with strongest protective effects seen in younger patients. CONCLUSION: Outcomes of COVID-19 inpatients were evolving throughout the pandemic and were affected by changing demographics, virus variants, and vaccination. KEY POINT: In this observational study of almost 10,000 patients hospitalized from March 2020-February 2022 with COVID-19, age and having multiple comorbidities remained consistent risk factors for mortality regardless of the variant. Vaccination was high in our hospitalized patients. Vaccination conveyed less severe illness and was associated with lower inpatient mortality.

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.

Epidemiology of chronic liver diseases in the USA in the past three decades.

OBJECTIVE: Given significant advances in treatment of viral hepatitis and the growing epidemic of obesity, the burden of the different types of liver diseases in the USA may be changing. Our aim was to assess the shift in the prevalence of different liver disease aetiologies in the USA over the past three decades. DESIGN: National Health and Nutrition Examination Surveys (NHANES; cross-sectional 1988-1994 and 1999-2016) were used. RESULTS: A total of 58 731 adults from NHANES (1988-2016) were included. Over the study period, the prevalence of chronic hepatitis B and alcoholic liver disease remained stable: 0.3%-0.4% and 0.8%-1.0%, respectively (p>0.05). The prevalence of chronic hepatitis C decreased nearly twofold: 1.6% in 1988-1994 to 0.9% in 2013-2016 (p=0.03). In contrast, the prevalence of non-alcoholic fatty liver disease (NAFLD; by US-Fatty Liver Index) increased from 20.0% (1988-1994) to 28.3% (1999-2004) to 33.2% (2009-2012) and 31.9% (2013-2016) (p<0.0001). Furthermore, steady increases were observed in the rates of obesity (22.2% in 1988-1994 to 31.0% in 1999-2004 to 38.9% in 2013-2016), type 2 diabetes mellitus (T2DM) (from 7.2% to 8.2% to 13.5% same years), insulin resistance and hypertension (all p<0.0001). Yearly trend analyses showed that the only LD with consistently increasing prevalence was NAFLD (trend p=0.01). Multivariable regression analysis showed that obesity (OR 10.4; 95% CI 9.5 to 11.3) and T2DM (OR 3.7; 95% CI 3.2 to 4.2) were the major independent predictors of NAFLD. CONCLUSIONS: Over the past 30 years in the USA, NAFLD is the only liver disease with growing prevalence, synchronous with the increasing rates of obesity and T2DM.

Primary Biliary Cholangitis in Medicare Population: The Impact on Mortality and Resource Use.

Primary biliary cholangitis (PBC) is a disease of small bile ducts, which can lead to morbidity and mortality. Our aim was to assess recent trends in mortality and healthcare use of PBC patients in the Medicare program. Data from Medicare beneficiaries between 2005 and 2015 (5% random samples) were used. The diagnosis of PBC was established with International Classification of Diseases-9 code 571.6 used for both primary and secondary diagnoses. Mortality was assessed by Medicare-linked death registry. Healthcare use included episodes of care, length of stay, and total charges/payments. Independent predictors of outcomes were evaluated in multiple generalized linear or logistic regression models. The study cohort included a total of 6,375 inpatient/outpatient Medicare beneficiaries (mean age 69.8 years, 17% male, 88% white, and 18% with disability). Over the study period, 1-year mortality remained stable (9.1% to 14.3%, P = 0.11). Independent predictors of 1-year mortality were older age, male gender, black race, the presence of ascites, encephalopathy, hepatocellular carcinoma, and higher Charlson score. Outpatient total yearly charges and payments per beneficiary with PBC increased from $3,065 and $777 (2005) to $5,773 and $967 (2014), respectively. Similarly, inpatient total yearly charges and payments per beneficiary with PBC increased from $59,765 and $19,406 (2007), to $98,941 and $27,948 (2013), respectively (P < 0.05). The presence of ascites, portal hypertension, and higher Charlson score were independent predictors of higher payments for both inpatient and outpatient resource use, and the presence of hepatic encephalopathy was an additional predictor of higher inpatient resource use (all P < 0.02). Conclusion: The prevalence of PBC among the Medicare beneficiaries has increased. Despite stable mortality rates, resource use for Medicare patients with PBC continues to rise.

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.

Outcomes of Liver Transplant Candidates with Primary Biliary Cholangitis: The Data from the Scientific Registry of Transplant Recipients.

BACKGROUND: Primary biliary cholangitis (PBC) is progressive and can cause end-stage liver disease necessitating a liver transplant (LT). PBC patients may be disadvantaged on LT waitlist due to MELD-based priority listing or other factors. AIM: The aim was to assess waitlist duration, waitlist mortality, and post-LT outcomes of PBC patients. METHODS: The Scientific Registry of Transplant Recipients data for 1994-2016 was utilized. Adult patients with PBC without hepatocellular carcinoma (HCC) were selected. Their clinico-demographic parameters and waitlist and post-transplant outcomes were compared to those of patients with hepatitis C (HCV) without HCC. RESULTS: Out of 223,391 listings for LT in 1994-2016, 8133 (3.6%) was for PBC without HCC. Mean age was 55.5 years, 76.9% white, 86.2% female, mean MELD score 21, 6.6% retransplants. There were 52,017 patients with hepatitis C included for comparison. The mean waitlist mortality was 17.9% for PBC and 17.6% for HCV (p > 0.05). The average transplantation rate was 57.7% for PBC and 53.3% for HCV (p < 0.0001), while waitlist dropout (death or removal due to deterioration) rate was 25.0% for PBC and 25.4% for HCV (p > 0.05). There was no significant difference in median waiting duration till transplantation between PBC patients and HCV after 2002 (103 vs. 95 days, p > 0.05). Post-LT mortality and graft loss rates were significantly lower in PBC than in HCV patients (all p < 0.02). CONCLUSIONS: Despite no evidence of impaired waitlist outcomes and favorable post-transplant survival in patients with PBC, there is still a high waitlist dropout rate suggesting the presence of an unmet need for effective treatment.

The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND & AIMS: Although non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and NASH with advanced fibrosis are closely associated with type 2 diabetes mellitus (T2DM), their global prevalence rates have not been well described. Our aim was to estimate the prevalence of NAFLD, NASH, and advanced fibrosis among patients with T2DM, by regions of the world. METHODS: We searched for terms including NAFLD, NASH and T2DM in studies published from January 1989 to September 2018, using PubMed, Ovid MEDLINE®, EMBASE and Web of Science. Strict exclusion criteria were applied. Regional and global mean prevalence weighted by population size in each country were estimated and pooled using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: Among 80 studies from 20 countries that met our inclusion criteria, there were 49,419 individuals with T2DM (mean age 58.5 years, mean body mass index 27.9 kg/m2, and males 52.9%). The global prevalence of NAFLD among patients with T2DM was 55.5% (95% CI 47.3-63.7). Studies from Europe reported the highest prevalence (68.0% [62.1-73.0%]). Among 10 studies that estimated the prevalence of NASH, the global prevalence of NASH among individuals with T2DM was 37.3% (95% CI 24.7-50.0%). Seven studies estimated the prevalence of advanced fibrosis in patients with NAFLD and T2DM to be 17.0% (95% CI 7.2-34.8). Meta-regression models showed that geographic region and mean age (p <0.5) were associated with the prevalence of NAFLD, jointly accounting for 63.9% of the heterogeneity. CONCLUSIONS: This study provides the global prevalence rates for NAFLD, NASH, and advanced fibrosis in patients with T2DM. These data can be used to estimate the clinical and economic burden of NASH in patients with T2DM around the world. LAY SUMMARY: Non-alcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is an important risk factor for NAFLD. Additionally, T2DM seems to accelerate the progression of liver disease in NAFLD. Despite the high prevalence and serious clinical implications of NAFLD in patients with T2DM, it is usually overlooked in clinical practice. This meta-analysis provides evidence of the high prevalence of NAFLD and NASH in patients with T2DM. In this context, increasing awareness about the importance of NAFLD in patients with T2DM among all important stakeholders (primary care physicians, specialists, and health policy makers) must be prioritized.

Prevalence, mortality and healthcare utilization among Medicare beneficiaries with Hepatitis C in Haemodialysis units.

Hepatitis C (HCV) is more common among patients with end-stage renal disease requiring haemodialysis compared to the general population. Thus, we aimed to assess trends in prevalence, health resource utilization and mortality among Medicare beneficiaries with HCV on haemodialysis. This is a retrospective study of outpatient and inpatient claims for Medicare beneficiaries receiving haemodialysis (2005-2016). A total of 291 663 subjects on haemodialysis were included (67.3 ± 15.2 years, 55% male, 55% white, 49% age-based eligibility). The prevalence of HCV in subjects on haemodialysis was stable and was significantly higher (mean 4.2% in 2005-2016, P = 0.50 for the trend) than in subjects not on haemodialysis (<1%). In multivariate analysis, liver cirrhosis (odds ratio = 3.4 (95% CI = 3.3-3.6)) was an independent predictor of 1-year mortality among haemodialysis patients. Mean total inpatient payments in dialysis patients with HCV remained stable during 2005 ($73 803) through 2016 ($72 133) (trend P = 0.54) while mean total outpatient payment decreased from 2005 ($53 497) to 2016 ($35 439; trend P = 0.0013). In multivariate analysis, after adjustment for age, gender, race and location, both HCV and cirrhosis remained significant contributors to greater spending [HCV: inpatient +22.1% (+19.2%-25%), HCV: outpatient +18.4% (+14.6%-22.2%), cirrhosis: inpatient +59.7% (+56.9%-62.6%), cirrhosis: outpatient +9.4% (+6.2%-12.6%)]. In conclusion, HCV-infected Medicare patients receiving haemodialysis incur greater resource utilization; mortality is higher in patients with cirrhosis only. Although HCV prevalence in Medicare haemodialysis recipients is higher than in patients without haemodialysis, these rates are lower than reported, suggesting potential under-screening for HCV in this high-risk population.

Chronic kidney disease is independently associated with increased mortality in patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease and chronic kidney disease share similar pathophysiologic features. Our aim was to assess the association between different stages of chronic kidney disease and mortality in patients with nonalcoholic fatty liver disease. METHODS: Third National Health and Nutrition Examination Survey-linked mortality files were utilized. Nonalcoholic fatty liver disease was diagnosed by hepatic ultrasound and chronic kidney disease was defined according to the Kidney Disease Improving Global outcomes guideline. Multivariable Cox proportional hazard model was used to assess the effect of chronic kidney disease on overall and cardiovascular mortality. RESULTS: Total cohort included 11 695 adult participants; mean age 43.3 years, 48.4% male, 76.4% white, 18.6% had nonalcoholic fatty liver disease and 9.3% had chronic kidney disease. 5.6% had diabetes, 21.3% had hypertension, 4.3% had cardiovascular disease. Compared to subjects without chronic kidney disease or nonalcoholic fatty liver disease, nonalcoholic fatty liver disease patients with chronic kidney disease were more likely to be older, had less income, and higher prevalence of comorbidities (all P < 0.001). Prevalence of chronic kidney disease among nonalcoholic fatty liver disease cohort was 11.31%. Compared to non-nonalcoholic fatty liver disease group, patients with nonalcoholic fatty liver disease had higher rates of stage 1, 2 and 3a chronic kidney disease, but similar rates for stage 3b, 4 and 5. Mortality rate was 18.5% in 17 years. Among nonalcoholic fatty liver disease cohort, the presence of chronic kidney disease stages 2-3a (HR = 2.31, 95% CI: 1.70-3.15) and stages 3b-5 (HR = 4.83, 95% CI: 2.40-9.71) were independently associated with increased overall mortality. CONCLUSIONS: Among patients with nonalcoholic fatty liver disease, moderate to advanced stages of chronic kidney disease are associated with overall mortality. Identification of chronic kidney disease in nonalcoholic fatty liver disease has important prognostic implications.

Prevalence and outcomes of non-alcoholic fatty liver disease (NAFLD) among Asian American adults in the United States.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) affects about 25% of the general population worldwide. Although epidemiology of NAFLD is well studied in the United States, there is paucity of data for the Asian Americans. Our aim was to assess the prevalence and risk factors for NAFLD among Asian Americans. METHODS: We utilized NHANES data for 2011-2016. We defined NAFLD using recently derived US-FLI. Relative risks (RRs) and population attributable fractions (PAFs) of metabolic components on atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis were calculated for Asian Americans, and these rates were compared to non-Hispanic whites. RESULTS: NAFLD prevalence was 18.3% among Asian Americans and 28.4% among non-Hispanic whites. Asian Americans with NAFLD had lower BMI and waist circumference than non-Hispanic whites with NAFLD and were less likely to have metabolic syndrome, cardiovascular disease (CVD), chronic obstructive pulmonary disease, cancer and incident ASCVD (P < 0.05). Hyperlipidaemia had the highest attributable fraction (76.6%) for risk of ASCVD among Asian Americans with NAFLD, followed by diabetes (24.0%), current smoking (9.2%), and obesity (3.7%). Advanced fibrosis in Asian American with NAFLD was independently associated with presence of type 2 diabetes (RR = 2.70, 95% CI: 1.00-7.27). CONCLUSIONS: Asian Americans have lower prevalence of NAFLD than non-Hispanic whites. However, Asian Americans with NAFLD have similar risk factors for advanced fibrosis and ASCVD than non-Hispanic Whites.