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.

Decreased Completion of Ordered Laboratories and Imaging in Telehealth Compared With In-person Hepatology Encounters.

OBJECTIVE: To evaluate order completion after telehealth compared with in-person encounters. BACKGROUND: Completion of ordered testing, including laboratories and imaging, is an important aspect of successful outpatient care of patients with liver disease. Whether the completion of orders from telehealth encounters differs from in-person visits is unknown. MATERIALS AND METHODS: Completion of ordered laboratories and imaging from hepatology encounters at our center from 2021 to 2022 were evaluated and compared between video telehealth and in-person visits. Laboratory completion was evaluated at 14 days, 30 days, and 90 days, and imaging completion was assessed at 1 year. RESULTS: Telehealth encounters were significantly less likely to have laboratories completed at all evaluated time points (14 d: 40.7% vs 90.9%; 30 d: 50.9% vs 92.2%; 90 d: 63.9% vs 94.3%, P< 0.001 for all). Among telehealth encounters, encounters in patients more remote from the center were less likely to have laboratories completed. Imaging ordered at telehealth encounters was also less likely to be completed within 1 year (62.5% vs 70.1%, P< 0.001), including liver ultrasounds (59.1% vs 67.6%, P= 0.001), which persisted when limited to encounters for cirrhosis (55.8% vs 66.4%, P= 0.01). CONCLUSIONS: Telehealth encounters were significantly less likely to have ordered laboratories and imaging completed compared with in-person visits, which has important clinical implications for effective outpatient care of patients with liver disease. Further research is needed to better understand the barriers to order completion for telehealth visits and ways to optimize this to improve the effectiveness of this visit modality.

Provider Attitudes Toward Risk-Based Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis in the United States.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance rates are suboptimal in clinical practice. We aimed to elicit providers' opinions on the following aspects of HCC surveillance: preferred strategies, barriers and facilitators, and the impact of a patient's HCC risk on the choice of surveillance modality. METHODS: We conducted a web-based survey among gastroenterology and hepatology providers (40% faculty physicians, 21% advanced practice providers, 39% fellow-trainees) from 26 US medical centers in 17 states. RESULTS: Of 654 eligible providers, 305 (47%) completed the survey. Nearly all (98.4%) of the providers endorsed semi-annual HCC surveillance in patients with cirrhosis, with 84.2% recommending ultrasound ± alpha fetoprotein (AFP) and 15.4% recommending computed tomography (CT) or magnetic resonance imaging (MRI). Barriers to surveillance included limited HCC treatment options, screening test effectiveness to reduce mortality, access to transportation, and high out-of-pocket costs. Facilitators of surveillance included professional society guidelines. Most providers (72.1%) would perform surveillance even if HCC risk was low (≤0.5% per year), while 98.7% would perform surveillance if HCC risk was ≥1% per year. As a patient's HCC risk increased from 1% to 3% to 5% per year, providers reported they would be less likely to order ultrasound ± AFP (83.6% to 68.9% to 57.4%; P < .001) and more likely to order CT or MRI ± AFP (3.9% to 26.2% to 36.1%; P < .001). CONCLUSIONS: Providers recommend HCC surveillance even when HCC risk is much lower than the threshold suggested by professional societies. Many appear receptive to risk-based HCC surveillance strategies that depend on patients' estimated HCC risk, instead of our current "one-size-fits all" strategy.

Telemedicine in Hepatology: Current Applications and Future Directions.

Telemedicine refers to the use of information and communication technologies for providing health care at a distance. Through the use of telecommunication technologies such as cell phones, computers, and other electronic devices, health care providers are able to conduct patient visits, mentor/train other providers, and monitor patients' chronic diseases remotely, potentially hundreds or thousands of miles away. Over the past 2 decades, the use of telemedicine has grown in the field of hepatology. In this review, we provide a focused primer on telemedicine and its current applications in hepatology. In particular, we discuss the use of telemedicine in the management of chronic hepatitis C, the complications of liver disease, as well as preliver transplantation evaluation and posttransplantation care. In addition, we provide a synopsis of the effect of the coronavirus disease 2019 (COVID-19) pandemic on the use of telemedicine in hepatology.

Burden of early hospitalization after simultaneous liver-kidney transplantation: Results from the US Multicenter SLKT Consortium.

The burden of early hospitalization (within 6 months) following simultaneous liver-kidney transplant (SLKT) is not known. We examined risk factors associated with early hospitalization after SLKT and their impact on patient mortality conditional on 6-month survival. We used data from the US Multicenter SLKT Consortium cohort study of all adult SLKT recipients between 2002 and 2017 who were discharged alive following SLKT. We used Poisson regression to model rates of early hospitalizations after SLKT. Cox regression was used to identify risk factors associated with mortality conditional on survival at 6 months after SLKT. Median age (N = 549) was 57.7 years (interquartile range [IQR], 50.6-63.9) with 63% males and 76% Whites; 33% had hepatitis C virus, 20% had non-alcohol-associated fatty liver disease, 23% alcohol-associated liver disease, and 24% other etiologies. Median body mass index (BMI) and Model for End-Stage Liver Disease-sodium scores were 27.2 kg/m2 (IQR, 23.6-32.2 kg/m2 ) and 28 (IQR, 23-34), respectively. Two-thirds of the cohort had at least one hospitalization within the first 6 months of SLKT. Age, race, hospitalization at SLKT, diabetes mellitus, BMI, and discharge to subacute rehabilitation (SAR) facility after SLKT were independently associated with a high incidence rate ratio of early hospitalization. Number of hospitalizations within the first 6 months did not affect conditional survival. Early hospitalizations after SLKT were very common but did not affect conditional survival. Although most of the risk factors for early hospitalization were nonmodifiable, discharge to SAR after initial SLKT was associated with a significantly higher incidence rate of early hospitalization. Efforts and resources should be focused on identifying SLKT recipients at high risk for early hospitalization to optimize their predischarge care, discharge planning, and long-term follow-up.

Identifying Ascites in Patients with Cirrhosis Using Administrative Codes and Diuretic Use: A Multicenter Study.

BACKGROUND: Ascites is associated with significantly increased morbidity, mortality, and health care costs. Large population studies are necessary to determine the burden and impact of ascites; however, ascites ICD-10 codes perform poorly in the identification of patients. METHODS: We utilized three independent retrospective cohorts at the University of Michigan (cohorts 1 and 2) and Duke University (cohort 3). Cohort 1: Child A5-6 patients followed up to 10 years (n = 150); cohort 2: Child A5-B7 patients with portal hypertension followed for up to 1 year (n = 65); cohort 3: cross-sectional cohort of patients evaluated for liver transplant (n = 100). We computed performance characteristics for ascites-related ICD-10 codes (K70.31, K70.11, K71.51, R18.8), as well as loop and/or potassium-sparing diuretics. RESULTS: A total of 315 patients were included across three cohorts. Algorithms including any ascites code provided better sensitivity and equivalent specificity to R18.8 alone for all cohorts. In cohort 2, we found that loop diuretics, potassium-sparing diuretics, and a combination of both with a cirrhosis code were highly sensitive (82.3% for each) and specific (89.1-93.5%). In contrast, ascites codes were insensitive. In patients with moderate-severe ascites, a combination of recorded diuretics showed high sensitivity and specificity (95.2% and 86.8%). In Cohort 3's transplant evaluation patients, we found that loop diuretics, potassium-sparing diuretics, and a combination of both with a cirrhosis code were highly sensitive (90.4%, 78.8% and 75.0%, respectively) and specific (85.0%, 90.0% and 95.0%, respectively). For moderate-severe cirrhosis, loop diuretics and R18.8 showed higher sensitivity (77.8%) and specificity (88.9%), respectively. CONCLUSION: Diuretic records with a cirrhosis code improve the identification of ascites. This method for identifying ascites should be used in future large dataset studies.

Racial and Socioeconomic Disparities in Utilization of Telehealth in Patients with Liver Disease During COVID-19.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic resulted in a rapid expansion of telehealth services in hepatology. However, known racial and socioeconomic disparities in internet access potentially translate into barriers for the use of telehealth, particularly video technology. The specific aim of this study was to determine if disparities in race or socioeconomic status exist among patients utilizing telehealth visits during COVID-19. METHODS: We performed a retrospective cohort study of all adult patients evaluated in hepatology clinics at Duke University Health System. Visit attempts from a pre-COVID baseline period (January 1, 2020 through February 29, 2020; n = 3328) were compared to COVID period (April 1, 2020 through May 30, 2020; n = 3771). RESULTS: On multinomial regression modeling, increasing age was associated with higher odds of a phone or incomplete visit (canceled, no-show, or rescheduled after May 30,2020), and non-Hispanic Black race was associated with nearly twice the odds of completing a phone visit instead of video visit, compared to non-Hispanic White patients. Compared to private insurance, Medicaid and Medicare were associated with increased odds of completing a telephone visit, and Medicaid was associated with increased odds of incomplete visits. Being single or previously married (separated, divorced, widowed) was associated with increased odds of completing a phone compared to video visit compared to being married. CONCLUSIONS: Though liver telehealth has expanded during the COVID-19 pandemic, disparities in overall use and suboptimal use (phone versus video) remain for vulnerable populations including those that are older, non-Hispanic Black, or have Medicare/Medicaid health insurance.

Temporal Trends and Evolving Outcomes After Simultaneous Liver-Kidney Transplantation: Results from the US SLKT Consortium.

We aimed to understand the contemporary changes in the characteristics and the determinants of outcomes among simultaneous liver-kidney transplantation (SLKT) recipients at 6 liver transplantation centers in the United States. We retrospectively enrolled SLKT recipients between 2002 and 2017 in the US Multicenter SLKT Consortium. We analyzed time-related trends in recipient characteristics and outcomes with linear regression and nonparametric methods. Clustered Cox regression determined the factors associated with 1-year and overall survival. We enrolled 572 patients. We found significant changes in the clinical characteristics of SLKT recipients: as compared with 2002, recipients in 2017 were older (59 versus 52 years; P < 0.001) and more likely to have chronic kidney disease (71% versus 33%; P < 0.001). There was a marked improvement in 1-year survival during the study period: 89% in 2002 versus 96% in 2017 (P < 0.001). We found that the drivers of 1-year mortality were SLKT year, hemodialysis at listing, donor distance, and delayed kidney allograft function. The drivers of overall mortality were an indication of acute kidney dysfunction, body mass index, hypertension, creatinine at SLKT, ventilation at SLKT, and donor quality. In this contemporary cohort of SLKT recipients, we highlight changes in the clinical characteristics of recipients. Further, we identify the determinants of 1-year and overall survival to highlight the variables that require the greatest attention to optimize outcomes.

Donor-Recipient Height Mismatch Is Associated With Decreased Survival in Pediatric-to-Adult Liver Transplant Recipients.

Liver grafts from pediatric donors represent a small fraction of grafts transplanted into adult recipients, and their use in adults requires special consideration of donor size to prevent perioperative complications. In the past, graft weight or volume ratios have been adopted from the living donor liver transplant literature to guide clinicians; however, these metrics are not regularly available to surgeons accepting deceased donor organs. In this study, we evaluated all pediatric-to-adult liver transplants in the United Network for Organ Sharing Standard Transplant Analysis and Research database from 1987 to 2019, stratified by donor age and donor-recipient height mismatch ratio (HMR; defined as donor height/recipient height). On multivariable regression controlling for cold ischemia time, age, and transplantation era, the use of donors from ages 0 to 4 and 5 to 9 had increased risk of graft failure (hazard ratio [HR], 1.81 [P < 0.01] and HR, 1.16 [P < 0.01], respectively) compared with donors aged 15 to 17. On Kaplan-Meier survival analysis, a HMR < 0.8 was associated with inferior graft survival (mean, 11.8 versus 14.6 years; log-rank P < 0.001) and inferior patient survival (mean, 13.5 versus 14.9 years; log-rank P < 0.01) when compared with pairs with similar height (HMR, 0.95-1.05; ie, donors within 5% of recipient height). This study demonstrates that both young donor age and low HMR confer additional risk in adult recipients of pediatric liver grafts.

The Impact of the 2017 Kidney Allocation Policy Change on Simultaneous Liver-Kidney Utilization and Outcomes.

Historically in the United States, kidneys for simultaneous liver-kidney transplantation (SLKT) candidates were allocated with livers, prioritizing SLKT recipients over much of the kidney waiting list. A 2017 change in policy delineated renal function criteria for SLKT and implemented a safety net for kidney-after-liver transplantation. We compared the use and outcomes of SLKT and kidney-after-liver transplant with the 2017 policy. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to identify adults who received liver transplantations (LT) from August 10, 2007 to August 10, 2012; from August 11, 2012 to August 10, 2017; and from August 11, 2017 to June 12, 2019. LT recipients with end-stage renal disease (ESRD) were defined by dialysis requirement or estimated glomerular filtration rate <25. We evaluated outcomes and center-level, regional, and national practice before and after the policy change. Nonparametric cumulative incidence of kidney-after-liver listing and transplant were modeled by era. A total of 6332 patients received SLKTs during the study period; fewer patients with glomerular filtration rate (GFR) ≥50 mL/min underwent SLKT over time (5.8%, 4.8%, 3.0%; P = 0.01 ). There was also less variability in GFR at transplant after policy implementation on center and regional levels. We then evaluated LT-alone (LTA) recipients with ESRD (n = 5408 from 2012-2017; n = 2321 after the policy). Listing for a kidney within a year of LT increased from 2.9% before the policy change to 8.8% after the policy change, and the rate of kidney transplantation within 1 year increased from 0.7% to 4% (P < 0.001). After the policy change, there was no difference in patient survival rates between SLKT and LTA among patients with ESRD. Implementation of the 2017 SLKT policy change resulted in reduced variability in SLKT recipient kidney function and increased access to deceased donor kidney transplantation for LTA recipients with kidney disease without negatively affecting outcomes.

Reduced Alcohol Use Is Sustained in Patients Provided Alcohol-Related Counseling During Direct-Acting Antiviral Therapy for Hepatitis C.

BACKGROUND: Patients with chronic hepatitis C and risky/harmful alcohol use experience poor outcomes. Granular data evaluating whether alcohol counseling during hepatitis C treatment impacts longitudinal alcohol consumption are lacking. AIMS: To evaluate whether provider-delivered counseling in the context of direct-acting antiviral hepatitis C treatment associates with decreased longitudinal alcohol consumption. METHODS: We performed secondary data analysis from the Hep ART study including adults with hepatitis C who underwent provider-delivered counseling during direct-acting antiviral treatment between October 2014 and September 2017. Demographics and disease characteristics were summarized. Alcohol consumption, abstinence, and heavy drinking were evaluated in periods before, during, and after direct-acting antiviral treatment. Multivariate regression analyses were performed to evaluate the association of alcohol consumption with each 12-week time period for all patients and a subsample with cirrhosis. RESULTS: One hundred twenty-three patients were included; 41 had cirrhosis. Most patients were male (74.0%) and Black (58.5%). Alcohol consumption improved during direct-acting antiviral treatment and was notably sustained (< 12 weeks before treatment 32.5 g/day; during treatment 20.0 g/day; and 12-24 weeks after treatment 23.7 g/day). Multivariable analyses showed significantly improved alcohol consumption metrics during and after antiviral treatment compared to < 12 weeks before treatment (during treatment 13.04 g/day less, p = 0.0001; > 24 weeks after treatment 15.29 g/day less, p = 0.0001). The subsample with cirrhosis showed similar results (during treatment 13.21 g/day less, p = 0.0001; > 24 weeks after treatment 7.69 g/day less, p = 0.0001). CONCLUSIONS: Patients with chronic HCV and risky/harmful alcohol use given provider-delivered alcohol-related counseling during HCV treatment sustain decreased alcohol consumption patterns during and after treatment.

Liver transplantation for hepatocellular carcinoma: Management after the transplant.

Hepatocellular carcinoma (HCC) is an increasingly common indication for liver transplantation (LT) in the United States and in many parts of the world. In the last decade, significant work has been done to better understand how to risk stratify LT candidates for recurrence of HCC following transplant using a combination of biomarker and imaging findings. However, despite the high frequency of HCC in the LT population, guidance regarding posttransplant management is lacking. In particular, there is no current evidence to support specific post-LT surveillance strategies, leading to significant heterogeneity in practices. In addition, there are no current recommendations regarding recurrence prevention, including immunosuppression regimen or secondary prevention with adjuvant chemotherapy. Finally, guidance on treatment of disease recurrence is also lacking and there is significant controversy about the use of immunotherapy in transplant recipients due to the risk of rejection. Thus, outcomes for patients with recurrence are poor. This paper therefore provides a comprehensive review of the current literature on post-LT management of patients with HCC and identifies gaps in our current knowledge that are in urgent need of further investigation.

Use of Skeletal Muscle Index as a Predictor of Wait-List Mortality in Patients With End-Stage Liver Disease.

The aim of this study is to validate a proposed definition of sarcopenia in predicting wait-list mortality. We retrospectively evaluated 355 adults (age ≥18 years) with cirrhosis listed for first-time LT from January 1, 2010, to April 1, 2018 from our center. Demographic, laboratory, and outcome data were collected in conjunction with computed tomography scans performed within 3 months of listing. Using imaging analysis software, the skeletal muscle index (SMI), which is a marker for sarcopenia-related mortality, was calculated. A survival analysis was performed to evaluate the association of the proposed sarcopenia definition of SMI <50 cm2 /m2 for men or <39 cm2 /m2 for women with wait-list mortality or delisting. Median SMI was 54.1 cm2 /m2 (range, 47-60 cm2 /m2 ). A total of 61 (17.2%) patients exhibited sarcopenia according to the proposed threshold, and 24.6% (57/232) of men were sarcopenic compared with 3.3% (4/123) of women (P < 0.001). Mean (standard deviation [SD]) SMI was also higher for men (56.6 ± 9.6 cm2 /m2 ) than for women (50.7 ± 8.0 cm2 /m2 ; P < 0.001). Median follow-up time among patients was 2.1 months (0-12 months), and 30 events were observed (hazard ratio, 0.98; 95% confidence interval, 0.95-1.02; P = 0.41). There was no statistically significant difference in time on the waiting list between patients with and without sarcopenia (P = 0.89) as defined at the threshold. Using the prespecified definitions of sarcopenia based on SMI, there was no statistically significant difference in mortality and delisting from the transplant waiting list between patients with and without sarcopenia in this population. Practice and region-specific patterns for pretransplant selection and median Model for End-Stage Liver Disease at transplant may affect SMI as a predictor of wait-list mortality.

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.

Correction to: Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration.

The original version of the article unfortunately contained errors in Table 3, Risk Factor column headings "Age > 50 (n = 115)," "Age > 50-64 (n = 154)," and "Age > 65 + (n = 60)."

Identifying Nonalcoholic Fatty Liver Disease Advanced Fibrosis in the Veterans Health Administration.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Severe NAFLD with advanced fibrosis results in substantial morbidity and mortality. Associated with metabolic syndrome, NAFLD is often initially clinically silent, yet intensive lifestyle intervention with 7% or greater weight loss can improve or resolve NAFLD. Using a Veterans Health Administration (VHA) liver biopsy cohort, we evaluated simple noninvasive fibrosis scoring systems to identify NAFLD with advanced fibrosis (or severe disease) to assist providers. METHODS: In our retrospective study of a national VHA sample of patients with biopsy-proven NAFLD or normal liver (2005-2015), we segregated patients by fibrosis stage (0-4). Non-NAFLD liver disease was excluded. We evaluated the diagnostic accuracy of the NAFLD fibrosis score (NFS), fibrosis-4 calculator (FIB-4), aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT ratio), AST-to-platelet ratio index (APRI), and body mass index, AST/ALT ratio, and diabetes (BARD) score by age groups. RESULTS: We included 329 patients with well-defined liver histology (296 NAFLD and 33 normal controls without fibrosis), in which 92 (28%) had advanced (stage 3-4) fibrosis. Across all age groups, NFS and FIB-4 best predicted advanced fibrosis (NFS with 0.676 threshold: AUROC 0.71-0.76, LR + 2.30-22.05, OR 6.00-39.58; FIB-4 with 2.67 threshold: AUROC of 0.62-0.80, LR + 4.70-27.45, OR 16.34-59.65). CONCLUSIONS: While NFS and FIB-4 scores exhibit good diagnostic accuracy, FIB-4 is optimal in identifying NAFLD advanced fibrosis in the VHA. Easily implemented as a point-of-care clinical test, FIB-4 can be useful in directing patients that are most likely to have advanced fibrosis to GI/hepatology consultation and follow-up.

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.

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.

Vitamin D is Not Associated With Severity in NAFLD: Results of a Paired Clinical and Gene Expression Profile Analysis.

OBJECTIVES: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is complex. Vitamin D (VitD) has been implicated in NAFLD pathogenesis because it has roles in immune modulation, cell differentiation and proliferation, and regulation of inflammation. We evaluated the association of VitD levels, hepatic gene expression for VitD metabolizing genes, and NAFLD histological severity. METHODS: Two adult cohorts, controls (n=39) and NAFLD (n=244), who underwent liver biopsy were compared. Two-sided t-tests or Wilcoxon's rank-sum tests for continuous predictors and chi-squared tests or Fisher's exact tests for categorical variables were used to analyze the association of VitD and NAFLD. Generalized linear models were used to analyze the association of VitD levels and VitD metabolizing genes with histological severity of NAFLD while adjusting for potential confounders and correcting for multiple comparisons. RESULTS: NAFLD patients were more likely than controls to have higher HbA1c (6.5±1.2 vs 5.9±1.0; P=0.009), a risk factor for VitD deficiency. However, no difference in VitD levels was observed between groups. VitD levels did not correlate with the severity of hepatic steatosis, lobular or portal inflammation, or ballooned hepatocytes after adjusting for confounding factors. Furthermore, no association was noted between VitD deficiency or differential expression of genes involved in VitD metabolism and severity of hepatic fibrosis or any other histologic feature of NAFLD. CONCLUSIONS: Neither VitD deficiency, nor hepatic expression of VitD-related genes, associate with the presence or histologic severity of NAFLD in patients. Hence, despite preclinical evidence implicating VitD in NAFLD pathogenesis, VitD deficiency does not appear to be associated with NAFLD severity in humans.