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.

Porto-Sinusoidal Vascular Disease in a Patient With Diffuse Aortitis and Massive Ascites.

A 69-year-old man with no history of liver disease presented with massive ascites. Imaging demonstrated diffuse wall thickening of the entire aorta, renal pelvis, and ureters along with an enlarged main portal vein, portosystemic collaterals, and peritoneal thickening concerning for large vessel vasculitis. Liver biopsy was consistent with obliterative portal venopathy. The patient was started on corticosteroid therapy with improvement in his ascites. This case study reveals a rare association between vasculitis and portal-sinusoidal vascular disease and idiopathic non-cirrhotic portal hypertension, highlighting the heterogenous clinical presentation of this disease entity.

The use of transient elastography in identifying sub-clinical chronic ductopenic rejection in adult liver transplant recipients: A case series.

BACKGROUND: Transient elastography has become a standard tool for the accurate non-invasive assessment of liver stiffness and fat content. Liver transplant recipients can develop allograft fibrosis during long-term follow-up despite normal or mildly abnormal liver chemistries. Tapering of immunosuppression in long-term liver transplant survivors is performed relying solely on liver chemistries. It is important to know if underlying liver histology would be abnormal or if rejection was present as this would alter the desire to decrease stable maintenance doses of immunosuppression. METHODS: We present our experience of five liver transplant recipients who had transient elastography performed prior to consideration of weaning of their immunosuppression. RESULTS: All five patients showed signs of elevated liver stiffness on transient elastography in the setting of normal to slightly abnormal liver tests with very stable immunosuppressant doses. This prompted the performance of liver biopsies which demonstrated immune-mediated liver injury and thus negated the immunosuppression withdrawal. CONCLUSION: Transient elastography has utility as a non-invasive method to evaluate allograft health in long-term liver transplant survivors and can be useful in the decision-making process for immunosuppression weaning.

Recurrent Liver Allograft Injury in Patients With Donor-Derived Malignancy Treated With Immunosuppression Cessation and Retransplantation.

OBJECTIVES: Donor-derived malignancy of the liver allograft is a rare but serious condition in the setting of necessary immunosuppression. Retransplantation after abrupt immunosuppression cessation has been performed with durable cancer-free survival. METHODS: We present 2 cases of patients with donor-derived malignancy who were treated with complete immunosuppression cessation, which induced rapidly progressive liver allograft rejection and failure, with a need for subsequent retransplantation. We reviewed all serial liver biopsies and explants from both patients and performed C4d immunostaining. RESULTS: Initial explants of both patients showed severe allograft rejection, with unusual features of sinusoidal obstruction syndrome and C4d positivity. Malignant tumors in the explants were necrotic, related to rejection of donor-derived cancer cells and tissue. Follow-up of both patients has shown long-term cancer-free survival but issues with recurrent allograft failure requiring a third transplant. The reasons for retransplantation in both cases were related to allograft failure from antibody-mediated rejection. CONCLUSIONS: Clinicians should be aware of a potentially increased risk of rejection and recurrent allograft failure when strategizing treatment of donor-derived malignancy with immunosuppression cessation and retransplantation.

Antibody-mediated rejection of the liver allograft: An update and a clinico-pathological perspective.

Antibody-mediated rejection after liver transplantation is an under-recognised cause of allograft injury. While definitions of acute and chronic antibody-mediated rejection have increased clinical awareness, timely identification and management of antibody-mediated rejection remain difficult because of complexities in diagnosis and histopathology, lack of treatment protocols, and unclear long-term outcomes. While recent cohort studies assessing the importance of donor-specific antibodies have aided in its diagnosis, literature on the treatment of antibody-mediated rejection in liver transplantation remain limited to case reports and small series. Further increasing the awareness and timely recognition of antibody-mediated rejection post-liver transplantation is crucial in order to stimulate future research and the development of protocols for its diagnosis and treatment. This review will summarise recent advances in the clinical diagnosis and treatment of antibody-mediated rejection in liver transplantation, as well as some of the histopathologic features (on liver biopsy tissue) of acute and chronic antibody-mediated rejection.

An Approach to Drug-Induced Liver Injury from the Geriatric Perspective.

PURPOSE OF REVIEW: With its high variability in both presentation and severity, drug-induced liver injury (DILI) is a complex condition increasingly confronting all providers. DILI has an even more muddled presentation among the geriatric population due to age-related changes in liver physiology and biochemistry as well as polypharmacy common in the geriatric population. RECENT FINDINGS: Most cases of DILI are idiosyncratic and unpredictable. DILI, especially related to herbal and dietary supplement (HDS) use, is increasingly recognized as a leading cause of acute liver failure and need for liver transplantation. Unfortunately, liver transplantation is a limited option for the elderly, a population that exhibits significant HDS use. One recent study suggests that early use of N-acetylcysteine may be useful in preventing progression to acute liver failure in non-acetaminophen DILI. In the future, a personalized medicine approach using genomic signatures may be feasible to prevent DILI. This review serves to raise recognition of the unique aspects of DILI in the geriatric population to promote rapid diagnosis and early intervention to prevent progression to liver failure and death. For now, DILI remains a diagnosis of exclusion, and care providers for the elderly must focus on obtaining a thorough history that includes HDS use and intervening early in suspected DILI cases.

Interaction of RIPK1 and A20 modulates MAPK signaling in murine acetaminophen toxicity.

Acetaminophen (APAP)-induced liver necrosis is a form of regulated cell death (RCD) in which APAP activates the mitogen-activated protein kinases (MAPKs) and specifically the c-Jun-N-terminal kinase (JNK) pathway, leading to necrotic cell death. Previously, we have shown that receptor interacting protein kinase-1 (RIPK1) knockdown is also protective against APAP RCD upstream of JNK. However, whether the kinase or platform function of RIPK1 is involved in APAP RCD is not known. To answer this question, we used genetic mouse models of targeted hepatocyte RIPK1 knockout (RIPK1HepCKO) or kinase dead knock-in (RIPK1D138N) and adult hepatocyte specific knockout of the cytoprotective protein A20 (A20HepCKO), known to interact with RIPK1, to study its potential involvement in MAPK signaling. We observed no difference in injury between WT and RIPK1D138N mice post APAP. However, RIPK1HepCKO was protective. We found that RIPK1HepCKO mice had attenuated pJNK activation, while A20 was simultaneously upregulated. Conversely, A20HepCKO markedly worsened liver injury from APAP. Mechanistically, we observed a significant upregulation of apoptosis signal-regulating kinase 1 (ASK1) and increased JNK activation in A20HepCKO mice compared with littermate controls. We also demonstrated that A20 coimmunoprecipitated (co-IP) with both RIPK1 and ASK1, and that in the presence of RIPK1, there was less A20-ASK1 association than in its absence. We conclude that the kinase-independent platform function of RIPK1 is involved in APAP toxicity. Adult RIPK1HepCKO mice are protected against APAP by upregulating A20 and attenuating JNK signaling through ASK1, conversely, A20HepCKO worsens injury from APAP.

Liver Injury in Patients Hospitalized with Coronavirus Disease 2019 Correlates with Hyperinflammatory Response and Elevated Interleukin-6.

Liver injury is commonly seen in coronavirus disease 2019 (COVID-19); however, the mechanism behind liver injury, particularly in patients with severe and critical COVID-19, remains unclear, and the clinical course is poorly described. We conducted a single-center retrospective cohort study of consecutive patients hospitalized with severe and critical COVID-19 with or without liver injury and who underwent immunologic testing (interleukin [IL]-6, IL-8, tumor necrosis factor alpha [TNF-α], and IL-1ß). Liver injury was defined as peak aminotransferases ≥3 times the upper limit of normal (40 U/L) or ≥120 U/L. Patients with liver injury were compared to those who had normal aminotransferases throughout the hospital course. We studied 176 patients: 109 with liver injury and 67 controls. Patients with liver injury were more likely to be men (71.6% vs. 37.3%, P < 0.001). Peak inflammatory markers and IL-6 were higher in the liver injury group: C-reactive protein (CRP), 247 vs. 168 mg/L, P < 0.001; lactate dehydrogenase (LDH), 706 vs. 421 U/L; ferritin, 2,973 vs. 751 ng/mL, P < 0.001; IL-6, 121.0 vs. 71.8 pg/mL, P < 0.001. There was no difference in the levels of IL-8, TNF-α, and IL-1ß. The liver injury group had a longer length of stay in the hospital and more severe COVID-19 despite having less diabetes and chronic kidney disease. Conclusion: An exaggerated hyperinflammatory response (cytokine storm) characterized by significantly elevated CRP, LDH, ferritin, and IL-6 levels and increasing severity of COVID-19 appears to be associated with the occurrence of liver injury in patients with severe/critical COVID-19.

UCSC Genome Browser enters 20th year.

The University of California Santa Cruz Genome Browser website (https://genome.ucsc.edu) enters its 20th year of providing high-quality genomics data visualization and genome annotations to the research community. In the past year, we have added a new option to our web BLAT tool that allows search against all genomes, a single-cell expression viewer (https://cells.ucsc.edu), a 'lollipop' plot display mode for high-density variation data, a RESTful API for data extraction and a custom-track backup feature. New datasets include Tabula Muris single-cell expression data, GeneHancer regulatory annotations, The Cancer Genome Atlas Pan-Cancer variants, Genome Reference Consortium Patch sequences, new ENCODE transcription factor binding site peaks and clusters, the Database of Genomic Variants Gold Standard Variants, Genomenon Mastermind variants and three new multi-species alignment tracks.

A rare systemic etiology of heart failure and liver dysfunction.

Systemic amyloidosis is a rare condition that can manifest with cardiomyopathy, hepatic dysfunction, and renal disease. Diagnosis is often missed and/or delayed due to chronic multi-system involvement and indeterminate signs and symptoms. Treatment generally involves systemic therapy and autologous stem-cell transplantation.

Risk factor control and adherence to treatment in patients with coronary heart disease in the Republic of Srpska, Bosnia and Herzegovina in 2005-2006.

INTRODUCTION: European treatment guidelines in persons with known coronary heart disease (CHD) focus on adherence to antiplatelet therapy, ß-blockers, ACE/ARBs, and lipid-lowering agents, with goals for blood pressure (BP) of < 140/90 mm Hg and LDL cholesterol of < 3.0 mmol/l. Data on adherence to these measures in Eastern Europe are limited. MATERIAL AND METHODS: The Third Republic of Srpska, Bosnia and Herzegovina, Coronary Prevention Study (ROSCOPS III) was conducted in 2005-2006 at 10 primary heath care centres in 601 patients (36% female, mean age 55 years) with CHD including acute myocardial infarction or ischaemia, coronary artery bypass graft, or angioplasty who were examined and interviewed at least 6 months after the event. We examined the proportion of subjects on recommended treatments and at goal for BP, LDL-C, and non-smoking. RESULTS: The proportion of subjects on recommended treatments included 61% for ß-blockers, 79% for ACE/ARBs, 63% for lipid-lowering agents and 74% for antiplatelet therapy. Only 30% of subjects were on all four of these treatments. 59% of subjects had BP at goal of < 140/90 mm Hg and 33% were controlled to < 130/80 mm Hg, 41% for LDL-C, and 88% were non-smokers. Improvements were seen in lipid-lowering and ACE/ARB drug use and non-smoking status from an earlier survey (ROSCOPS II) in 2002-2003. CONCLUSIONS: Our data show, despite improvement over recent years, that many persons with CHD in the Republic of Srpska, Bosnia and Herzegovina are neither on recommended treatments nor at target for BP and/or LDL-C. Improved efforts targeted at both physicians and patients to address these issues are needed.