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Periplakin Attenuates Liver Fibrosis via Reprogramming CD44Low Cells into CD44High Liver Progenitor Cells.

BACKGROUND & AIMS: Liver progenitor cells (LPCs) contribute significantly to the restoration of injured liver parenchyma and promote liver regeneration, thereby ameliorating liver fibrosis. However, the mechanism of the derivation of LPCs remains poorly understood. METHODS: We first examined the expression of periplakin (PPL) in patients and mouse models with liver fibrosis. Adenovirus overexpressing PPL was injected into the tail vein of mouse models to detect the regulatory effect of PPL on liver fibrosis. Single-cell sequencing explored how PPL influences liver fibrosis progression. Additi…

Betaine regulates the gut-liver axis: a therapeutic approach for chronic liver diseases.

Chronic liver disease is defined by persistent harm to the liver that might result in decreased liver function. The two prevalent chronic liver diseases are alcohol-associated liver disease (ALD) and metabolic dysfunction-associated steatotic liver disease (MASLD). There is ample evidence that the pathogenesis of these two chronic liver diseases is closely linked to gastrointestinal dysfunctions that alters the gut-liver crosstalk. These alterations are mediated through the imbalances in the gut microbiota composition/function that combined with disruption in the gut barrier integrity allows f…

Early liver transplant for alcohol-associated liver disease: Current state and future directions.

Alcohol-associated liver disease (ALD) is a rapidly increasing indication for liver transplantation (LT) globally with a significant rise in transplants for ALD with limited sobriety including patients with alcohol-associated hepatitis (AH). This evolution challenges the older paradigm that mandates prolonged periods of alcohol abstinence prior to LT. Due to the limited armamentarium of effective pharmacotherapy to treat severe AH, the mortality rates are significantly higher when LT is not available. In the patients who are transplanted for ALD with limited sobriety including AH, patient and …

Liver Disease and Periodontal Pathogens: A Bidirectional Relationship Between Liver and Oral Microbiota.

Background: Periodontal dysbiosis contributes to liver injury through systemic inflammation, oral-gut microbial translocation, and endotoxemia. Lipopolysaccharides (LPSs) and virulence factors derived from periodontal pathogens, particularly Porphyromonas gingivalis (P. gingivalis) activate Toll-like receptor (TLR) signaling, trigger NF-κB-mediated cytokine release (e.g., TNF-α, IL-1β, IL-6), and promote oxidative stress and Kupffer cell activation within the liver. The present systematic review summarized clinical evidence supporting these mechanistic links between periodontal pathogens and h…

Long-Term Outcomes of Incidental Liver Malignancies in Simultaneous Liver-Kidney Transplant Recipients.

BACKGROUND: The pretransplant diagnosis of liver malignancies in nodular cirrhotic livers remains a diagnostic challenge despite current advances. Although the prognostic impact of incidental hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCC) in liver transplant recipients is well documented, there are no data on the impact in simultaneous liver kidney transplant (LKT) recipients. METHODS: This is a single-center observational, retrospective study of all LKT performed from May 1993 to April 2022. Among these patients, demographic data, immunosuppressive therapy, rejection…

Pregnane X Receptor Activation in Liver Macrophages Protects against Endotoxin-Induced Liver Injury.

Endotoxemia-related acute liver injury has a poor prognosis and high mortality, and macrophage polarization plays a central role in the pathological process. Pregnane X receptor (PXR) serves as a nuclear receptor and xenosensor, safeguarding the liver from toxic stimuli. However, the effect and underlying mechanism of PXR activation on endotoxemic liver injury remain largely unknown. Here, the expression of PXR is reported in human and murine macrophages, and PXR activation modified immunotypes of macrophages. Moreover, PXR activation significantly attenuated endotoxemic liver injury and promo…

The gut-liver axis in fatty liver disease: role played by natural products.

Fatty liver disease, a condition characterized by fatty degeneration of the liver, mainly classified as non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), has become a leading cause of cirrhosis, liver cancer and death. The gut-liver axis is the bidirectional relationship between the gut and its microbiota and its liver. The liver can communicate with the gut through the bile ducts, while the portal vein transports the products of the gut flora to the liver. The intestinal flora and its metabolites directly and indirectly regulate hepatic gene expression, leading to a…

Muscle strength and non-alcoholic fatty liver disease/metabolic-associated fatty liver disease.

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology, entitled "Association of low muscle strength with metabolic dysfunction-associated fatty liver disease: A nationwide study". We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD), as well as the mechanisms underlying the correlation and related clinical applications. NAFLD, which is now redefined as MAFLD, is one of the most common chronic liver diseases globally with an increa…

Ghrelin regulating liver activity and its potential effects on liver fibrosis and Echinococcosis.

Ghrelin widely exists in the central nervous system and peripheral organs, and has biological activities such as maintaining energy homeostasis, regulating lipid metabolism, cell proliferation, immune response, gastrointestinal physiological activities, cognition, memory, circadian rhythm and reward effects. In many benign liver diseases, it may play a hepatoprotective role against steatosis, chronic inflammation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress and apoptosis, and improve liver cell autophagy and immune response to improve disease progression. However,…

Coexistence of metabolic-associated fatty liver disease and autoimmune or toxic liver disease.

Fatty liver disease (FLD) affects approximately 25% of global adult population. Metabolic-associated fatty liver disease (MAFLD) is a term used to emphasize components of metabolic syndrome in FLD. MAFLD does not exclude coexistence of other liver disease, but impact of coexisting MAFLD is unclear. We investigated prevalence and characteristics of MAFLD in patients with biopsy-proven autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or toxic liver disease. Liver histopathology and clinical data from Helsinki University Hospital district (1.7 m…

Человеческие печени MSCs сохраняют свои основные клеточные свойства в хроническо воспламенённой печени.

Каждая 25-ая смерть во всем мире связана с патологией печени. Необходимо срочно разработать новые подходы к лечению заболеваний печени и протоколы для сохранения жизненно важных функций пациентов, включенных в список ожидания трансплантации печени. Мезенхимальные стволовые клетки (МСЦ) играют важную роль в поддержании целостности печени и улучшении состояния печени после вливания. Вместе с тем остается неясным, являются ли МСЦ, изолированные от хронически воспаленных печени, аналогичными по своим основным свойствам клеточным свойствам МСЦ, получаемым из здоровой печени. Мы провели большое коли

Совпадение в аннотации оригинала
Every 25th death worldwide is associated with liver pathology. The development of novel approaches to liver diseases therapy and protocols for maintaining the vital functions of patients on the liver transplant waiting list are urgently needed. Resident mesenchymal stem cells (MSCs) play a significant role in supporting liver tissue integrity and improve the…

Gas6 in chronic liver disease-a novel blood-based biomarker for liver fibrosis.

The expression of the receptor tyrosine kinase Axl and its cleavage product soluble Axl (sAxl) is increased in liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). In this multicenter study, we evaluated the diagnostic value of Gas6, the high-affinity ligand of Axl, in patients with chronic liver disease. Levels of sAxl and Gas6, and their albumin (alb) ratios were analyzed in serum samples of patients with biopsy-proven liver fibrosis, end-stage liver disease, HCC, and healthy controls, and were compared to Fibrosis-4 (FIB-4), enhanced liver fibrosis (ELF™) test, Child-Pugh score (C…

Emerging Evidence Linking the Liver to the Cardiovascular System: Liver-derived Secretory Factors.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Recently, accumulating evidence has revealed hepatic mediators, termed as liver-derived secretory factors (LDSFs), play an important role in regulating CVDs such as atherosclerosis, coronary artery disease, thrombosis, myocardial infarction, heart failure, metabolic cardiomyopathy, arterial hypertension, and pulmonary hypertension. LDSFs presented here consisted of microbial metabolite, extracellular vesicles, proteins, and microRNA, they are primarily or exclusively synthesized and released by the li…

Haemodynamic and prognostic associations of liver fibrosis scores in Fontan-associated liver disease.

OBJECTIVES: Fontan-associated liver disease (FALD) is universal post-Fontan palliation; however, its impact on survival remains controversial and current diagnostic tools have limitations. We aimed to assess the prognostic role of liver fibrosis scores (aminotransferase to platelet ratio [APRI] and fibrosis-4 [FIB-4]) and their association with haemodynamics and other markers of liver disease. METHODS: 159 adults (age ≥18 years) post-Fontan undergoing catheterisation at Mayo Clinic, Minnesota, between 1999 and 2017 were included. Invasive haemodynamics and FALD-related laboratory, imaging and…

Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation.

BACKGROUND: The impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown. OBJECTIVES: The purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients. METHODS: We performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calc…

Ficolin-2 Plasma Level Assesses Liver Fibrosis in Non-Alcoholic Fatty Liver Disease.

Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level…

Liver transplantation in patients with liver failure: Twenty years of experience from China.

Liver transplantation (LT) is the only effective method of treating end-stage liver disease, such as various types of liver failure. China has the largest number of patients with hepatitis B virus-related disease, which is also the main cause of liver failure. From the first LT performed in 1977, and especially over the past two decades, LT has experienced rapid development as a result of continuous research and innovation in China. China performs the second-highest number of LTs every year worldwide, and the quality of LT continues to improve. Starting January 1, 2015, all donor's livers have…

Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention.

BACKGROUND: Liver cancer is one of the common malignancies. The dysregulation of metabolism is a driver of accelerated tumourigenesis. Metabolic changes are well documented to maintain tumour growth, proliferation and survival. Recently, a variety of polyphenols have been shown to have a crucial role both in liver disease prevention and metabolism regulation. METHODS: We conducted a literature search and combined recent data with systematic analysis to comprehensively describe the molecular mechanisms that link polyphenols to metabolic regulation and their contribution in liver protection and…

Nonalcoholic Fatty Liver Disease and the Gut-Liver Axis: Exploring an Undernutrition Perspective.

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition affecting one quarter of the global population. Although primarily linked to obesity and metabolic syndrome, undernutrition and the altered (dysbiotic) gut microbiome influence NAFLD progression. Both undernutrition and NAFLD prevalence are predicted to considerably increase, but how the undernourished gut microbiome contributes to hepatic pathophysiology remains far less studied. Here, we present undernutrition conditions with fatty liver features, including kwashiorkor and micronutrient deficiency. We then review the gut microbi…

Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients.

Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and …