Helpful or Harmful? A Case Report of Nutritional Supplements Causing Drug-Induced Liver Injury

Herbal supplement-induced liver injury represents a growing concern in the body of drug-induced liver injury (DILI) literature, with recent studies in mainland China, Iceland, and the United States reporting estimated rates of herb/dietary supplement-induced liver injury (HILI) between 1.16-6.38 per 100,000 (Björnsson et al., 2013; Shen et al., 2019; Vega et al., 2017). Notably, a recent 2020 study demonstrated an increasing prevalence of hepatotoxicity secondary to herbal and dietary supplements in the US and worldwide (Zheng et al., 2020). Recognizing the hepatotoxicity of various supplements is crucial, given the increasing usage of dietary and herbal supplements and the lack of regulation of herbal supplements in the United States. HRP-AID is marketed as a twice-daily immune system booster to reduce the intensity and frequency of cold sore outbreaks. The product ingredients include 200 mg ascorbic acid, 20 mcg cholecalciferol, 20 mg a-tocopherol, 10 mg pyridoxine HCl, 50 mcg methylcobalamin, 25 mg zinc citrate, 70 mcg selenium, 250 mg L-lysine, 50 mg Astralagus extract (Astragalus membranaceus), 50 mg Echinacea (Echinacea purpurea), 50 mg garlic powder (Allium salivum), 50 mg natural caffeine (coffee arabica), 50 mg olive leaf extract Oleuropin 20% (Olea Europaea), 50 mg oregano powder (Thymus captatus), 50 mg of elderberry extract (Sambucus nigra) and 50 mg Red Panax ginseng extract (Panax ginseng). A literature review demonstrates that this is the first reported case of DILI secondary to HRP-AID supplementation

Integrated Transcriptomics and Histopathology Approach Identifies a Subset of Rejected Donor Livers With Potential Suitability for Transplantation

BACKGROUND: Liver transplantation is an effective treatment for liver failure. There is a large unmet demand, even as not all donated livers are transplanted. The clinical selection criteria for donor livers based on histopathological evaluation and liver function tests are variable. We integrated transcriptomics and histopathology to characterize donor liver biopsies obtained at the time of organ recovery. We performed RNA sequencing as well as manual and artificial intelligence-based histopathology (10 accepted and 21 rejected for transplantation). RESULTS: We identified two transcriptomically distinct rejected subsets (termed rejected-1 and rejected-2), where rejected-2 exhibited a near-complete transcriptomic overlap with the accepted livers, suggesting acceptability from a molecular standpoint. Liver metabolic functional genes were similarly upregulated, and extracellular matrix genes were similarly downregulated in the accepted and rejected-2 groups compared to rejected-1. The transcriptomic pattern of the rejected-2 subset was enriched for a gene expression signature of graft success post-transplantation. Serum AST, ALT, and total bilirubin levels showed similar overlapping patterns. Additional histopathological filtering identified cases with borderline scores and extensive molecular overlap with accepted donor livers. CONCLUSIONS: Our integrated approach identified a subset of rejected donor livers that are likely suitable for transplantation, demonstrating the potential to expand the pool of transplantable livers

Longitudinal Ultrasound Imaging and Network Modeling in Rats Reveal Sex-Dependent Suppression of Liver Regeneration After Resection in Alcoholic Liver Disease

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5–7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow rates were seen in most animals, with ethanol-fed males showing higher peak portal flow than any other experimental group. A computational model of liver regeneration was used to evaluate the contribution of physiological stimuli and estimate the animal-specific parameter intervals. The results implicate lower metabolic load, over a wide range of cell death sensitivity, in matching the model simulations to experimental data of ethanol-fed male rats. However, in the ethanol-fed female rats and controls of both sexes, metabolic load was higher and in combination with cell death sensitivity matched the observed volume recovery dynamics. We conclude that adaptation to chronic ethanol intake has a sex-dependent impact on liver volume recovery following liver resection, likely mediated by differences in the physiological stimuli or cell death responses that govern the regeneration process. Immunohistochemical analysis of pre- and post-resection liver tissue validated the results of computational modeling by associating lack of sensitivity to cell death with lower rates of cell death in ethanol-fed male rats. Our results illustrate the potential for non-invasive ultrasound imaging to assess liver volume recovery towards supporting development of clinically relevant computational models of liver regeneration

Dietary L-Tryptophan Consumption Determines the Number of Colonic Regulatory T cells and Susceptibility to Colitis via GPR15

Environmental factors are the major contributor to the onset of immunological disorders such as ulcerative colitis. However, their identities remain unclear. Here, we discover that the amount of consumed L-Tryptophan (L-Trp), a ubiquitous dietary component, determines the transcription level of the colonic T cell homing receptor, GPR15, hence affecting the number of colonic FOXP3+ regulatory T (Treg) cells and local immune homeostasis. Ingested L-Trp is converted by host IDO1/2 enzymes, but not by gut microbiota, to compounds that induce GPR15 transcription preferentially in Treg cells via the aryl hydrocarbon receptor. Consequently, two weeks of dietary L-Trp supplementation nearly double the colonic GPR15+ Treg cells via GPR15-mediated homing and substantially reduce the future risk of colitis. In addition, humans consume 3–4 times less L-Trp per kilogram of body weight and have fewer colonic GPR15+ Treg cells than mice. Thus, we uncover a microbiota-independent mechanism linking dietary L-Trp and colonic Treg cells, that may have therapeutic potential

The significance of so-called equivocal immunohistochemical staining for cytomegalovirus in colorectal biopsies

© 2019 College of American Pathologists. All rights reserved. Context.-Recent studies examining immunohistochemical staining of colorectal biopsies for cytomegalovirus (CMV) reported that some cases showed only occasional small positive nuclei that were called equivocal for CMV. Objectives.-To determine the extent and clinical significance of equivocal CMV staining in colorectal biopsies. Design.-Two-hundred twenty-one consecutive cases of colon and rectal biopsies that were stained for CMV by immunohistochemistry were retrieved from our files and reviewed. Staining results were recorded as negative, unequivocal, or equivocal. Results were correlated with clinicopathologic data, results of polymerase chain reaction studies for CMV, and treatment history. Results.-Fifty-two cases (24% of all tested, 63% of positive cases) showed equivocal staining for CMV, and of these, 41 had follow-up information. Polymerase chain reaction for CMV was performed largely on blood samples and was not found to be sensitive for the detections of CMV proctocolitis. Of 25 patients who received antiviral treatment, 21 (84%) had complete resolution of symptoms, compared with 8 of 16 (50%) who did not receive antivirals (P ¼ .02). There was no statistically significant difference in response to antiviral drugs in patients with equivocal and unequivocal CMV staining (P ¼ .17). Conclusions.-Equivocal CMV staining likely represents true CMV proctocolitis. Prospective studies are needed to confirm these findings

Primary pulmonary lymphoproliferative neoplasms

Pulmonary lymphoproliferative neoplasms are rare lung tumors and account for <1% of all lung tumors. Among them, primary pulmonary lymphomas (PPL) constitute the majority, which include Non-Hodgkin's lymphoma (NHL) that comprise of mucosa-associated lymphoid tissue lymphoma, diffuse large B-cell lymphomas and other rare types of NHL and lymphomatoid granulomatosis. HL, which arises secondary to contiguous spread from the mediastinum, is the rarest type of PPL. Other entities described within the umbrella of pulmonary lymphoproliferative neoplasms include pleural lymphomas and posttransplant lymphoproliferative disorders (PTLD) – which occurs in the poststem cell and organ transplant patients. These neoplasms although rare, have a favorable prognosis, which does not depend on disease resectability. Moreover, with its nonspecific presentation, diagnosis is challenging, which often leads to delayed diagnosis or misdiagnosis in many cases. Therefore, knowledge of this entity is important for the practicing pulmonologist. This review article aims to describe the clinical presentation, diagnosis and management of primarily the entities within PPL, as well as pleural lymphomas and PTLD