Andrew Joseph Muir

Liver transplant (LT) recipients are at risk of post-transplant diabetes mellitus (PTDM), and the incidence varies by region. We explored the relationship between county-level food environment and PTDM and whether food insecurity mediates regional variation. First-time LT recipients from July 2004 to December 2022 without pre-existing diabetes were identified in the UNOS SRTR database. Data on 3 measures of healthy food access at the county level were obtained: population experiencing food insecurity, low-income population with low access to grocery stores (food deserts), and ratio of unhealthy to healthy food options (food swamps), all expressed by quartile. The primary endpoint was PTDM. Subdistribution hazard models were used to estimate associations, adjusting for demographic and clinical characteristics and county-level social vulnerability. Mediation analyses quantified the extent to which the food environment explained regional variation in PTDM. A total of 68,273 LT recipients met the inclusion criteria; 15.5% developed PTDM. All 3 food environment measures were independently associated with higher PTDM risk, even after adjustment for recipient, donor, and county-level factors. These measures were also significant mediators of regional variation in PTDM. Food insecurity mediated 48% of regional variation in PTDM, while food deserts and food swamps mediated 20% and 23%, respectively. LT recipients in counties with decreased access to healthy foods were significantly more likely to develop PTDM. Food environment accounted for a meaningful proportion of regional differences in PTDM. Identifying and addressing food insecurity among LT recipients may represent a modifiable pathway to improve long-term outcomes.

Purpose The Liver Imaging Reporting and Data System (LI-RADS, LR) provides a framework for diagnosing hepatocellular carcinoma (HCC, LR-5). However, not all HCCs meet LR-5 criteria and are instead categorized as LR-M, probably or definitely malignant but not specific for HCC, necessitating biopsy for diagnosis. The purpose is to identify factors associated with HCC in LR-M observations. Methods This is an IRB-approved, retrospective analysis of participants from 8 institutions that had a LR-M observation on CT or MRI with corresponding histopathologic diagnosis. Demographics and biochemical data were examined. Central review using the LI-RADS v2018 algorithm was performed. Kappa statistics defined inter-reader agreement. Random forest and logistic regression analyses generated a model for HCC diagnosis. Results 162 participants with 162 LR-M observations were included. 46% of observations (74/162) were HCC and 37% were cholangiocarcinoma (60/162). Two of 34 imaging features– observation size and intra-lesion iron– showed moderate to strong inter-reader agreement (Kappa ≥ 0.60) while the remainder showed weak or no agreement (Kappa < 0.60). Random forest analysis showed biochemical features to be more predictive of HCC than imaging features. Logistic regression analysis of a model based on INR and AFP provided a 72% sensitivity and 61% specificity for HCC by Youden’s index and a 90% specificity threshold yielded 38% sensitivity, 75% positive predictive value, and 66% negative predictive value. Conclusions Our results show INR and AFP are associated with HCC in LR-M observations. A high-specificity threshold may assist in the non-invasive diagnosis of HCC in the appropriate setting. Summary statement In certain at-risk patients with a LR-M observation on diagnostic imaging, serum AFP and INR maybe useful tools for the non-invasive diagnosis of HCC.

Primary sclerosing cholangitis (PSC) is a chronic biliary inflammation associated with periductular fibrosis of the intrahepatic and extrahepatic bile ducts leading to strictures, bacterial cholangitis, decompensated liver disease and need for liver transplantation. This rare focal liver disease affects all races and ages, with a predominance of young males. There is an up to 88% association with inflammatory bowel disease. Although the aetiology is unknown and the pathophysiology is poorly understood, PSC is regarded as an autoimmune liver disease based on a strong immunogenetic background. Further, the associated risk for various malignancies, particularly cholangiocellular carcinoma, is also poorly understood. No medical therapy has been approved so far nor has been shown to improve transplant-free survival. However, ursodeoxycholic acid is widely used since it improves the biochemical parameters of cholestasis and is safe at low doses. MRI of the biliary tract is the primary imaging technology for diagnosis. Endoscopic interventions of the bile ducts should be limited to clinically relevant strictures for balloon dilatation, biopsy and brush cytology. End-stage liver disease with decompensation is an indication for liver transplantation with recurrent PSC in up to 38% of patients. Several novel therapeutic strategies are in various stages of development, including apical sodium-dependent bile acid transporter and ileal bile acid transporter inhibitors, integrin inhibitors, peroxisome proliferator-activated receptor agonists, CCL24 blockers, recombinant FGF19, CCR2/CCR5 inhibitors, farnesoid X receptor bile acid receptor agonists, and nor-ursodeoxycholic acid. Manipulation of the gut microbiome includes faecal microbiota transplantation. This article summarizes present knowledge and defines unmet medical needs to improve quality of life and survival.

Background: Novel noninvasive predictors of disease severity and prognosis in primary sclerosing cholangitis (PSC) are needed. This study evaluated the ability of extracellular matrix remodeling markers to diagnose fibrosis stage and predict PSC-related fibrosis progression and clinical events. Methods: Liver histology and serum markers of collagen formation (propeptide of type III collagen [Pro-C3], propeptide of type IV collagen, propeptide of type V collagen), collagen degradation (type III collagen matrix metalloproteinase degradation product and type IV collagen matrix metalloproteinase degradation product), and fibrosis (enhanced liver fibrosis [ELF] score and its components [metalloproteinase-1, type III procollagen, hyaluronic acid]) were assessed in samples from baseline to week 96 in patients with PSC enrolled in a study evaluating simtuzumab (NCT01672853). Diagnostic performance for advanced fibrosis (Ishak stages 3–6) and cirrhosis (Ishak stages 5–6) was evaluated by logistic regression and AUROC. Prognostic performance for PSC-related clinical events and fibrosis progression was assessed by AUROC and Wilcoxon rank-sum test. Results: Among 234 patients, 51% had advanced fibrosis and 11% had cirrhosis at baseline. Baseline Pro-C3 and ELF score and its components provided moderate diagnostic ability for discrimination of advanced fibrosis (AUROC 0.73–0.78) and cirrhosis (AUROC 0.73–0.81). Baseline Pro-C3, ELF score, and type III procollagen provided a moderate prognosis for PSC-related clinical events (AUROC 0.70–0.71). Among patients without cirrhosis at baseline, median changes in Pro-C3 and ELF score to week 96 were higher in those with than without progression to cirrhosis (both p < 0.001). Conclusions: Pro-C3 correlated with fibrosis stage, and Pro-C3 and ELF score provided discrimination of advanced fibrosis and cirrhosis and predicted PSC-related events and fibrosis progression. The results support the clinical utility of Pro-C3 and ELF score for staging and as prognostic markers in PSC.

Background: The presence of workplace bias around child-rearing and inadequate parental leave may negatively impact childbearing decisions and sex equity in hepatology. This study aimed to understand the influence of parental leave and child-rearing on career advancement in hepatology. Methods: A cross-sectional survey of physician members of the American Association for the Study of Liver Diseases (AASLD) was distributed through email listserv in January 2021. The 33-item survey included demographic questions, questions about bias, altering training, career plans, family planning, parental leave, and work accommodations. Results: Among 199 US physician respondents, 65.3% were women, and 83.4% (n = 166) were attendings. Sex and racial differences were reported in several domains, including paid leave, perceptions of bias, and child-rearing. Most women (79.3%) took fewer than the recommended 12 paid weeks of parental leave for their first child (average paid leave 7.5 wk for women and 1.7 for men). A majority (75.2%) of women reported workplace discrimination, including 83.3% of Black and 62.5% of Hispanic women. Twenty percent of women were asked about their/their partners’ pregnancy intentions or child-rearing plans during interviews for training. Women were more likely to alter career plans due to child-rearing (30.0% vs. 15.9%, p = 0.030). Women were also more likely to delay having children than men (69.5% vs.35.9%). Conclusions: Women reported sex and maternity bias in the workplace and during training interviews, which was more frequently experienced by Black and Hispanic women. As two-thirds of women had children during training, it is a particularly influential time to reevaluate programmatic support to address long-term gender disparities in career advancement.

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.

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.