Histopathological impact of SARS-CoV-2 on the liver:Cellular damage and long-term complications

Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

Optimizing nutrition in hepatic cirrhosis:A comprehensive assessment and care approach

Cirrhosis is considered a growing cause of morbidity and mortality,which represents a significant public health problem.Currently,there is no effective treatment to reverse cirrhosis.Treatment primarily centers on addressing the underlying liver condition,monitoring,and managing portal hypertension-related complications,and evaluating the potential for liver transplantation in cases of decompensated cirrhosis,marked by rapid progression and the emer-gence of complications like variceal bleeding,hepatic encephalopathy,ascites,malnutrition,and more.Malnutrition,a prevalent complication across all disease stages,is often underdiagnosed in cirrhosis due to the complexities of nutritional assessment in patients with fluid retention and/or obesity,despite its crucial impact on prognosis.Increasing emphasis has been placed on the collaboration of nutritionists within hepatology and Liver transplant teams to deliver compre-hensive care,a practice that has shown to improve outcomes.This review covers appropriate screening and assessment methods for evaluating the nutritional status of this population,diagnostic approaches for malnutrition,and context-specific nutrition treatments.It also discusses evidence-based recommendations for supplementation and physical exercise,both essential elements of the standard care provided to cirrhotic patients.

Increased incidence of and microbiologic changes in pyogenic liver abscesses in the Mexican population

BACKGROUND Pyogenic liver abscess(PLA)is a rare disease with an estimated incidence that varies widely across the globe,being as high as 115.4/100000 habitants in Taiwan and as low as 1.1-1.2/100000 habitants in Europe and Canada.Even though there are multiple microorganisms capable of producing an abscess in the liver,including Entamoeba histolytica,fungi,and viruses,most abscesses are derived from bacterial infections.The epidemiology of PLA in Mexico is currently unknown.AIM To describe the clinical,demographic and microbiologic characteristics of PLA in Mexico.METHODS This is a retrospective study carried out in two centers,and included patients seen between 2006 and 2018 with the diagnosis of pyogenic abscess.We collected demographic,clinical,and microbiological information,treatment,complications,and outcomes.A logistic regression analysis was used to determine the association between different variables and mortality rates.RESULTS A total of 345 patients were included in this study.233(67.5%)had confirmed PLA,133(30%)patients had no positive culture and negative serology and 9(2.5%)had mixed abscesses.The mean age was 50 years(ranging from 16-97 years)and 63%were female.65%of the patients had positive cultures for Extended Spectrum Beta-Lactamases(ESBL)-Escherichia coli and Klebsiella pneumoniae.Cefotaxime was administered in 60%of cases.The most common sources of infection were ascending cholangitis and cholecystitis in 34(10%)and 31(9%),respectively.The median length of hospital stay was 14 d.165 patients underwent percutaneous catheter drainage.The inpatient mortality rate was 63%.Immunocompromised state[OR 3.9,95%CI:1.42-10.46],ESBL-Escherichia coli[OR 6.7,95%CI:2.7-16.2]and Klebsiella pneumoniae[OR 4-8,95%CI:1.6-14.4]predicted inpatient mortality by multivariate analysis.CONCLUSION The prevalence of PLA is increasing in Mexico and has a very high mortality rate.ESBL-Escherichia coli and Klebsiella pneumoniae are the most common microorganisms causing PLA and are independent predictors of inpatient mortality.

Liver transplantation is beneficial regardless of cirrhosis stage or acute-on-chronic liver failure grade:A single-center experience

BACKGROUND Liver transplantation for the most critically ill remains controversial;however,it is currently the only curative treatment option.AIM To assess immediate posttransplant outcomes and compare the short(1 year)and long-term(6 years)posttransplant survival among cirrhotic patients stratified by disease severity.METHODS We included cirrhotic patients undergoing liver transplantation between 2015 and 2019 and categorized them into compensated cirrhosis(CC),decompensated cirrhosis(DC),and acute-on-chronic liver failure(ACLF).ACLF was further divided into severity grades.Our primary outcomes of interest were total days of intensive care unit(ICU)and hospital stay,development of complications and posttransplant survival at 1 and 6 years.RESULTS 235 patients underwent liver transplantation(CC=11,DC=129 and ACLF=95).Patients with ACLF had a significantly longer hospital stay[8.0(6.0-13.0)vs CC,6.0(3.0-7.0),and DC 7.0(4.5-10.0);P=0.01]and developed more infection-related complications[47(49.5%),vs CC,1(9.1%)and DC,38(29.5%);P<0.01].Posttransplant survival at 1-and 6-years was similar among groups(P=0.60 and P=0.90,respectively).ACLF patients stratified according to ACLF grade[ACLF-1 n=40(42.1%),ACLF-2 n=33(34.7%)and ACLF-3 n=22(23.2%)],had similar ICU and hospital stay length(P=0.68,P=0.54),as well as comparable frequencies of overall and infectious posttransplant complications(P=0.58,P=0.80).There was no survival difference between ACLF grades at 1 year and 6 years(P=0.40 and P=0.15).CONCLUSION Patients may benefit from liver transplantation regardless of the cirrhosis stage.ACLF patients have a longer hospital stay and frequency of infectious complications;however,excellent,and comparable 1 and 6-year survival rates support their enlisting and transplantation including those with ACLF-3.

CD47:a new player in phagocytosis and xenograft rejection

Organ transplantation is limited by the availability of human donor organs.The transplantation of organs and tissues from other species(xenotransplantation)would supply an unlimited number of organs and offer many other advantages for which the pig has been identified as the most suitable source.However,the robust immune responses to xenografts remain a major obstacle to clinical application of xenotransplantation.The more vigorous xenograft rejection relative to allograft rejection is largely accounted for by the extensive genetic disparities between the donor and recipient.Xenografts activate host immunity not only by expressing immunogenic xenoantigens that provide the targets for immune recognition and rejection,but also by lacking ligands for the host immune inhibitory receptors.This review is focused on recent findings regarding the role of CD47,a ligand of an immune inhibitory receptor,signal regulatory protein alpha(SIRPa),in phagocytosis and xenograft rejection.