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.

Iatrogenic bile duct injury with loss of confluence

AIM: To describe our experience concerning the surgical treatment of Strasberg E-4(Bismuth Ⅳ) bile duct injuries. METHODS: In an 18-year period, among 603 patients referred to our hospital for surgical treatment of complex bile duct injuries, 53 presented involvement of the hilar confluence classified as Strasberg E4 injuries. Imagenological studies, mainly magnetic resonance imaging showed a loss of confluence. The files of these patients were analyzed and general data were recorded, including type of operation and postoperative outcome with emphasis on postoperative cholangitis, liver function test and quality of life. The mean time of follow-up was of 55.9 ± 52.9 mo(median = 38.5, minimum = 2, maximum = 181.2). All other patients with Strasberg A, B, C, D, E1, E2, E3, or E5 biliary injuries were excluded from this study.RESULTS: Patients were divided in three groups: G1(n = 21): Construction of neoconfluence + Roux-en-Y hepatojejunostomy. G2(n = 26): Roux-en-Y portoenterostomy. G3(n = 6): Double(right and left) Rouxen-Y hepatojejunostomy. Cholangitis was recorded in two patients in group 1, in 14 patients in group 2, and in one patient in group 3. All of them required transhepatic instrumentation of the anastomosis and six patients needed live transplantation.CONCLUSION: Loss of confluence represents a surgicalchallenge. There are several treatment options at different stages. Roux-en-Y bilioenteric anastomosis(neoconfluence, double-barrel anastomosis, portoenterostomy) is the treatment of choice, and when it is technically possible, building of a neoconfluence has better outcomes. When liver cirrhosis is shown, liver transplantation is the best choice.

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.

Random noise stimulation in the treatment of patients with neurological disorders

Random noise stimulation technique involves applying any form of energy(for instance,light,mechanical,electrical,sound)with unpredictable intensities through time to the brain or sensory receptors to enhance sensory,motor,or cognitive functions.Random noise stimulation initially employed mechanical noise in auditory and cutaneous stimuli,but electrical energies applied to the brain or the skin are becoming more frequent,with a series of clinical applications.Indeed,recent evidence shows that transcranial random noise stimulation can increase corticospinal excitability,improve cognitive/motor performance,and produce beneficial aftereffects at the behavioral and psychological levels.Here,we present a narrative review about the potential uses of random noise stimulation to treat neurological disorders,including attention deficit hyperactivity disorder,schizophrenia,amblyopia,myopia,tinnitus,multiple sclerosis,post-stroke,vestibular-postural disorders,and sensitivity loss.Many of the reviewed studies reveal that the optimal way to deliver random noise stimulation-based therapies is with the concomitant use of neurological and neuropsychological assessments to validate the beneficial aftereffects.In addition,we highlight the requirement of more randomized controlled trials and more physiological studies of random noise stimulation to discover another optimal way to perform the random noise stimulation interventions.