Imaging characteristics of hypervascular focal nodular hyperplasialike lesions in patients with chronic alcoholic liver disease

BACKGROUND Focal nodular hyperplasia(FNH)-like lesions are hyperplastic formations in patients with micronodular cirrhosis and a history of alcohol abuse.Although pathologically similar to hepatocellular carcinoma(HCC)lesions,they are benign.As such,it is important to develop methods to distinguish between FNH-like lesions and HCC.AIM To evaluate diagnostically differential radiological findings between FNH-like lesions and HCC.METHODS We studied pathologically confirmed FNH-like lesions in 13 patients with alco-holic cirrhosis[10 men and 3 women;mean age:54.5±12.5(33-72)years]who were negative for hepatitis-B surface antigen and hepatitis-C virus antibody and underwent dynamic computed tomography(CT)and magnetic resonance imaging(MRI),including superparamagnetic iron oxide(SPIO)and/or gadoxetic acid-enhanced MRI.Seven patients also underwent angiography-assisted CT.RESULTS The evaluated lesion features included arterial enhancement pattern,washout appearance(low density compared with that of surrounding liver parenchyma),signal intensity on T1-weighted image(T1WI)and T2-weighted image(T2WI),central scar presence,chemical shift on in-and out-of-phase images,and uptake pattern on gadoxetic acid-enhanced MRI hepatobiliary phase and SPIO-enhanced MRI.Eleven patients had multiple small lesions(<1.5 cm).Radiological features of FNH-like lesions included hypervascularity despite small lesions,lack of“corona-like”enhancement in the late phase on CT during hepatic angiography(CTHA),high-intensity on T1WI,slightly high-or iso-intensity on T2WI,no signal decrease in out-of-phase images,and complete SPIO uptake or incomplete/partial uptake of gadoxetic acid.Pathologically,similar to HCC,FNH-like lesions showed many unpaired arteries and sinusoidal capillarization.CONCLUSION Overall,the present study showed that FNH-like lesions have unique radiological findings useful for differential diagnosis.Specifically,SPIO-and/or gadoxetic acid-enhanced MRI and CTHA features might facilitate differential diagnosis of FNH-like lesions and HCC.

Adenosine triphosphate-binding pocket inhibitor for mixed lineage kinase domain-like protein attenuated alcoholic liver disease via necroptosis-independent pathway

BACKGROUND Mixed lineage kinase domain-like protein(MLKL)serves as a critical mediator in necroptosis,a form of regulated cell death linked to various liver diseases.This study aims to specifically investigate the role of MLKL’s adenosine triphosphate(ATP)-binding pocket in facilitating necroptosis-independent pathways that may contribute to liver disease progression.By focusing on this mechanism,we seek to identify potential therapeutic targets that can modulate MLKL activity,offering new strategies for the prevention and treatment of liver-related pathologies.AIM To investigate the possibility of using the ATP-binding pocket-associated,necro-ptosis-independent MLKL pathway as a target for liver diseases.METHODS Cell death following necroptosis stimuli was evaluated using cell proliferation assays,flow cytometry,and electron microscopy in various cells.The human liver organoid system was used to evaluate whether the MLKL ATP pocket-binding inhibitor could attenuate inflammation.Additionally,alcoholic and non-alcoholic fatty liver diseases animal models were used to determine whether MLKL ATP pocket inhibitors could attenuate liver injury.RESULTS While an MLKL ATP pocket-binding inhibitor did not prevent necroptosis-induced cell death in RAW 264.7 cells,it did reduce the necroptosis-led expression of CXCL2,ICAM,and VCAM.Notably,MLKL ATP pocket inhibitor diminishes the expression of CXCL2,ICAM,and VCAM by inhibiting the IκB kinase and nuclear factor kappa-B pathways without inducing necroptosis-induced cell death in two-dimensional cell culture as well as the human-derived liver organoid system.Although MLKL ATP-binding inhibitor was ineffective in non-alcoholic fatty liver disease animal models,MLKL ATP-binding inhibitor attenuated hepatic inflammation in the alcoholic liver disease model.CONCLUSION MLKL ATP pocket-binding inhibitor exerted anti-inflammatory effects through the necroptosis-independent MLKL pathway in an animal model of alcoholic liver disease.

Predictors of survival in autoimmune liver disease overlap syndromes

BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is unclear.AIM To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death.METHODS Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort study.Liver-related death or transplantation(liver-related mortality)was determined using a population-based data linkage system.Prognostic scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and AIH-PSC.LOS was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group.CONCLUSION Survival in the rare,AILDOS is unclear.The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients.Further trials investigating predictors of survival in AILDOS are required.

Trends of autoimmune liver disease inpatient hospitalization and mortality from 2011 to 2017:A United States nationwide analysis

BACKGROUND Autoimmune liver diseases(AiLD)encompass a variety of disorders that target either the liver cells(autoimmune hepatitis,AIH)or the bile ducts[primary biliary cholangitis(PBC),and primary sclerosing cholangitis(PSC)].These conditions can progress to chronic liver disease(CLD),which is characterized by fibrosis,cirrhosis,and hepatocellular carcinoma.Recent studies have indicated a rise in hospitalizations and associated costs for CLD in the US,but information regarding inpatient admissions specifically for AiLD remains limited.AIM To examine the trends and mortality of inpatient hospitalization of AiLD from 2011 to 2017.METHODS This study is a retrospective analysis utilizing the National Inpatient Sample(NIS)databases.All subjects admitted between 2011 and 2017 with a diagnosis of AiLD(AIH,PBC,PSC)were identified using the International Classification of Diseases(ICD-9)and ICD-10 codes.primary AiLD admission was defined if the first admission code was one of the AiLD codes.secondary AiLD admission was defined as having the AiLD diagnosis anywhere in the admission diagnosis(25 diagnoses).Subjects aged 21 years and older were included.The national estimates of hospitalization were derived using sample weights provided by NIS.χ^(2)tests for categorical data were used.The primary trend characteristics were in-hospital mortality,hospital charges,and length of stay.RESULTS From 2011 to 2017,hospitalization rates witnessed a significant decline,dropping from 83263 admissions to 74850 admissions(P<0.05).The patients hospitalized were predominantly elderly(median 53%for age>65),mostly female(median 59%)(P<0.05),and primarily Caucasians(median 68%)(P<0.05).Medicare was the major insurance(median 56%),followed by private payer(median 27%)(P<0.05).The South was the top geographical distribution for these admissions(median 33%)(P<0.05),with most admissions taking place in big teaching institutions(median 63%)(P<0.05).Total charges for admissions rose from 66031 in 2011 to 78987 in 2017(P<0.05),while the inpatient mortality rate had a median of 4.9%(P<0.05),rising from 4.67%in 2011 to 5.43%in 2017.The median length of stay remained relatively stable,changing from 6.94 days(SD=0.07)in 2011 to 6.51 days(SD=0.06)in 2017(P<0.05).Acute renal failure emerged as the most common risk factor associated with an increased death rate,affecting nearly 68%of patients(P<0.05).CONCLUSION AiLD-inpatient hospitalization showed a decrease in overall trends over the studied years,however there is a significant increase in financial burden on healthcare with increasing in-hospital costs along with increase in mortality of hospitalized patient with AiLD.

Respiratory Mechanics, Respiratory Muscle Strength, Control of Ventilation and Gas Exchange in Patients with Autoimmune Liver Disease

Objectives: To assess respiratory elastance and resistive properties in patients with autoimmune liver disorders using the passive relaxation expiration technique and compare findings to a group of patients with non-autoimmune liver disease and control subjects. These findings were then related to control of ventilation and gas exchange. A secondary objective was to assess respiratory muscle strength and gas exchange and their relation to respiratory mechanics. Methods: Measurements included respiratory elastance and resistance using the passive relaxation method. Pulmonary function, gas exchange and control of ventilation were assessed using standard methods. Results: a) Compared to control subjects, Ers in patients with liver disease was on average 50% greater than in controls;b) mean respiratory resistance, expressed as the respiratory constants, K1 and K2 in the Rohrer relationship, Pao/V’ = K1 + K2V’, was not different from control resistance;c) mean maximal inspiratory and maximal expiratory pressures averaged 36% and 55% of their respective control values;d) inspiratory occlusion pressure in 0.1 sec (P0.1) was increased and negatively associated with FVC;and e) increases in P0.1, mean inspiratory flow (Vt/Ti) and presence of respiratory alkalosis confirmed the increase in ventilatory drive. Despite inspiratory muscle weakness in patients, P0.1/Pimax averaged 5-fold higher than in control subjects. Conclusions: Despite inspiratory muscle weakness and a V’E similar to that in normal subjects, central drive is increased in patients with chronic liver disease. The increase in ventilatory drive is related to smaller lung volumes and weakly associated with increase in respiratory elastance. Findings confirm that P0.1 is a reliable measure of central drive and is an approach that can be used in the evaluation of control of ventilation in patients with chronic liver disease.

Elafibranor:A promising treatment for alcoholic liver disease,metabolic-associated fatty liver disease,and cholestatic liver disease

Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.

Peroxisome proliferator-activated receptor agonists:A new hope towards the management of alcoholic liver disease

In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD.

Clinical significance of changes in the Th17/Treg ratio in autoimmune liver disease

AIM To investigate the levels, ratios, and clinical significance of T helper 17(Th17) cells and regulatory T(Treg) cells in the peripheral blood of patients with autoimmune liver disease(AILD). METHODS F o r t y-t w o A I L D p a t i e n t s w e r e i n c l u d e d i n t h e experimental group(group E), and 11 healthy subjects were recruited as the control group(group C). Flow cytometry was performed to determine the percentages of Th17 and Treg cells in peripheral blood lymphocytes. Furthermore, a range of biochemical indices was measured simultaneously in the blood of group E patients. RESULTS The percentage of Th17 cells and the Th17/Treg ratio were higher in group E than in group C(P < 0.01), whereas the percentage of Tregs was lower in the group E patients(P < 0.05). Patients in group E who were admitted with AILD in the active stage showed significantly higher Th17 percentages and Th17/Treg ratios than those measured in patients with AILD in remission(P < 0.05). In addition, among patients with AILD in the active stage, individuals that remained unhealed after hospitalization showed significantly higher baseline values of the Th17 percentage and the Th17/Treg ratio than those detected in patients who improved after treatment(P < 0.05). The results suggested that imbalance in the Th17/Treg ratio plays an important role in the pathogenesis and development of AILD.CONCLUSION A high Th17/Treg ratio appears to predict poor shortterm prognosis in patients with AILD in the active stage.

Non-invasive assessment of liver fibrosis using twodimensional shear wave elastography in patients with autoimmune liver diseases

AIM To determine the diagnostic accuracy of two-dimensional shear wave elastography(2D-SWE) for the noninvasive assessment of liver fibrosis in patients with autoimmune liver diseases(AILD) using liver biopsy as the reference standard.METHODS Patients with AILD who underwent liver biopsy and 2D-SWE were consecutively enrolled. Receiver operating characteristic(ROC) curves were constructed to assess the overall accuracy and to identify optimal cut-off values.RESULTS The characteristics of the diagnostic performance were determined for 114 patients with AILD. The areas under the ROC curves for significant fibrosis, severe fibrosis, and cirrhosis were 0.85, 0.85, and 0.86, respectively, and the optimal cut-off values associated with significant fibrosis(≥ F2), severe fibrosis(≥ F3), and cirrhosis(F4) were 9.7 k Pa, 13.2 k Pa and 16.3 k Pa, respectively. 2D-SWE showed sensitivity values of 81.7% for significant fibrosis, 83.0% for severe fibrosis,and 87.0% for cirrhosis, and the respective specificity values were 81.3%, 74.6%, and 80.2%. The overall concordance rate of the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages was 53.5%.CONCLUSION2D-SWE showed promising diagnostic performance for assessing liver fibrosis stages and exhibited high cut-off values in patients with AILD. Low overall concordance rate was observed in the liver stiffness measurements obtained using 2D-SWE vs fibrosis stages.

Autoimmune liver diseases in systemic rheumatic diseases

Systemic rheumatic diseases(SRDs)are chronic,inflammatory,autoimmune disorders with the presence of autoantibodies that may affect any organ or system.Liver dysfunction in SRDs can be associated with prescribed drugs,viral hepatitis,alternative hepatic comorbidities and coexisting autoimmune liver diseases(AILDs),requiring an exclusion of secondary conditions before considering liver involvement.The patterns of overlap diseases depend predominantly on genetic determinants with common susceptible loci widely distributing in both disorders.In AILDs,it is important to identify the overlapping SRDs at an early stage since such a coexistence may influence the disease course and prognosis.Commonly co-occurring SRDs in AILDs are Sjögren syndrome(SS),rheumatoid arthritis(RA)or systemic lupus erythematosus(SLE)in autoimmune hepatitis(AIH),and SS,RA or systemic sclerosis in primary biliary cholangitis.Owing to different disease complications and therapies,it is imperative to differentiate between SLE liver involvement and SLE-AIH overlap disease.Therapeutic options can be personalized to control coexisting conditions of liver autoimmunity and rheumatic manifestations in AILD-SRD overlap diseases.The collaboration between hepatologists and rheumatologists can lead to significant advances in managing such a complex scenario.In this review,we provide a comprehensive overview on coexisting AILDs in different SRDs and the therapeutic approach in managing these overlap diseases.

Hepatocellular carcinoma in viral and autoimmune liver diseases:Role of CD4+CD25+Foxp3+regulatory T cells in the immune microenvironment

More than 90%of cases of hepatocellular carcinoma(HCC)occurs in patients with cirrhosis,of which hepatitis B virus and hepatitis C virus are the leading causes,while the tumor less frequently arises in autoimmune liver diseases.Advances in understanding tumor immunity have led to a major shift in the treatment of HCC,with the emergence of immunotherapy where therapeutic agents are used to target immune cells rather than cancer cells.Regulatory T cells(Tregs)are the most abundant suppressive cells in the tumor microenvironment and their presence has been correlated with tumor progression,invasiveness,as well as metastasis.Tregs are characterized by the expression of the transcription factor Foxp3 and various mechanisms ranging from cell-to-cell contact to secretion of inhibitory molecules have been implicated in their function.Notably,Tregs amply express checkpoint molecules such as cytotoxic T lymphocyte-associated antigen 4 and programmed cell-death 1 receptor and therefore represent a direct target of immune checkpoint inhibitor(ICI)immunotherapy.Taking into consideration the critical role of Tregs in maintenance of immune homeostasis as well as avoidance of autoimmunity,it is plausible that targeting of Tregs by ICI immunotherapy results in the development of immune-related adverse events(irAEs).Since the use of ICI becomes common in oncology,with an increasing number of new ICI currently under clinical trials for cancer treatment,the occurrence of irAEs is expected to dramatically rise.Herein,we review the current literature focusing on the role of Tregs in HCC evolution taking into account their opposite etiological function in viral and autoimmune chronic liver disease,and we discuss their involvement in irAEs due to the new immunotherapies.

Autoimmune liver diseases and SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),causing coronavirus disease 2019(COVID-19),can trigger autoimmunity in genetically predisposed individuals through hyperstimulation of immune response and molecular mimicry.Here we summarise the current knowledge about autoimmune liver diseases(AILDs)and SARS-CoV-2,focusing on:(1)The risk of SARS-CoV-2 infection and the course of COVID-19 in patients affected by AILDs;(2)the role of SARS-CoV-2 in inducing liver damage and triggering AILDs;and(3)the ability of vaccines against SARS-CoV-2 to induce autoimmune responses in the liver.Data derived from the literature suggest that patients with AILDs do not carry an increased risk of SARS-Cov-2 infection but may develop a more severe course of COVID-19 if on treatment with steroids or thiopurine.Although SARSCoV-2 infection can lead to the development of several autoimmune diseases,few reports correlate it to the appearance of de novo manifestation of immunemediated liver diseases such as autoimmune hepatitis(AIH),primary biliary cholangitis(PBC)or AIH/PBC overlap syndrome.Different case series of an AIHlike syndrome with a good prognosis after SARS-CoV-2 vaccination have been described.Although the causal link between SARS-CoV-2 vaccines and AIH cannot be definitively established,these reports suggest that this association could be more than coincidental.

Prevalence and clinical characteristics of autoimmune liver disease in hospitalized patients with cirrhosis and acute decompensation in China

BACKGROUND Autoimmune liver disease(AILD)has been considered a relatively uncommon disease in China,epidemiological data for AILD in patients with cirrhosis and acute decompensation(AD)is sparse.AIM To investigate the prevalence,outcome and risk factors for AILD in cirrhotic patients complicated with AD in China.METHODS We collected data from patients with cirrhosis and AD from two prospective,multicenter cohorts in hepatitis B virus endemic areas.Patients were regularly followed up at the end of 28-d,90-d and 365-d,or until death or liver transplantation(LT).The primary outcome in this study was 90-d LTfree mortality.Acute-on-chronic liver failure(ACLF)was assessed on admission and during 28-d hospitalization,according to the diagnostic criteria of the European Association for the Study of the Liver(EASL).Risk factors for death were analyzed with logistic regression model.RESULTS In patients with cirrhosis and AD,the overall prevalence of AILD was 9.3%(242/2597).Prevalence of ACLF was significantly lower in AILD cases(14%)than those with all etiology groups with cirrhosis and AD(22.8%)(P<0.001).Among 242 enrolled AILD patients,the prevalence rates of primary biliary cirrhosis(PBC),autoimmune hepatitis(AIH)and PBC-AIH overlap syndrome(PBC/AIH)were 50.8%,28.5%and 12.0%,respectively.In ACLF patients,the proportions of PBC,AIH and PBC/AIH were 41.2%,29.4% and 20.6%.28-d and 90-d mortality were 43.8% and 80.0% in AILD-related ACLF.The etiology of AILD had no significant impact on 28-d,90-d or 365-d LTfree mortality in patients with cirrhosis and AD in both univariate and multivariate analysis.Total bilirubin(TB),hepatic encephalopathy(HE)and blood urea nitrogen(BUN)were independent risk factors for 90-d LT-free mortality in multivariate analysis.The development of ACLF during hospitalization only independently correlated to TB and international normalized ratio.CONCLUSION AILD was not rare in hospitalized patients with cirrhosis and AD in China,among which PBC was the most common etiology.90-d LT-free mortality were independently associated with TB,HE and BUN.

Clinical analysis of liver transplantation in autoimmune liver diseases

Background: Autoimmune liver diseases(ALDs) consist of autoimmune hepatitis(AIH), primary biliary cirrhosis(PBC), primary sclerosing cholangitis(PSC), Ig G4-associated cholangitis and overlap syndromes.Patients with these diseases may gradually progress to end-stage liver diseases and need liver transplantation. The present study aimed to explore the prognosis of patients with ALDs after liver transplantation.Methods: The clinical data of 80 patients with ALD(24 cases of AIH, 35 of PBC, 15 of PSC and 6 of AIHPBC overlap syndromes) who underwent liver transplantation in Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2004 to September 2016 were collected retrospectively. The causes of death were analyzed and the postoperative cumulative survival rate was estimated by the Kaplan–Meier method. Recurrence and other complications were also analyzed.Results: Of the 80 patients, 18 were males and 62 were females. The average age was 50.5 years and the average Model for End-stage Liver Disease(MELD) score was 14.1. After a median follow-up of 19.8 months, 8 patients died. The 1-, 3-and 5-year cumulative survival rates were all 89.0%. Three cases of recurrent ALDs were diagnosed(3.8%) but they were not totally consistent with primary diseases. Biliary tract complication occurred in 10 patients(12.5%). The new onset of tumor was observed in 1 patient(1.3%). De novo HBV/CMV/EBV infection was found in 3, 8 and 3 patients, respectively.Conclusion: Liver transplantation is an effective and safe treatment for end-stage ALD.

Evaluation of controlled attenuation parameter in assessing hepatic steatosis in patients with autoimmune liver diseases

BACKGROUND Hepatic steatosis commonly occurs in some chronic liver diseases and may affect disease progression.AIM To investigate the performance of controlled attenuation parameter(CAP)for the diagnosis of hepatic steatosis in patients with autoimmune liver diseases(AILDs).METHODS Patients who were suspected of having AILDs and underwent liver biopsy were consistently enrolled.Liver stiffness measurement(LSM)and CAP were performed by transient elastography.The area under the receiver operating characteristic(AUROC)curve was used to evaluate the performance of CAP for diagnosing hepatic steatosis compared with biopsy.RESULTS Among 190 patients with biopsy-proven hepatic steatosis,69 were diagnosed with autoimmune hepatitis(AIH),18 with primary biliary cholangitis(PBC),and 27 with AIH-PBC overlap syndrome.The AUROCs of CAP for the diagnosis of steatosis in AILDS were 0.878(0.791-0.965)for S1,0.764(0.676-0.853)for S2,and 0.821(0.716-0.926)for S3.The CAP value was significantly related to hepatic steatosis grade(P<0.001).Among 69 patients with AIH,the median CAP score was 205.63±47.36 dB/m for S0,258.41±42.83 dB/m for S1,293.00±37.18 dB/m for S2,and 313.60±27.89 dB/m for S3.Compared with patients with nonalcoholic fatty liver disease(NAFLD)presenting with autoimmune markers,patients with AIH concomitant with NAFLD were much older and had higher serum IgG levels and LSM values.CONCLUSION CAP can be used as a noninvasive diagnostic method to evaluate hepatic steatosis in patients with AILDs.Determination of LSM combined with CAP may help to identify patients with AIH concomitant with NAFLD from those with NAFLD with autoimmune phenomena.

Diagnostic role of transient elastography in patients with autoimmune liver diseases:A systematic review and meta-analysis

BACKGROUND Noninvasive methods have been developed to detect fibrosis in many liver diseases due to the limits of liver biopsy.However,previous studies have focused primarily on chronic viral hepatitis and nonalcoholic fatty liver disease.The diagnostic value of transient elastography for autoimmune liver diseases(AILDs)is worth studying.AIM To compare the diagnostic accuracy of imaging techniques with serum biomarkers of fibrosis in AILD.METHODS The PubMed,Cochrane Library and EMBASE databases were searched.Studies evaluating the efficacy of noninvasive methods in the diagnosis of AILDs[autoimmune hepatitis(AIH),primary biliary cholangitis(PBC)and primary sclerosing cholangitis(PSC)]were included.The summary area under the receiver operating characteristic curve(AUROC),diagnostic odds ratio,sensitivity and specificity were used to assess the accuracy of these noninvasive methods for staging fibrosis.RESULTS A total of 60 articles were included in this study,and the number of patients with AIH,PBC and PSC was 1594,3126 and 501,respectively.The summary AUROC of transient elastography in the diagnosis of significant fibrosis,advanced fibrosis and cirrhosis in patients with AIH were 0.84,0.88 and 0.90,respectively,while those in patients with PBC were 0.93,0.93 and 0.91,respectively.The AUROC of cirrhosis for patients with PSC was 0.95.However,other noninvasive indices(aspartate aminotransferase to platelet ratio index,aspartate aminotransferase/alanine aminotransferase ratio,fibrosis-4 index)had corresponding AUROCs less than 0.80.CONCLUSION Transient elastography exerts better diagnostic accuracy in AILD patients,especially in PBC patients.The appropriate cutoff values for staging advanced fibrosis and cirrhosis ranged from 9.6 to 10.7 and 14.4 to 16.9 KPa for PBC patients.

Autoimmune liver diseases

The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.

Use of oral vancomycin in children with autoimmune liver disease:A single centre experience

BACKGROUND Previous reports showed some beneficial effect of oral vancomycin treatment(OVT)in children with primary sclerosing cholangitis;conversely,the experience in patients with other autoimmune liver diseases(AILD),including autoimmune hepatitis(AIH)and autoimmune sclerosing cholangitis(ASC),is scant.AIM To assess the response to immunosuppressive treatment(IS)and to OVT in children diagnosed with AILD.METHODS Retrospective study of children diagnosed with AIH(normal biliary tree at cholangiography)and ASC(abnormal biliary tree at cholangiography)in the last 10 years.All underwent standard immunosuppressive therapy(IS),but nonresponders received also OVT.Biochemical remission[normal aspartate aminotransferase(AST)]and immunological remission(normal IgG and negative autoantibodies)rates and Sclerosing Cholangitis Outcomes in Pediatrics(SCOPE)index were assessed and compared during the follow up.RESULTS 75 children were included[69%female,median age 10.5 years(5.6-13.4 years),AIH=54,ASC=21].Sixty-three patients(84%,AIH=52,ASC=11)were treated with standard IS and 61 achieved biochemical remission,whereas 12 not responding to IS[16%,F=75%,median age 13.5 years,(12.2-15.7),10 with ASC]required OVT and 8 achieved biochemical remission.Overall OVT increased the biochemical remission rate of the whole group of AILD patients from 81%(61/75)to 92%(69/75).Median values of AST,alanine aminotransferase(ALT)and gamma-glutamyl transferase(GGT)decreased significantly after OVT start(P<0.05).Complete normalization of livers enzymes(AST,ALT and GGT)was observed in 6/12 patients(50%).Decrease in SCOPE index score was reported in 5/12 patients(42%).At last follow up(median of 4.4 years,range 0.6-13.8 years)all 75 patients are alive,6(8%,1 with ASC)successfully discontinued medications,1(with ASC)required liver transplantation.CONCLUSION Children with AIH and ASC respond well to IS treatment.OVT may represent a valuable treatment option to achieve biochemical remission in patients not responding to standard IS.These promising preliminary results suggest that a prospective study is indicated to define the efficacy of OVT in AILD.

Growing burden of alcoholic liver disease in China: A review

Explosive economic growth and increasing social openness in China over the last30 years have significantly boosted alcohol consumption, and consequently, the incidence of alcoholic liver disease(ALD) in China has increased. Because the epidemiologic and clinical features of ALD in the Chinese population may differ from those of the Caucasian population, this review describes the epidemiology,pathogenesis, genetic polymorphisms, diagnosis, and treatment of ALD in the Chinese population. This updated knowledge of ALD in China provides information needed for a global understanding of ALD and may help in the development of useful strategies for reducing the global ALD burden.