The latest medical research on Hepatology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about hepatology gathered by our medical AI research bot.

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Mesenchymal stem cells alleviate mouse liver fibrosis by inhibiting pathogenic function of intrahepatic B cells.

Hepatology

The immunomodulatory characteristics of mesenchymal stem cells (MSCs) make them a promising therapeutic approach for liver fibrosis (LF). Here, we postulated that MSCs could potentially suppress the pro-fibrotic activity of intrahepatic B cells, thereby inhibiting LF progression.

Administration of MSCs significantly ameliorated LF as indicated by reduced myofibroblast activation, collagen deposition, and inflammation. The treatment efficacy of MSCs can be attributed to decreased infiltration, activation, and pro-inflammatory cytokine production of intrahepatic B cells. Single-cell RNA sequencing revealed a distinct intrahepatic B cell atlas and a subtype of naive B cells (B-II) was identified, which were markedly abundant in fibrotic liver, displaying mature features with elevated expression of several proliferative and inflammatory genes. Transcriptional profiling of total B cells revealed that intrahepatic B cells displayed activation, proliferation, and pro-inflammatory gene profile during LF. Fibrosis was attenuated in mice ablated with B cells (μMT) or in vivo treatment with anti-CD20. Moreover, fibrosis was recapitulated in μMT after adoptive transfer of B cells, which in turn could be rescued by MSC injection, validating the pathogenic function of B cells and the efficacy of MSCs on B cell-promoted LF progression. Mechanistically, MSCs could inhibit the proliferation and cytokine production of intrahepatic B cells through exosomes, regulating the MAPK and NF-kappa B signaling pathways.

Intrahepatic B-cell serve as a target of MSCs, play an important role in the process of MSC-induced amelioration of LF, and may provide new clues for revealing the novel mechanisms of MSC action.

Nutritional aspects of prehabilitation in adults with cirrhosis awaiting liver transplant.

Hepatology

Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as thes...

Quality measures in pre-liver transplant care by the Practice Metrics Committee of the American Association for the Study of Liver Diseases.

Hepatology

The LT evaluation and waitlisting process is subject to variations in care that can impede quality. The American Association for the Study of Liver Diseases (AASLD) Practice Metrics Committee (PMC) developed quality measures and patient-reported experience measures (PREMs) along the continuum of pre-LT care to reduce care variation and guide patient-centered care.

Following a systematic literature review, candidate pre-LT measures were grouped into four phases of care: referral, evaluation and waitlisting, waitlist management, and organ acceptance. A modified Delphi panel with content expertise in hepatology, transplant surgery, psychiatry, transplant infectious disease, palliative care and social work selected the final set. Candidate PREMs spanned domains of cognitive health, emotional health, social well-being, and understanding the LT process.

Of the 71 candidate measures, 41 were selected: 9 for referral; 20 for evaluation and waitlisting; 7 for waitlist management; and 5 for organ acceptance. A total of 14 were related to structure, 17 were process measures and 10 were outcome measures that focused on elements not typically measured in routine care. Among the PREMs, LT candidates rated items from understanding the LT process domain as the most important.

The proposed pre-LT measures provide a framework for quality improvement and care standardization among LT candidates. Select measures apply to various stakeholders such as referring practitioners in the community and LT centers. Clinically meaningful measures that are distinct from those used for regulatory transplant reporting may facilitate local QI initiatives to improve access and quality of care.

Genetic variation in severe cystic fibrosis liver disease is associated with novel mechanisms for disease pathogenesis.

Hepatology

It is not known why severe cystic fibrosis (CF) liver disease (CFLD) with portal hypertension occurs in only ~7% of people with CF (pwCF). We aimed to identify genetic modifiers for severe CFLD to improve understanding of disease mechanisms.

Whole genome sequencing was available in 4,082 pwCF with pancreatic insufficiency (n=516 with severe CFLD; n=3,566 without CFLD). We tested ~15.9 million SNPs for association with severe CFLD versus no-CFLD, using pre-modulator clinical phenotypes including: 1) genetic variant (SERPINA1; Z-allele) previously associated with severe CFLD; 2) candidate SNPs (n=205) associated with non-CF liver diseases; 3) genome-wide association study (GWAS) of common/rare SNPs; 4) transcriptome-wide association (TWAS); and 5) gene-level and pathway analyses. The Z-allele was significantly associated with severe CFLD (p=1.1×10-4). No significant candidate SNPs were identified. GWAS identified genome-wide significant SNPs in 2 loci and 2 suggestive loci. These 4 loci contained genes [significant, PKD1 (p=8.05×10-10) and FNBP1 (p=4.74×10-9); suggestive, DUSP6 (p=1.51×10-7) and ANKUB1 (p=4.69×10-7)] relevant to severe CFLD pathophysiology. TWAS identified 3 genes [CXCR1 (p=1.01×10-6), AAMP (p=1.07×10-6), and TRBV24 (p=1.23×10-5)] involved in hepatic inflammation and innate immunity. Gene-ranked analyses identified pathways enriched in genes linked to multiple liver pathologies.

These results identify loci/genes associated with severe CFLD that point to disease mechanisms involving hepatic fibrosis, inflammation and innate immune function, vascular pathology, intracellular signaling, actin cytoskeleton and tight junction integrity, and mechanisms of hepatic steatosis and insulin resistance. These discoveries will facilitate mechanistic studies and the development of therapeutics for severe CFLD.

The association between mean arterial pressure and acute kidney injury reversal among decompensated cirrhosis patients.

Hepatology

This study informs how mean arterial pressure (MAP) impacts AKI recovery among all patients hospitalized with cirrhosis, regardless of etiology.

We identified incident AKI episodes among subjects in our cohort of decompensated cirrhosis patients. AKI was defined as a ≥50% increase in creatinine (sCr) from an outpatient baseline (≥7 days prior) that required hospitalization. Linear mixed-effects models were completed to determine the impact between AKI recovery, MAP, and time. To determine the impact of MAP on AKI reversal, we completed time-dependent Cox-regression models with time beginning at the time of peak sCr and ending at death, discharge, or AKI reversal, among those hospitalized with AKI and those with Persistent AKI (≥48 hours).

We identified 702 hospitalized cirrhosis patients with AKI. We found those with AKI reversal had, on average, higher MAP (2.1 mmHg, p<0.05) and a greater increase in MAP over time (0.1 mmHg per hour, p<0.001). Among all 702 hospitalized patients with AKI and adjusted for confounders, each 5 mmHg increase in MAP was associated with 1.07x the hazard of AKI reversal (p<0.01). Similarly, among those with persistent AKI after adjusting for confounders, each 5 mmHg increase in MAP was associated with 1.19x greater likelihood of AKI reversal (p<0.001). Discussion: Our data demonstrate that MAP significantly increases the likelihood of AKI recovery regardless of severity or injury or AKI phenotype. We believe these data highlight the importance of MAP as a clinical tool to promote kidney function recovery among cirrhosis patients hospitalized with AKI.

Comprehensive molecular classification predicted microenvironment profiles and therapy response for hepatocellular carcinoma.

Hepatology

Tumor microenvironment (TME) heterogeneity leads to a discrepancy in survival prognosis and clinical treatment response for hepatocellular carcinoma (HCC) patients. The clinical applications of documented molecular subtypes are constrained by several issues.

We integrated three single-cell datasets to describe the TME landscape and identified six prognosis-related cell subclusters. Unsupervised clustering of subcluster-specific markers was performed to generate transcriptomic subtypes. The predictive value of these molecular subtypes for prognosis and treatment response was explored in multiple external HCC cohorts and the Xiangya HCC cohort. TME features were estimated using single-cell immune repertoire sequencing, mass cytometry and multiplex immunofluorescence. The prognosis-related score (PRS) was constructed based on machine learning algorithm. Comprehensive single-cell analysis described TME heterogeneity in HCC. The five transcriptomic subtypes possessed different clinical prognoses, stemness characteristics, immune landscapes and therapeutic responses. Class 1 exhibited an inflamed phenotype with better clinical outcomes, while Classes 2 and 4 were characterized by a lack of T cell infiltration. Classes 5 and 3 indicated an inhibitory tumor immune microenvironment. Analysis of multiple therapeutic cohorts suggested that Classes 5 and 3 were sensitive to ICB and targeted therapy, whereas Classes 1 and 2 were more responsive to transcatheter arterial chemoembolization treatment. Class 4 displayed resistant to all conventional HCC therapies. Three potential therapeutic agents and four targets were further identified for high-PRS HCC patients.

Our study generated a clinically valid molecular classification to guide precision medicine in patients with HCC.

NK-cell-elicited gasdermin-D-dependent hepatocyte pyroptosis induces neutrophil extracellular traps that facilitates HBV-related acute-on-chronic liver failure.

Hepatology

Hepatitis B virus (HBV) infection is a major etiology of acute-on-chronic liver failure (ACLF). At present, the pattern and regulation of hepatocyte death during HBV-ACLF progression are still undefined. Evaluating the mode of cell death and its inducers will provide new insights for developing therapeutic strategies targeting cell death. In this study, we aimed to elucidate whether and how immune landscapes trigger hepatocyte death and lead to the progression of HBV-related ACLF.

We identified that pyroptosis represented the main cell death pattern in the liver of patients with HBV-related ACLF. Deficiency of MHC-I in HBV-reactivated hepatocytes activated cytotoxic NK cells, which in turn operated in a perforin/granzyme-dependent manner to trigger GSDMD/caspase-8-dependent pyroptosis of hepatocytes. Neutrophils selectively accumulated in pyroptotic liver, and HMGB1 derived from pyroptotic liver constituted an important factor triggering generation of pathogenic extracellular traps in neutrophils (NETs). Clinically, elevated plasma levels of MPO-DNA complexes were a promising prognostic biomarker for HBV-related ACLF. More importantly, targeting GSDMD pyroptosis-HMGB1 release in the liver abrogates NETs that intercept the development of HBV-related ACLF.

Studying the mechanisms that selectively modulate GSDMD-dependent pyroptosis, as well as its immune landscapes, will provide a novel strategy for restoring liver function of HBV-related ACLF patients.

Novel proteomic signatures may indicate MRI-assessed intrahepatic fat state and changes; the DIRECT PLUS clinical trial.

Hepatology

We demonstrated in the randomized 18-month DIRECT PLUS trial (n=294) that a Mediterranean (MED) diet, supplemented with polyphenol-rich Mankai duckweed, green tea, and walnuts and restricted in red/processed meat, caused substantial intrahepatic fat (IHF%) loss compared with two other healthy diets, reducing NAFLD by half, regardless similar weight loss. Here, we investigated the baseline proteomic profile associated with IHF% and the changes in proteomics associated with IHF% changes induced by lifestyle intervention.

We calculated IHF% by proton-magnetic-resonance-spectroscopy (H-MRS; normal-IHF%<5%; abnormal-IHF%>=5%). We assayed baseline and 18-month samples for 95 proteomic biomarkers.

Participants (age=51.3±10.8years; 89%men; body-mass-index=31.3±3.9 kg/m2) had an 89.8% 18-month-retention-rate; 83% had eligible follow-up proteomics-measurements, and 78% had follow-up H-MRS. At baseline, 39-candidate-proteins were significantly associated with IHF% (FDR<0.05), mostly related to immune-function-pathways (e.g., HAOX1). An IHF%-prediction based on the DIRECT PLUS by combined-model (R2=0.47, RMSE=1.05) successfully predicted IHF% (R2=0.53) during testing and was stronger than separately-inputting-proteins/traditional markers (R2=0.43/0.44). The 18-month lifestyle intervention induced changes in 18 of the 39-candidate-proteins, which were significantly associated with IHF% change, with proteins related to metabolism, extracellular-matrix-remodeling, and immune-function pathways. THBS2 protein-change was higher in the green-MED compared to the MED group, beyond weight-and-IHF%-loss (p-value=0.01). Protein principal-component-analysis revealed differences in the 3rd-principal-component time-distinct interactions across abnormal/normal-IHF% trajectory combinations; p<0.05 for all).

Our findings suggest novel proteomic signatures that may indicate MRI-assessed intrahepatic fat state and changes during lifestyle intervention. Specifically, CA5A, HAOX1, and THBS2 protein changes are independently associated with IHF% change, and THBS2 protein change is greater in the green-MED/high-polyphenols diet.

The future of Liver Transplantation.

Hepatology

Over the last 50 years, liver transplantation has evolved into a procedure routinely performed in many countries worldwide. Those able to access th...

Effects of empagliflozin on liver fat in metabolic-dysfunction associated steatotic liver disease patients without diabetes mellitus: A randomized, double-blind, placebo-controlled trial.

Hepatology

We investigated whether empagliflozin reduces hepatic steatosis in metabolic-dysfunction associated steatotic liver disease (MASLD) patients without diabetes mellitus (DM).

This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without DM (fasting plasma glucose <7 mmol/L and HbA1c <6.5%) who had magnetic resonance imaging-proton density fat fraction [MRI-PDFF] ≥5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. Primary outcome was difference in change of MRI-PDFF between two groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF <5%), ALT drop≥17U/L, MRI-PDFF decline≥30%, combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age:55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. Empagliflozin group had greater reduction in median MRI-PDFF compared to placebo group (-2.49% vs -1.43%;p=0.025), with a non-significant trend of resolution of hepatic steatosis (44.9% vs 28.6%;p=0.094). There was no significant difference in ALT drop≥17U/L (16.3% vs 12.2%;p=0.564), MRI-PDFF drop≥30% (49.0% vs 40.8%;p=0.417), and composite outcome (8.2% vs 8.2%;p=1.000). Empagliflozin group had greater drop in body weight (-2.7 vs -0.2 kg), waist circumference (-2.0 vs 0 cm), fasting glucose (-0.3 vs 0 mmol/L) and ferritin (-126 vs -22 pmol/L) (all p<0.05).

Empagliflozin for 52 weeks reduces hepatic fat content in non-diabetic MASLD subjects. (ClinicalTrials.gov Identifier: NCT04642261).

Digital pathology and spatial omics in steatohepatitis: Clinical applications and discovery potentials.

Hepatology

Steatohepatitis with diverse etiologies is the most common histological manifestation in patients with liver disease. However, there are currently ...

Primary biliary cholangitis drug evaluation and regulatory approval: Where do we go from here?

Hepatology

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The management landscape was transformed 20 years ago with the advent of ...