Telehealth interventions in patients with chronic liver diseases: A systematic review.

BACKGROUND AND AIM: Telehealth interventions may improve access to care, disease-specific, and quality outcomes in chronic liver diseases (CLDs). We aimed to systematically evaluate outcomes of telehealth interventions in CLDs. MATERIALS AND METHODS: We used key terms and searched PubMed/EMBASE from inception to January 10, 2022. Two authors independently screened abstracts. Disagreements were resolved by a third reviewer. We included any type of CLD, including posttransplant patients, and extracted outcomes as defined by authors for each etiology of CLD (sustained virological response in HCV or weight loss in NAFLD). Meta-analysis was not performed because of the heterogeneity of data. Quality assessment was performed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias tool for clinical trials. RESULTS: Of 4250 studies screened, 43 met the inclusion criteria. Of these, 28 reported HCV treatment outcomes. All studies showed no statistically significant differences between sustained virological response rates in TH groups compared with control groups or historic cohorts. Eight studies evaluating liver transplant-related processes and outcomes demonstrated improved rates of transplant evaluation and referrals and decreased short-term readmission rates. Three randomized controlled trials and 1 observational study on NAFLD showed improved weight loss outcomes. One retrospective study showed reduced mortality risk in CLD patients with at least 1 TH encounter. CONCLUSIONS: TH interventions in patients with CLDs consistently show equivalent or improved clinical outcomes compared with traditional encounters. TH in CLDs can bridge the gap in access while maintaining the quality of care for underserved populations.

Depression in nonalcoholic fatty liver disease and all-cause/cause-specific mortality.

BACKGROUND: Depression has been associated with nonalcoholic fatty liver disease (NAFLD). Data addressing the impact of depression on NAFLD-related mortality are evolving. We aim to study the association of depression in NAFLD and all-cause/cause-specific mortality in the United States. METHODS: A total of 11,877 individuals with NAFLD in the 2007-2016 National Health and Nutrition Examination Survey with the availability of linked mortality through 2019 were analysed. NAFLD was defined by utilizing the hepatic steatosis index in the absence of known causes of chronic liver disease. Depression and functional impairment due to depression were assessed using the Patient Health Questionnaire. RESULTS: During the median follow-up of 7.6 years, individuals with depression among individuals with NAFLD had a 35% higher all-cause mortality than those without depression (hazard ratio [HR]: 1.35, 95% confidence interval [CI]: 1.03-1.75) after adjusting for demographic, lifestyle and clinical risk factors. NAFLD with functional impairment due to depression had a 62% higher all-cause mortality than NAFLD without functional impairment (HR: 1.62, 95% CI: 1.10-2.39). Depression in NAFLD was associated with an approximately 50% increase in the risk for cardiovascular mortality, with a 2-fold higher cardiovascular mortality in those with functional impairment compared to those without (HR: 2.07, 95% CI: 1.30-3.30). However, there was no significant difference in cancer- and accident-related mortalities in NAFLD with or without depression. CONCLUSIONS: Depression among individuals with NAFLD was associated with a higher risk for all-cause and cardiovascular mortality in the United States.

Endogenous sex hormones and nonalcoholic fatty liver disease in US adults.

BACKGROUND AND AIMS: Sex steroid hormones and sex hormone-binding globulin (SHBG) have a role in predisposing individuals to nonalcoholic fatty liver disease (NAFLD), but their effects are known to differ between men and women. The testosterone-to-estradiol ratio (T/E2 ratio) and free androgen index (FAI) were known biomarkers for the hormonal milieu. We investigated whether sex steroid hormones, T/E2 ratio, FAI, and SHBG were associated with NAFLD in US adults. METHODS: A cross-sectional analysis using the 2013-2016 National Health and Nutrition Examination Survey (NHANES) was performed. NAFLD was defined by utilizing the Hepatic Steatosis Index (HSI) and the US fatty liver index (USFLI) without other causes of chronic liver disease. RESULTS: Out of 8687 subjects (49.5% male), low total testosterone levels were associated with progressively higher odds of NAFLD in men. Increasing T/E2 ratio was inversely associated with higher odds of NAFLD in men. Low serum SHBG levels were independently associated with an increased risk of NAFLD regardless of sex and menopausal status. Increasing FAI was independently associated with NAFLD. When we additionally adjusted for SHBG, T/E2 ratio, not total testosterone, was inversely associated with NAFLD in a dose-dependent manner. Increasing FAI was associated with higher odds of NAFLD in premenopausal women and marginally associated with NAFLD in postmenopausal women. CONCLUSION: The T/E2 ratio and SHBG were inversely associated with an increased risk of NAFLD in men. In women, increasing FAI was associated with NAFLD, whereas SHBG was inversely associated with NAFLD.

Association between food insecurity and metabolic dysfunction-associated steatotic liver disease/significant fibrosis measured by fibroscan.

PURPOSE: Studies evaluating food insecurity and metabolic dysfunction-associated steatotic liver disease (MASLD) and significant hepatic fibrosis are currently scarce. We evaluated the characteristics of food insecure individuals and whether food insecurity was associated with MASLD and significant hepatic fibrosis in the US population. METHODS: In this cross-sectional study from the National Health and Nutrition Examination Survey 2017-2018, 3441 participants with complete data were enrolled. We defined MASLD and significant hepatic fibrosis (≥ F2) by transient elastography in the absence of other causes of liver disease. The detailed questionnaire assessed and categorized food security as high, marginal, low, and very low food security. RESULTS: Food-insecure subjects were more likely to be female, younger, more impoverished, non-Hispanic blacks, Hispanics, and less likely to be educated, married, and physically active. Food insecurity increased the odds of the prevalence of MASLD by 42% (odds ratio [OR]: 1.42, 95% confidence interval [CI]: 1.12-1.78) after adjustment for demographic, lifestyle, and metabolic risk factors. The addition of diabetes and obesity did not change this association (OR: 1.36, 95% CI: 1.03-1.78). The multivariable model showed an independent relationship between food insecurity and significant hepatic fibrosis (OR: 1.40, 95% CI: 1.04-1.88) after adjustment for demographic, lifestyle, and metabolic risk factors, although the association was attenuated and changed insignificantly after adjustment for diabetes and obesity. CONCLUSIONS: Food insecurity was associated with higher odds for MASLD. While there is a relationship between food insecurity and significant hepatic fibrosis, this relationship changed insignificantly after adjustment of diabetes and obesity.

The prevalence and predictors of metabolic dysfunction-associated steatotic liver disease and fibrosis/cirrhosis among adolescents/young adults.

OBJECTIVES: We investigated the current prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and fibrosis/cirrhosis and identified at-risk populations for MASLD and MASLD-related fibrosis among US adolescents and young adults in the United States. METHODS: Utilizing the National Health and Nutrition Examination Survey 2017-2020, the prevalence of MASLD and fibrosis/cirrhosis was assessed via controlled attenuation parameter (CAP) score and liver stiffness measurements by transient elastography in participants aged 12-29 years with at least one cardiometabolic criteria and absence of other chronic liver disease. Multivariable logistic regression was performed to determine predictors of MASLD and MASLD-related fibrosis. RESULTS: The overall prevalence of MASLD was 23.9% (95% confidence interval [CI]: 21.3-26.5 for CAP ≥ 263 dB/m) and 17.3% (95% CI: 14.7-20.0 for ≥285 dB/m), respectively. The prevalence of fibrosis and cirrhosis in MASLD was 11.0% and 3.1%, respectively. When categorized by age, the prevalence of MASLD varied from 16.8% (of which 6.2% [fibrosis], 1.8% [cirrhosis]) in early and middle adolescents (12-17 years), to 25.5% (11.8% [fibrosis], 4.8% [cirrhosis]) in late adolescents and young adults (18-24 years), and to 30.4% (of which 13.2% [fibrosis] and 2.1% [cirrhosis]) in older young adults (25-29 years). The independent predictors for MASLD included male sex, Hispanic, non-Hispanic Asian, body mass index, and low HDL-cholesterol. In contrast, diabetes and body mass index were associated with an increased risk of fibrosis in individuals with MASLD. CONCLUSIONS: The prevalence of MASLD and related fibrosis in adolescents and young adults in the United States has reached a significant level, with a substantial proportion of cirrhosis.

Estimated pulse wave velocity in metabolic dysfunction-associated steatotic liver disease and all-cause/cause-specific mortality.

BACKGROUND AND AIM: Several reports show a significant association between metabolic dysfunction-associated steatotic liver disease (MASLD) and arterial stiffness (estimated pulse wave velocity [ePWV]) as a surrogate marker of vascular age. We investigate whether ePWV as arterial stiffness in MASLD is associated with all-cause/cause-specific mortality. METHODS: This cohort study was based on the third National Health and Nutrition Examination Survey (NHANES, 1988-1994) and NHANES 2007-2014 and linked mortality datasets through 2019. Cox regression models assessed the association between ePWV categorized by quartile and all-cause/cause-specific mortality among individuals with MASLD. RESULTS: During the follow-up of a median of 26.3 years (interquartile range: 19.9-27.9), higher levels of ePWV among individuals with MASLD were associated with increased all-cause mortality, which remained significant after adjusting for demographic, lifestyle, clinical, and metabolic risk factors. Furthermore, higher ePWV in MASLD was associated with higher cardiovascular mortality. There was a 44% (hazard ratio: 1.44, 95% confidence interval: 1.32-1.58) increase in all-cause mortality and a 53% (hazard ratio: 1.53, 95% confidence interval: 1.32-1.77) increase in cardiovascular mortality for every 1 m/s increase in ePWV in MASLD. However, there was no significant association between ePWV and cancer-related mortality. Sensitivity analyses using the NHANES 2007-2014 dataset showed results identical to the original analysis. CONCLUSION: Higher ePWV in MASLD was associated with a higher risk of all-cause and cardiovascular mortality beyond traditional cardiovascular risk factors. Screening for ePWV in individuals with MASLD may be an effective and beneficial approach to reducing all-cause and cardiovascular mortality.

Current Challenges and Future Direction in Surveillance for Hepatocellular Carcinoma in Patients with Nonalcoholic Fatty Liver Disease.

The burden for hepatocellular carcinoma (HCC) attributed to nonalcoholic fatty liver disease (NAFLD) continues to grow in parallel with rising global trends in obesity. The risk of HCC is elevated among patients with NAFLD-related cirrhosis to a level that justifies surveillance based on cost-effectiveness argument. The quality of current evidence for HCC surveillance in all patients with chronic liver disease is poor, and even lower in those with NAFLD. For a lack of more precise risk-stratification tools, current approaches to defining a target population in noncirrhotic NAFLD are limited to noninvasive tests for liver fibrosis, as a proxy for liver-related morbidity and mortality. Beyond etiology and severity of liver disease, traditional and metabolic risk factors, such as diabetes mellitus, older age, male gender and tobacco smoking, are not enough for HCC risk stratification for surveillance efficacy and effectiveness in NAFLD. There is an association between molecular and genetic factors and HCC risk in NAFLD, and risk models integrating both clinical and genetic factors will be key to personalizing HCC risk. In this review, we discuss concerns regarding defining a target population, surveillance test accuracy, surveillance underuse, and other cost-effective considerations for HCC surveillance in individuals with NAFLD.

Improved Survival After Liver Transplantation for Patients With Human Immunodeficiency Virus (HIV) and HIV/Hepatitis C Virus Coinfection in the Integrase Strand Transfer Inhibitor and Direct-Acting Antiviral Eras.

BACKGROUND: People with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTIs) and direct-acting antivirals (DAAs) have changed the treatment landscape for HIV and HCV, respectively, but their impact on LT outcomes remains unclear. METHODS: This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before versus after approval of INSTIs and in patients with HIV/HCV coinfection who received LT before versus after approval of DAAs. In secondary analysis, we compared the outcomes in the different eras with those of propensity score-matched control cohorts of LT recipients without HIV or HCV infection. RESULTS: LT recipients with HIV monoinfection did not experience a significant improvement in survival between the pre-INSTI and INSTI recipients with HIV (adjusted hazard ratio [aHR], 0.70 [95% confidence interval {CI}, .36-1.34]). However, recipients with HIV/HCV coinfection in the DAA era had a 47% reduction (aHR, 0.53 [95% CI, .31-9.2] in 1-year mortality compared with coinfected recipients in the pre-DAA era. Compared to recipients without HIV or HCV, HIV-monoinfected recipients had higher mortality during the pre-INSTI era, but survival was comparable between groups during the INSTI era. HIV/HCV-coinfected recipients also experienced comparable survival during the DAA era compared to recipients without HCV or HIV. CONCLUSIONS: Post-LT survival for people with HIV monoinfection and HIV/HCV coinfection has improved with the introduction of INSTI and DAA therapy, suggesting that LT has become safer in these populations.

Transplanting hepatitis B surface antigen-positive livers in the United States: Outcomes and opportunities.

Livers from donors with positive hepatitis B surface antigens (HBsAg+) have been used to expand the donor pool; however, outcome data are limited. We aim to evaluate survival following liver transplant (LT) from HBsAg+ donors. Using the United Network for Organ Sharing registry, we identified HBsAg+ donors used for LT from 2009 to 2020. We used Kaplan-Meier survival and Cox proportional hazards regression to compare post-LT survival in hepatitis B virus-negative recipients who utilized HBsAg+ donors to propensity-matched cohorts who utilized other types of donors. From 2009-2020, 70 patients received HBsAg+ livers, and 58 of them did not carry a diagnosis of chronic hepatitis B virus. The 1- and 3-year post-LT survival for hepatitis B virus-negative patients who received livers from HBsAg+ donors were 96.6% and 91.4%, respectively, with no statistical differences compared with patients who received livers from hepatitis C virus viremic donors (96.5%/93.0%, P = .961/.427), donation after cardiac death donors (93.0%/86.0%, P = .651/.598), average-risk donors (89.5%/86.0%, P = 0.264/0.617), and a combination of extended-criteria donors, including donation after cardiac death, donor age over 70, and graft with greater than 30% steatosis (93.0%/91.2%, P = .621/.785). Recipients of HBsAg+ livers have similar post-LT survival compared with those receiving other types of grafts. Increasing the utilization of HBsAg+ livers could safely expand the donor pool.

Longitudinal changes in fibrosis markers are associated with risk of cirrhosis and hepatocellular carcinoma in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Currently, there is no consistent information on the course of fibrosis-4 (FIB-4) score changes in non-alcoholic fatty liver disease (NAFLD) or their association with subsequent risk of cirrhosis and/or hepatocellular carcinoma (HCC). Thus, we aimed to evaluate the association between longitudinal changes in FIB-4 and subsequent risk of HCC and a composite endpoint of cirrhosis and HCC in patients with NAFLD. METHODS: We conducted a retrospective cohort study of patients with NAFLD seen in 130 Veterans Administration hospitals between 1/1/2004-12/31/2008, with follow-up through to 12/31/2018. We calculated FIB-4 longitudinally and categorized patients based on risk of advanced fibrosis (low-risk FIB-4 <1.45, indeterminate-risk FIB-4 1.45-2.67, and high-risk FIB-4 >2.67). We used landmark Fine-Gray competing risks models to determine the effects of change in FIB-4 between NAFLD diagnosis date and 3-year landmark time on the subsequent risk of HCC and a composite endpoint. RESULTS: Among the 202,319 patients with NAFLD in the 3-year landmark analysis, 473 progressed to HCC at an incidence rate of 0.28 per 1,000 person years (PY) (95% CI 0.26-0.30). The incidence rate of the composite endpoint was 1.31 per 1,000 PY (95% CI 1.25-1.37). At baseline, 74.7%, 21.4%, and 3.8% of patients had a low, indeterminate, and high FIB-4, respectively. Compared to patients who were at stable low FIB-4 at both time points, the risk of HCC and that of the composite endpoint was higher for all other subgroups with the highest risk in patients with persistently high FIB-4 (HCC adjusted sub-distribution hazard ratio 57.7, 95% CI 40.5-82.2 and composite endpoint hazard ratio 28.6, 95% CI 24.6-33.2). CONCLUSION: Longitudinal changes in FIB-4 were strongly associated with progression to cirrhosis and HCC. IMPACT AND IMPLICATIONS: Tools to stratify the risk of HCC development in patients with NAFLD are currently lacking. The fibrosis-4 (FIB-4) score is a widely available non-invasive test for liver fibrosis, a primary determinant of the development of cirrhosis and HCC. In a large retrospective cohort of patients with NAFLD, we found that serial changes in FIB-4 over time were strongly associated with progression to cirrhosis and HCC. Integrating serial measurements of non-invasive tests for fibrosis into the care pathway for patients with NAFLD could help tailor HCC risk prevention.

The novel SALT-M score predicts 1-year post-transplant mortality in patients with severe acute-on-chronic liver failure.

BACKGROUND & AIMS: Twenty-eight-day mortality ranges from 30-90% in patients with acute-on-chronic liver failure grades 2/3 (severe ACLF). Though liver transplantation (LT) has demonstrated a survival benefit, the scarcity of donor organs and uncertainty regarding post-LT mortality among patients with severe ACLF may cause hesitancy. We developed and externally validated a model to predict 1-year post-LT mortality in severe ACLF, called the Sundaram ACLF-LT-Mortality (SALT-M) score, and estimated the median length of stay (LoS) after LT (ACLF-LT-LoS). METHODS: In 15 LT centers in the US, we retrospectively identified a cohort of patients with severe ACLF transplanted between 2014-2019, followed up to Jan'2022. Candidate predictors included demographics, clinical and laboratory values, and organ failures. We selected predictors in the final model using clinical criteria and externally validated them in two French cohorts. We provided measures of overall performance, discrimination, and calibration. We used multivariable median regression to estimate LoS after adjusting for clinically relevant factors. RESULTS: We included 735 patients, of whom 521 (70.8%) had severe ACLF (120 ACLF-3, external cohort). The median age was 55 years, and 104 with severe ACLF (19.9%) died within 1-year post-LT. Our final model included age >50 years, use of 1/≥2 inotropes, presence of respiratory failure, diabetes mellitus, and BMI (continuous). The c-statistic was 0.72 (derivation) and 0.80 (validation), indicating adequate discrimination and calibration based on the observed/expected probability plots. Age, respiratory failure, BMI, and presence of infection independently predicted median LoS. CONCLUSIONS: The SALT-M score predicts mortality within 1-year after LT in patients with ACLF. The ACLF-LT-LoS score predicted median post-LT stay. Future studies using these scores could assist in determining transplant benefits. IMPACT AND IMPLICATIONS: Liver transplantation (LT) may be the only life-saving procedure available to patients with acute-on-chronic liver failure (ACLF), but clinically instability can augment the perceived risk of post-transplant mortality at 1 year. We developed a parsimonious score with clinically and readily available parameters to objectively assess 1-year post-LT survival and predict median length of stay after LT. We developed and externally validated a clinical model called the Sundaram ACLF-LT-Mortality score in 521 US patients with ACLF with 2 or ≥3 organ failure(s) and 120 French patients with ACLF grade 3. The c-statistic was 0.72 in the development cohort and 0.80 in the validation cohort. We also provided an estimation of the median length of stay after LT in these patients. Our models can be used in discussions on the risks/benefits of LT in patients listed with severe ACLF. Nevertheless, the score is far from perfect and other factors, such as patient's preference and center-specific factors, need to be considered when using these tools.

Gallstone Disease and Its Association With Nonalcoholic Fatty Liver Disease, All-Cause and Cause-Specific Mortality.

BACKGROUND & AIMS: Presence of gallstone disease may influence outcomes in patients with nonalcoholic fatty liver disease (NAFLD). We studied the impact of gallstone disease on mortality in individuals with and without NAFLD. METHODS: Prospective cohort study used the Third National Health and Nutrition Examination Survey (1988-1994) with mortality data through 2015. Gallstone disease was defined as ultrasonographic evidence of gallstones or absence of the gallbladder (prior cholecystectomy). NAFLD was defined using standardized ultrasonographic criteria. RESULTS: Gallstone disease and cholecystectomy were independently associated with NAFLD (odds ratio [OR], 1.75; 95% confidence interval [CI], 1.43-2.15 for gallstone disease and OR, 2.77; 95% CI, 2.01-3.83 for cholecystectomy compared with no gallstone disease). During the median follow-up of 23 years, gallstone disease was associated with a higher risk of all-cause mortality (hazard ratio [HR], 1.19; 95% CI, 1.05-1.37) and cause-specific mortality. Gallstone disease was associated with a higher risk of all-cause mortality in non-NAFLD sub-cohort (HR, 1.42; 95% CI, 1.23-1.64) but not in NAFLD (HR, 1.03; 95% CI, 0.87-1.22). Gallstone disease was associated with a higher risk of cardiovascular-related (HR, 1.40; 95% CI, 1.10-1.78) and cancer-related (HR, 1.71; 95% CI, 1.18-2.48) mortality in non-NAFLD sub-cohort. Gallstone disease was associated with increased cardiovascular mortality (HR, 1.36; 95% CI, 1.05-1.77) in NAFLD. CONCLUSIONS: Gallstone disease is an independent risk factor for NAFLD, but gallstone disease is not associated with all-cause mortality in individuals with NAFLD. Screening for gallstone disease in individuals at risk for developing NAFLD may help with risk stratification for all-cause mortality related to gallstone disease.

Comparable Survival for Hepatitis C-Related Hepatocellular Carcinoma After Liver Transplantation Irrespective of Viremic Status.

Direct-acting antiviral (DAA) therapy for the treatment of chronic hepatitis C virus (HCV) infection is efficacious and well-tolerated in the post-liver transplant (LT) setting, prompting increased use of donors with HCV infection in patients waitlisted for LT.1,2 Although the incidence of nonviral hepatocellular carcinoma (HCC) is rising, HCV remains the most common risk factor for HCC among patients listed for LT in the United States.3 The use and outcomes of HCV-infected donors among patients with active HCV viremia waitlisted for (HCV-HCC) is lacking. Our aim was to evaluate post-LT survival among patients with HCV-HCC based on both recipient (active vs cured HCV) and donor (HCV+ vs HCV-) viremic status. Using the United Network for Organ Sharing (UNOS) registry, we analyzed all adult patients with HCV-HCC who underwent LT and had available recipient/donor HCV nucleic acid test (NAT) results from March 31, 2015 (date UNOS began reporting donor NAT) through June 30, 2021. Patients with acute liver failure, simultaneous organ transplant, previous LT, and those missing recipient and/or donor NAT results were excluded.

Reduction in Racial and Ethnic Disparity in Survival Following Liver Transplant for Hepatocellular Carcinoma in the Direct-acting Antiviral Era.

BACKGROUND & AIMS: Black patients with hepatocellular cancer (HCC), often attributed to hepatitis C virus (HCV) infection, have suboptimal survival following liver transplant (LT). We evaluated the impact of direct-acting antiviral (DAA) availability on racial and ethnic disparities in wait list burden post-LT survival for candidates with HCC. METHODS: Using the United Network for Organ Sharing registry, we identified patients with HCC who were listed and/or underwent LT from 2009 to 2020. Based on date of LT, patients were categorized into 2 era-based cohorts: the pre-DAA era (LT between 2009 and 2011) and DAA era (LT between 2015 and 2017, with follow-up through 2020). Kaplan-Meier and Cox proportional hazards analyses were used to compare post-LT survival, stratified by era and race and ethnicity. RESULTS: Annual wait list additions for HCV-related HCC decreased significantly in White and Hispanic patients during the DAA era, with no change (P = .14) in Black patients. Black patients had lower 3-year survival than White patients in the pre-DAA era (70.6% vs 80.1%, respectively; P < .001) but comparable survival in the DAA era (82.1% vs 85.5%, respectively; P = .16). 0n multivariable analysis, Black patients in the pre-DAA era had a 53% higher risk (adjusted hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.28-1.84), for mortality than White patients, but mortality was comparable in the DAA era (adjusted HR, 1.23; 95% CI, 0.99-1.52). In a stratified analysis in Black patients, HCV-related HCC carried more than a 2-fold higher risk of mortality in the pre-DAA era (adjusted HR, 2.86; 95% CI, 1.50-5.43), which was reduced in the DAA era (adjusted HR, 1.34; 95% CI, 0.78-2.30). CONCLUSIONS: With the availability of DAA therapy, racial disparities in post-LT survival have improved.

Cost of Care for Patients With Cirrhosis.

INTRODUCTION: There are limited longitudinal data on the cost of treating patients with cirrhosis, which hampers value-based improvement initiatives. METHODS: We conducted a retrospective cohort study of patients with cirrhosis seen in the Veterans Affairs health care system from 2011 to 2015. Patients were followed up through 2019. We identified a sex-matched and age-matched control cohort without cirrhosis. We estimated incremental annual health care costs attributable to cirrhosis for 4 years overall and in subgroups based on severity (compensated, decompensated), cirrhosis complications (ascites, encephalopathy, varices, hepatocellular cancer, acute kidney injury), and comorbidity (Deyo index). RESULTS: We compared 39,361 patients with cirrhosis with 138,964 controls. The incremental adjusted costs for caring of patients with cirrhosis were $35,029 (95% confidence interval $32,473-$37,585) during the first year and ranged from $14,216 to $17,629 in the subsequent 3 years. Cirrhosis complications accounted for most of these costs. Costs of managing patients with hepatic encephalopathy (year 1 cost, $50,080) or ascites ($50,364) were higher than the costs of managing patients with varices ($20,488) or hepatocellular cancer ($37,639) in the first year. Patients with acute kidney injury or those who had multimorbidity were the most costly at $64,413 and $66,653 in the first year, respectively. DISCUSSION: Patients with cirrhosis had substantially higher health care costs than matched controls and multimorbid patients had even higher costs. Cirrhosis complications accounted for most of the excess cost, so preventing complications has the largest potential for cost saving and could serve as targets for improvement.

Trends in mortality of liver cancer before and during the COVID-19 pandemic, 2017-2021.

We studied the trends in liver cancer-related mortality before and during the COVID-19 pandemic. Quarterly age-standardized mortality and quarterly percentage change (QPC) for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) were estimated using the US national mortality database 2017-2021. Quarterly age-standardized mortality from HCC decreased steadily with an average QPC of -0.4% (95% confidence interval [CI]: -0.6% to -0.2%). A decrease in hepatitis C virus and hepatitis B virus-related HCC mortality of -2.2% (95% CI: -2.4% to -1.9%) and -1.1% (95% CI: -2.0% to -0.3%) was noted. In contrast, mortality for HCC from nonalcoholic fatty liver disease (3.0%, 95% CI: 2.0%-4.0%) and alcohol-related liver disease (1.3%, 95% CI: 0.8%-1.9%) demonstrated a linear increase. There was a linear increase in the quarterly age-standardized ICC-related mortality (0.8%, 95% CI: 0.5%-1.0%). While ICC-related mortality continued to increase, HCC-related mortality tended to decline mainly due to a decline in mortality due to viral hepatitis.

Biliary atresia and liver transplantation in the United States: A contemporary analysis.

BACKGROUND: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. METHODS: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non-BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing-risk regression analysis, graft survival rates were compared using Kaplan-Meier time-to-event analysis and Cox proportional hazards modelling provided adjusted estimates. RESULTS: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non-BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living-donor liver transplantations (LDLT) and 611 (27.7%) split deceased-donor LTs. Five-year graft survival was significantly higher among BA versus non-BA cholestatic patients in the older group (88.3% vs. 79.5%, p < .01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03-3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87-6.2). CONCLUSION: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes.

Clinical Course and Outcomes of Patients with Nonalcoholic Fatty Liver Disease-Related Hepatocellular Cancer (NAFLD-HCC).

BACKGROUND & AIMS: Among etiologies for hepatocellular (HCC), nonalcoholic fatty liver disease (NAFLD) carries a high risk of competing non-cancer mortality. The effect of cancer and non-cancer factors on risk of death after NAFLD-HCC diagnosis remains unclear. We aimed to evaluate the role of non-cancer mortality with NAFLD-HCC. METHODS: Using a retrospective cohort of patients with NAFLD diagnosed at 130 facilities in the Veterans Administration, we identified patients with incident HCC diagnosed between January 1, 2005 and June 30, 2018. We determined cause of death as HCC-related, non-HCC liver-related, and non-liver-related after HCC diagnosis. We used Cox proportional hazards regression models to evaluate the effect of clinical factors on cause-specific mortality after NAFLD-HCC diagnosis. RESULTS: We identified 776 patients with incident HCC. Mean age at HCC diagnosis was 70.1 year, 22.2% had Barcelona Clinic Liver Cancer (BCLC) stage 0-A, and 67.0% had more than one comorbidity. 1- and 3-year mortality rates were 47.0% and 69.6%, respectively. Most deaths (72.2% at 3 years) were attributable to HCC. In HCC patients who received curative treatment, non-cancer mortality accounted for 40% of all deaths between 3 and 5 years after treatment. Poor performance status (ECOG 3/4, HR 5.03, 95% CI: 2.59-9.77) and older age (65-75, HR 1.94, 95% CI: 1.06-3.54) were strongly associated with non-cancer mortality. CONCLUSION: Although most patients with NAFLD-HCC die of HCC, non-cancer mortality represents a clinically meaningful competing event for patients receiving curative treatment, underscoring the importance of assessing and managing risk factors of non-cancer morbidity and mortality. TRIAL AND REGISTRATION: N/A.

Predictive Algorithm for Hepatic Steatosis Detection Using Elastography Data in the Veterans Affairs Electronic Health Records.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) has reached pandemic proportions. Early detection can identify at-risk patients who can be linked to hepatology care. The vibration-controlled transient elastography (VCTE) controlled attenuation parameter (CAP) is biopsy validated to diagnose hepatic steatosis (HS). We aimed to develop a novel clinical predictive algorithm for HS using the CAP score at a Veterans' Affairs hospital. METHODS: We identified 403 patients in the Greater Los Angeles VA Healthcare System with valid VCTEs during 1/2018-6/2020. Patients with alcohol-associated liver disease, genotype 3 hepatitis C, any malignancies, or liver transplantation were excluded. Linear regression was used to identify predictors of NAFLD. To identify a CAP threshold for HS detection, receiver operating characteristic analysis was applied using liver biopsy, MRI, and ultrasound as the gold standards. RESULTS: The cohort was racially/ethnically diverse (26% Black/African American; 20% Hispanic). Significant positive predictors of elevated CAP score included diabetes, cholesterol, triglycerides, BMI, and self-identifying as Hispanic. Our predictions of CAP scores using this model strongly correlated (r = 0.61, p < 0.001) with actual CAP scores. The NAFLD model was validated in an independent Veteran cohort and yielded a sensitivity of 82% and specificity 83% (p < 0.001, 95% CI 0.46-0.81%). The estimated optimal CAP for our population cut-off was 273.5 dB/m, resulting in AUC = 75.5% (95% CI 70.7-80.3%). CONCLUSION: Our HS predictive algorithm can identify at-risk Veterans for NAFLD to further risk stratify them by non-invasive tests and link them to sub-specialty care. Given the biased referral pattern for VCTEs, future work will need to address its applicability in non-specialty clinics. Proposed clinical algorithm to identify patients at-risk for NAFLD prior to fibrosis staging in Veteran.

Physical Activity Is Associated With Nonalcoholic Fatty Liver Disease and Significant Fibrosis Measured by FibroScan.

BACKGROUND AND AIMS: Studies evaluating the association of 2018 Physical Activity Guidelines for Americans (PA Guidelines) with nonalcoholic fatty liver disease (NAFLD) and significant fibrosis or cirrhosis are needed. We evaluated the association of meeting PA Guidelines with NAFLD and significant fibrosis or cirrhosis by transient elastography in the United States. METHODS: A cross-sectional analysis was performed using the 2017-2018 U.S. National Health and Nutrition Examination Survey data. NAFLD and significant fibrosis or cirrhosis were defined by transient elastography in the absence of other causes of chronic liver disease. The detailed PA questionnaire assessed the leisure-time, occupation-related, and transportation-related PA. PA was categorized based on the PA Guidelines. RESULTS: Of the 4304 subjects, leisure-time PA, which met the PA Guidelines (≥150 min/wk), was associated with 44% lower risk of NAFLD (odds ratio [OR]: 0.56; 95% confidence interval [CI]: 0.46-0.67). Subjects who reported 1-2 times (150-299 min/wk) or over 2 times (≥300 min/wk) the recommended amount of PA Guidelines had 40% (OR, 0.60; 95% CI, 0.41-0.90) and 49% (OR, 0.51; 95% CI, 0.40-0.65) lower odds of NAFLD, respectively. Over 8 hours of sitting time had a 44% higher risk of NAFLD (OR, 1.44; 95% CI, 1.01-2.05) when we considered leisure-time PA and sitting time simultaneously. Over 2 times (≥300 min/wk) the recommended amount of PA Guidelines for leisure-time PA had 59% (OR, 0.41; 95% CI, 0.22-0.74) lower risk for significant fibrosis and 63% (OR, 0.37; 95% CI, 0.21-0.64) lower odds of cirrhosis. CONCLUSIONS: Meeting PA Guidelines for leisure-time PA has beneficial effects on NAFLD, and over 2 times the recommended amount of PA Guidelines had lower risk for significant fibrosis or cirrhosis.