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 mo...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.展开更多
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 nonalcoholi...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.展开更多
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...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.展开更多
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 live...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.展开更多
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 r...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.展开更多
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,...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.展开更多
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 st...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.展开更多
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...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.展开更多
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(AIL...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.展开更多
The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-gr...The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-ground mainly consisting of some risk alleles of the major histocompatibility complex(HLA).Many drugs have been linked to AIH phenotypes,which sometimes persist after drug discontinuation,suggesting that they awaken latent autoimmunity.At least three clini-cal scenarios have been proposed that refers to drug- induced autoimmune liver disease(DIAILD):AIH with drug-induced liver injury(DILI); drug induced-AIH(DI-AIH); and immune mediated DILI(IM-DILI).In addi-tion,there are instances showing mixed features of DI-AIH and IM-DILI,as well as DILI cases with positive autoantibodies.Histologically distinguishing DILI from AIH remains a challenge.Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however,a detailed standard-ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag-nosis between both entities.Growing information on the relationship of drugs and AIH is being available,being drugs like statins and biologic agents more fre-quently involved in cases of DIAILD.In addition,there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepa-totoxicity.Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of展开更多
AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA contr...AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies(ANAs), by line-blot assay; ANA and antineutrophil cytoplasmic antibody(ANCA), by indirect immunofluorescence assay; specific ANCAs and antiM2-3 E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA(i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman's correlation coefficient.RESULTS The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls(14.8% vs 2.2%, P < 0.05). Accordingly, 32(25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3 E. By comparison, the controls had a remarkably lower frequency of anti-M2-3 E(P < 0.05), with 6/92(8.6%) of patients with other liver diseases and 2/48(4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls(3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs(ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls(37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis(r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.CONCLUSION High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmunemediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.展开更多
Primary biliary cirrhosis(PBC),primary sclerosing cholangitis(PSC) and autoimmune hepatitis(AIH) constitute the classic autoimmune liver diseases(AILDs).While AIH target the hepatocytes,in PBC and PSC the targets of t...Primary biliary cirrhosis(PBC),primary sclerosing cholangitis(PSC) and autoimmune hepatitis(AIH) constitute the classic autoimmune liver diseases(AILDs).While AIH target the hepatocytes,in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells.Persistent liver injury,associated with chronic AILD,leads to un-resolving inflammation,cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts.Liver cirrhosis,and the resultant loss of normal liver function,inevitably ensues.Patients with cirrhosis have higher risks or morbidity and mortality,and that in the decompensated phase,complications of portal hypertension and/or liver dysfunction lead to rapid deterioration.Accurate diagnosis and monitoring of cirrhosis is,therefore of upmost importance.Liver biopsy is currently the gold standard technique,but highly promising non-invasive methodology is under development.Liver transplantation(LT) is an effective therapeutic option for the management of endstage liver disease secondary to AIH,PBC and PSC.LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy;in addition,LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids.展开更多
Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis...Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis(PBC), but not for primary sclerosing cholangitis(PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease(AIH, PBC, PSC) following LT.展开更多
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 t...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.展开更多
Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms.The shortage of organs for transplantation has resulted in the need for rationing.A var...Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms.The shortage of organs for transplantation has resulted in the need for rationing.A variety of approaches to selection and allocation have been developed and vary from country to country.The shortage of donors has meant that new approaches have to be adopted to make maximal use of the available organs;these include splitting grafts,use of extended criteria livers,livers from non-heart-beating donors and from living donors.Post transplantation,most patients will need life-long immunosuppression,although a small proportion can have immunosuppression successfully withdrawn.Newer immunosuppressive drugs and different strategies may allow a more targeted approach with a reduction in side-effects and so improve the patient and graft survival.For autoimmune diseases,transplantation is associated with significant improvement in the quality and length of life.Disease may recur after transplantation and may affect patient and graft survival.展开更多
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...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.展开更多
This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwid...This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.展开更多
Background:The discovery of regulatory cell death has led to a breakthrough in the therapeutic field.Various forms of cell death,such as necrosis,apoptosis,pyroptosis,autophagy,and ferroptosis,play an important role i...Background:The discovery of regulatory cell death has led to a breakthrough in the therapeutic field.Various forms of cell death,such as necrosis,apoptosis,pyroptosis,autophagy,and ferroptosis,play an important role in the development of liver diseases.In general,more than one form of cell death pathways is responsible for the disease state.Therefore,it is particularly important to study the regulation and interaction of various cell death forms in liver diseases.Data sources:We performed a PubMed search up to November 2022 with the following keywords:ferritinophagy,ferroptosis,and liver disease.We also used terms such as signal path,inducer,and inhibitor to supplement the query results.Results:This review summarized the basic characteristics of ferritinophagy and ferroptosis and the regulation of ferroptosis by ferritinophagy and reviewed the key targets and treatment strategies of ferroptosis in different liver diseases.Conclusions:Ferritinophagy is a potential therapeutic target in ferroptosis-related liver diseases.展开更多
As a common hyperglycemic disease,type 1 diabetes mellitus(T1DM)is a complicated disorder that requires a lifelong insulin supply due to the immunemediated destruction of pancreaticβcells.Although it is an organ-spec...As a common hyperglycemic disease,type 1 diabetes mellitus(T1DM)is a complicated disorder that requires a lifelong insulin supply due to the immunemediated destruction of pancreaticβcells.Although it is an organ-specific autoimmune disorder,T1DM is often associated with multiple other autoimmune disorders.The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease(AITD),which mainly exhibits two extremes of phenotypes:hyperthyroidism[Graves'disease(GD)]and hypothyroidism[Hashimoto's thyroiditis,(HT)].However,the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications.Thus,routine screening of thyroid function has been recommended when T1DM is diagnosed.Here,first,we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases.Subsequently,an updated review of the association between T1DM and AITD is offered.Finally,we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD,suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient popula...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient population.However,these conditions seem to have disparate rates and outcomes between different ethnic populations.The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma(HCC),and Hispanic patients experience the greatest burden,particularly those in South Texas.AIM To compare outcomes between Hispanic and non-Hispanic patients in the United States,while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic consideration.METHODS This cohort analysis was conducted with data obtained from TriNetX,LLC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations worldwide.Two cohort networks were used:University of Texas Medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast Texas.RESULTS This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino groups.Allcause mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB cohort.CONCLUSION This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.展开更多
文摘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.
基金Natural Science and Technology Major Project of Fujian Province,No.2021D033Natural Science Foundation of Shanghai,No.20ZR1410900+1 种基金Medical Innovation Project of Fujian Province,No.2022CXB020National Science and Technology Major Project,No.2017ZX 10203202-003-002.
文摘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.
基金Supported by the Tianqing Liver Disease Research Foundation,China Foundation for Hepatitis Prevention and Control,No.TQGB20150026Kejiaoxingwei Project of Suzhou,No.KJXW2016004
文摘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.
文摘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.
文摘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.
文摘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.
基金Supported by National Natural Science Foundation of China,No.81470842 and No.81770572.
文摘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.
基金Supported by Shanghai Hospital Development Commission,No.SHDC2020CR1037Bthe National Key R&D Program of China,No.2017YFC0908100+7 种基金the National Science and Technology Major Project,No.2018ZX10302206,2018ZX10723203 and 2017ZX10202202Shanghai Municipal Education Commission-Guofeng Clinical Medicine Grant,No.20152213the National Natural Science Foundation of China,No.82170629,81930061,81900579,81970550,82070613,82070650,and 81972265Chongqing Natural Science Foundation,No.CSTC2019jcyj-zdxmX0004Beijing Municipal Science&Technology Commission,No.Z191100006619033Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program,No.2017BT01S131the Foundation for Innovative Research Groups of Hubei Provincial Natural Science Foundation,No.2018CFA031Guangdong Basic and Applied Basic Research Foundation,No.2020A1515010052.
文摘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.
文摘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.
文摘The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-ground mainly consisting of some risk alleles of the major histocompatibility complex(HLA).Many drugs have been linked to AIH phenotypes,which sometimes persist after drug discontinuation,suggesting that they awaken latent autoimmunity.At least three clini-cal scenarios have been proposed that refers to drug- induced autoimmune liver disease(DIAILD):AIH with drug-induced liver injury(DILI); drug induced-AIH(DI-AIH); and immune mediated DILI(IM-DILI).In addi-tion,there are instances showing mixed features of DI-AIH and IM-DILI,as well as DILI cases with positive autoantibodies.Histologically distinguishing DILI from AIH remains a challenge.Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however,a detailed standard-ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag-nosis between both entities.Growing information on the relationship of drugs and AIH is being available,being drugs like statins and biologic agents more fre-quently involved in cases of DIAILD.In addition,there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepa-totoxicity.Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of
基金the Guangdong Provincial Science and Technology Planning Project,No.2014A020212520the Guangzhou Science and Technology Project,No.201707010014
文摘AIM To investigate the prevalence and clinical significance of autoimmune liver disease(ALD)-related autoantibodies in patients with biliary atresia(BA).METHODS Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies(ANAs), by line-blot assay; ANA and antineutrophil cytoplasmic antibody(ANCA), by indirect immunofluorescence assay; specific ANCAs and antiM2-3 E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA(i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman's correlation coefficient.RESULTS The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls(14.8% vs 2.2%, P < 0.05). Accordingly, 32(25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3 E. By comparison, the controls had a remarkably lower frequency of anti-M2-3 E(P < 0.05), with 6/92(8.6%) of patients with other liver diseases and 2/48(4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls(3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs(ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls(37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis(r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.CONCLUSION High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmunemediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.
文摘Primary biliary cirrhosis(PBC),primary sclerosing cholangitis(PSC) and autoimmune hepatitis(AIH) constitute the classic autoimmune liver diseases(AILDs).While AIH target the hepatocytes,in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells.Persistent liver injury,associated with chronic AILD,leads to un-resolving inflammation,cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts.Liver cirrhosis,and the resultant loss of normal liver function,inevitably ensues.Patients with cirrhosis have higher risks or morbidity and mortality,and that in the decompensated phase,complications of portal hypertension and/or liver dysfunction lead to rapid deterioration.Accurate diagnosis and monitoring of cirrhosis is,therefore of upmost importance.Liver biopsy is currently the gold standard technique,but highly promising non-invasive methodology is under development.Liver transplantation(LT) is an effective therapeutic option for the management of endstage liver disease secondary to AIH,PBC and PSC.LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy;in addition,LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids.
文摘Liver transplantation(LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis(AIH) and primary biliary cirrhosis(PBC), but not for primary sclerosing cholangitis(PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease(AIH, PBC, PSC) following LT.
基金supported by grants from Clinical and Fundamental Research on Pediatric Liver Transplantation,Shanghai Science and Technology Committee(15411950401)Clinical Application Research of Individual Treatment of Immunosuppressive Agent and Immune Monitoring in Pediatric Liver Transplantation,Shanghai Jiao Tong University School of Medicine(DLY201606)
文摘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.
文摘Liver transplantation remains an effective treatment for those with end-stage disease and with intractable liver-related symptoms.The shortage of organs for transplantation has resulted in the need for rationing.A variety of approaches to selection and allocation have been developed and vary from country to country.The shortage of donors has meant that new approaches have to be adopted to make maximal use of the available organs;these include splitting grafts,use of extended criteria livers,livers from non-heart-beating donors and from living donors.Post transplantation,most patients will need life-long immunosuppression,although a small proportion can have immunosuppression successfully withdrawn.Newer immunosuppressive drugs and different strategies may allow a more targeted approach with a reduction in side-effects and so improve the patient and graft survival.For autoimmune diseases,transplantation is associated with significant improvement in the quality and length of life.Disease may recur after transplantation and may affect patient and graft survival.
文摘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.
基金Supported by National Natural Science Foundation of China,No.82000625the Doctoral Scientific Research Foundation of Liaoning Province,No.2020-BS-109.
文摘This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.
基金This study was supported by grants from the National Natural Science Foundation of China(82360132)the Natural Science Foundation of Gansu Province(20JR5RA364)+3 种基金the Fund of the First Hospital of Lanzhou University(ldyyyn2020-02,ldyyyn2020-14)Gansu Clinical Medical Research Center of Infection&Liver Diseases(21JR7RA392)the Natural Science Foundation of Gansu Province(21JR1RA070)Lanzhou Science and Technology Planning Project(2023-2-76).
文摘Background:The discovery of regulatory cell death has led to a breakthrough in the therapeutic field.Various forms of cell death,such as necrosis,apoptosis,pyroptosis,autophagy,and ferroptosis,play an important role in the development of liver diseases.In general,more than one form of cell death pathways is responsible for the disease state.Therefore,it is particularly important to study the regulation and interaction of various cell death forms in liver diseases.Data sources:We performed a PubMed search up to November 2022 with the following keywords:ferritinophagy,ferroptosis,and liver disease.We also used terms such as signal path,inducer,and inhibitor to supplement the query results.Results:This review summarized the basic characteristics of ferritinophagy and ferroptosis and the regulation of ferroptosis by ferritinophagy and reviewed the key targets and treatment strategies of ferroptosis in different liver diseases.Conclusions:Ferritinophagy is a potential therapeutic target in ferroptosis-related liver diseases.
文摘As a common hyperglycemic disease,type 1 diabetes mellitus(T1DM)is a complicated disorder that requires a lifelong insulin supply due to the immunemediated destruction of pancreaticβcells.Although it is an organ-specific autoimmune disorder,T1DM is often associated with multiple other autoimmune disorders.The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease(AITD),which mainly exhibits two extremes of phenotypes:hyperthyroidism[Graves'disease(GD)]and hypothyroidism[Hashimoto's thyroiditis,(HT)].However,the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications.Thus,routine screening of thyroid function has been recommended when T1DM is diagnosed.Here,first,we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases.Subsequently,an updated review of the association between T1DM and AITD is offered.Finally,we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD,suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.
基金Supported by Institute for Translational Sciences at the University of Texas Medical Branch,supported in part by a Clinical and Translational Science Award from the National Center for Advancing Translational Sciences at the National Institutes of Health,UL1TR001439Moody Endowment Grant,2014-07.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient population.However,these conditions seem to have disparate rates and outcomes between different ethnic populations.The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma(HCC),and Hispanic patients experience the greatest burden,particularly those in South Texas.AIM To compare outcomes between Hispanic and non-Hispanic patients in the United States,while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic consideration.METHODS This cohort analysis was conducted with data obtained from TriNetX,LLC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations worldwide.Two cohort networks were used:University of Texas Medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast Texas.RESULTS This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino groups.Allcause mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB cohort.CONCLUSION This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.
