NON-ALCOHOLIC STEATOHEPATITIS (NASH) HAS BECOME THE MOST COMMON INDICATION FOR LIVER TRANSPLANTATION AMONG CANDIDATES WITH HEPATOCELLULAR CARCINOMA IN THE UNITED STATES

<div><p><b>Background:</p> </b><p>High prevalence of obesity in the U.S. is driving the burden of non-alcoholic steatohepatitis (NASH) and associated adverse clinical outcomes including NASH-related end-stage liver disease and hepatocellular carcinoma (HCC). Our aim was to assess the most recent trends in patients with chronic liver disease (CLD) listed for liver transplantation (LT) in the U.S. using a national registry.</p>

ARTIFICIAL INTELLIGENCE TO MEASURE FIBROSIS CHANGE ON LIVER BIOPSY IN MAESTRO-MASH: A PHASE 3 SERIAL LIVER BIOPSY STUDY IN 966 PATIENTS WITH MASH TREATED WITH RESMETIROM OR PLACEBO

<div><p><b>Background: </b>MAESTRO-MASH (NCT03900429), an ongoing, randomized, double-blind, placebo-controlled Phase 3 serial liver biopsy study, achieved both primary endpoints on liver biopsy (MASH resolution and fibrosis reduction) at Week 52 with both resmetirom doses, including a ≥1-stage reduction in fibrosis without worsening of MASH of 24%, 26% (mITT) at 80 and 100 mg resmetirom compared with placebo (14%).

PREDICTORS OF RENAL RECOVERY AND SURVIVAL OUTCOMES IN LIVER TRANSPLANT RECIPIENTS MEETING SLK ELIGIBILITY CRITERIA

<div><p><b>Background:</p> </b><p>The 2017 UNOS simultaneous liver-kidney transplant (SLK) policy establishes the minimum eligibility criteria for SLK listing and a mechanism to expedite kidney after liver transplantation (Safety Net). Candidate selection for SLK versus Safety Net requires further refinement.

INCREASING LIVER STIFFNESS VALUES ABOVE 20 KILOPASCALS ARE ASSOCIATED WITH HIGHER RISKS OF DECOMPENSATED CIRRHOSIS AND MORTALITY BUT NOT HCC

<div><p><b>Background:</p> </b><p>FibroScan®-derived liver stiffness (LS) values above a threshold of 20 kilopascals (kPa) has been used to guide endoscopic screening for gastro-esophageal varices. However, there is limited data on the clinical significance of LS values above this threshold. We aimed to assess whether LS values ≥ 20 kPa are associated with death, decompensation, and hepatocellular carcinoma (HCC).</p>

RELATIONSHIP OF NON-INVASIVE MEASURES WITH HISTOLOGICAL RESPONSE IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS AND FIBROSIS: 52-WEEK DATA FROM THE PHASE 3 MAESTRO-NASH TRIAL

<div><p><b>Background: </b>MAESTRO-NASH (NCT03900429) is an ongoing 54-month, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy of resmetirom in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH) and fibrosis. 966 patients with biopsy-confirmed NASH were randomized 1:1:1 to resmetirom 80mg, resmetirom 100mg, or placebo administered once daily. Histologic endpoints were assessed after 52 weeks.

PNPLA3 GENOTYPES ARE SIGNIFICANTLY ASSOCIATED WITH LIVER-RELATED OUTCOMES IN INDIVIDUALS WITH BIOPSY-PROVEN NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)

<div><p><b>Background:</p> </b><p>The effect of <em>PNPLA3</em> rs738409 I148M variant (G allele) on the clinical course of adults with biopsy-proven nonalcoholic fatty liver disease (NAFLD) has not been prospectively investigated. We examined (1) the association between <em>PNPLA3</em> G allele and clinical outcomes and (2) how relationships among <em>PNPLA3</em> G allele, age, and type 2 diabetes mellitus (T2DM) impact clinical outcomes in patients with biopsy-proven NAFLD.</p>

MICROBIAL MONOTHERAPY WITH LEUCONOSTOC SP. LB-P8 IMPROVES INFLAMMATION AND FIBROSIS IN MOUSE MODELS OF PRIMARY SCLEROSING CHOLANGITIS.

<div><p><b>Background: </b>PSC is an archetypical example of a disease with an impaired gut-liver axis and PSC patients with or without inflammatory bowel disease exhibit enteric microbial dysbiosis. Gut microbiota produce diverse metabolic products but how microbes influence PSC disease progression is unclear. By screening bacterial species (sp.) in a transwell gut-liver axis model, we identified novel <em>Leuconostoc sp</em>. (LB-P8) that may have anti-fibrotic properties via inhibition of TGF-β/SMAD signaling.

ALBUMIN IS INTERNALIZED BY PRIMARY MONOCYTES USING CLATHRIN-INDEPENDENT ENDOCYTOSIS WHICH IS REQUIRED FOR ITS ANTI-INFLAMMATORY EFFECT.

<div><p><strong><b>Background:</strong> </b>Albumin has been shown to modulate systemic inflammation in patients with decompensated liver cirrhosis receiving infusions of this protein as therapy. Although the anti-inflammatory effect of albumin has been described to be secondary to its internalization into mononuclear leukocytes, the cell type and the mechanism by which albumin is internalized by these immune cells are at present unknown.</p>

ETHANOL-INDUCED REDUCTION IN THE INTESTINAL METHYLATION POTENTIAL PROMOTES TIGHT JUNCTION DISRUPTION: PROTECTION BY BETAINE TREATMENT

<div><p><b>Background: </b>The gut-liver interaction has emerged as a critical component in alcohol-associated liver disease (ALD) pathogenesis. The central mediators are the gut luminal antigens, especially endotoxins that translocate to the liver. This occurs because of (i) compromised gut barrier integrity due to epithelial tight junction (TJ) disruption; and (ii) qualitative/quantitative gut microbiota changes and increased production of pathogenic antigens.</p>

NOVEL MECHANISMS UNDERLYING GUT LEAKINESS AND SYSTEMIC ENDOTOXEMIA IN PROMOTING LIVER FIBROSIS VIA THE GUT-LIVER AXIS AND THE MECHANISTIC PROTECTION OF MELATONIN

<div><p><strong><b>Background:</strong> </b>Liver fibrosis is the consequence of chronic liver diseases that can progress to cirrhosis and liver failure. However, the role and mechanism of gut leakiness in liver fibrosis are poorly understood, and there is no FDA-approved drug to treat liver fibrosis.

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