Liver Transplantation Profile Among Teenagers in the United States.

PURPOSE: Indications for liver transplantation (LT) vary across age groups. We identified predictors of outcomes for teenage LT waitlisted candidates and recipients in the United States from 2008 to 2022. METHODS: The Scientific Registry of Transplant Recipients 2008-2022 provided data (clinical, sociodemographic, indications for LT, outcomes) for all teenagers (13-19 years) waitlisted for LT in the United States. Sociodemographic and clinical characteristics, including primary listing diagnoses, were evaluated and compared by age group (13-16 vs. 17-19 years) among waitlisted teenage candidates. RESULTS: There were 2,813 teenage LT candidates listed between 2008 and 2022. The most common LT indication was acute liver disease (23.5%), followed by biliary atresia or hypoplasia (11.9%), autoimmune hepatitis (11.1%), and primary sclerosing cholangitis (9.7%). In contrast, chronic viral hepatitis, metabolic dysfunction-associated steatotic liver disease, and alcohol-related liver disease (the most common indications in adults) did not exceed 1% each; 2.8% had hepatocellular carcinoma. Excluding the two most recent years, 67.2% of candidates received a transplant; mean time to transplant was 217.0 days (standard deviation 371.6). Independent predictors of receiving a transplant were a more recent calendar year, younger age, higher model for end-stage liver disease score, and an acute liver disease diagnosis (all p < .05). Among the LT group, 3-year survival was 90%, with an improving survival trend. Higher post-transplant mortality was associated with earlier years of transplantation, older age, having Medicaid, being retransplanted, and having hepatocellular carcinoma (adjusted hazard ratios >1, all p < .05). DISCUSSION: Indications for LT among US teenagers are different from adults or younger children. There is a trend toward improved post-transplant outcomes.

Determination of Liver Function Tests and Liver Ultrasonographic Findings in Patients with Leptospirosis in a Tertiary Hospital.

Introduction: Leptospirosis is an important zoonotic disease commonly found in tropical or sub-tropical countries. The most severe form is Weil's syndrome which presents with jaundice, renal failure, and bleeding diatheses. Although jaundice occurs in 38% of patients with leptospirosis, no studies in Asia have focused on the liver biochemical profile of these patients. Characterization of liver biochemical profile and ultrasonographic findings may shed more light on the disease process. Identification of liver biochemical parameters that portend a poor prognosis may also allow for early aggressive intervention. Objective: To describe the liver biochemical profile and liver ultrasonographic findings in adult patients with laboratory-confirmed leptospirosis, admitted at a tertiary hospital in Manila, Philippines. The association of clinical and laboratory features with clinical outcomes (i.e., severe liver injury, Weil's syndrome, and mortality) was also investigated. Methods: This retrospective cross-sectional study reviewed all available cases of adult patients with laboratory-confirmed leptospirosis admitted in the Philippine General Hospital from January 2009 to August 2018. The clinical features, liver biochemical profiles, and ultrasound findings were recorded and analyzed. Comparison between the means of each group based on clinical outcome (i.e., mortality, Weil's syndrome) was done via Students' t-test for continuous variables, and calculation of the Odds Ratio for categorical variables. Results: Total and direct bilirubin levels were elevated in patients with leptospirosis compared to serum amino-transferases and alkaline phosphatase levels which were only mildly elevated. Abdominal ultrasound showed typically un-enlarged livers with normal parenchymal echogenicity, normal spleens, and non-dilated biliary trees. Dyspnea was associated with an increased odds for mortality. Although jaundice was present in 39.5% of patients and significantly associated with severe liver injury, this was not associated with mortality. Liver biochemical test values did not differ among patients who expired and those who survived to discharge. The presence of myalgia and abdominal pain increased the odds for Weil's syndrome. Conclusion: To date, no local studies have fully described the liver biochemical profile of patients with leptospirosis. Our findings are compatible with previous studies showing that leptospirosis typically presents with predominantly elevated direct bilirubin from cholestasis and systemic infection. Contrary to previous literature, however, our study found no association between jaundice and mortality.

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease.

Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

Barriers and enablers to people-centred viral hepatitis care in Vietnam and the Philippines: Results of a patient journey mapping study.

In Vietnam and the Philippines, viral hepatitis is the leading cause of cirrhosis and liver cancer. This study aims to understand the barriers and enablers of people receiving care for hepatitis B and C to support both countries' efforts to eliminate viral hepatitis as a public health threat by 2030. Retrospective, semi-structured interviews were conducted with a purposive, quota-based sample of 63 people living with hepatitis B or C in one province of Vietnam and one region of the Philippines. A rapid deductive approach to thematic analysis produced key findings among the three phases of care: (1) pre-awareness and testing, (2) linkage and treatment initiation and (3) ongoing treatment and recovery. The research found that participants followed five typical journeys, from a variety of entry points. Barriers during the pre-awareness and testing phase included limited awareness about hepatitis and its management, stigma and psychological impacts. Enablers included being familiar with the health system and/or patients benefiting from social connections within the health systems. During the linkage and treatment initiation phase, barriers included difficult physical access, complex navigation and inadequate counselling. In this phase, family support emerged as a critical enabler. During the ongoing treatment and recovery phase, the cost of care and socially and culturally informed perceptions of the disease and medication use were both barriers and enablers. Exploring peoples' journeys with hepatitis B and C in Vietnam and the Philippines revealed many similarities despite the different cultural and health system contexts. Insights from this study may help generate a contextualized, people-centred evidence base to inform the design and improvement of primary care services for hepatitis in both research sites.

Embedding viral hepatitis into primary healthcare: results of a strategic landscape analysis in Vietnam and the Philippines.

Chronic viral hepatitis is a significant public health concern in the Western Pacific, including in Vietnam and the Philippines. To accelerate progress toward meeting the 2030 elimination goals, the World Health Organization (WHO) encourages countries to adopt an integrated, people-centered health sector response to hepatitis, grounded in Primary Health Care (PHC). A review of the academic and grey literature, along with policy documents, was conducted to describe the national health system and PHC response to hepatitis B and C in Vietnam and the Philippines. Information was analyzed against the four strategic levers of the WHO Operational Framework for PHC to identify challenges and opportunities. The findings suggest that both countries have relatively robust policy frameworks, with some room for improvement. Vietnam may have stronger political commitment and funding than the Philippines, while the Philippines appears to be stronger in community engagement. Both countries share challenges and opportunities for learning to actualize viral hepatitis elimination utilizing a PHC approach.

Clinical profiles and mortality rates are similar for metabolic dysfunction-associated steatotic liver disease and non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Concern remains regarding whether the evidence generated under the NAFLD definition can be used for MASLD. We compared the clinical profile and outcomes of NAFLD to MASLD using tertiary care- and population-based data. METHODS: Comparison data were obtained from our NAFLD database and the National Health and Nutrition Examination Survey (NHANES III). Clinical profiles and non-invasive tests (enhanced liver fibrosis [ELF] score, fibrosis-4 index [FIB-4] and vibration-controlled transient elastography) were compared. Mortality data were obtained from NHANES-National Death Index. All-cause mortality was assessed by Cox proportional hazards regression models and cause-specific mortality by competing risk analysis. RESULTS: There were 6,429 patients in the NAFLD database (age: 54 ± 12 years, 42% male, BMI 35.4 ± 8.3, waist circumference 112 ± 17 cm, 52% type 2 diabetes). Average scores for ELF, FIB-4 and liver stiffness were 9.6 ± 1.2, 1.69 ± 1.24,14.0 ± 11.8 kPa, respectively; 99% met MASLD criteria; 95% met MASLD on BMI only. Predictive accuracy of ELF and FIB-4 were identical between MASLD and NAFLD. We included 12,519 eligible participants from NHANES (age 43.00 years, 47.38% male, 22.70% obese, 7.28% type 2 diabetes, 82.51% ≥1 cardiometabolic criteria). Among the NHANES study population, there was excellent concordance between MASLD and NAFLD diagnoses: Cohen's kappa coefficient: 0.968 (95% CI 0.962-0.973) with 5.29% of NAFLD cases not meeting MASLD criteria. After a median follow-up of 22.83 years, there were no mortality differences between MASLD and NAFLD diagnoses (p values ≥0.05). CONCLUSIONS: NAFLD and MASLD are similar except individuals with MASLD seem to be older with slightly higher mortality risk, likely owing to cardiometabolic risk factors. Clinical profiles and non-invasive test thresholds were also identical. These data provide evidence that NAFLD and MASLD terminologies can be used interchangeably. For the small proportion of patients with NAFLD who do not meet MASLD criteria, further consideration is needed. IMPACT AND IMPLICATIONS: In June 2023, new terminology (MASLD) was adopted to replace the term NAFLD as a means to better describe what the liver disease is rather than what it is not, as well as to potentially reduce stigma. Given that MASLD requires at least one cardiometabolic risk factor, questions were raised as to whether this change in the definition would nullify the similarities between NAFLD and MASLD and require new evidence to be generated for MASLD. We used our NAFLD database and a US population-based database to show that the vast majority of patients with NAFLD fulfill criteria for MASLD. Non-invasive tests performed similarly in both groups. Mortality risk was slightly higher in those with MASLD, which is attributed to the presence of cardiometabolic risks. These results provide evidence that data generated in the past three decades for NAFLD can be used interchangeably for MASLD.

Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Patients with fatty liver disease may experience stigma from the disease or comorbidities. In this cross-sectional study, we aimed to understand stigma among patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and healthcare providers. METHODS: Members of the Global NASH Council created two surveys about experiences/attitudes toward NAFLD and related diagnostic terms: a 68-item patient and a 41-item provider survey. RESULTS: Surveys were completed by 1,976 patients with NAFLD across 23 countries (51% Middle East/North Africa [MENA], 19% Europe, 17% USA, 8% Southeast Asia, 5% South Asia) and 825 healthcare providers (67% gastroenterologists/hepatologists) across 25 countries (39% MENA, 28% Southeast Asia, 22% USA, 6% South Asia, 3% Europe). Of all patients, 48% ever disclosed having NAFLD/NASH to family/friends; the most commonly used term was "fatty liver" (88% at least sometimes); "metabolic disease" or "MAFLD" were rarely used (never by >84%). Regarding various perceptions of diagnostic terms by patients, there were no substantial differences between "NAFLD", "fatty liver disease (FLD)", "NASH", or "MAFLD". The most popular response was being neither comfortable nor uncomfortable with either term (56%-71%), with slightly greater discomfort with "FLD" among the US and South Asian patients (47-52% uncomfortable). Although 26% of patients reported stigma related to overweight/obesity, only 8% reported a history of stigmatization or discrimination due to NAFLD. Among providers, 38% believed that the term "fatty" was stigmatizing, while 34% believed that "nonalcoholic" was stigmatizing, more commonly in MENA (43%); 42% providers (gastroenterologists/hepatologists 45% vs. 37% other specialties, p = 0.03) believed that the name change to metabolic dysfunction-associated steatotic liver disease (or MASLD) might reduce stigma. Regarding the new nomenclature, the percentage of providers reporting "steatotic liver disease" as stigmatizing was low (14%). CONCLUSIONS: The perception of NAFLD stigma varies among patients, providers, geographic locations and sub-specialties. IMPACT AND IMPLICATIONS: Over the past decades, efforts have been made to change the nomenclature of nonalcoholic fatty liver disease (NAFLD) to better align with its underlying pathogenetic pathways and remove any potential stigma associated with the name. Given the paucity of data related to stigma in NAFLD, we undertook this global comprehensive survey to assess stigma in NAFLD among patients and providers from around the world. We found there is a disconnect between physicians and patients related to stigma and related nomenclature. With this knowledge, educational programs can be developed to better target stigma in NAFLD among all stakeholders and to provide a better opportunity for the new nomenclature to address the issues of stigma.

The changing epidemiology of adult liver transplantation in the United States in 2013-2022: The dominance of metabolic dysfunction-associated steatotic liver disease and alcohol-associated liver disease.

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

The impact of hepatitis B and C positive serologies on the outcomes of non-hepatic solid organ transplantation in the United States.

Chronic viral hepatitis B (HBV) and C (HCV) infection could negatively affect outcomes of non-hepatic solid organ transplantations due to the risk of viral reactivation in the presence of immunosuppression. This study aimed to determine post-transplant outcomes in patients with HBV or HCV positivity receiving non-hepatic solid-state organ transplant. Data was collected from the Scientific Registry of Transplant Recipients (SRTR) 2006-2021 for patients (≥18) who received a lung, heart, or kidney single organ transplant in the U.S. Hepatitis C positivity (HCV+) was determined as positive HCV Ab and hepatitis B positivity (HBV+) as positive HBsAg. We included N = 30,872 lung, N = 36,990 heart and N = 280,162 kidney transplant recipients. The prevalence of HBV+ was 1.3% in lung, 1.5% in heart and 1.7% in kidney patients, HCV+ was 2.2%, 2.2% and 5.0%, respectively. Post-transplant survival of patients with vs. without HBV+ was similar in all solid organ transplants (all p > .05). Similarly, there was no difference in post-transplant survival between lung transplant recipients with vs. without anti-HCV (all p > .05). Heart transplant recipients with HCV+ had higher crude post-transplant mortality (all p < .01). Similarly, there was higher post-transplant mortality in kidney transplant recipients with HCV+ (1-year: 6% vs. 3%; 5-year: 21% vs. 13%; 10-year: 47% vs. 31%; all p < .0001). In multivariate analysis controlling for confounders, only the association of HCV+ with higher post-kidney transplant mortality remained significant: adjusted hazard ratio (aHR) (95% CI) = 1.16 (1.12-1.20), p < .0001. There was no association of viral hepatitis seropositivity with the risk of graft failure in all groups (p > .05). In most cases, the presence of HBV or HCV serologies is not associated with adverse post-transplant outcomes in non-hepatic solid organ transplants. However, kidney transplant recipients who are positive for HCV serology have an increased risk for post-transplant mortality.

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.

Nonalcoholic Fatty Liver Disease in Asia, Africa, and Middle East Region.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. The global prevalence of the disease varies according to the geographical region. Despite having distinct models for the western patterns of NAFLD, Africa, Asia, and the Middle East regions exhibited varying prevalence rates of NAFLD. The disease burden is anticipated to significantly increase in these areas. Furthermore, with an increase in NAFLD risk factors in these regions, the disease burden is expected to rise even more. Policies at the regional and international levels are required to address such growing burden of NAFLD consequences.

Liver diseases: Perspective from the Philippines.

Liver diseases are a major cause of morbidity and mortality globally. In the Philippines, a lower middle-income country in Southeast Asia, liver diseases accounted for 27.3 cases per 1000 deaths. In this review, we discussed the prevalence, risk factors, and management of hepatitis B, hepatitis C and other viral hepatitis, non-alcoholic fatty liver disease, alcohol-associated liver disease, liver cirrhosis, and hepatocellular carcinoma. The true burden of liver disease in the Philippines is likely underestimated due to limited epidemiological studies. Thus, surveillance of liver disease should be strengthened. Clinical practice guidelines tailored to the local needs of the country have been developed for important liver diseases. Multisectoral cooperation among different stakeholders is needed to manage the burden of liver disease in the Philippines.

Clinical and patient-reported outcome profile of patients with hepatitis B viral infection from the Global Liver Registry™.

Chronic hepatitis B (CHB) infection is one of the most common causes of cirrhosis and liver cancer worldwide. Our aim was to assess clinical and patient-reported outcome (PRO) profile of CHB patients from different regions of the world using the Global Liver Registry. The CHB patients seen in real-world practices are being enrolled in the Global Liver Registry. Clinical and PRO (FACIT-F, CLDQ, WPAI) data were collected and compared to baseline data from CHB controls from clinical trials. The study included 1818 HBV subjects (48 ± 13 years, 58% male, 14% advanced fibrosis, 7% cirrhosis) from 15 countries in 6/7 Global Burden of Disease super-regions. The rates of advanced fibrosis varied (3-24%). The lowest PRO scores across multiple domains were in HBV subjects from the Middle East/North Africa (MENA), the highest - Southeast/East and South Asia. Subjects with advanced fibrosis had PRO impairment in 3 CLDQ domains, Activity of WPAI (p < 0.05). HBV subjects with superimposed fatty liver had more PRO impairments. In multivariate analysis adjusted for location, predictors of PRO impairment in CHB included female sex, advanced fibrosis, and non-hepatic comorbidities (p < 0.05). In comparison to Global Liver Registry patients, 242 controls from clinical trials had better PRO scores (Abdominal, Emotional, and Systemic scores of CLDQ, all domains of WPAI) (p < 0.05). In multivariate analysis with adjustment for location and clinicodemographic parameters, the associations of PROs with the enrollment setting (real-life Global Liver Registry vs. clinical trials) were no longer significant (all p > 0.10). The clinico-demographic portrait of CHB patients varies across regions of the world and enrollment settings. Advanced fibrosis and non-hepatic comorbidities are independently associated with PRO impairment in CHB patients.

Severe impairment of patient-reported outcomes in patients with chronic hepatitis C virus infection seen in real-world practices across the world: Data from the global liver registry.

Cure of chronic hepatitis C (CHC) can lead to improvement of health-related quality of life and other patient-reported outcomes (PROs). While extensive PRO data for CHC patients who were enrolled in clinical trials are available, similar data for patients seen in real-world practices are scarce. Our aim was to assess PROs of CHC patients enrolled from real-world practices from different regions and to compare them with those enrolled in clinical trials. CHC patients seen in clinical practices and not receiving treatment were enrolled in the Global Liver Registry (GLR). Clinical and PRO (FACIT-F, CLDQ-HCV, WPAI) data were collected and compared with the baseline data from CHC patients enrolled in clinical trials. N = 12,171 CHC patients were included (GLR n = 3146, clinical trial subjects n = 9025). Patients were from 30 countries from 6 out of 7 Global Burden of Disease (GBD) super-regions. Compared with clinical trial enrollees, patients from GLR were less commonly enrolled from High-Income GBD super-region, older, more commonly female, less employed, had more type 2 diabetes, anxiety and clinically overt fatigue but less cirrhosis (all p < 0.001). Out of 15 PRO domain and summary scores, 12 were lower in GLR patients than in subjects enrolled in clinical trials (p < 0.001). In multiple regression models, anxiety, depression, and fatigue were associated with significant PRO impairment in CHC patients (p < 0.05). After adjustment for the clinico-demographic confounders, the association of PRO scores of CHC patients with enrolment settings was no longer significant (all p > 0.05). In conclusion, hepatitis C patients seen in the real-world practices have PRO impairment driven by fatigue and psychiatric comorbidities.

Nonalcoholic steatohepatitis is the most common indication for liver transplantation among the elderly: Data from the United States Scientific Registry of Transplant Recipients.

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

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.

Contextual and individual factors associated with knowledge, awareness and attitude on liver diseases: A large-scale Asian study.

There are limited data to provide better understanding of the knowledge/awareness of general population towards liver health in Asia. We sought to identify the knowledge gaps and attitudes towards liver health and liver diseases as well as evaluate associated individual-level and macro-level factors based on contextual analysis. An online survey assessing knowledge, awareness and attitudes towards liver health and disease was conducted among 7500 respondents across 11 countries/territories in Asia. A liver index was created to measure the respondents' knowledge level and the degree of awareness and attitudes. Multilevel logistic regression was performed to identify individual factors and contextual effects that were associated with liver index. The overall liver index (0-100-point scale) was 62.4 with 6 countries/territories' liver indices greater than this. In the multilevel model, the inclusion of geographical information could explain for 9.6% of the variation. Residing in a country/territory with higher HBV prevalence (80% IOR: 1.20-2.79) or higher HCV death rate (80% IOR: 1.35-3.13) increased the individual probability of obtaining a high overall liver index. Individual factors like age, gender, education, household income, disease history and health screening behaviour were also associated with liver index (all p-values<0.001). The overall liver index was positively associated with the two macro-level factors viz. HBV prevalence and HCV death rate. There is a need to formulate policies especially in regions of lower HBV prevalence and HCV death rate to further improve the knowledge, awareness and attitudes of the general public towards liver diseases.

Clinical and Patient-Reported Outcomes From Patients With Nonalcoholic Fatty Liver Disease Across the World: Data From the Global Non-Alcoholic Steatohepatitis (NASH)/ Non-Alcoholic Fatty Liver Disease (NAFLD) Registry.

BACKGROUND & AIMS: Globally, nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. We assessed the clinical presentation and patient-reported outcomes (PROs) among NAFLD patients from different countries. METHODS: Clinical, laboratory, and PRO data (Chronic Liver Disease Questionnaire-nonalcoholic steatohepatitis [NASH], Functional Assessment of Chronic Illness Therapy-Fatigue, and the Work Productivity and Activity Index) were collected from NAFLD patients seen in real-world practices and enrolled in the Global NAFLD/NASH Registry encompassing 18 countries in 6 global burden of disease super-regions. RESULTS: Across the global burden of disease super-regions, NAFLD patients (n = 5691) were oldest in Latin America and Eastern Europe and youngest in South Asia. Most men were enrolled at the Southeast and South Asia sites. Latin America and South Asia had the highest employment rates (>60%). Rates of cirrhosis varied (12%-21%), and were highest in North Africa/Middle East and Eastern Europe. Rates of metabolic syndrome components varied: 20% to 25% in South Asia and 60% to 80% in Eastern Europe. Chronic Liver Disease Questionnaire-NASH and Functional Assessment of Chronic Illness Therapy-Fatigue PRO scores were lower in NAFLD patients than general population norms (all P < .001). Across the super-regions, the lowest PRO scores were seen in Eastern Europe and North Africa/Middle East. In multivariate analysis adjusted for enrollment region, independent predictors of lower PRO scores included younger age, women, and nonhepatic comorbidities including fatigue (P < .01). Patients whose fatigue scores improved over time experienced a substantial PRO improvement. Nearly 8% of Global NAFLD/NASH Registry patients had a lean body mass index, with fewer metabolic syndrome components, fewer comorbidities, less cirrhosis, and significantly better PRO scores (P < .01). CONCLUSIONS: NAFLD patients seen in real-world practices in different countries experience a high comorbidity burden and impaired quality of life. Future research using global data will enable more precise management and treatment strategies for these patients.