Access to technology to support telehealth in areas without specialty care for liver disease.

BACKGROUND AND AIMS: Telehealth may be a successful strategy to increase access to specialty care for liver disease, but whether the areas with low access to care and a high burden of liver-related mortality have the necessary technology access to support a video-based telehealth strategy to expand access to care is unknown. APPROACH AND RESULTS: Access to liver disease specialty care was defined at the county level as <160.9 km (100 miles) from a liver transplant (LT) center or presence of local gastroenterology (GI). Liver-related mortality rates were compared by access to care, and access to technology was compared by degree of access to care and burden of liver-related mortality. Counties with low access to liver disease specialty care had higher rates of mortality from liver disease, and this was highest in areas both >160.9 km from an LT center and without local GI. These counties were more rural, had higher poverty, and had decreased access to devices and internet at broadband speeds. Technology access was lowest in areas with low access to care and the highest burden of liver-related mortality. CONCLUSIONS: Areas with poor access to liver disease specialty care have a greater burden of liver-related mortality, and many of their residents lack access to technology. Therefore, a telehealth strategy based solely on patient device ownership and internet access will exclude a large proportion of individuals in the areas of highest need. Further work should be done at the local and state levels to design optimal strategies to reach their populations of need.

Evaluation of the Potential Utility of an Artificial Intelligence Chatbot in Gastroesophageal Reflux Disease Management.

INTRODUCTION: Artificial intelligence chatbots could serve as an information resource for patients and a tool for clinicians. Their ability to respond appropriately to questions regarding gastroesophageal reflux disease is unknown. METHODS: Twenty-three prompts regarding gastroesophageal reflux disease management were submitted to ChatGPT, and responses were rated by 3 gastroenterologists and 8 patients. RESULTS: ChatGPT provided largely appropriate responses (91.3%), although with some inappropriateness (8.7%) and inconsistency. Most responses (78.3%) contained at least some specific guidance. Patients considered this a useful tool (100%). DISCUSSION: ChatGPT's performance demonstrates the potential for this technology in health care, although also its limitations in its current state.

Characterization of social determinants of health of a liver transplant referral population.

Disparities exist in referral and access to the liver transplant (LT) waitlist, and social determinants of health (SDOH) are increasingly recognized as important factors driving health inequities, including in LT. The SDOH of potential transplant candidates is therefore important to characterize when designing targeted interventions to promote equity in access to LT. Yet, it is uncertain how a transplant center should approach this issue, characterize SDOH, identify disparities, and use these data to inform interventions. We performed a retrospective study of referrals for first-time, single-organ LT to our center from 2016 to 2020. Addresses were geoprocessed and mapped to the corresponding county, census tract, and census block group to assess their geospatial distribution, identify potential disparities in referrals, and characterize their communities across multiple domains of SDOH to identify potential barriers to evaluation and selection. We identified variability in referral patterns and areas with disproportionately low referrals, including counties in the highest quartile of liver disease mortality (9%) and neighborhoods in the highest quintile of socioeconomic deprivation (17%) and quartile of poverty (21%). Black individuals were also under-represented compared with expected state demographics (12% vs. 18%). Among the referral population, several potential barriers to evaluation and selection for LT were identified, including poverty, educational attainment, access to healthy food, and access to technology. This approach to the characterization of a transplant center's referral population by geographic location and associated SDOH demonstrates a model for identifying disparities in a referral population and potential barriers to evaluation that can be used to inform targeted interventions for disparities in LT access.

Performance of the Pooled Cohort Equations in non-alcoholic fatty liver disease: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of cardiovascular disease. Whether risk scores developed in the general population accurately assess cardiovascular risk in the NAFLD population is unknown. This study aimed to evaluate the performance of the Pooled Cohort Equations (PCE) in NAFLD. METHODS: Individuals in the Multi-Ethnic Study of Atherosclerosis with baseline non-contrast cardiac computed tomography scans with sufficient data to determine the presence of hepatic steatosis were identified and assessed for the development of incident 10-year atherosclerotic cardiovascular disease. The discrimination and calibration of the PCE were evaluated, and the observed and expected events by risk category (<5%, 5-<7.5%, 7.5-<20%, ≥20%) were determined. Risk reclassification with the addition of NAFLD to the PCE was assessed. RESULTS: Of 4014 participants included, 698 (17.4%) with NAFLD were identified, including 247 (35.3%) with moderate-to-severe steatosis. Discrimination of the PCE was suboptimal in NAFLD (c-statistic 0.69), particularly moderate-to-severe steatosis (0.65), and calibration was overall poor. While risk was overestimated in non-NAFLD, it was underestimated in NAFLD in lower/intermediate risk categories, predominantly in women (5-<7.5% observed/expected ratio = 1.67). The addition of NAFLD to the PCE improved risk classification in women. CONCLUSIONS: The PCE overall performed suboptimally in cardiovascular risk assessment in NAFLD, particularly in women and individuals with moderate-to-severe steatosis in clinically relevant risk categories. Primary prevention may need to be considered at a lower risk threshold in these groups, and further work is needed to improve risk stratification in this growing high-risk population.

Social determinants of health data in solid organ transplantation: National data sources and future directions.

Health equity research in transplantation has largely relied on national data sources, yet the availability of social determinants of health (SDOH) data varies widely among these sources. We sought to characterize the extent to which national data sources contain SDOH data applicable to end-stage organ disease (ESOD) and transplant patients. We reviewed 10 active national data sources based in the United States. For each data source, we examined patient inclusion criteria and explored strengths and limitations regarding SDOH data, using the National Institutes of Health PhenX toolkit of SDOH as a data collection instrument. Of the 28 SDOH variables reviewed, eight-core demographic variables were included in ≥80% of the data sources, and seven variables that described elements of social status ranged between 30 and 60% inclusion. Variables regarding identity, healthcare access, and social need were poorly represented (≤20%) across the data sources, and five of these variables were included in none of the data sources. The results of our review highlight the need for improved SDOH data collection systems in ESOD and transplant patients via: enhanced inter-registry collaboration, incorporation of standardized SDOH variables into existing data sources, and transplant center and consortium-based investigation and innovation.

Patient-Predicted Outcomes Are Associated with Quality of Life in Patients with Primary Sclerosing Cholangitis.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, progressive liver disease, and many patients ultimately require liver transplantation (LT). PSC also confers an increased risk of malignancies, including cholangiocarcinoma (CCA) and colorectal cancer. AIMS: This study aimed to evaluate patient-perceived outcomes and the extent to which these impact health-related quality of life (HRQoL). METHODS: Patients with PSC completed a risk perception questionnaire, the Short Form-36 (SF-36), and the Chronic Liver Disease Questionnaire. Multivariable models were used to determine factors associated with patient-perceived risks of malignancy, LT, and life expectancy, as well as their relationship with HRQoL scores. RESULTS: A total of 95 patients completed the risk perception questionnaire, and 73 returned the remaining instruments. The estimated risks varied widely. Half overestimated their one-year or lifetime CCA risk, while some predicted zero chance. Predicted LT risk was the only outcome concordant with disease severity. Pruritus was associated with higher predicted one-year risks and lower life expectancy. Lifetime CCA and LT risks were associated with the SF-36 physical component score, while perceived life expectancy was strongly associated with mental health domains, including the SF-36 mental component score. CONCLUSIONS: Predicted prognosis varies widely among patients with PSC and is influenced more by symptoms than objective disease severity. The psychological burden of shorter perceived life expectancy impacts mental HRQoL more than the risks of malignancy or LT. These findings highlight an opportunity for improved patient communication regarding these outcomes, as well as the importance of discussing them, as they may impact HRQoL.

Daily Aspirin Use Associated With Reduced Risk For Fibrosis Progression In Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: There are few data from prospective studies on the effects of aspirin on fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We performed a prospective cohort study of 361 adults with biopsy-confirmed NAFLD, from 2006 through 2015, examined every 3-12 months for incident advanced fibrosis defined using serial measurements of validated indices (the Fibrosis-4, NAFLD fibrosis score, and aspartate aminotransferase to platelet ratio indices). Histologic analyses of liver biopsies collected at baseline were performed by a blinded pathologist. Information collected at baseline and at each examination included frequency and duration of aspirin and nonsteroidal anti-inflammatory drug (NSAID) use. Using multivariable-adjusted logistic regression, we estimated the association of aspirin use with prevalent steatohepatitis (NASH) and fibrosis. Using multivariable-adjusted Cox proportional hazards modeling, we estimated the association between aspirin use and risk for fibrosis progression. RESULTS: At enrollment, 151 subjects used aspirin daily. Compared with non-regular use, daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% CI, 0.37-0.89) and fibrosis (adjusted odds ratio, 0.54; 95% CI, 0.31-0.82). Among individuals with baseline F0-F2 fibrosis (n = 317), 86 developed advanced fibrosis over 3692 person-years. Daily aspirin users had significantly lower risk for developing incident advanced fibrosis vs non-regular users (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.43-0.85). This relationship appeared to be duration dependent (adjusted P trend=.026), with the greatest benefit found with at least 4 years or more of aspirin use (aHR, 0.50; 95% CI, 0.35-0.73). Conversely, use of nonaspirin NSAIDs was not associated with risk for advanced fibrosis (aHR, 0.93; 95% CI, 0.81-1.05). CONCLUSIONS: In a prospective study of patients with biopsy-proven NAFLD, daily aspirin use was associated with less severe histologic features of NAFLD and NASH, and lower risk for progression to advanced fibrosis with time.

The association of hepatitis C infection with the onset of CKD and progression into ESRD.

Hepatitis C virus (HCV) infection is not only an important cause of chronic liver disease, but extrahepatic manifestations are common and include chronic kidney disease (CKD). HCV is classically associated with cryoglobulinemic glomerulonephritis in the context of mixed cryoglobulinemia syndrome, but other glomerular diseases also occur and may be significantly under-recognized. HCV may cause glomerular disease by immune complex deposition; however, other potential mechanisms by which HCV promotes CKD include a direct cytopathic effect of the virus on renal tissue, and by its association with accelerated atherosclerosis, insulin resistance, and chronic inflammation. Epidemiologic studies show HCV infection confers an increased risk of incident CKD and accelerates progression of CKD to end-stage renal disease (ESRD) in the general population, as well as subpopulations including diabetic patients, those coinfected with human immunodeficiency virus (HIV), and kidney transplant recipients. Patients with CKD and HCV infection experience inferior clinical outcomes, including poorer quality of life and an increased risk of mortality. Treatment with interferon-based regimens is associated with decreased risk of incident CKD and ESRD, though prior studies are limited by the small number of patients with HCV and CKD who underwent treatment. With the advent of new, well-tolerated direct-acting antiviral combinations that are not cleared by the kidneys, it is possible to treat all genotypes of HCV infection in patients with CKD and ESRD. More data on the effect of direct-acting antivirals on CKD incidence and progression are necessary. However, there is every expectation that with improved access to HCV treatment, the burden of CKD in patients with HCV could significantly decline.

The impact of human leukocyte antigen donor and recipient serotyping and matching on liver transplant graft failure in primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cholangitis.

Human leukocyte antigen (HLA) serotyping is not considered to have significant impact on liver graft survival and does not factor into U.S. organ allocation. Immune-related liver diseases such as primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and primary biliary cholangitis (PBC) have been speculated to represent a disease subgroup that may have significantly different graft outcomes depending on HLA donor/recipient characterization. The aim of this study was to investigate whether HLA serotyping/matching influenced post-transplant graft failure for immune-related liver diseases using the United Network for Organ Sharing database. From 1994 to 2015, 5665 patients underwent first-time liver-only transplants for PSC, AIH, and PBC with complete graft survival and donor/recipient HLA data. Graft failure was noted in 38.6% (2188/5665), and all groups had comparable 5-year graft survival (75.1%-78.8%, P = 0.069). The overall degree of, and loci-specific mismatch level, did not influence outcomes. Multivariable Cox proportional hazards regression noted increased graft failure risk for recipient HLA-B7, HLA-B57, HLA-B75, HLA-DR13 and donor HLA-B55, HLA-B58, and HLA-DR8 for PSC patients, protective effects for recipient HLA-DR1 and HLA-DR3 for AIH patients, and increased risk for HLA-DR7 for AIH patients. These findings warrant further investigation to evaluate the impact of HLA serotyping on post-transplant outcomes.

Outcomes of liver retransplantation in patients with primary sclerosing cholangitis.

Liver retransplantation in patients with primary sclerosing cholangitis (PSC) has not been well studied. The aims of this study were to characterize patients with PSC listed for and undergoing retransplantation and to describe the outcomes in these patients. The United Network for Organ Sharing/Organ Procurement and Transplantation Network database was used to identify all primary liver transplantations and subsequent relistings and first retransplantations in adults with PSC between 1987 and 2015. A total of 5080 adults underwent primary transplantation for PSC during this period, and of the 1803 who experienced graft failure (GF), 762 were relisted, and 636 underwent retransplantation. Younger patients and patients with GF due to vascular thrombosis or biliary complications were more likely to be relisted, whereas those with Medicaid insurance or GF due to infection were less likely. Both 5-year graft and patient survival after retransplantation were inferior to primary transplantation (P < 0.001). Five-year survival after retransplantation for disease recurrence (REC), however, was similar to primary transplantation (graft survival, P = 0.45; patient survival, P = 0.09) and superior to other indications for retransplantation (graft and patient survival, P < 0.001). On multivariate analysis, mechanical ventilation, creatinine, bilirubin, albumin, advanced donor age, and a living donor were associated with poorer outcomes after retransplantation. In conclusion, although survival after liver retransplantation in patients with PSC was overall inferior to primary transplantation, outcomes after retransplantation for PSC REC were similar to primary transplantation at 5 years. Retransplantation may therefore represent a treatment option with the potential for excellent outcomes in patients with REC of PSC in the appropriate clinical circumstances. Liver Transplantation 23 769-780 2017 AASLD.

Complementary and Alternative Medicine Use in United States Adults With Liver Disease.

GOALS: To describe the complementary and alternative medicine (CAM) use in US adults with liver disease. BACKGROUND: The prevalence and patterns of CAM use among US adults with liver disease have not been well characterized. The 2012 National Health Interview Survey is considered the most current and comprehensive source of information on CAM use in US adults. STUDY: Using the results of the 2012 National Health Interview Survey, the prevalence of CAM use, most common modalities used, reasons for CAM use, perceived benefits, perceived helpfulness and importance, and disclosure of CAM to health care providers were compared between adults with and without liver disease. RESULTS: Of the 647 adults with liver disease, 41% reported using CAM in the prior year, compared with 33% of adults without liver disease. The most common modality was herbs and supplements (23%), and 3% of respondents reported consumption of a potentially hepatotoxic substance in the previous 30 days. Only a small proportion of CAM therapies were used specifically for liver disease, with milk thistle being the most common. Among respondents with liver disease, CAM was used more commonly for anxiety or depression, fatigue, and substance use. The majority believed that these therapies improved health. Nearly one-third of therapies were not reported to health care providers, mostly due to failure of the provider to ask. CONCLUSIONS: CAM use, particularly herbs and supplements, is prevalent among US adults with liver disease. Many do not disclose their CAM use to their providers, despite some using potentially hepatotoxic substances.

Differences in Phenotypes and Liver Transplantation Outcomes by Age Group in Patients with Primary Sclerosing Cholangitis.

BACKGROUND: There is increasing evidence for a heterogeneity of phenotypes in primary sclerosing cholangitis (PSC), but differences across the age spectrum in adults with PSC have not been well characterized. AIMS: To characterize phenotypic variations and liver transplantation outcomes by age group in adults with PSC. METHODS: The United Network for Organ Sharing database was used to identify waitlist registrations for primary liver transplantation in adults with PSC. Patients were split into three age groups: 18-39 (young), 40-59 (middle-aged), and ≥60 (older). Their clinical characteristics and outcomes on the waitlist and post-transplant were compared. RESULTS: Overall, 8272 adults with PSC were listed for liver transplantation during the study period, of which 28.9% were young, 52.0% were middle-aged, and 19.1% were older. The young age group had the greatest male predominance (70.0 vs. 66.2 vs. 65.1%, p = 0.001), the highest proportion of black individuals (20.0 vs. 11.0 vs. 5.5%, p < 0.001), and the most patients listed with concomitant autoimmune hepatitis (2.2 vs. 1.0 vs. 0.8%, p < 0.001). Older patients experienced the greatest waitlist and post-transplant mortality. Graft survival was greatest in the middle-aged group. Young patients were most likely to experience acute rejection (31 vs. 22.8 vs. 18.0%, p < 0.001) and have graft failure due to chronic rejection or PSC recurrence (47.8 vs. 42.3 vs. 17.9%, p < 0.001). CONCLUSIONS: Age-related differences exist among adults with PSC and are associated with outcomes pre- and post-transplant. Young patients may have a more robust immune-related phenotype that is associated with poorer graft survival. Future studies are needed to further investigate these findings.

Post-Transplant Management and Complications of Autoimmune Hepatitis, Primary Biliary Cholangitis, and Primary Sclerosing Cholangitis including Disease Recurrence.

Autoimmune liver diseases have unique post-transplant considerations. These recipients are at increased risk of rejection, and recurrent disease may also develop, which can progress to graft loss and increase mortality. Monitoring for and managing these complications is therefore important, though data on associated risk factors and immunosuppression strategies has in most cases been mixed. There are also other disease-specific complications that require management and may impact these decisions, including inflammatory bowel disease in PSC. Further work to better understand the optimal management strategies for these patients post-transplant is needed.

Hypophosphatemia as a Predictor of Clinical Outcomes in Acute Pancreatitis: A Retrospective Study.

OBJECTIVE: Phosphate is crucial for cellular repair after injury and may be important in recovery following acute pancreatitis (AP). This study aimed to evaluate the association between hypophosphatemia and severity of AP. METHODS: Patients admitted with AP between 2014-2018 were identified and their records were retrospectively reviewed. Pancreatitis severity was defined using the modified Atlanta Criteria. Hypophosphatemia was defined as phosphate <2 mg/dL and was assessed at three time points: within one day, within two days, at any time during admission. The proportion of patients who developed severe AP was compared between patients with and without hypophosphatemia. RESULTS: Of 312 patients, 30.1% (n = 94) developed severe AP. Hypophosphatemia occurred in 25.0% overall, within one day in 19.7%, and within two days in 20.0%. A higher proportion of patients with hypophosphatemia developed severe AP (overall: 47.4% vs. 24.4%, P < 0.001; one day: 47.4% vs. 23.9%, P = 0.004; two days: 42.9% vs. 24.5%, P = 0.01). Patients with hypophosphatemia within one day were also more likely to have ICU admission ( P < 0.001) and longer length of stay ( P < 0.001). CONCLUSIONS: Early hypophosphatemia during an admission for AP was associated with increased AP severity, ICU admission, and longer length of stay.

Evaluation of an Abnormal Liver Panel After Liver Transplantation.

Abnormal liver tests are common after liver transplantation. The differential diagnosis depends on the clinical context, particularly the time course, pattern and degree of elevation, and donor and recipient factors. The perioperative period has distinct causes compared with months and years after transplant, including ischemia-reperfusion injury, vascular thrombosis, and primary graft nonfunction. Etiologies seen beyond the perioperative period include biliary complications, rejection, infection, recurrent disease, and non-transplant-specific causes. The evaluation begins with a liver ultrasound with Doppler as well as appropriate laboratory testing and culminates in a liver biopsy if the imaging and laboratory testing is unrevealing.

Rates of employment after liver transplant: A nationwide cohort study.

BACKGROUND: Employment outcomes after liver transplant (LT) over the past decade have not been described. METHODS: LT recipients ages 18-65 from 2010-2018 were identified in Organ Procurement and Transplantation Network data. Employment within two years post-transplant was assessed. RESULTS: Of 35,340 LT recipients, 34.2% were employed post-LT, including 70.4% who were working pre-transplant, compared to only 18.2% not working preLT. Younger age, male sex, educational attainment, and functional status were associated with returning to employment. CONCLUSION: Returning to employment is an important goal for many LT candidates and recipients, and these findings can be used to guide their expectations.

Recent updates in preemptive transjugular intrahepatic portosystemic shunt for acute variceal bleeding.

Content available: Author Interview and Audio Recording.

Risk of Cardiovascular Disease in Individuals With Nonobese Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is independently associated with obesity and cardiovascular disease (CVD). CVD is the primary cause of mortality in the predominantly obese population of adults with NAFLD. NAFLD is increasingly seen in individuals who are lean and overweight (i.e., nonobese), but it is unclear whether their risk of CVD is comparable to those with NAFLD and obesity. Using a prospective cohort of patients with NAFLD, we compared the prevalence and incidence of CVD in individuals with and without obesity. NAFLD was diagnosed by biopsy or imaging after excluding other chronic liver disease etiologies. Logistic regression was used to compare the odds of baseline CVD by obesity status. Cox proportional hazards regression was used to evaluate obesity as a predictor of incident CVD and to identify predictors of CVD in subjects with and without obesity. At baseline, adults with obesity had a higher prevalence of CVD compared to those without obesity (12.0% vs. 5.0%, P = 0.02). During follow-up, however, obesity did not predict incident CVD (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.69-2.22) or other metabolic diseases. Findings were consistent when considering body mass index as a continuous variable and after excluding subjects who were overweight. Age (adjusted HR [aHR], 1.05; 95% CI, 1.03-1.08), smoking (aHR, 4.61; 95% CI, 1.89-11.22), and decreased low-density lipoprotein levels (aHR, 0.98; 95% CI, 0.96-1.00) independently predicted incident CVD in the entire cohort, in subjects with obesity, and in those without obesity, respectively. Conclusion: Individuals with overweight or lean NAFLD are not protected from incident CVD compared to those with NAFLD and obesity, although CVD predictors appear to vary between these groups. Patients without obesity also should undergo rigorous risk stratification and treatment.