Fournier gangrene in an infant, complicated with severe sepsis and liver dysfunction: A case report

BACKGROUND Fournier gangrene is a rare,life-threatening infection characterized by necrotizing fasciitis in the perineal,genital and/or lower abdominal regions.Despite its rarity,the unfavorable prognosis associated with this disease is dependent on the timing of medical care.CASE SUMMARY A 3-month-old boy was admitted to our pediatric intensive care unit in critical condition after a 5-day history of fever and scrotal erythema with breaching skin lesions and swelling.Despite ambulatory antibiotic treatment,the child’s clinical condition deteriorated.At the time of admission,the child had necrotizing scrotal fasciitis that had spread to the abdomen.Following reanimation,the surgeon decided on an immediate intervention to rule out testicular torsion and to debride the affected area.Despite optimal antibiotic and supportive therapy,the patient developed severe sepsis with liver dysfunction,making treatment more challenging.CONCLUSION Recognizing Fournier gangrene,prompt referral to pediatric surgery,and appropriate antibiotic coverage are critical for avoiding sepsis and multiorgan dysfunction.

Liver dysfunction-related COVID-19:A narrative review

The coronavirus 2019 disease(COVID-19)is caused by a novel coronavirus,severe acute respiratory syndrome coronavirus 2.This disease was designated by the World Health Organization as a pandemic on March 11,2020,which is not seen before.There are no classical features among the cases of the disease owing to the involvement of nearly all body tissues by the virus.Hepatic involvement is one of the characteristics of the COVID-19 course.There are six possible mechanisms of such involvement:Direct virus injury,drug-induced effect,inflammatory cytokine storm,hypoxia-ischemic destruction,abnormalities in liver function tests,and pre-existing chronic liver diseases.Liver abnormalities are seen commonly in the severe or critical stage of COVID-19.Therefore,these abnormalities determine the COVID-19 severity and carry a high rate of morbidity and mortality.The elderly and patients with comorbidities like diabetes mellitus and hypertension are more vulnerable to liver involvement.Another issue that needs to be disclosed is the liver manifestations following the COVID-19 vaccination,such as autoimmune hepatitis.Of note,complete vaccination with third and fourth booster doses is necessary for patients with previous chronic liver diseases or those who have been subjected to liver transplantation.This review aims to explore the various aspects of liver dysfunction during the COVID-19 course regarding the epidemiological features,predisposing factors,pathophysiological mechanisms,hepatic manifestations due to COVID-19 or following vaccination,role of liver function tests in the assessment of COVID-19 severity,adverse effects of the therapeutic agents for the disease,and prognosis.

Effectiveness and Safety of Double-balloon Catheter versus Intra-amniotic Injection of Ethacridine Lactate for Termination of Second Trimester Pregnancy in Patients with Liver Dysfunction

Severe liver dysfunction in pregnancy（SLDP） is rare but serious complications with high mortality rate. This study compared the effectiveness and safety of double-balloon catheter versus intra-amniotic injection of ethacridine lactate for the termination of second trimester pregnancy in patients with SLD. A total of 55 patients with indications of labor induction were enrolled and analyzed by retrospective control analysis method. Twenty-three cases adopted Cook double balloon dilation as Cook group, and 32 cases received intra-amniotic injection of ethacridine lactate as EL group. The primary outcome was evaluated by successful abortion rate and the difference in the induction-to-abortion interval. Secondary outcomes included liver function recovery and the frequency of adverse events. Both Cook and EL regimens were effective, with successful abortion rate of 87.0% and 93.8%, respectively（P=0.639）. The induction-to-delivery interval was similar between Cook group and EL group（38.1±21.5 vs. 41.3±17.4, P=0.543）. The liver disease status was more severe in Cook group than in EL group, but it did not show any significant difference after pregnancy termination between the two groups and the improvement rate also did not show any significant difference. Both treatments were safe and there was no significant difference in bleeding and cervical laceration adverse events between the two groups. Our study firstly compared double-balloon catheter and ethacridine lactate for the induction of labor in women with SLD during second trimester pregnancy.

Liver dysfunction as a cytokine storm manifestation and prognostic factor for severe COVID-19

patients with or without preexisting liver disorders,posing a significant complication and mortality risk.During coronavirus disease 2019(COVID-19),abnormal liver function is typically observed.However,liver injury may occur because of the treatment as well.Ischemia,cytokine storm,and hypoxia were identified as the three major factors contributing to liver damage during COVID-19.Indeed,raised liver enzymes during hospitalizations may be attributed to medications used,as well as sepsis and shock.As a result,the proportion of hospitalized patients afflicted with COVID-19 and pathological liver biomarkers varies from 14%to 53%.Aminotransferases and bilirubin are found most often elevated.Usually,increased gamma-glutamyltransferase,alkaline phosphatase,and decreased serum albumin levels are demonstrated.Additionally,although there is no specific treatment for COVID-19,many of the drugs used to treat the infection are hepatotoxic.In this mini-review,we focus on how liver dysfunction can be one of the features associated with the COVID-19 cytokine storm.Furthermore,data show that liver injury can be an independent predictor of severe COVID-19,the need for hospitalization,and death.

COVID-19 and liver dysfunction:What nutritionists need to know

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus-2 has brought serious challenges for the medical field.Patients with COVID-19 usually have respiratory symptoms.However,liver dysfunction is not an uncommon presentation.Additionally,the degree of liver dysfunction is associated with the severity and prognosis of COVID-19.Prevention,diagnosis,and treatment of malnutrition should be routinely recommended in the management of patients with COVID-19,especially in those with liver dysfunction.Recently,a large number of studies have reported that nutrition therapy measures,including natural dietary supplements,vitamins,minerals and trace elements,and probiotics,might have potential hepatoprotective effects against COVID-19-related liver dysfunction via their antioxidant,antiviral,anti-inflammatory,and positive immunomodulatory effects.This review mainly focuses on the possible relationship between COVID-19 and liver dysfunction,nutritional and metabolic characteristics,nutritional status assessment,and nutrition therapy to provide a reference for the nutritionists while making evidence-based nutritional decisions during the COVID-19 pandemic.

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

Metabolic dysfunction-associated fatty liver disease and low muscle strength: A comment

The diagnosis of non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease only on the basis of laboratory parameter score such as Hepatic Steatosis Index which includes liver enzymes,gender,basal metabolic index,and presence of diabetic mellitus is not sufficient to exclude other causes of deranged liver enzymes especially medications and autoimmune related liver diseases.As the guideline suggests ultrasound is the preferred first-line diagnostic procedure for imaging of NAFLD,as it provides additional diagnostic information and the combination of biomarkers/scores and transient elastography might confer additional diagnostic accuracy and evident from previous similar studies too.

Novel Time-dependent Multi-omics Integration in Sepsis-associated Liver Dysfunction

The recently developed technologies that allow the analysis of each single omics have provided an unbiased insight into ongoing disease processes.However,it remains challenging to specify the study design for the subsequent integration strategies that can associate sepsis pathophysiology and clinical outcomes.Here,we conducted a time-dependent multi-omics integration(TDMI)in a sepsis-associated liver dysfunction(SALD)model.We successfully deduced the relation of the Toll-like receptor 4(TLR4)pathway with SALD.Although TLR4 is a critical factor in sepsis progression,it is not specified in single-omics analyses but only in the TDMI analysis.This finding indicates that the TDMI-based approach is more advantageous than single-omics analyses in terms of exploring the underlying pathophysiological mechanism of SALD.Furthermore,TDMI-based approach can be an ideal paradigm for insightful biological interpretations of multi-omics datasets that will potentially reveal novel insights into basic biology,health,and diseases,thus allowing the identification of promising candidates for therapeutic strategies.

Liver dysfunction on admission worsens clinical manifestations and outcomes of coronavirus disease 2019

Background:Liver dysfunction was common in coronavirus disease 2019(COVID-19),but its association with clinical features and poor prognosis has not been fully delineated.Our study aimed to determine the role of liver dysfunction in COVID-19 and understand the predictors for worse outcomes in patients with liver injury.Methods:We conducted this multicenter,retrospective study in five designated hospitals for COVID-19 manage-ment.Laboratory-confirmed COVID-19 patients were enrolled and classified into the normal live function group and liver dysfunction group according to liver enzymes,bilirubin,and albumin on admission,respectively.Data of baseline,clinical manifestations,and outcomes were collected and compared in the paired groups.Results:Of the 649 included COVID-19 patients,200(30.8%),69(10.6%),and 267(41.1%)patients had elevated liver enzymes,increased bilirubin,and low-level albumin,respectively.Fever,cough,and dyspnea were the most common symptoms and showed an increased proportion in the liver dysfunction group.Compared with patients in the normal liver function group,patients with liver dysfunction manifested decreased lymphocytes,higher level of leukocytes,neutrophils,inflammatory indicators,and cytokines,as well as more severe impairment in kidney function and myocardium.They were more likely to show bilateral involvement and more pulmonary lobes involved according to chest images.With increased proportion of patients who developed severe/critical conditions and needed mechanical ventilation and systemic glucocorticoid therapy,patients with liver dysfunc-tion on admission showed significantly higher in-hospital mortality.Moreover,cardiac troponin I≥1.5 ng/mL was identified as an independent mortality predictor in the elevated liver enzymes group.Conclusion:Patients with liver dysfunction on admission had worse clinical manifestation,and resulted in higher rate of severe/critical type,receiving mechanical ventilation and in-hospital mortality.

Insulin resistance and adipose tissue interactions as the cornerstone of metabolic(dysfunction)-associated fatty liver disease pathogenesis

The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.

COVID-19 and Liver Dysfunction:Current Insights and Emergent Therapeutic Strategies

The outbreak of coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has attracted increasing worldwide attention.Cases of liver damage or dysfunction(mainly characterized by moderately elevated serum aspartate aminotransferase lev-els)have been reported among patients with COVID-19.However,it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions,such as the use of potentially hepatotoxic drugs and the coexistence of sys-temic inflammatory response,respiratory distress syndrome-induced hypoxia,and multiple organ dysfunction.Based on the current evidence from case reports and case series,this review article focuses on the demographic and clinical characteristics,potential mechanisms,and treatment options for COVID-19-related liver dysfunction.This review also describes the geo-graphical and demographic distribution of COVID-19-related liver dysfunction,as well as possible underlying mechanisms linking COVID-19 to liver dysfunction,in order to facilitate future drug development,prevention,and control measures for COVID-19.

Liver Dysfunction and Its Association with the Risk of Death in COVID-19 Patients:A Prospective Cohort Study

Background and Aims:Coronavirus disease 2019(COVID-19)is a new respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2(commonly known as SARS-CoV-2)with multiple organ injuries.The aim of this study was to analyze COVID-19-associated liver dysfunction(LD),its association with the risk of death and prognosis after discharge.Methods:Three-hundred and fifty-five COVID-19 patients were recruited.Clinical data were collected from electronic medical records.LD was evaluated and its prognosis was tracked.The association between LD and the risk of death was analyzed.Results:Of the 355 COVID-19 patients,211 had mild disease,88 had severe disease,and 51 had critically ill disease.On admission,223(62.8%)patients presented with hypoproteinemia,151(42.5%)with cholestasis,and 101(28.5%)with hepatocellular injury.As expected,LD was more common in critically ill patients.By multivariate logistic regression,male sex,older age and lymphopenia were three important independent risk factors predicting LD among COVID-19 patients.Risk of death analysis showed that the fatality rate was higher in patients with hypoproteinemia than in those without hypoproteinemia(relative risk=9.471,p<0.01).Moreover,the fatality rate was higher in patients with cholestasis than those without cholestasis(relative risk=2.182,p<0.05).Follow-up observation found that more than one hepatic functional index of two-third patients remained abnormal at 14 days after discharge.Conclusions:LD at early disease stage elevates the risk of death of COVID-19 patients.COVID-19-associated LD does not recover completely by 14 days after discharge.

Impact renaming non-alcoholic fatty liver disease to metabolic associated fatty liver disease in prevalence,characteristics and risk factors

BACKGROUND Recently,a group of hepatologists proposed to rename non-alcoholic fatty liver disease(NAFLD)as metabolic associated fatty liver disease(MAFLD)with modified diagnostic criteria.It is important to note,however,that there are some differences between the diagnostic criteria used for NAFLD and MAFLD.Since the research on MAFLD is just beginning,however,evidence on its incidence and prevalence in the general population and in speci
c subpopulations remains limited.AIM To assess epidemiology of fatty liver in new definition and compare MAFLD with NAFLD.Exploring risk factors of MAFLD individuals.METHODS This was a retrospective,cross-sectional study.A total of 85242 adults were selected from the Chinese health management database in 2017–2022.The data of general information,laboratory indicators,lifestyle management and psychological status were obtained.MAFLD was diagnosed as ultrasound diagnosis of fatty liver and at least one between these three conditions:Overweight/obesity,type 2 diabetes mellitus(T2DM)or metabolic dysregulation.Metabolic factors were not considered in NAFLD diagnosis standard.The clinical characteristics of MAFLD and NAFLD were analysed using descriptive statistics.Continuous variables normally distributed were expressed as means±SD.Categorical variables were expressed as frequencies and proportions.Binary logistic regression was used to determine risk factors of the MAFLD.RESULTS The prevalence of MAFLD and NAFLD was 40.5%and 31.0%,respectively.The MAFLD or NAFLD population is more likely to be older(M:47.19±10.82 vs 43.43±11.96;N:47.72±11.17 vs 43.71±11.66),male(M:77.21%vs 44.43%;N:67.90%vs 53.12%)and high body mass index(M:26.79±2.69 vs 22.44±2.48;N:26.29±2.84 vs 23.29±3.12)than the non-MAFLD or non-MAFLD population.In multivariate analysis,general information(e.g.,≥2 metabolic abnormalities OR=3.38,(95%CI:2.99-3.81),P<0.001;diastolic blood pressure OR=1.01,(95%CI:1.00–1.01),P=0.002),laboratory results[e.g.,total bilirubin(TBIL)OR=0.98,(95%CI:0.98-0.99),P<0.001;serum uric acid(SUA)OR=1.01,(95%CI:1.01-1.01),P<0.001],and lifestyle factors[e.g.,drink beverage OR=0.32,(95%CI:0.17-0.63),P=0.001]were influence factors for MAFLD.Our study results offer new insight into potential risk factors associated with fatty liver disease,including SUA,TBIL and creatinine,all of which are related to chronic renal disease(CKD).CONCLUSION MAFLD is more prevalent than NAFLD,with two-fifths of individuals meeting the diagnosis criteria.MAFLD and NAFLD populations have different clinical characteristics.CKD may be related with MAFLD.

A new scoring system for assessment of liver function after successful hepatectomy in patients with hepatocellular carcinoma

BACKGROUND:Whether a major liver resection is safe has been judged mainly from the patient’s hepatic reserve.However,a safe limit for liver resection does not exist yet.This study aimed to construct a new scoring system as a guide to determine a safe limit for liver resection and avoid liver dysfunction after hepatectomy.METHODS:Eighty-six patients with hepatocellular carcinoma who had undergone hepatectomy in West China Hospital from March 2007 to June 2010 were reviewed.The patients were classified according to the levels of total bilirubin after hepatectomy and the parameters in the perioperative period were compared.Receiver operating characteristic (ROC) analysis was made to assess the liver function compensatory (LFC) value to predict liver dysfunction of the patients after hepatectomy.LFC value is defined as the preoperative KICG value×22.487+standard remnant liver volume (SRLV)×0.020.RESULTS:Patients were classified into group Ⅰ (normal group,n=69) and group Ⅱ (with total bilirubin >85.5 μmol/L for 7 days after hepatectomy,n=17) based on the levels of total bilirubin after hepatectomy.Group II was further divided into two subgroups:recovered subgroup (n=14) and fatal subgroup (n=3).There were no significant differences in preoperative data or intraoperative findings except the indocyanine green test parameters (KICG and ICG R15) and SRLV.ROC analysis showed that the sensitivity and specificity of an LFC value ≤13.01 were 94.1% and 82.6% respectively for predicting liver dysfunction of the patients after hepatectomy.CONCLUSIONS:The LFC value appears to be a good predictor of postoperative liver dysfunction in patients who undergo hepatectomy for HCC.An expected LFC value of 13.01 seems to be a safe limit for liver resection.

Liver injury associated with acute pancreatitis:The current status of clinical evaluation and involved mechanisms

Acute pancreatitis(AP)is a very common acute disease,and the mortality rate of severe AP(SAP)is between 15%and 35%.The main causes of death are multiple organ dysfunction syndrome and infections.The mortality rate of patients with SAP related to liver failure is as high as 83%,and approximately 5%of the SAP patients have fulminant liver failure.Liver function is closely related to the progression and prognosis of AP.In this review,we aim to elaborate on the clinical manifestations and mechanism of liver injury in patients with AP.

A review: Systematic research approach on toxicity model of liver and kidney in laboratory animals

Therapeutic experiments are commonly performed on laboratory animals to inves-tigate the possible mechanism(s)of action of toxic agents as well as drugs or sub-stances under consideration.The use of toxins in laboratory animal models,including rats,is intended to cause toxicity.This study aimed to investigate different models of hepatotoxicity and nephrotoxicity in laboratory animals to help researchers advance their research goals.The current narrative review used databases such as Medline,Web of Science,Scopus,and Embase and appropriate keywords until June 2021.Nephrotoxicity and hepatotoxicity models derived from some toxic agents such as cisplatin,acetaminophen,doxorubicin,some anticancer drugs,and other materials through various signaling pathways are investigated.To understand the models of renal or hepatotoxicity in laboratory animals,we have provided a list of toxic agents and their toxicity procedures in this review.

COVID-19 and the liver:A brief and core review

Coronavirus disease 2019 has a wide range of clinical spectrum from asymptomatic infection to severe infection resulting in death within a short time.Currently,it is known that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)does not only cause a respiratory tract infection but a more complicated disease that can lead to multiple system involvement including the liver.Herein,we evaluate the epidemiology,the impact of liver injury/dysfunction on disease prognosis,the pathophysiological mechanisms and management of liver injury.More than one-fourth of the patients have abnormal liver function tests,mostly a mild-to-moderate liver dysfunction.Liver injury is significantly associated with a poor clinical outcome.Direct cytotoxic effect of SARS-CoV-2,the immune response(“cytokine storm”),the complications related to the disease,and drugs used in the treatments are the pathophysiological mechanisms responsible for liver injury.However,the exact mechanism is not yet clearly explained.The binding of SARS-CoV-2 to the angiotensin-converting enzyme 2 receptors and entering the hepatocyte and cholangiocytes can cause cytotoxic effects on the liver.Excessive immune response has an important role in disease progression and causes acute respiratory distress syndrome and multiorgan failures accompanied by liver injury.Treatment drugs,particularly lopinavir/ritonavir,remdesivir and antibiotics are a frequent reason for liver injury.The possible reasons should be meticulously investigated and resolved.

Current management of liver diseases and the role of multidisciplinary approach

Liver is an organ having extremely diversified functions,ranging from metabolic and synthetic to detoxification of harmful chemicals.The multifunctionality of the liver in principle requires the multidisciplinary and pluralistic interventions for its management.Several studies have investigated liver function,dysfunction and clinic.This editorial work discusses new ideas,challenges and perspectives of current research regarding multidisciplinary and pluralistic management of liver diseases.In one hand the discussions have carried out on the involvement of extracellular vesicles,Na^(+)/H^(+) exchangers,severe acute respiratory syndrome coronavirus 2 and Epstein–Barr virus infections,Drug-induced liver injury,sepsis,pregnancy,and food supplements in hepatic disorders.In the other hand this study has discussed hepatocellular carcinoma algorithms and new bio-chemical and imaging experiments pertaining to liver diseases.Relevant articles with an impact index value">0"from reference citation analysis,which is an open multidisciplinary citation analysis database based on artificial intelligence technology,have served for the study’s argumentation.This work may be a useful tool for the clinical practice and research in managing and investigating liver disorders.

COVID-19 and hemolysis,elevated liver enzymes and thrombocytopenia syndrome in pregnant women-association or causation?

Pregnant women are among the high-risk population for severe coronavirus disease 2019(COVID-19)with unfavorable peripartum outcomes and increased incidence of preterm births.Hemolysis,the elevation of liver enzymes,and low platelet count(HELLP)syndrome and severe preeclampsia are among the leading causes of maternal mortality.Evidence supports a higher odd of pre-eclampsia in women with COVID-19,given overlapping pathophysiology.Involvement of angiotensin-converting enzyme 2 receptors by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)for the entry to the host cells and its downregulation cause dysregulation of the renin-angiotensin-aldosterone system.The overexpression of Angiotensin II mediated via p38 Mitogen-Activated Protein Kinase pathways can cause vasoconstriction and uninhibited platelet aggregation,which may be another common link between COVID-19 and HELLP syndrome.On PubMed search from January 1,2020,to July 30,2022,we found 18 studies on of SARS-COV-2 infection with HELLP Syndrome.Most of these studies are case reports or series,did not perform histopathology analysis of the placenta,or measured biomarkers linked to pre-eclampsia/HELLP syndrome.Hence,the relationship between SARS-CoV-2 infection and HELLP syndrome is inconclusive in these studies.We intend to perform a mini-review of the published literature on HELLP syndrome and COVID-19 to test the hypothesis on association vs causation,and gaps in the current evidence and propose an area of future research.

Transient elastography(FibroScan)in critical care:Applications and limitations

FibroScan®is a non-invasive device that assesses the‘hardness’(or stiffness)of the liver via the technique of transient elastography.Because fibrous tissue is harder than normal liver,the degree of hepatic fibrosis can be inferred from the liver hardness.This technique is increasingly being employed to diagnose liver fibrosis,even in critically ill patients.It is now being used not only for diagnosis and staging of liver cirrhosis,but also for outcome prognostication.However,the presence of several confounding factors,especially in critically ill patients,may make interpretation of these results unreliable.Through this review we aim to describe the indications and pitfalls of employing FibroScan in patients admitted to intensive care units.