Fecal Butyrate and Deoxycholic Acid Concentrations Correlate With Mortality in Patients With Liver Disease.

Background And Aims: The intestinal microbiome produces metabolites, including short chain fatty acids (SCFAs) and secondary bile acids (BAs), that impact host physiology. Loss of intestinal microbiome diversity is associated with cirrhosis progression, but the impact of microbiome-associated metabolites on liver disease remains largely undefined. We aimed to correlate fecal metabolite concentrations with the severity and progression of liver disease.

Successful Treatment of Refractory Chylous Ascites With Octreotide in a Patient With Decompensated Cirrhosis.

Chylous ascites is a rare manifestation of decompensated cirrhosis that is associated with increased short-term mortality. Exclusion of other etiologies must be performed to allow for appropriate management, which itself can be a challenge in the setting of decompensated cirrhosis. We report a case of chylous ascites in a patient with decompensated cirrhosis that was successfully managed with octreotide before liver transplantation.

Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration.

Respiratory reductases enable microorganisms to use molecules present in anaerobic ecosystems as energy-generating respiratory electron acceptors. Here we identify three taxonomically distinct families of human gut bacteria (Burkholderiaceae, Eggerthellaceae and Erysipelotrichaceae) that encode large arsenals of tens to hundreds of respiratory-like reductases per genome. Screening species from each family (Sutterella wadsworthensis, Eggerthella lenta and Holdemania filiformis), we discover 22 metabolites used as respiratory electron acceptors in a species-specific manner.

Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease.

Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production.

Evolving challenges with long-term care of liver transplant recipients.

The number of liver transplants (LT) performed worldwide continues to rise, and LT recipients are living longer post-transplant. This has led to an increasing number of LT recipients requiring lifelong care. Optimal care post-LT requires careful attention to both the allograft and systemic issues that are more common after organ transplantation.

PRO: Coronavirus disease 2019 vaccination should be mandatory for liver transplant candidates.

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Viral hepatitis: Past, present, and future.

Each hepatitis virus-Hepatitis A, B, C, D, E, and G-poses a distinct scenario to the patient and clinician alike. Since the discovery of each virus, extensive knowledge regarding epidemiology, virologic properties, and the natural clinical and immunologic history of acute and chronic infections has been generated. Basic discoveries about host immunologic responses to acute and chronic viral infections, combined with virologic data, has led to vaccines to prevent Hepatitis A, B, and E and highly efficacious antivirals for Hepatitis B and C.

Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival.

Epithelial cells are the first line of mucosal defense. In the intestine, a single layer of epithelial cells must establish a selectively permeable barrier that supports nutrient absorption and waste secretion while preventing the leakage of potentially harmful luminal materials. Key to this is the tight junction, which seals the paracellular space and prevents unrestricted leakage.

Preservation solutions for static cold storage in donation after circulatory death and donation after brain death liver transplantation in the United States.

Static cold preservation remains the cornerstone for storing donor livers following procurement; however, the choice between University of Wisconsin solution (UW) and histidine-tryptophan-ketoglutarate solution (HTK) remains controversial. Recent International Liver Transplantation Society (ILTS) guidelines have recommended avoiding HTK for donation after circulatory death (DCD) grafts based on older reports. We studied the latest US adult graft outcomes in three recent eras (2006-2010, 2011-2015, 2016-2020) comparing HTK and UW among 5956 DCD LTs: 3873 (65.

The Practice of Retransplantation for Recurrent Alcohol-associated Liver Disease in the United States Is Uncommon With Acceptable Outcomes.

Unlabelled: Alcohol-associated liver disease (ALD) is the leading indication for liver transplantation (LT) in the United States. Alcohol use disorder relapse can lead to graft failure and the need for liver retransplantation (re-LT). Despite the rising incidence of LT for ALD, the practice of re-LT for recurrent ALD is not well understood.

The Tight Junction Protein ZO-1 Is Dispensable for Barrier Function but Critical for Effective Mucosal Repair.

Backgrounds & Aims: Increased permeability is implicated in the pathogenesis of intestinal disease. In vitro and in vivo studies have linked down-regulation of the scaffolding protein ZO-1, encoded by the TJP1 gene, to increased tight junction permeability. This has not, however, been tested in vivo.

"Raising HOPE": Improved Outcomes for HIV/HCV-coinfected Liver Transplant Recipients in the Direct-acting Antiviral Era.

Unlabelled: The 2013 HIV Organ Policy Equity Act has increased liver transplantation (LT) in HIV patients; however, transplant centers may remain reluctant to perform LT in HIV/hepatitis C virus (HCV)-coinfected patients due to inferior outcomes. We aimed to assess how direct-acting antivirals (DAAs) have impacted HIV/HCV-coinfected LT recipient outcomes.

Methods: national data including 70 125 adult LT recipients between 2008 and 2019 were analyzed.

Hepatotoxicity From Immune Checkpoint Inhibitors: A Systematic Review and Management Recommendation.

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies targeting immune checkpoint molecules. ICIs are an immunotherapy for the treatment of many advanced malignancies. The advent of ICIs has been a major breakthrough in the field of oncology, a fact recognized by the 2018 Nobel Prize in Physiology or Medicine being awarded for the discovery.

Quantification of Proliferative and Dead Cells in Enteroids.

The intestinal epithelium acts as a barrier that prevents luminal contents, such as pathogenic microbiota and toxins, from entering the rest of the body. Epithelial barrier function requires the integrity of intestinal epithelial cells. While epithelial cell proliferation maintains a continuous layer of cells that forms a barrier, epithelial damage leads to barrier dysfunction.

Interleukin 22 Expands Transit-Amplifying Cells While Depleting Lgr5 Stem Cells via Inhibition of Wnt and Notch Signaling.

Background & Aims: Epithelial regeneration is essential for homeostasis and repair of the mucosal barrier. In the context of infectious and immune-mediated intestinal disease, interleukin (IL) 22 is thought to augment these processes. We sought to define the mechanisms by which IL22 promotes mucosal healing.

Epithelial Organization: The Gut and Beyond.

Epithelial cells are essential to the survival and homeostasis of complex organisms. These cells cover the surfaces of all mucosae, the skin, and other compartmentalized structures essential to physiological function. In addition to maintenance of barriers that separate internal and external compartments, epithelia display a variety of organ-specific differentiated functions.

The Microbiome Activates CD4 T-cell-mediated Immunity to Compensate for Increased Intestinal Permeability.

Background & Aims: Despite a prominent association, chronic intestinal barrier loss is insufficient to induce disease in human subjects or experimental animals. We hypothesized that compensatory mucosal immune activation might protect individuals with increased intestinal permeability from disease. We used a model in which intestinal barrier loss is triggered by intestinal epithelial-specific expression of constitutively active myosin light chain kinase (CA-MLCK).

IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance.

Diarrhea is a host response to enteric pathogens, but its impact on pathogenesis remains poorly defined. By infecting mice with the attaching and effacing bacteria Citrobacter rodentium, we defined the mechanisms and contributions of diarrhea and intestinal barrier loss to host defense. Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2.

The intestinal epithelial barrier: a therapeutic target?

A fundamental function of the intestinal epithelium is to act as a barrier that limits interactions between luminal contents such as the intestinal microbiota, the underlying immune system and the remainder of the body, while supporting vectorial transport of nutrients, water and waste products. Epithelial barrier function requires a contiguous layer of cells as well as the junctions that seal the paracellular space between epithelial cells. Compromised intestinal barrier function has been associated with a number of disease states, both intestinal and systemic.