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Clinical utility of two-dimensional shear-wave elastography in monitoring disease course in Autoimmune hepatitis-primary biliary cholangitis overlap syndrome

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World Journal of Gastroenterology 2022年第18期28卷 2021-2033页

作者： Yu-Ling Yan Xian Xing Yi Wang Xiao-Ze Wang Zhi Wang Li Yang Department of Gastroenterology and Hepatology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Sichuan University University of Oxford Huaxi Joint for Gastrointestinal Cancer CentreChengdu 610207Sichuan ProvinceChina

BACKGROUND Autoimmune hepatitis-primary biliary cholangitis(AIH-PBC)overlap syndrome has a worse prognosis than AIH or PBC alone.Therefore,accurately staging liver fibrosis and dynamically monitoring disease progression are essential.AIM To investigate the performance of two-dimensional shear-wave elastography(2DSWE)for noninvasively staging liver fibrosis and assessing the clinical utility of repeated 2D-SWE for monitoring treatment response in AIH-PBC overlap syndrome.METHODS A total of 148 patients diagnosed with AIH-PBC overlap syndrome were retrospectively enrolled.Among them,82 patients had a 2D-SWE follow-up time of more than 1 year.The Scheuer scoring system was used to evaluate stages of hepatic inflammation and liver fibrosis.The performance of 2D-SWE for staging liver fibrosis was evaluated with the liver biopsy.Changes in liver stiffness(LS)measured by 2D-SWE in patients with or without complete biochemical remission were evaluated.RESULTS LS value was strongly correlated with liver fibrosis stage(Spearman r=0.84,P<0.0001).The areas under the receiver operating characteristic curves of LS for diagnosing significant fibrosis(≥S2),severe fibrosis(≥S3),and cirrhosis(S4)were 0.91,0.97,and 0.96,respectively.Patients with complete biochemical remission had a considerable decrease in LS values(P<0.0001).More importantly,the declined LS in patients with S0-S2 was significantly lower than that in patients with S3-S4(P=0.0002).In contrast,patients who failed to achieve biochemical remission had a slight but not significant decrease in LS(P=0.37).CONCLUSION LS measured by 2D-SWE is an accurate and reliable method in assessing liver fibrosis,especially for diagnosing severe fibrosis(≥3)and monitoring treatment response in patients with AIH-PBC overlap syndrome.

关键词： Liver fibrosis Liver biopsy Diagnostic tests Autoimmune hepatitis Primary biliary cholangitis Inflammation

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Vitamin D supplementation for Autoimmune hepatitis: A need for further investigation

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World Journal of Hepatology 2022年第1期14卷 295-299页

作者： Consolato M Sergi Anatomic Pathology Division Children’s Hospital of Eastern Ontario(CHEO)University of OttawaOttawa K1H 8L1ONCanada

Autoimmune hepatitis is a chronic liver disease harboring an autoimmune basis and progressive character.Despite still obscurity in etiology and pathogenesis,some evidence supports the importance of sustaining the immune system.Vitamin D is a lipo-soluble vitamin,which has been identified as decreased in our body.It is often due to the daily habit change and decrease of individual sun exposure due to the increase of the ultraviolet-induced potential melanocytic transformation.Here,we emphasize the importance of vitamin D supplementation in patients affected with liver disease.

关键词： Vitamin D Autoimmune hepatitis Supplementation Immunostimulants Liver

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Possible benefit of splenectomy in liver transplantation for Autoimmune hepatitis

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Hepatobiliary & Pancreatic Diseases International 2014年第3期13卷 328-331页

作者： Yan-Tian Xu De-Jie Liu Fan-Ying Meng Guang-Bing Li Jun Liu Department of Liver Transplantation and Hepatobiliary Surgery Shandong Provincial Hospital Affiliated to Shandong University Department of Anesthesiology Qilu Hospital of Shandong University

Liver transplantation for Autoimmune hepatitis(AIH) is usually successful with excellent long-term outcomes,but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy.Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.

关键词： Autoimmune hepatitis liver transplantation recurrence splenectomy

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Severe progression of Autoimmune hepatitis in a young COVID-19 adult patient: A case report

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Journal of Acute Disease 2022年第4期11卷 161-164页

作者： Neeraj Kumar Sushant Satyapriya Shaik Mohammad Tahaseen Kunal Singh Abhyuday Kumar Department of Trauma&Emergency AIIMS PatnaBiharIndia801505 Department of Anaesthesiology AIIMS PatnaBiharIndia801505 Department of Medicine AIIMS PatnaBiharIndia801505

Rationale:The impact of COVID-19 in patients with autoimmune liver disease treated with immunosuppressive therapy has not been described so far.This case report describes the clinical course of a patient with Autoimmune hepatitis(AIH)who developed COVID-19 and the features of cytokine syndrome leading to its deterioration in our intensive care unit.Patient’s Concern:A 28-year-old male presented with generalized anasarca for two weeks and chronic liver disease for 8 months.Diagnosis:AIH and Covid-19 with features of cytokine storm syndrome.Interventions:Intravenous furosemide,mannitol,syrup lactulose,steroids(prednisolone 40 mg),azathioprine 1 mg/kg body weight,rifaximin,vitamin K,and blood products.Outcomes:The patient had hepatic encephalopathy and AIH and died on the 10th day after admission despite ventilatory support,sustained low-efficiency hemodialysis,and resuscition.Lessons:The dramatic release of cytokines and the inflammatory‐immune responses not only alter the pathophysiology but also affects the onset and severity of disease progression in patients with AIH.

关键词： COVID-19 Autoimmune hepatitis Cytokine storm syndrome Immunosuppressant drugs Liver dysfunction

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Clinical characteristics and outcomes of COVID-19 in patients with Autoimmune hepatitis:A population-based matched cohort study

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World Journal of Hepatology 2023年第1期15卷 68-78页

作者： Arunkumar Krishnan Ruhee A Patel Yousaf Bashir Hadi Diptasree Mukherjee Sarah Shabih Shyam Thakkar Shailendra Singh Tinsay A Woreta Saleh A Alqahtani Section of Gastroenterology and Hepatology West Virginia University School of MedicineMorgantownWV 26505United States Division of Gastroenterology and Hepatology Johns Hopkins University School of MedicineBaltimoreMD 21287United States Department of Medicine Apex Institute of Medical ScienceKolkata 700075West BengalIndia Liver Transplant Center King Faisal Specialist Hospital and Research CenterRiyadh 12713Saudi Arabia

BACKGROUND Patients with Autoimmune hepatitis(AIH)require life-long immunosuppressive agents that may increase the risk of poor coronavirus disease 2019(COVID-19)outcomes.There is a paucity of large data at the population level to assess whether patients with AIH have an increased risk of severe diseases.AIM To evaluate the impact of pre-existing AIH on the clinical outcomes of patients with COVID-19.METHODS We conducted a population-based,multicenter,propensity score-matched cohort study with consecutive adult patients(≥18 years)diagnosed with COVID-19 using the TriNeTx research network platform.The outcomes of patients with AIH(main group)were compared to a propensity score-matched cohort of patients:(1)Without chronic liver disease(CLD);and(2)Patients with CLD except AIH(non-AIH CLD)control groups.Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects.The primary outcome was all-cause mortality,and secondary outcomes were hospitalization rate,need for critical care,severe disease,mechanical ventilation,and acute kidney injury(AKI).For each outcome,the risk ratio(RR)and confidence intervals(CI)were calculated to compare the association of AIH with the outcome.RESULTS We identified 375 patients with AIH,1647915 patients with non-CLD,and 15790 patients with non-AIH CLD with COVID-19 infection.Compared to non-CLD patients,the AIH cohort had an increased risk of all-cause mortality(RR=2.22;95%CI:1.07-4.61),hospitalization rate(RR=1.78;95%CI:1.17-2.69),and severe disease(RR=1.98;95%CI:1.19-3.26).The AIH cohort had a lower risk of hospitalization rate(RR=0.72;95%CI:0.56-0.92),critical care(RR=0.50;95%CI:0.32-0.79),and AKI(RR=0.56;95%CI:0.35-0.88)compared to the non-AIH CLD patients.CONCLUSION Patients with AIH are associated with increased hospitalization risk,severe disease,and all-cause mortality compared to patients without pre-existing CLD from the diagnosis of COVID-19.However,patients with AIH were not at risk for worse outc

关键词： Autoimmune hepatitis SARS-CoV-2 COVID-19 Mortality Outcomes Liver disease Severe

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Tacrolimus and mycophenolate mofetil as second-line treatment in Autoimmune hepatitis:Is the evidence of sufficient quality to develop recommendations?

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World Journal of Gastroenterology 2020年第38期26卷 5896-5910页

作者： Mohammadreza Abdollahi Neda Khalilian Ekrami Morteza Ghojazadeh H Marike Boezen Mohammadhossein Somi Behrooz Z Alizadeh Department of Epidemiology University of GroningenGroningen 9700 RBNetherlands Research Center for Evidence Based Medicine Tabriz University of Medical SciencesTabriz ***Iran Liver and Gastrointestinal Diseases Research Center Tabriz University of Medical SciencesTabriz ***Iran

BACKGROUND The standard management of Autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,high-quality data on the alternative management of AIH are scarce.AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil(MMF)and the quality of evidence by using the Grading of Recommendations Assessment,Development and Evaluation approach(GRADE).METHODS A systematic review and meta-analysis of the available data were performed.We calculated pooled event rates for three outcome measures:Biochemical remission,adverse events,and mortality,with their corresponding 95%confidence intervals(CI).RESULTS The pooled biochemical remission rate was 68.9%(95%CI:60.4-76.2)for tacrolimus,and 59.6%(95%CI:54.8-64.2)for MMF,and rates of adverse events were 25.5%(95%CI:12.4-45.3)for tacrolimus and 24.1%(95%CI:15.4-35.7)for MMF.The pooled mortality rate was estimated at 11.5%(95%CI:7.1-18.1)for tacrolimus and 9.01%(95%CI:6.2-12.8)for MMF.Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6%(CI:43.4-56.6)vs 73.5%(CI:58.1-84.7),and among non-responders were 59.1%(CI:48.7-68.8)vs 40.8%(CI:32.3-50.0),respectively.Moreover,the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment,but we found no high-quality evidence to support this statement.

关键词： Autoimmune hepatitis Efficacy Grading of Recommendations Assessment,Development and Evaluation approach Systematic review Meta-analysis Second-line

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Autoimmune hepatitis: Clinical Review with Insights into the Purinergic Mechanism of Disease

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Journal of Clinical and Translational Hepatology 2013年第2期1卷 79-86页

作者： Nikhil Kapila Jennifer T.Higa Maria Serena Longhi Simon C.Robson Department of Medicine University of Connecticut Farmington CT USA Gastroenterology Division and Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School Boston MA USA Gastroenterology Division and Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School Boston MA USA Institute of Liver Studies King's College London School of Medicine at King's College Hospital Denmark Hill London UK

Autoimmune hepatitis (AIH) is an important disorder that predominantly results in inflammatory liver disease in genetically predisposed women.The clinicopathological picture is characterized by symptoms associated with both systemic inflammation and hepatic dysfunction,and with increased serum aminotransferases,elevated IgG,autoantibodies,and interface hepatitis on liver biopsy.AIH usually results in liver injury as a consequence of chronic hepatitis and cirrhosis.However,rarely,patients may present with fulminant liver failure.Early diagnosis is important in all instances because the disease can be highly responsive to immunosuppressive therapeutic options.Left untreated,the disease is associated with high morbidity and mortality.Here we provide an overview of the current state of knowledge on AIH and summarize the treatment options for this serious condition in adults.We also discuss the pathogenesis of the disease as a possible consequence of autoimmunity and the breakdown of hepatic tolerance.We focus on regulatory T cell impairments as a consequence of changes in CD39 ectonucleotidase expression and altered purinergic signaling.Further understanding of hepatic tolerance may aid in the development of specific and well-tolerated therapies for AIH.

关键词： Autoimmune hepatitis Pathogenesis Immunology Purinergic CD39 Therapeutic overview

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Difficult treatment decisions in Autoimmune hepatitis

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World Journal of Gastroenterology 2010年第8期16卷 934-947页

作者： Albert J Czaja Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine

Treatment decisions in Autoimmune hepatitis are complicated by the diversity of its clinical presentations,uncertainties about its natural history,evolving opinions regarding treatment end points,varied nature of refractory disease,and plethora of alternative immu-nosuppressive agents. The goals of this article are to review the difficult treatment decisions and to provide the bases for making sound therapeutic judgments. The English literature on the treatment problems in au-toimmune hepatitis were identifi ed by Medline search up to October 2009 and 32 years of personal experi-ence. Autoimmune hepatitis may have an acute severe presentation,mild in? ammatory activity,lack autoan-tibodies,exhibit atypical histological changes (centri-lobular zone 3 necrosis or bile duct injury),or have variant features reminiscent of another disease (overlap syndrome). Corticosteroid therapy must be instituted early,applied despite the absence of symptoms,or modified in an individualized fashion. Pursuit of normal liver tests and tissue is the ideal treatment end point,but this objective must be tempered against the risk of side effects. Relapse after treatment withdrawal requires long-term maintenance therapy,preferably with azathioprine. Treatment failure or an incomplete response warrants salvage therapy that can include conventional medications in modified dose or empiricaltherapies with calcineurin inhibitors or mycophenolate mofetil. Liver transplantation supersedes empirical drug therapy in decompensated patients. Elderly and pregnant patients warrant treatment modifications. Difficult treatment decisions in Autoimmune hepatitis can be simplified by recognizing its diverse manifestations and individualizing treatment,pursuing realistic goals,applying appropriate salvage regimens,and identifying problematic patients early.

关键词： Autoimmune hepatitis Fulminant hepatitis Salvage therapy Treatment end points

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Autoimmune hepatitis and liver transplantation:Indications,and recurrent and de novo Autoimmune hepatitis

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World Journal of Transplantation 2022年第3期12卷 59-64页

作者： Murat Harputluoglu Ali Riza Caliskan Sami Akbulut Department of Gastroenterology and Transplant Hepatology Inonu University Faculty of MedicineMalatya 44280Turkey Department of Gastroenterology Adiyaman Education and Research HospitalAdıyaman 04120Turkey Liver Transplant Institute Inonu UniversityMalatya 44280Turkey

Autoimmune hepatitis is a chronic inflammatory disease of the liver that is characterized by circulating autoantibodies and elevated serum globulin levels.Liver transplantation may be required for patients with acute liver failure,decompensated cirrhosis,and hepatocellular carcinoma.Recurrence is defined as development of the same disease in the allograft following liver transplantation.Autoimmune hepatitis recurs in 36%-68%of the recipients 5 years after liver transplantation.De novo Autoimmune hepatitis is the development of Autoimmune hepatitis like clinical and laboratory characteristics in patients who had undergone liver transplantation for causes other than Autoimmune hepatitis.Diagnostic work up for recurrent and de novo Autoimmune hepatitis is similar to the diagnosis of the original disease,and it is usually difficult.Predniso(lo)ne with or without azathioprine is the main treatment for recurrent and de novo Autoimmune hepatitis.Early diagnosis and treatment are vital for patient prognosis because de novo Autoimmune hepatitis and recurrent Autoimmune hepatitis cause graft loss and result in subsequent retransplantation if medical treatment fails.

关键词： Liver transplantation Autoimmune hepatitis Recurrence Autoimmune hepatitis De novo Autoimmune hepatitis

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Characteristics and Inpatient Outcomes of Primary Biliary Cholangitis and Autoimmune hepatitis Overlap Syndrome

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 392-398页

作者： Yi Jiang Bing-Hong Xu Brandon Rodgers Nikolaos Pyrsopoulos Department of Medicine Rutgers New Jersey Medical SchoolNewarkNew JerseyUSA Liver Center&Center for Asian Health RWJBH-Saint Barnabas Medical CenterFlorham ParkNew JerseyUSA Division of Gastroenterology and Hepatology Rutgers New Jersey Medical SchoolNewarkNew JerseyUSA

Background and Aims:Primary biliary cholangitis(PBC)and Autoimmune hepatitis(AIH)are hepatobiliary diseases of presumed immune-mediated origin that have been shown to overlap.The aim of this retrospective trial was to use national data to examine the characteristics and outcomes of patients hospitalized with overlapping PBC and AIH(PBC/AIH).Methods:The National Inpatient Sample was used to identify hospitalized adult patients with PBC,AIH,and PBC/AIH from 2010 to 2014 by International Classification of Diseases-Ninth Edition Revision codes;patients with hepatitis B virus and hepatitis C virus infection were excluded.Primary outcomes measures were in-hospital outcomes that included mortality,respiratory failure,septic shock,length of stay,and total hospital charges.Secondary outcomes were the clinical characteristics of PBC/AIH,including the comorbid extrahepatic autoimmune disease pattern and complications of cirrhosis.Results:A total of 3,478 patients with PBC/AIH were included in the study.PBC/AIH was associated with higher rates of Sjögren’s syndrome(p<0.001;p<0.001),lower rates of Crohn’s disease(p<0.05;p<0.05),and higher rates of cirrhosis-related complications when compared to PBC or AIH alone.There were similar rates of mortality between the PBC/AIH,PBC,and AIH groups.The PBC/AIH group had higher rates of septic shock when compared to the PBC group(p<0.05)and AIH group(p<0.05)after adjusting for possible confounders.Conclusions:PBC/AIH is associated with a lower rate of Crohn’s disease,a higher rate of Sjögren’s syndrome,higher rates of cirrhosis-related complications,and significantly increased risk of septic shock compared to PBC and AIH individually.

关键词： Primary biliary cholangitis Autoimmune hepatitis Extrahepatic autoimmune diseases Cirrhosis-related complications Septic shock Hospital burden

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