The burden of nonalcoholic fatty liver disease (NAFLD) is rapidly growing in every region of the world from 1990 to 2019.

BACKGROUND: The latest meta-analyses suggest NAFLD is increasing globally. Its limitations may preclude accurate estimates. We evaluated the global NAFLD burden and its' trends in prevalence and NAFLD liver-related mortality (LRM) by sex, age, region, and country over the past 3 decades using data from the Global Burden of Disease (GBD) 2019 study. METHODS: Crude and age-standardized NAFLD prevalence and NAFLD-LRM rates were obtained for all-age individuals with NAFLD from 204 countries/territories between 1990 and 2019. Joinpoint trend analysis assessed time trends. Weighted average of the annual percent change (APC) over the period 1990-2019 and 2010-2019 were reported. RESULTS: All-age (children and adults) crude global NAFLD prevalence increased:10.5% (561 million)-16.0% (1,236 million); an APC increase: + 1.47% (95% CI, 1.44%, 1.50%). Among adults (+20 y), crude NAFLD prevalence increased (1990: 17.6%, 2019:23.4%; APC: + 1.00%, 95% CI: 0.97%, 1.02%). In all-age groups, the crude NAFLD-LRM rate (per 100,000) increased (1990: 1.75%, 2019: 2.18%; APC: + 0.77% (95% CI, 0.70%, 0.84%). By Joinpoint analysis, from 2010 to 2019, worsening all-age trends in NAFLD prevalence and LRM were observed among 202 and 167 countries, respectively. In 2019, there were 1.24 billion NAFLD prevalent cases and 168,969 associated deaths; Asia regions accounted for 57.2% of all-age prevalent cases and 46.2% of all-age NAFLD-LRM. The highest all-age crude NAFLD prevalence rate was the Middle East and North Africa (LRM 26.5%); the highest all-age crude NAFLD-LRM rate was Central Latin America (5.90 per 100,000). CONCLUSIONS: NAFLD is increasing globally in all-age groups-over 80% of countries experienced an increase in NAFLD and NAFLD-LRM. These data have important policy implications for affected countries and for global health.

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 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.

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.

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.

The Impact of NASH to Liver Transplantations With Hepatocellular Carcinoma in the United States.

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide.1,2 It is believed that about one fourth of the world population may have NAFLD.3 The Global Burden of Disease data suggest that NAFLD and nonalcoholic steatohepatitis (NASH) are the main drivers of liver disease burden in most regions of the world, including that of hepatocellular carcinoma (HCC).4,5.

Dietary Risks for Liver Mortality in NAFLD: Global Burden of Disease Data.

Nonalcoholic fatty liver disease (NAFLD) is a common but complex chronic liver disease, driven by environmental and genetic factors. We assessed metabolic and dietary risk factor associations with NAFLD liver mortality using the Global Burden of Disease (GBD) 2017 data. NAFLD liver deaths were calculated (per 100,000) as age-standardized rates (ASRs) from 195 countries and territories (21 GBD regions; 7 GBD superregions). Dietary risks included low intake of fruits, vegetables, legumes, whole grains, nuts/seeds, milk, fiber, calcium, seafood omega-3 fatty acids, and polyunsaturated fatty acids, and high intake of red meat, processed meat, sugar-sweetened beverages, trans fatty acids, and sodium. Metabolic risks included high low-density lipoprotein cholesterol, systolic blood pressure (BP), fasting glucose (FG), body mass index (BMI), as well as low bone mineral density and impaired kidney function (IKF). Socio-demographic index (SDI)-adjusted partial Spearman correlation coefficients and multivariable generalized linear regression models/bidirectional stepwise selection (significance level for entry, 0.2; for stay, 0.05) determined the associations. The ASR for NAFLD liver deaths was 2.3 per 100,000 (2017) and correlated with dietary risk factors (0.131, -0.010-0.267) and metabolic risk factors (SDI-adjusted = 0.225, 95% CI 0.086-0.354). High intake of sugar-sweetened beverages and red meat (0.358, 0.229-0.475; 0.162, 0.022-0.296), and low intake of nuts/seed and milk (0.154, 0.014-0.289; 0.145, 0.004-0.280) was significant for NAFLD liver deaths. Other risk factors for liver death included IKF (0.402, 0.276-0.514), increased BMI (0.353, 0.223-0.407), FG (0.248, 0.111-0.376), and BP (0.163, 0.022-0.297). High intake of trans fatty acids (2.84% increase [1.65%-4.03%]) was the largest associated risk of NAFLD liver deaths. In addition to metabolic risks, dietary risks independently drive the global burden of NAFLD-related liver mortality. Conclusion: These data provide additional support for policies to improve dietary environment for NAFLD burden reduction.

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.

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.

Mortality of NAFLD According to the Body Composition and Presence of Metabolic Abnormalities.

Although nonalcoholic fatty liver disease (NAFLD) is associated with obesity, it can also occur in lean and metabolically normal individuals. Our aim was to determine the effect of different combinations of abdominal adiposity and overall adiposity on the mortality of NAFLD. The Third National Health and Nutrition Examination Survey with mortality data from the National Death Index were used. NAFLD was defined as steatosis without other liver diseases. Body composition was categorized according to waist circumference (WC) and body mass index (BMI). Obesity pattern was defined according to BMI (lean, overweight, and obese) and WC (normal and obese) using accepted definitions. The "metabolically abnormal" group had visceral obesity, insulin resistance, type 2 diabetes, hypertension, or hyperlipidemia. Of the 9,341 study individuals (47.9% male; 76.8% white), NAFLD was present in 3,140 (33.6%), of whom 0.6% had lean BMI and normal WC, and 1.7% had lean BMI and obese WC. The prevalence of metabolically normal NAFLD was 3.26% (95% confidence interval [CI]: 2.62%-3.90%), with most of these subjects having lean BMI (79.2%). During an average follow-up of 22.4 years, 24.1% of the subjects died from all causes. Among these deceased individuals, 41.7% had NAFLD at baseline. Causes of death were cardiovascular disease (24.8%), cancer-related (24.3%), type 2 diabetes-related (4.4%), and liver-related (1.7%). Individuals with NAFLD who were lean by BMI but obese by WC had higher risk of all-cause mortality. Individuals with NAFLD with normal BMI but obese WC had a higher risk of cardiovascular mortality (hazard ratio 2.63 [95% CI: 1.15-6.01]) as compared with overweight (by BMI) NAFLD with normal WC. Conclusion: The risk of mortality in NAFLD can be affected by the presence of visceral obesity, especially in the lean BMI group. These data have important management implications for patients with 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.

In an era of highly effective treatment, hepatitis C screening of the United States general population should be considered.

BACKGROUND & AIMS: Hepatitis C virus (HCV) treatment with all oral direct acting antiviral agents (DAA's) achieve sustained virologic response (SVR) rates of 98%. Re-assessment of general US population screening for HCV is imperative. This study compared the cost-effectiveness (CE) of three HCV screening strategies: screen all (SA), screen Birth Cohort (BCS), and screen high risks (HRS). METHODS: Using a previous designed decision-analytic Markov model, estimations of the natural history of HCV and CE evaluation of the three HCV screening strategies over a lifetime horizon in the US population was undertaken. Based on age and risk status, 16 cohorts were modelled. Health states included: Fibrosis stages 0 to 4, decompensated cirrhosis, hepatocellular carcinoma, LT, post-LT, and death. The probability of liver disease progression was based on the presence or absence of virus. Treatment was with approved all-oral DAAs; 86% were assumed to be seen annually by a primary care provider; SVR rates, transition probabilities, utilities, and costs were from the literature. One-way sensitivity analyses tested the impact of key model drivers. RESULTS: SA cost $272.0 billion [$135 279 per patient] and led to 12.19 QALYs per patient. BCS and HRS cost $274.5 billion ($136 568 per patient) and $284.5 billion ($141 502 per patient) with 11.65 and 11.25 QALYs per patient respectively. Compared to BCS, SA led to an additional 0.54 QALYs per patient and saved $2.59 billion; compared to HRS, SA led to 0.95 additional QALYs per patient and saved $12.5 billion. CONCLUSIONS: Screening the entire US population and treating active viraemia was projected as cost-saving.

The economic and clinical burden of nonalcoholic fatty liver disease in the United States and Europe.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. There is uncertainty around the economic burden of NAFLD. We constructed a steady-state prevalence model to quantify this burden in the United States and Europe. Five models were constructed to estimate the burden of NAFLD in the United States and four European countries. Models were built using a series of interlinked Markov chains, each representing age increments of the NAFLD and the general populations. Incidence and remission rates were calculated by calibrating against real-world prevalence rates. The data were validated using a computerized disease model called DisMod II. NAFLD patients transitioned between nine health states (nonalcoholic fatty liver, nonalcoholic steatohepatitis [NASH], NASH-fibrosis, NASH-compensated cirrhosis, NASH-decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, post-liver transplant, and death). Transition probabilities were sourced from the literature and calibrated against real-world data. Utilities were obtained from NAFLD patients using the Short Form-6D. Costs were sourced from the literature and local fee schedules. In the United States, over 64 million people are projected to have NAFLD, with annual direct medical costs of about $103 billion ($1,613 per patient). In the Europe-4 countries (Germany, France, Italy, and United Kingdom), there are ∼52 million people with NAFLD with an annual cost of about €35 billion (from €354 to €1,163 per patient). Costs are highest in patients aged 45-65. The burden is significantly higher when societal costs are included. CONCLUSION: The analysis quantifies the enormity of the clinical and economic burdens of NAFLD, which will likely increase as the incidence of NAFLD continues to rise. (Hepatology 2016;64:1577-1586).

Adherence to treatment of chronic hepatitis C: from interferon containing regimens to interferon and ribavirin free regimens.

Patients' experience during treatment may affect treatment adherence. Our aim was to assess the impact of patient-reported outcomes (PROs) on adherence to different anti-hepatitis C virus (HCV) regimens.Clinical, demographic, and PRO data (short form-36 [SF-36], chronic liver disease questionnaire-hepatitis C version [CLDQ-HCV], functional assessment of chronic illness therapy-fatigue [FACIT-F], work productivity and activity impairment: specific health problem [WPAI:SHP]) from 13 multinational clinical trials of anti-HCV treatment were available. Treatment adherence was defined as >80% of prescribed doses taken.Included were 4825 HCV patients. Regimens were grouped into: interferon- and ribavirin (RBV)-containing (±sofosbuvir [SOF]), interferon-free RBV-containing (RBV + SOF ±â€Šledipasvir [LDV]), and interferon-free RBV-free (LDV/SOF). The adherence to these regimens were 77.6%, 84.3%, and 96.2%, respectively (P < 0.0001). Nonadherent patients were more likely to be unemployed and to have a greater PRO impairment at baseline (up to -5.3% lower PRO scores, P < 0.0001). During treatment with interferon- or RBV-based regimens, nonadherent patients experienced lower PROs and had larger decrements from their baseline PRO scores. In contrast, there were no significant declines in PRO scores (all P > 0.05) for the small number of patients who were nonadherent to LDV/SOF. In multivariate analysis, being treatment-naive, longer treatment duration, and receiving an interferon- or RBV-containing regimen were associated with a lower likelihood of adherence (all P < 0.003). Better baseline and on-treatment PRO scores were associated with a higher likelihood of adherence to interferon and RBV.The use of interferon and/or RBV, longer duration of treatment, and lower baseline and on-treatment PRO scores were linked to a decreased likelihood of being adherent to interferon + RBV-containing or interferon-free RBV-containing antiviral regimens. Interferon- and RBV-free regimens were associated with excellent adherence.

Nonalcoholic fatty liver disease in lean individuals in the United States.

The presence of hepatic steatosis in individuals without a known cause of chronic liver disease, including excessive alcohol consumption, is the hallmark of nonalcoholic fatty liver disease (NAFLD). Although NAFLD is usually associated with obesity, nonobese patients can also present with NAFLD ("lean NAFLD"). Our objective was to determine factors independently associated with lean NAFLD in the United States population. For this purpose, we used data from National Health and Nutrition Examination Survey III (NHANES III) conducted between 1988 and 1994 with available hepatic ultrasound, clinico-demographic, and laboratory data. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by ultrasound), the absence of excessive alcohol use (>20 g/d in men and 10 g/d in women), hepatitis B surface antigen(-), and hepatitis C antibody(-). Nonalcoholic steatohepatitis (NASH) was defined as having moderate-severe steatosis and elevated aminotransferases in the presence of type 2 diabetes or insulin resistance (IR). Logistic regression was used to identify independent predictors of lean NAFLD. As a result, of the 11,613 participants included in the study, 2185 (18.77% ± 0.76%) had NAFLD; of these, 307 (11.78% ± 1.03%) had NASH. Multivariate analysis showed that lean NAFLD was independently associated with younger age, female sex, and a decreased likelihood of having IR and hypercholesterolemia (p values < 0.05). Additionally, multivariate analysis showed that NASH was independently associated with being Hispanic, having a younger age, and having components of metabolic syndrome such as hypertension (p values < 0.05). Therefore, we conclude that lean individuals with NAFLD have a different clinical profile than overweight-obese individuals with NAFLD. Furthermore, patients with NASH are commonly Hispanic and have components of metabolic syndrome.

Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008.

BACKGROUND & AIMS: Chronic liver diseases (CLDs) are major causes of morbidity and mortality worldwide. We assessed changes in the prevalence of different types of CLD in the United States. METHODS: National Health and Nutrition Examination Surveys conducted between 1988 and 2008 were used to estimate changes in the prevalence and predictors of CLDs. Serologic and clinical data were used to establish the diagnoses of CLDs in 39,500 adults. Statistical analyses were conducted with SUDAAN 10.0 (SAS Institute, Inc, Cary, NC). RESULTS: The prevalence rates for CLD were 11.78% (1988-1994), 15.66% (1999-2004), and 14.78% (2005-2008). During the same period, the prevalence of hepatitis B virus infection (0.36%, 0.33%, and 0.34%), hepatitis C virus (1.95%, 1.97%, and 1.68%), and alcoholic liver disease (1.38%, 2.21%, and 2.05%) remained generally stable. In contrast, the prevalence of nonalcoholic fatty liver disease (NAFLD) increased from 5.51% to 9.84% to 11.01%. From 1988 to 1994, NAFLD accounted for 46.8% of CLD cases; from 1994 to 2004 its prevalence increased to 62.84%, and then to 75.1% from 2005 to 2008. During these time periods, steady increases were observed in obesity (21.74%, 30.02%, and 33.22%), visceral obesity (35.18%, 48.16%, and 51.43%), type II diabetes (5.55%, 7.88%, and 9.11%), insulin resistance (23.29%, 32.50%, and 35.00%), and hypertension (22.68%, 33.11%, and 34.08%). A multivariate analysis showed that during all time periods, obesity was an independent predictor of NAFLD. CONCLUSIONS: National Health and Nutrition Examination Surveys data collected from 1988 to 2008 show that the prevalence of major causes of CLD remained stable, except for NAFLD, which increased steadily, along with the prevalence of metabolic conditions. Given the increasing rates of obesity, NAFLD prevalence is expected to contribute substantially to the burden of CLD in the United States.

Non-alcoholic steatohepatitis (NASH) in patients with polycystic ovarian syndrome (PCOS).

BACKGROUND: Both non-alcoholic steatohepatitis (NASH) and polycystic ovary syndrome (PCOS) are associated with metabolic syndrome (MS) and insulin resistance (IR). Except for a few case reports, there are no systematic assessments of NASH in PCOS patients. AIM: To determine the prevalence of NASH and independent factors associated with NASH in a cohort of patients with documented PCOS. METHODS: Patients with established diagnosis of PCOS and matched controls (matched for gender, age, and body mass index (BMI)) were included in the study. Causes of other liver diseases were systematically excluded by clinical and laboratory tests. Excessive alcohol use was defined as alcohol consumption of greater than 10 g/day. All liver biopsies were read by a single pathologist blinded to the clinical data. Histologic NASH was defined as steatosis with lobular inflammation and ballooning degeneration of hepatocytes with or without Mallory-Denk bodies or pericellular fibrosis. Univariate and multivariate analyses with logistic regression were performed to compare PCOS to matched controls. RESULTS: Sixty-six patients were included in the study (34 PCOS and 32 matched controls). Of PCOS patients, 73% had a liver biopsy while 78% of the matched controls had a liver biopsy. In comparing PCOS patients to the matched controls, clinical (BMI, waist circumference, type 2 diabetes, MS, or its components, any alcohol consumption in the prior year, ethnic background, age, gender, etc.) and laboratory data (aminotransferases, ferritin, glucose, etc.) were not significantly different (p > 0.05). However, PCOS patients tended to have more histologic NASH on their liver biopsies (44.0% vs. 20.8%, p = 0.08). Independent predictors of histologic NASH in PCOS patients were elevated aspartate aminotransferase (AST), high triglycerides and small amounts of alcohol consumption (p = 0.019, 10-fold cross-validated AUC = 0.80, 95% CI = 0.56-0.94). Although about half of PCOS patients did not report any alcohol consumption, 50% did report rare alcohol use. In fact, PCOS patients with histologic NASH tended to report higher alcohol consumption per week than PCOS without NASH (3.80 ± 6.16 vs. 1.11 ± 1.87 g/week, p = 0.1). Nevertheless, these amounts of alcohol consumption were quite minimal. CONCLUSIONS: Despite similar clinical and laboratory profiles to the matched controls, PCOS patients seem to have more histologic NASH. Although alcohol consumption was rare for both PCOS and controls, even rare alcohol consumption in PCOS patients was independently associated with histologic NASH.