Validation of a Primary Biliary Cholangitis-Specific Version of Chronic Liver Disease Questionnaire: CLDQ-PBC.

INTRODUCTION: Primary biliary cholangitis (PBC) is a chronic liver disease, leading to cirrhosis and impairment of patient-reported outcomes. We aimed to develop a PBC-specific version of the Chronic Liver Disease Questionnaire (CLDQ) instrument to assess health-related quality of life of patients with PBC. METHODS: From our Liver Database, we included patients with PBC who had CLDQ, clinicolaboratory data, and completed Short Form-36 and The Functional Assessment of Chronic Illness Therapy-Fatigue. The 29 items of CLDQ were subjected to item reduction, exploratory factor analysis, and fed into a standard instrument validation pipeline. RESULTS: Data were available for 108 patients with PBC: 57 ± 11 years, 7% male, 58% cirrhosis, and 24% decompensated cirrhosis (Child B and C). Of 29 CLDQ items, none met the exclusion criteria. Exploratory factor analysis (95% of variance) returned 7 factors. Based on evaluation of factor loadings and face validity, those factors yielded 7 domains (Diet, Emotion, Fatigue, Itch, Symptoms, Sleep, and Worry). Good to excellent internal consistency (Cronbach's α 0.85-0.93) was observed for 5/7 domains. For the remaining 2 domains (Diet and Itch), additional items obtained from patients, experts, and review of the literature were included. For 5 domains, known-group validity tests discriminated between patients with PBC with and without cirrhosis, advanced cirrhosis, and depression ( P < 0.05 for 3-5 domains). The CLDQ-PBC domains were correlated with relevant domains of Short Form-36, CLDQ-PBC Fatigue correlated with Fatigue Scale of Functional Assessment of Chronic Illness Therapy-Fatigue (rho = +0.85), and CLDQ-PBC Worry domain negatively correlated with alkaline phosphatase (rho = -0.38, P = 0.0082). DISCUSSION: The CLDQ-PBC has been developed based on the original CLDQ. The new instrument has evidence for internal consistency and validity and is being fully validated using an external cohort.

Development and validation of a primary sclerosing cholangitis-specific health-related quality of life instrument: CLDQ-PSC.

OBJECTIVES: To understand the full impact of primary sclerosing cholangitis (PSC) on patients' health, it is important to assess their health-related quality of life (HRQL). Using the Chronic Liver Disease Questionnaire (CLDQ), we aimed to develop and validate a PSC-specific HRQL instrument. METHODS: Previously collected clinical and patient-reported outcome data from PSC patients were used. The original CLDQ with 29 items was subjected to item reduction, followed by factor analysis. A standard HRQL instrument validation pipeline was then applied to the new CLDQ-PSC. RESULTS: There were 100 PSC patients (44±13 y, 32% male, 79% college educated, 39% cirrhosis, 67% inflammatory bowel disease, 66% ulcerative colitis, and 50% on ursodeoxycholic acid After item reduction and exploratory factor analysis, there were 24 items and 5 factors left; based on factor loadings, the factors were named emotional function, fatigue, symptoms, worry, and sleep. Internal consistency assessment returned Cronbach alpha 0.85-0.94, item-to-own domain correlations >0.66 for 22/24 items. Known-groups validity suggests discrimination between PSC patients with and without cirrhosis or its complications, obesity, history of depression, weight loss, and PSC patients on versus not on ursodeoxycholic acid (p<0.05 for all or select CLDQ-PSC domains). Relevant items of Short Form-36 and CLDQ-PSC were highly correlated (all p<0.0001). Matching with items of another PSC-specific instrument (PSC-patient-reported outcome; 42 items) for relevance and redundancy suggests that CLDQ-PSC is a relevant, comprehensive, and short HRQL instrument, which can be used for patients with PSC. CONCLUSIONS: The CLDQ-PSC is a PSC-specific HRQL instrument that was developed using an established methodology and demonstrated good psychometric characteristics.

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.

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

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

The Potential Role of Fatigue in Identifying Patients With NASH and Advanced Fibrosis Who Experience Disease Progression.

BACKGROUND AND AIMS: Fatigue is common in patients with advanced liver disease. We investigated fatigue and clinical outcomes among patients with advanced nonalcoholic steatohepatitis (NASH). METHODS: In this study, patients with biopsy confirmed NASH and bridging fibrosis (F3) or compensated cirrhosis (F4) were followed for up to 2 years. The Chronic Liver Disease Questionnaire for Nonalcoholic Steatohepatitis (CLDQ-NASH) fatigue domain at baseline (range, 1-7; lower score indicating worse fatigue) quantified fatigue. The Cox proportional hazards model was used to study time to liver-related clinical events (progression to histologic cirrhosis or hepatic decompensation in F3, hepatic decompensation in F4). RESULTS: Of the 1679 NASH patients with fibrosis, 802 had F3 and 877 had F4 (58 ± 9 years of age, 40% male, 74% type 2 diabetes). During median follow-up of 16 months (interquartile range, 14-18), 15% (n = 123) of NASH F3 patients experienced liver-related events and 3.5% (n = 31) of NASH F4 patients experienced hepatic decompensation. Mean baseline CLDQ-NASH fatigue score in F3 patients was 4.77 ± 1.36; NASH F3 patients who experienced liver-related events had lower baseline scores: 4.47 ± 1.36 vs 4.83 ± 1.35 (P = .0091). The mean fatigue score in F4 was 4.56 ± 1.44; these scores were lower in patients who decompensated in follow-up: 3.74 ± 1.31 vs 4.59 ± 1.43 (P = .0011). The association of lower fatigue scores and risk of liver-related or decompensation events was significant after adjustment for confounders (adjusted hazard ratio per 1 point in fatigue score in F3, 0.85; 95% confidence interval, 0.74-0.97; P = .02; adjusted hazard ratio in F4, 0.62; 95% confidence interval, 0.48-0.81; P = .0004). CONCLUSION: Worse fatigue at baseline is associated with a higher risk of adverse clinical events in patients with NASH-related advanced fibrosis and cirrhosis.

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.

The impact of the COVID-19 pandemic on patients with chronic liver disease: Results from the Global Liver Registry.

Patients with preexisting chronic liver disease (CLD) may experience a substantial burden from both coronavirus 2019 (COVID-19) infection and pandemic-related life disruption. We assessed the impact of the COVID-19 pandemic on patients with CLD. Patients enrolled in our Global Liver Registry were invited to complete a COVID-19 survey. As of June 2021, 2500 patients (mean age ± SD, 49 ± 13 years; 53% men) from seven countries completed the survey. Of all survey completers, 9.3% had COVID-19. Of these patients, 19% were hospitalized, 13% needed oxygen support, but none required mechanical ventilation. Of all patients including those not infected with COVID-19, 11.3% reported that the pandemic had an impact on their liver disease, with 73% of those reporting delays in follow-up care. The Life Disruption Event Perception questionnaire confirmed worsening in at least one area (food/nutrition, exercise, social life, vocation/education, financial situation, housing, or health care) in 81% and 69% of patients with and without a history of COVID-19, respectively (p = 0.0001). On a self-assessed Likert health score scale (range, 1-10; 10 indicates perfect health), patients with a COVID-19 history scored lower (mean ± SD, 6.7 ± 2.2 vs. 7.4 ± 2.2, respectively; p < 0.0001) despite reporting similar health scores if there was no pandemic (mean ± SD, 8.5 ± 1.4 vs. 8.4 ± 1.6, respectively; p = 0.59). After adjustment for country of enrollment, liver disease etiology and severity, age, sex, body mass index, diabetes, and history of psychiatric comorbidities, COVID-19 was found to be independently associated with lower self-assessed health scores (beta = -0.71 ± 0.14; p < 0.0001). The COVID-19 pandemic resulted in a substantial burden on the daily life of patients with CLD.

Health-Related Quality of Life and Health Care Resource Utilization in Patients With Chronic Liver Disease and Primary Liver Cancer in the United States: Analysis of Medical Expenditure Panel Survey.

Background: Worldwide, liver cancer (LC) is the fifth and third most common type of cancer and cancer-related mortality, respectively. Our aim was to assess health-related quality of life (HRQL) and resource utilization in chronic liver disease (CLD) patients with LC. Methods: We used the Medical Expenditure Panel Survey 2004-2013. All patients had HRQL (Short Form-12, Patient Health Questionnaire-2, Kessler Psychological Distress Scale) and resource utilization data. We used patients with CLD without LC and colon cancer (CC) as controls. Results: A total of 1882 CLD patients (53 ± 14 years, 45% male, 53% white, 15% black, 23% Hispanic, 6% Asian, 42% employed, 48% private insurance, and 11% uninsured) were included. Of the cohort, 102 (5.4%) patients had LC. LC patients were older, more likely to be male and white, less employed but less likely uninsured than CLD patients without LC (all P < 0.05). In comparison to both non-LC CLD and CC controls, LC had worse health: 40% vs. 27% vs. 25% reported fair health and 29% vs. 20% vs. 16% poor health status (P < 0.05). Furthermore, LC patients more frequently reported physical limitations: 51% vs. 35% vs. 35%, respectively (P = 0.01). Physical HRQL scores were lower in LC patients compared with both CLD and CC controls. Although mental health scores in LC were similar to non-LC CLD controls, they were lower than in CC. In addition, most aspects of healthcare resource utilization were higher for LC patients compared with both non-LC CLD and CC controls. Conclusion: While having CLD causes impairment of patients' HRQL, LC further adds to this impairment and also contributes to a substantial resource utilization.

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.

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.

Long-term Patient-Centered Outcomes in Cirrhotic Patients With Chronic Hepatitis C After Achieving Sustained Virologic Response.

BACKGROUND & AIMS: Achieving sustained virologic response (SVR) among patients with hepatitis C virus (HCV) leads to patient reported outcome (PRO) improvement. We aimed to assess the long-term post-SVR PRO trends in HCV patients with cirrhosis. METHODS: Patients with HCV and cirrhosis treated in clinical trials with direct acting antiviral agents (DAAs) who achieved SVR-12 were prospectively enrolled in a long-term registry (clinicaltrials.gov #NCT02292706). PROs were collected every 24 weeks using the Short Form-36v2 (SF-36), CLDQ-HCV, and WPAI-HCV. RESULTS: Pre-treatment baseline data were available for 854 cirrhotic patients who achieved SVR after DAAs. Of these, 730 had compensated (CC) and 124 had decompensated cirrhosis (DCC) before treatment- patients with DCC reported severe impairment in their PROs in comparison to CC patients (by mean -5% to -16% of a PRO range size; p < .05 for 16 out of 20 studied PROs]. After achieving SVR and registry enrollment, significant PRO improvements were noted from pre-treatment levels in 11/20 domains for those with DCC (+4% to +21%) and 19/20 PRO domains in patients with CC (+3% to +17%). Patients with baseline DCC had higher rates of hepatocellular carcinoma and mortality (P < .05). In patients with CC, the PRO gains persisted up to 168 weeks (3.5 years) of registry follow-up. In patients with DCC, the improvements lasted for at least 96 weeks but a declining trend after year 2. CONCLUSIONS: Patients with HCV cirrhosis experience severe PRO impairment at baseline with sustainable improvement after SVR. Though those with DCC experience improvement, there is a decline after 2 years.

A Global Survey of Physicians Knowledge About Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally. METHODS: NAFLD knowledge surveys containing 54 and 59 questions covering 3 domains (epidemiology/pathogenesis, diagnostics, and treatment) were completed electronically by hepatologists, gastroenterologists (GEs), endocrinologists (ENDOs), and primary care physicians (PCPs) from 40 countries comprising 5 Global Burden of Disease super-regions. Over 24 months, 2202 surveys were completed (488 hepatologists, 758 GEs, 148 ENDOs, and 808 PCPs; 50% high-income Global Burden of Disease super-region, 27% from North Africa and Middle East, 12% Southeast Asia, and 5% South Asian and Latin America). RESULTS: Hepatologists saw the greatest number of NAFLD patients annually: median 150 (interquartile range, 60-300) vs 100 (interquartile range, 35-200) for GEs, 100 (interquartile range, 30-200) for ENDOs, and 10 (interquartile range, 4-50) for PCPs (all P < .0001). The primary sources of NAFLD knowledge acquisition for hepatologists were international conferences (33% vs 8%-26%) and practice guidelines for others (39%-44%). The Internet was the second most common source of NAFLD knowledge for PCPs (28%). NAFLD knowledge scores were higher for hepatologists than GEs: epidemiology, 62% vs 53%; diagnostics, 80% vs 73%; and treatment, 61% vs 58% (P < .0001), and ENDOs scores were higher than PCPs: epidemiology, 70% vs 60%; diagnostics, 71% vs 64%; and treatment, 79% vs 68% (P < .0001). Being a hepatologist or ENDO was associated with higher knowledge scores than a GE or PCP, respectively (P < .05). Higher NAFLD knowledge scores were associated independently with a greater number of NAFLD patients seen (P < .05). CONCLUSIONS: Despite the growing burden of NAFLD, a significant knowledge gap remains for the identification, diagnosis, and management of NAFLD.

Liver Transplant Center Size and the Impact on Clinical Outcomes and Resource Utilization.

BACKGROUND: Prior studies suggest that transplant center volume is associated with liver transplantation (LT) outcomes. We compared patient characteristics and waitlist outcomes among transplant centers in the United States with different volumes. METHODS: Data for adult waitlisted candidates and LT recipients in the United States between 2008 and 2017 were extracted from the Scientific Registry of Transplant Recipients database. Transplant centers were categorized by transplants/year into tertiles: low-volume centers (LVCs; <20 transplantations/y); medium-volume centers (MVCs; 20-55 transplantations/y); and high-volume centers (HVCs; >55 transplantations/y). Patient characteristics, waitlist outcomes, and factors associated with posttransplantation mortality were compared. RESULTS: From 141 centers, 112 110 patients were waitlisted for LT: 6% at LVCs, 26% at MVCs, and 68% at HVCs. Patients listed at LVCs were less likely to have private insurance but had higher Medicaid and Veterans Affairs healthcare rates. Patients at LVCs were less likely to receive LT (47% versus 53% in MVC versus 61% in HVC), had higher transfer rates to other centers, and were more likely to be removed from the waitlist. In competing risk survival analysis, adjusted for center location, MELD score, and clinicodemographic factors, patients listed at an HVC were more likely to receive LT (adjusted hazard ratio:1.30; 95% confidence interval = 1.27-1.33; P < 0.001). Among LT recipients (n = 62 131), receiving a transplant at an LVC was associated with higher post-LT mortality (adjusted hazard ratio: 1.16; 95% confidence interval = 1.05-1.28; P = 0.003). CONCLUSIONS: Patients at LVCs were less likely to receive a LT and had a higher risk of post-LT death.

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

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

Nonalcoholic Steatohepatitis Is the Most Rapidly Increasing Indication for Liver Transplantation in the United States.

BACKGROUND & AIMS: The profile of chronic liver disease (CLD) in the United States has changed due to obesity trends and advances in treatment of viral hepatitis. We assessed liver transplant listing trends by CLD etiology. METHODS: Adult candidates for liver transplantation were selected from the Scientific Registry of Transplant Recipients (2002 through 2019). We calculated proportion trends for common CLD etiologies at time of placement on the wait list, including chronic infection with hepatitis B virus, chronic infection with hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH, including cryptogenic cirrhosis), alcohol-related liver disease (ALD) without or with chronic HCV infection, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, in patients with and without hepatocellular carcinoma (HCC). RESULTS: From the 168,441 patients with known etiology and non-acute liver failure on the liver transplant waitlist, 27,799 patients (16.5%) had HCC. In 2002, the most common etiologies in patients without HCC were chronic HCV infection (37%) and ALD (16%), whereas only 5% had NASH. Among patients with HCC, 58% had chronic HCV infection and 10% had ALD and only 1% had NASH. In 2019, among patients without HCC, NASH was the second leading indication for liver transplantation (28% of patients), after ALD (38% of patients). Among patients with HCC, chronic HCV infection remained the leading indication (40% of patients) but NASH (24% of patients) surpassed ALD (16% of patients) to become the second leading indication. NASH was the leading indication in women without HCC (34%), in patients older than 54 years (36%), and in patients on Medicare (41%). In trend analysis, NASH was the most rapidly increasing indication for liver transplantation in patients without HCC (Kendall tau=0.97; P < .001) and in patients with HCC (tau=0.94; P < .0001). CONCLUSIONS: In an analysis of data from the Scientific Registry of Transplant Recipients (2002 through 2019), we found NASH to be the second most common indication for liver transplant in 2019, and the fastest increasing indication. In 2019, NASH was the leading indication for liver transplantation among women without HCC.

Development and validation of a hepatitis B-specific health-related quality-of-life instrument: CLDQ-HBV.

Hepatitis B virus (HBV) carries a large global burden. Efforts abound to decrease the burden, which necessitates reporting of patient-reported outcomes (PROs). We aimed to develop and validate an HBV-specific PRO instrument using the Chronic Liver Disease Questionnaire (CLDQ). Data were obtained from patients enrolled in our HBV registries who completed the CLDQ, Short Form-36 (SF-36) and FACIT-F. The sample was split randomly 1:1 into training and testing groups. A standard PRO instrument validation pipeline was used to develop and validate the new CLDQ-HBV instrument. HBV patients (n = 1,339) were 48 ± 13 years old, 60% male, 8% cirrhosis, with 53% receiving oral antivirals (OAV). After reduction of 10 redundant items, exploratory factor analysis for the remaining 19 items found 95% of variance was explained by five factors-emotional function, fatigue, systemic symptoms, worry and sleep. Good-to-excellent internal consistency was found: Cronbach's alphas 0.70-0.90 and item-to-own-domain correlations >0.50 for 18/19 items. Known-group validity tests discriminated between HBV patients with and without cirrhosis, with FIB-4 ≥ 3.25 vs <3.25, with and without history of depression or clinically overt fatigue (all p < 0.0001), and treatment (all p < 0.05, all but one <0.0001). After 48-week follow-up, HBV patients receiving OAV (N = 144) with ≥2.7 log 10/mL decline in HBV viral load experienced significant improvements in fatigue, worry and total CLDQ-HBV scores (p < 0.05). The newly developed CLDQ-HBV is a short, disease-specific PRO instrument for HBV patients which was developed and validated using large data set and an established methodology showing excellent psychometric characteristics.

Outcomes of liver transplantation by insurance types in the United States.

OBJECTIVES: The outcomes of liver transplantation may vary according to socioeconomic factors such as insurance coverage. The aim of this study was to assess the association between the type of insurance payer and outcomes of liver transplant candidates and recipients in the United States. STUDY DESIGN: This was a retrospective cohort study of a national database. METHODS: The US Scientific Registry of Transplant Recipients was used to select adults (≥18 years) wait-listed for liver transplantation in the United States (2001-2017); patients were followed until March 2018. RESULTS: There were 177,862 liver transplant candidates with payer and outcomes data: The mean (SD) age was 54.1 (10.4) years, 64% were male, 39% had chronic hepatitis C with or without alcoholic liver disease (ALD), 19% had ALD alone, 17% had nonalcoholic steatohepatitis, and 16% had hepatocellular carcinoma. Fifty-nine percent were primarily covered by private insurance, 21% by Medicare, and 16% by Medicaid. After listing, 56% eventually received transplants (mean wait time of 229 days) and 22% dropped off the list. In multivariate analysis, adjusted for demographic and clinical factors, being covered by Medicare (odds ratio [OR], 0.81; 95% CI, 0.78-0.84) or Medicaid (OR, 0.76; 95% CI, 0.73-0.79) was independently associated with a lower chance of receiving a transplant (reference: private insurance). Posttransplant mortality was 11.6% at 1 year, 20.1% at 3 years, 26.8% at 5 years, and 41.6% at 10 years. Having Medicare (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.17-1.31) or Medicaid (aHR, 1.14; 95% CI, 1.06-1.21) was independently associated with higher posttransplant mortality (P <.001) but not with the risk of graft loss (P >.05). CONCLUSIONS: Liver transplant candidates covered by Medicare or Medicaid have poorer wait-list outcomes and higher posttransplant mortality.

Hypothetical treatment of patients with non-alcoholic steatohepatitis: Potential impact on important clinical outcomes.

BACKGROUND & AIMS: Currently, standard of care (SOC) treatment for NASH is limited to lifestyle modifications. Drug regimens are being evaluated currently. We assessed the impact of a short-term hypothetical treatment on clinical outcomes of NASH. METHODS: Markov models estimated differences in outcomes between SOC and 2 hypothetical NASH treatments (A and B). We modelled 10 000 50-year-old biopsy-proven NASH patients over lifetime horizon. Health states included NASH with fibrosis (F1-F3), cirrhosis, hepatocellular carcinoma, liver transplant and mortality. Fibrosis Regression Factor (FRF) variable modelled the probability of 1-3 stage fibrosis improvement with treatment. Annual probability of treatment (ATP) ranged from 10%-70%. Treatment success was defined as regression to fibrosis, whereas failure was defined as progression to stages beyond cirrhosis. In treatment-A, successful treatment was followed by a maintenance regimen which stopped disease progression. After a successful treatment-B, patients remained at risk of disease progression. Differences in outcomes were calculated between both treatments and SOC models. We conducted a probabilistic sensitivity analysis. RESULTS: At 10% to 70% ATP, treatment-A averts 353 to 782 liver transplants and 1277 to 2381 liver-related deaths relative to SOC. Treatment-B averts 129 to 437 liver transplants and 386 to 1043 liver-related deaths. Sensitivity analysis shows our model is robust in estimating liver-related mortality and LTs averted, but is sensitive when estimating QALYs gained. CONCLUSIONS: With a small annual probability of treatment and FRF = 1, a 2-year treatment followed by maintenance of histologic improvement for patients would be highly beneficial relative to short-term treatment alone.

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.