The evolving paradigm of alcohol-associated hepatitis and liver transplantation.

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Living Liver Donation Does not Significantly Affect Long-Term Life, Disability, or Medical Insurability.

INTRODUCTION: The growing practice of living liver donation requires comprehensive understanding of the financial implications for living liver donors. While obtaining and maintaining insurance is important to financial health, little is known about the impact of liver donation on future insurability. RESEARCH QUESTIONS: The purpose of this study was to evaluate the donors' experiences with insurance following donation and identify the insurance provider-driven factors that contribute to donor insurability. DESIGN: A two center cohort of living donors with donation between January 2000 and December 2018 (N = 442) were surveyed about postdonation insurance experiences. To understand insurance provider practices towards liver donors, life (n = 11) and disability (n = 4) insurance underwriters were asked to provide policy quotes for a standardized living liver donor profile. RESULTS: Responses (N = 101) were received by August 2020 (response rate = 22.9%). Living liver donors reported owning life (58%), disability (35%), and medical (87%) insurance at rates comparable to the general population with low proportions reporting difficulty obtaining these insurance types (9%, 9%, 4%, respectively). Post-donation life insurance ownership was associated with post-donation employment (P = 0.01). Underwriter responses indicate life and disability insurability were adversely affected up to 12 months following donation. CONCLUSIONS: Living liver donors did not have difficulty maintaining insurance in the long-term but should be counseled to purchase insurance prior to surgery as short-term insurability may be affected. Perception of difficulty obtaining insurance following donation remains of significant concern among living donors. Further collaboration between the transplant community and insurance companies is warranted.

Differential IgG4-Producing Plasma Cell Infiltration in Non- and Post-Transplant Plasma Cell Hepatitis.

Autoimmune hepatitis (AIH), post-transplant recurrent AIH (rAIH), and plasma cell-rich rejection (PCR) are clinical diagnoses with the shared histopathologic hallmark of plasma cell hepatitis (PCH). As these histologically and serologically indistinguishable diagnoses are differentiated by clinical context, it remains uncertain whether they represent distinct immunologic phenomena. Improved understanding of immunoglobulin subclass 4-producing plasma cells (IgG4-PC) has brought attention to IgG4 as an immunophenotypic biomarker. To date, degree and clinical significance of IgG4-PC infiltration in PCH remain elusive. This retrospective, single-center study assessed IgG4-PC infiltration in AIH, rAIH, and PCR via standardized immunohistochemistry analysis. Identified cases from 2005 to 2020 (n = 47) included AIH (treatment-naïve AIH (tnAIH): n = 15 and AIH-flare on treatment (fAIH); n = 10), rAIH (n = 8), and PCR (n = 14) were analyzed and correlated with clinical characteristics. IgG4-Positivity (# IgG4-PC/# pan-IgG-expressing cells) distribution was heterogenous and overlapping [tnAIH: 0.060 (IQR 0.040-0.079), fAIH: 0.000 (0.000-0.033), rAIH: 0.000 (0.000-0.035), PCR: 0.228 (0.039-0.558)]. IgG4-Positivity was inversely correlated with corticosteroid use (p < 0.001). IgG4-Positivity ≥0.500 was associated with rapid AST improvement (p = 0.03). The variable IgG4-Positivity of AIH, rAIH and PCR suggests diverse and overlapping immunopathologic mechanisms and that current diagnostic schemes inadequately capture PCH immunopathology. We propose incorporation of IgG4-Positivity to refine current PCH classification and treatment strategies.

Transfusion-free Retransplantation for Post-liver Transplantation Hepatic Artery Thrombosis: How Much Augmentation Is Too Much?

Liver transplantation presents unique challenges in patients who do not accept blood transfusions. The difficulty of balancing chemical augmentation and handling the technical difficulty of the surgery make transfusion-free liver transplantation an exception rather than the norm. However, at our center, we have performed 27 successful living donor liver transplants in transfusion-free patients. We describe a case of hepatic artery thrombosis (HAT) after living donor liver transplantation requiring retransplantation. This first report of safe retransplantation without blood products demonstrates that even graft-threatening complications can be safely managed in a transfusion-free setting. However, it remains unclear if the medical augmentation to meet hematologic and coagulation parameters before transfusion-free transplantation may increase the risk of postoperative HAT and other thrombotic complications. Although it is our center's experience that the thrombosis rate is comparable with the published rate in standard transfusion-eligible living donor liver transplantations and this case demonstrates that HAT can be safely managed in this setting, further study on the risks and benefits of hematopoietic stimulants as pretransplant optimization is warranted.

Gender-Specific Risk Factors for Reflux Esophagitis in a Predominantly Hispanic Population of a Large Safety-Net Hospital.

BACKGROUND: Defining factors associated with severe reflux esophagitis allows for identification of subgroups most at risk for complications of strictures and esophageal malignancy. We hypothesized there might be unique clinical features in patients with reflux esophagitis in a predominantly Hispanic population of a large, safety-net hospital. AIM: Define clinical and endoscopic features of reflux esophagitis in a predominantly Hispanic population of a large, safety-net hospital. METHODS: This is retrospective comparative study of outpatients and hospitalized patients identified with mild (Los Angeles Grade A/B) and severe (Los Angeles Grade C/D) esophagitis through an endoscopy database review. The electronic medical record was reviewed for demographic and clinical data. RESULTS: Reflux esophagitis was identified in 382/5925 individuals: 56.5% males and 79.8% Hispanic. Multivariable logistic regression model adjusted for age, gender, race, body mass index (BMI), tobacco and alcohol use, and hospitalization status with severity as the outcome showed an interaction between gender and BMI (p ≤ 0.01). Stratification by gender showed that obese females had decreased odds of severe esophagitis compared to normal BMI females (OR = 0.18, 95% CI = 0.07-0.47; p < 0.01). In males, the odds of esophagitis were higher in inpatient status (OR = 2.84, 95% CI = 1.52 - 5.28; p < 0.01) and as age increased (OR = 1.37, 95% CI = 1.03 - 1.83; p = 0.03). CONCLUSIONS: We identify gender-specific associations with severe esophagitis in a predominantly Hispanic cohort. In females, obese BMI appears to be protective against severe esophagitis compared to normal BMI, while in men inpatient status and increasing age were associated with increased odds of severe esophagitis.

Image-based ß-adrenergic sweat rate assay captures minimal cystic fibrosis transmembrane conductance regulator function.

BACKGROUND: There is a need to prognosticate the severity of cystic fibrosis (CF) detected by newborn screening (NBS) by early assessment of CF transmembrane conductance regulator (CFTR) protein function. We introduce novel instrumentation and protocol for evaluating CFTR activity as reflected by ß-adrenergically stimulated sweat secretion. METHODS: A pixilated image sensor detects sweat rates. Compounds necessary for maximum sweat gland stimulation are applied by iontophoresis, replacing ID injections. Results are compared to a validated ß-adrenergic assay that measures sweat secretion by evaporation (evaporimetry). RESULTS: Ten healthy controls (HC), 6 heterozygous (carriers), 5 with CFTR-related metabolic syndrome (CRMS)/CF screen-positive, inconclusive diagnosis (CFSPID), and 12 CF individuals completed testing. All individuals with minimal and residual function CFTR mutations had low ratios of ß-adrenergically stimulated sweat rate to cholinergically stimulated sweat rate (ß/chol) as measured by either assay. CONCLUSIONS: ß-Adrenergic assays quantitate CFTR dysfunction in the secretory pathway of sweat glands in CF and CRMS/CFSPID populations. This novel image-sensor and iontophoresis protocol detect CFTR function with minimal and residual function and is a feasible test for young children because it is insensible to movement and it decreases the number of injections. It may also assist to distinguish between CF and CRMS/CFSPID diagnosis.