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Environmental toxicant-induced maladaptive mitochondrial changes:A potential unifying mechanism in fatty Liver disease?

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3756-3767页

作者： Regina D.Schnegelberger Anna L.Lang Gavin E.Arteel Juliane I.Beier Department of Pharmacology&Chemical Biology University of PittsburghPittsburghPA 15213USA Department of Neurology University of Miami Miller School of MedicineMiamiFL 33136USA Department of Medicine Division of GastroenterologyHepatology&NutritionUniversity of PittsburghPittsburghPA 15213USA Pittsburgh liver Research Center University of PittsburghPittsburghPA 15213USA Department of Environmental&Occupational Health University of PittsburghPittsburghPA 15213USA

Occupational and environmental exposures to industrial chemicals are well known to cause hepatotoxicity and liver injury.However,despite extensive evidence showing that exposure can lead to disease,current research approaches and regulatory policies fail to address the possibility that subtle changes caused by low level exposure to chemicals may also enhance preexisting conditions.In recent years,the conceptual understanding of the contribution of environmental chemicals to Liver disease has progressed significantly.Mitochondria are often target of toxicity of environmental toxicants resulting in multisystem disorders involving different cells,tissues,and organs.Here,we review persistent maladaptive changes to mitochondria in response to environmental toxicant exposure as a mechanism of hepatotoxicity.With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of toxicant-induced Liver disease,rational targeted therapy can be developed to better predict risk,as well as to treat or prevent this disease.

关键词： Organochlorines Metals Persistent organic pollutants TASH Liver disease Hepatotoxicity Mitochondrial maladaptation Mitohormesis

Visual analysis of mesenchymal stem cell research in Liver disease based on bibliometrics

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iliver 2022年第4期1卷 283-291页

作者： Chengzuo Han Rui Wang Nan Xu Xuyong Wei Qiang Wei Xiao Xu Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou310006China Westlake Laboratory of Life Sciences and Biomedicine Hangzhou310024China

The research of mesenchymal stem cells(MSCs)in the field of Liver diseases has received more and more attention.This paper introduces the current situation,hot spots,and development trends in this field.Compre-hensive searches were conducted using Web of Science Core Collection from January 1,2000 to December 13,2021 with the following keywords:TS(topic)¼(liver*OR hepatic*OR hepatocyte)AND TS(topic)¼(Mesen-chymal stem cell*).VOSviewer(version 1.6.16)and CiteSpace V are used as bibliometric tools to analyze and visualize the knowledge graph.A total of 4452 papers were included in this study,and the number of research papers on MSCs in the field of Liver diseases increased from January 2000 to December 2020.Eighty-four countries and regions have published articles on research in this field,among which China and the United States are the main two countries of publication.Based on the keyword burst detection,we find that the research in this field has shifted from basic research to clinical application,from medical research to interdisciplinary research.Tissue engineering and regenerative medicine are the frontier fields of MSCs research in Liver diseases.Multicountry,multi-author cooperation,and multi-disciplinary intersection are the research trends in this field.Exocrine body,obesity,and tissue engineering are the hotspots in this field.

关键词： Mesenchymal stem cells Liver disease Bibliometrics Visualization

Iron as a therapeutic target in chronic Liver disease

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World Journal of Gastroenterology 2023年第4期29卷 616-655页

作者： Elias Kouroumalis Ioannis Tsomidis Argyro Voumvouraki liver Research Laboratory University of Crete Medical SchoolHeraklion 71003Greece First Department of Internal Medicine AHEPA University HospitalThessaloniki 54621Greece

It was clearly realized more than 50 years ago that iron deposition in the liver may be a critical factor in the development and progression of Liver disease.The recent clarification of ferroptosis as a specific form of regulated hepatocyte death different from apoptosis and the description of ferritinophagy as a specific variation of autophagy prompted detailed investigations on the association of iron and the liver.In this review,we will present a brief discussion of iron absorption and handling by the liver with emphasis on the role of liver macrophages and the significance of the iron regulators hepcidin,transferrin,and ferritin in iron homeostasis.The regulation of ferroptosis by endogenous and exogenous modulators will be examined.Furthermore,the involvement of iron and ferroptosis in various Liver diseases including alcoholic and non-alcoholic Liver disease,chronic hepatitis B and C,liver fibrosis,and hepatocellular carcinoma(HCC)will be analyzed.Finally,experimental and clinical results following interventions to reduce iron deposition and the promising manipulation of ferroptosis will be presented.Most Liver diseases will be benefited by ferroptosis inhibition using exogenous inhibitors with the notable exception of HCC,where induction of ferroptosis is the desired effect.Current evidence mostly stems from in vitro and in vivo experimental studies and the need for well-designed future clinical trials is warranted.

关键词： Iron overload Liver disease Ferroptosis Ferritinophagy Ferroptosis modulators

Prevention,diagnostic evaluation,management and prognostic implications of Liver disease in critically ill patients with COVID-19

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World Journal of Clinical Cases 2023年第3期11卷 514-527页

作者： Asimina Valsamaki Maria Xanthoudaki Katerina G Oikonomou Panagiotis J Vlachostergios AntoniosPapadogoulas Periklis Katsiafylloudis Ioanna Voulgaridi Apostolia-Lemonia Skoura Apostolos Komnos Panagiotis Papamichalis Intensive Care Unit General Hospital of LarissaLarissa 41221Greece Division of Hematology and Medical Oncology Department of MedicineWeill Cornell MedicineNew YorkNY 10065United States Department of Microbiology General Hospital of LarissaLarissa 41221Greece Transfusion Medicine Department University Hospital of LarissaLarissa 41110Greece

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2,broke out in December 2019 in Wuhan city of China and spread rapidly worldwide.Therefore,by March 2020,the World Health Organization declared the disease a global pandemic.Apart from the respiratory system,various other organs of the human body are also seriously affected by the virus.liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%.Elevated levels of total bilirubin,aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings.Patients with pre-existing chronic Liver disease and cirrhosis are much more prone to develop severe liver injury.This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19,the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients.Moreover,it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic Liver disease.

关键词： Coronavirus disease 2019 Severe acute respiratory syndrome coronavirus 2 Liver disease Intensive care unit liver unit Prealbumin

Outcomes of COVID-19 among patients with Liver disease

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World Journal of Gastroenterology 2023年第5期29卷 815-824页

作者： Isidora Vujčić Institute of Epidemiology Faculty of MedicineUniversity of BelgradeBelgrade 11000BelgradeSerbia

Coronavirus disease 2019(COVID-19)is primarily a respiratory disease with multi-organ involvement,including impaired liver function.It has been noticed that a significant proportion of COVID-19 patients have liver dysfunction,especially those with a more severe disease course.The coronavirus causes direct damage to the liver using the angiotensin-converting enzyme 2,a cell-surface receptor for cellular entry,that is expressed in the liver.According to previous research,liver enzyme abnormalities were observed in a considerable proportion of COVID-19 patients,and elevated liver transaminases were found in about 20%of these patients,alkaline phosphatase in 6.1%,and gamma-glutamyl transferase in 21.1%.COVID-19 might trigger a deterioration of liver function in patients with pre-existing chronic Liver diseases(CLDs)and also in those without previous liver disorders.The majority of COVID-19 patients who develop liver injury are men,the elderly,and those with a higher body mass index.Compared to the general population,COVID-19 is associated with significant morbidity and mortality in patients with Liver disease(cirrhosis and liver transplantation recipients).However,some studies indicate that CLDs have a lesser role in determining patient progression towards higher disease severity.

关键词： Liver disease COVID-19 Mortality Prognosis liver function

Microbiome-liver crosstalk:A multihit therapeutic target for Liver disease

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World Journal of Gastroenterology 2023年第11期29卷 1651-1668页

作者： Jorum Kirundi Sheida Moghadamrad Camilla Urbaniak Department of Biomedical Research University of BernBern 3014Switzerland Department of Gastroenterology/Hepatology Laboratories for Translational ResearchEnte Ospedaliero CantonaleBellinzona and Faculty of Biomedical SciencesUniversitàdella Svizzera italianaLugano 6900Switzerland Biotechnology and Planetary Protection Group NASA Jet Propulsion LaboratoryPasadenaCA 91011United States ZIN Technologies Middleburg HeightsOH 44130United States

Liver disease has become a leading cause of death,particularly in the West,where it is attributed to more than two million deaths annually.The correlation between gut microbiota and Liver disease is still not fully understood.However,it is well known that gut dysbiosis accompanied by a leaky gut causes an increase in lipopolysaccharides in circulation,which in turn evoke massive hepatic inflammation promoting liver cirrhosis.Microbial dysbiosis also leads to poor bile acid metabolism and low short-chain fatty acids,all of which exacerbate the inflammatory response of liver cells.Gut microbial homeostasis is maintained through intricate processes that ensure that commensal microbes adapt to the low oxygen potential of the gut and that they rapidly occupy all the intestinal niches,thus outcompeting any potential pathogens for available nutrients.The crosstalk between the gut microbiota and its metabolites also guarantee an intact gut barrier.These processes that protect against destabilization of gut microbes by potential entry of pathogenic bacteria are collectively called colonization resistance and are equally essential for liver health.In this review,we shall investigate how the mechanisms of colonization resistance influence the liver in health and disease and the microbial-liver crosstalk potential as therapeutic target areas.

关键词： Microbiome Nonalcoholic fatty Liver disease Nonalcoholic steatohepatitis Liver disease Microbiome-host crosstalk Gut homeostasis Microbial metabolites

Cardiac Syndromes in Liver disease:A Clinical Conundrum

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 975-986页

作者： Milos Brankovic Paul Lee Nikolaos Pyrsopoulos Mark Klapholz Department of Medicine Rutgers New Jersey Medical SchoolNewarkNJUSA Transatlantic Cardiovascular Study Group BloomfieldNJUSA Division of Gastroenterology and Hepatology Department of MedicineRutgers New Jersey Medical SchoolNewarkNJUSA Division of Cardiology Heart Failure Prevention and Treatment ProgramRutgers New Jersey Medical SchoolNewarkNJUSA

Understanding the interaction between the heart and liver is pivotal for managing patients in whom both organs are affected.Studies have shown that cardio-hepatic interactions are bidirectional and that their identification,assessment,and treatment remain challenging.Congestive hepatopathy is a condition that develops in the setting of long-standing systemic venous congestion.If left untreated,congestive hepatopathy may lead to hepatic fibrosis.Acute cardiogenic liver injury develops as a combination of venous stasis and sudden arterial hypoperfusion due to cardiac,circulatory,or pulmonary failure.The treatment of both conditions should be directed toward optimizing the cardiac substrate.Hyperdynamic syndrome may develop in patients with advanced Liver disease and lead to multiorgan failure.Cirrhotic cardiomyopathy or abnormalities in pulmonary vasculature,such as hepatopulmonary syndrome and portopulmonary hypertension may also develop.Each complication has unique treatment challenges and implications for liver transplantation.The presence of atrial fibrillation and atherosclerosis in Liver disease brings another layer of complexity,particularly in terms of anticoagulation and statin use.This article provides an overview of cardiac syndromes in Liver disease,focusing on current treatment options and future perspectives.

关键词： Liver disease Congestive hepatopathy Cardiogenic liver injury Cirrhotic cardiomyopathy Hepatopulmonary syndrome Portopulmonary hypertension

Gastrointestinal and Liver disease in patients with schizophrenia:A narrative review

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World Journal of Gastroenterology 2022年第38期28卷 5515-5529页

作者： Rebecca K Grant William M Brindle Mhairi C Donnelly Pauline M McConville Thomas G Stroud Lorenzo Bandieri John N Plevris The Centre for liver and Digestive Disorders Royal Infirmary of EdinburghEdinburghEH164SAUnited Kingdom General Adult Psychiatry Royal Edinburgh HospitalEdinburghEH105HFUnited Kingdom

Schizophrenia is a severe mental illness which can have a devastating impact onan individual’s quality of life. Comorbidities are high amongst patients and lifeexpectancy is approximately 15 years less than the general population. Despite thewell-known increased mortality, little is known about the impact of gastrointestinaland Liver disease on patients with schizophrenia. We aimed to reviewthe literature and to make recommendations regarding future care. Literaturesearches were performed on PubMed to identify studies related to gastrointestinaland Liver disease in patients with schizophrenia. High rates of chronic liverdisease were reported, with Non-Alcoholic Fatty Liver disease being of particularconcern;antipsychotics and metabolic syndrome were contributing factors. Ratesof acute liver failure were low but have been associated with antipsychotic useand paracetamol overdose. Coeliac disease has historically been linked to schizophrenia;however, recent research suggests that a causal link is yet to be proven.Evidence is emerging regarding the relationships between schizophrenia andpeptic ulcer disease, inflammatory bowel disease and irritable bowel syndrome;clinical vigilance regarding these conditions should be high. Patients with schizophreniapoorly engage with bowel cancer screening programmes, leading to latediagnosis and increased mortality. Clozapine induced constipation is a significantissue for many patients and requires close monitoring. There is a significantburden of gastrointestinal and Liver disease amongst patients with schizophrenia.Better levels of support from all members of the medical team are essential toensure that appropriate, timely care is provided.

关键词： Schizophrenia Gastrointestinal disease Liver disease Mental health

COVID-19 vaccination and Liver disease

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World Journal of Gastroenterology 2022年第48期28卷 6791-6810页

作者： Sotaro Ozaka Takashi Kobayashi Kazuhiro Mizukami Kazunari Murakami Department of Gastroenterology Faculty of MedicineOita UniversityYufu 879-5593OitaJapan Department of Infectious disease Control Faculty of MedicineOita UniversityYufu 879-5593OitaJapan

Various vaccines against severe acute respiratory syndrome coronavirus 2 have been developed in response to the coronavirus disease 2019(COVID-19)global pandemic,several of which are highly effective in preventing COVID-19 in the general population.Patients with chronic Liver diseases(CLDs),particularly those with liver cirrhosis,are considered to be at a high risk for severe COVID-19 and death.Given the increased rates of disease severity and mortality in patients with Liver disease,there is an urgent need to understand the efficacy of vaccination in this population.However,the data regarding efficacy and safety of COVID-19 vaccination in patients with CLDs is limited.Indeed,several organ-specific or systemic immune-mediated side effects following COVID-19 vaccination,including liver injury similar to autoimmune hepatitis,have been recently reported.Although the number of cases of vaccine-related liver injury is increasing,its frequency,clinical course,and mechanism remain unclear.Here,we review the current findings on COVID-19 vaccination and Liver disease,focusing on:(1)The impact of COVID-19 in patients with CLD;(2)The efficacy,safety,and risk-benefit profiles of COVID-19 vaccines in patients with CLD;and(3)liver injury following COVID-19 vaccination.

关键词： COVID-19 vaccine Liver disease Side effect liver injury Immune-related hepatitis Autoimmune hepatitis