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False positive anti-hepatitis A virus immunoglobulin M in Autoimmune hepatitis/primary biliary cholangitis overlap syndrome:A case report

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World Journal of Clinical Cases 2021年第22期9卷 6464-6468页

作者： Jun Yan Yan-Sha He Yi Song Xin-Yu Chen Hua-Bao Liu Chun-Yan Rao Department of Hepatology Chongqing Hospital of Traditional Chinese MedicineChongqing 400021China

BACKGROUND Autoimmune hepatitis(AIH)is an immune-mediated liver disease affecting all age groups.Associations between hepatitis A virus(HAV)and AIH have been described for many years.Herein,we report a case of an AIH/primary biliary cholangitis(PBC)overlap syndrome with anti-HAV immunoglobulin M(IgM)false positivity.CASE SUMMARY A 55-year-old man was admitted with manifestations of anorexia and jaundice along with weakness.He had marked transaminitis and hyperbilirubinemia.Viral serology was positive for HAV IgM and negative for others.Autoantibody screening was positive for anti-mitochondria antibody but negative for others.Abdominal ultrasound imaging was normal.He was diagnosed with acute hepatitis A.After symptomatic treatment,liver function tests gradually recovered.Several months later,his anti-HAV IgM positivity persisted and transaminase and bilirubin levels were also more than 10 times above of the upper limit of normal.Liver histology was prominent,and HAV RNA was negative.Therefore,AIH/primary biliary cholangitis(PBC)overlap syndrome diagnosis was made based on the“Paris Criteria”.The patient was successfully treated by immunosuppression.CONCLUSION This case highlights that autoimmune diseases or chronic or acute infections,may cause a false-positive anti-HAV IgM result because of cross-reacting antibodies.Therefore,the detection of IgM should not be the only method for the diagnosis of acute HAV infection.HAV nucleic acid amplification tests should be employed to confirm the diagnosis.

关键词： Autoimmune hepatitis Primary biliary cholangitis hepatitis A virus Case report

Is Autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?

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World Journal of Gastroenterology 2010年第29期16卷 3704-3708页

作者： Rosilene G Badiani Vitória Becker Renata M Perez Carla AL Matos Lara B Lemos Valéria P Lanzoni Luis Eduardo C Andrade Alessandra Dellavance Antonio Eduardo B Silva Maria Lucia G Ferraz Division of Gastroenterology Federal University of Sao Paulo04023-900Sao PauloBrazil Department of Internal Medicine Federal University of Rio de Janeiro21941-913Rio de JaneiroBrazil Department of Pathology Immunology Group Fleury Medicine and Health 不详

AIM:To evaluate the overlap of Autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to Autoimmune hepatitis(plasma cell infiltrate and presence of rosettes).RESULTS:Among patients with hepatitis C and intense interface hepatitis there was a low prevalence of autoantibodies(ANA=12%,SMA=5%,LKM-1=0%) and the median γ-globulin level was within the normal range.Typical histological findings of autoimmune disease were observed in only two cases(2%).After applying the score for diagnosis of Autoimmune hepatitis,only one patient was classified with a definitive diagnosis of Autoimmune hepatitis.Since overlap with Autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis C we sought to identify the variables associated with this finding.The presence of intense interface hepatitis was associated with more advanced age,both at the time of infection and at the time of the biopsy,and higher prevalence of blood transfusion and alcohol abuse.CONCLUSION:Although possible,overlap with Autoimmune hepatitis is a very rare association in HCV-infected patients with intense interface hepatitis,an unusual presentation which seems to be related to other host variables.

关键词： hepatitis C Liver biopsy Antinuclear antibody Autoimmune hepatitis Interface hepatitis

Is simultaneous presence of IgG4-positive plasma cells and giantcell hepatitis a coincidence in Autoimmune hepatitis?A case report

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World Journal of Clinical Cases 2021年第25期9卷 7527-7534页

作者： You-Wen Tan Jia-Min Wang Li Chen Department of Hepatology The Third Hospital of Zhenjiang Affiliated Jiangsu UniversityZhenjiang 212003Jiangsu ProvinceChina

BACKGROUND The immune-mediated invasion of IgG4-positive plasma cells in the liver is found in some Autoimmune hepatitis.Giant-cell hepatitis(GCH)is a very rare pathological feature in adults,and the clinical characteristics of the simultaneous appearance of the two pathological phenomena are not clear.CASE SUMMARY A 68-year-old woman was hospitalized with fatigue,poor appetite,and yellow urine for 20 d.Liver function tests and immunological indexes were significantly abnormal and accompanied by elevated serum IgG4 levels.Liver pathology revealed severe inflammation of the interface between the portal tract and hepatocytes,portal area inflammation,plasma cell infiltration,formation of rosette cells,IgG4-positive plasma cells>10/high-power field,IgG4/IgG>40%,and multinucleated liver cell swelling.IgG4-related Autoimmune hepatitis(AIH)combined with GCH was diagnosed,and methylprednisolone was administered at 40 mg/day.Two weeks later,the clinical symptoms disappeared,and the liver function and immunological indicators were significantly improved.Methylprednisolone was reduced at a rate of 4–8 mg per week to 8 mg/day for maintenance.A second liver biopsy 48 wk later indicated that liver inflammation and fibrosis were significantly improved.IgG4-positive plasma cells and GCH were not detected.A literature search was conducted to analyze articles reporting similar pathological phenomena.CONCLUSION AIH with simultaneous IgG4-positive plasma cell infiltration and GCH,liver inflammation,and fibrosis is possibly more severe than typical AIH but sensitive to corticosteroids.

关键词： IgG4 Autoimmune hepatitis Giant-cell hepatitis Case report

Expression of programmed death 1 and its ligands in the liver of Autoimmune hepatitis C57BL/6 mice

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Chinese Medical Journal 2009年第16期122卷 1941-1946页

作者： CAO Jin LIU Feng-Xia YU Meng-xue Department of Rheumatology Peking Union Medical College Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100730 China

Background Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease with unknown etiology. Programmed death 1 （PD-1） and its ligands （PD-L1 and PD-L2）, BT-H1/PD-L1 and B7-DC/PD-L2, are new CD28-B7 family members that are involved in the regulation of immune responses. Previous observation suggests that PD-1 system plays an inhibitory role in regulating peripheral blood T cells, B cells and myeloid cells, thus their abnormality may be related to autoimmune diseases. This study aimed to explore the role of PD-1/PD-L1, L2 system in the pathogenesis of AIH. Methods The mice model of experimental Autoimmune hepatitis （EAH） was established in C57BL/6 mice and the expression levels of PD-1 and PD-L1, L2 in the murine liver and the cytokines, including interferon （IFN）-γ, tumor necrosis factor （TNF）-α and interleukin （IL）-4 in the spleen were detected using reverse transcription-polymerase chain reaction （RT-PCR）, and the results were compared with those of normal controls. Results The expression levels of PD-1, PD-L1, PD-L2 mRNA were higher in EAH compared with normal controls （P 〈0.05）, the PD-L2/PD-1 ratio was relatively lower in EAH （EAH -0.08±0.35, normal controls 0.52±0.07, P=0.009）. In the EAH, the expression of the three cytokines were all upregulated compared with normal controls. PD-L1 had a positive correlation with the expression of IFN-γ （r =0.289, P 〈0.05）, while PD-L2 showed a positive correlation with both expressions of IL-4 （r=0.378, P 〈0.01） and IFN-γ （r =0.261, P 〈0.05）. While TNF-α showed no correlation with PD-L1 （r=0.044, P=0.736） or PD-L2 （r=0.127, P=0.335）. Conclusions The expression of PD-1/PD-L1, L2 is upregulated in EAH and regulated by IFN-γ and IL-4. PD-1 system may play an important role in the pathogenesis of AIH.

关键词： Autoimmune hepatitis programmed death 1 programmed death 1 ligands reverse transcription-polymerase chain reaction cytokine

Stem cells from human exfoliated deciduous teeth ameliorate concanavalin A-induced Autoimmune hepatitis by protecting hepatocytes from apoptosis

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World Journal of Stem Cells 2020年第12期12卷 1623-1639页

作者： Yi-Kun Zhou Ling-Su Zhu Hua-Ming Huang Sheng-Jie Cui Ting Zhang Yan-Heng Zhou Rui-Li Yang Department of Orthodontics Peking University School and Hospital of StomatologyNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China Department of Orthodontics The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide,which emphasizes the urgent need to identify novel treatments.Stem cells from human exfoliated deciduous teeth(SHED),which are easy to obtain in a non-invasive manner,show pronounced proliferative and immunomodulatory capacities.AIM To investigate the protective effects of SHED on concanavalin A(ConA)-induced hepatitis in mice,and to elucidate the associated regulatory mechanisms.METHODS We used a ConA-induced acute hepatitis mouse model and an in vitro co-culture system to study the protective effects of SHED on ConA-induced Autoimmune hepatitis,as well as the associated underlying mechanisms.RESULTS SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3+,CD4+,tumor necrosis-alpha+,and interferon-gamma+inflammatory cells.Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice.SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations.Mechanistically,ConA upregulated tumor necrosisalpha and interferon-gamma expression,which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis,resulting in acute liver injury.SHED administration protected hepatocytes from ConA-induced apoptosis.CONCLUSION SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway.Our findings could provide a potential treatment strategy for hepatitis.

关键词： Autoimmune hepatitis Stem cells from human exfoliated deciduous teeth Concanavalin A Apoptosis Nuclear factor-kappa B

Extremely rare case of necrotizing gastritis in a patient with Autoimmune hepatitis: A case report

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World Journal of Clinical Cases 2021年第14期9卷 3472-3477页

作者： Seung Ki Moon Jeong-Ju Yoo Sang Gyune Kim Young Seok Kim Department of Internal Medicine Soonchunhyang University Bucheon HospitalBucheon 14584South Korea Department of Gastroenterology and Hepatology Soonchunhyang University School of MedicineBucheon 14584South Korea

BACKGROUND Autoimmune hepatitis can cause liver fibrosis,liver cirrhosis,and hepatocellular carcinoma.Its treatment option include the use of steroids and/or immunesuppressive agents such as azathioprine.However,these drugs have some side effects.Thus,close follow-up is needed during treatment.Here,we present an extremely rare case of a patient with an Autoimmune hepatitis who died from necrotizing gastritis during immunosuppressive treatment.CASE SUMMARY A 52-year-old female patient was diagnosed with Autoimmune hepatitis.We treated this patient with immunosuppressive agents.High-dose steroid treatment was initially started.Then azathioprine treatment was added while steroid was tapering.Five weeks after the start of treatment,she visited the emergency room due to generalized abdominal pain and vomiting.After computed tomography scan,the patient was diagnosed with necrotizing gastritis and the patient progressed to septic shock.Treatment for sepsis was continued in the intensive care unit.However,the patient died at 6 h after admission to the emergency room.CONCLUSION In patients with autoimmune infections undergoing immunosuppressant therapy,rare complications such as necrotizing gastritis may occur,thus requiring clinical attention.

关键词： Autoimmune hepatitis Azathioprine Case report

Primary sclerosing cholangitis and Autoimmune hepatitis overlap syndrome associated with inflammatory bowel disease:A case report and systematic review

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World Journal of Clinical Cases 2020年第18期8卷 4075-4093页

作者： Vinícius Remus Ballotin Lucas Goldmann Bigarella Floriano Riva Georgia Onzi Raul Angelo Balbinot Silvana Sartori Balbinot Jonathan Soldera Faculty of Medicine Universidade de Caxias do Sul(UCS)Caxias do Sul 95070560Brazil CPM Laboratório de Caxias do Sul Caxias do Sul 95070561Brazil Clinical Gastroenterology Universidade de Caxias do Sul(UCS)Caxias do Sul 95070560Brazil

BACKGROUND A previously healthy 22-year-old woman presented with abdominal pain and jaundice.She had a reagent antinuclear factor(1:640,with a homogeneous nuclear pattern)and hypergammaglobulinemia(2.16 g/dL).Anti-smooth muscle,antimitochondrial and anti-liver-kidney microsomal antibody type 1 antibodies were negative.Magnetic resonance cholangiography showed a cirrhotic liver with multiple focal areas of strictures of the intrahepatic bile ducts,with associated dilations.Liver biopsy demonstrated periportal necroinflammatory activity,plasmocyte infiltration and advanced fibrosis.Colonoscopy showed ulcerative pancolitis and mild activity(Mayo score 1),with a spared rectum.Treatment with corticosteroids,azathioprine,ursodeoxycholic acid and mesalamine was initiated,with improvement in laboratory tests.The patient was referred for a liver transplantation evaluation.AIM To report the case of a female patient with Autoimmune hepatitis and primary sclerosing cholangitis(PSC)overlap syndrome associated with ulcerative colitis and to systematically review the available cases of Autoimmune hepatitis and PSC overlap syndrome.METHODS In accordance with preferred reporting items for systematic reviews and metaanalysis protocols guidelines,retrieval of studies was based on medical subject headings and health sciences descriptors,which were combined using Boolean operators.Searches were run on the electronic databases Scopus,Web of Science,MEDLINE(PubMed),Biblioteca Regional de Medicina,Latin American and Caribbean Health Sciences Literature,Cochrane Library for Systematic Reviews and Opengray.eu.Languages were restricted to English,Spanish and Portuguese.There was no date of publication restrictions.The reference lists of the studies retrieved were searched manually.RESULTS The search strategy retrieved 3349 references.In the final analysis,44 references were included,with a total of 109 cases reported.The most common clinical finding was jaundice and 43.5%of cases were associated with inflammatory bowel disease.Of these,27.

关键词： Autoimmune hepatitis Primary sclerosing cholangitis Crohn’s disease Ulcerative colitis Inflammatory bowel diseases

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World Journal of Hepatology 2021年第11期13卷 1642-1652页

作者： Romée JALM Snijders Piotr Milkiewicz Christoph Schramm Tom JG Gevers Department of Gastroenterology and Hepatology RadboudumcNijmegen 6525GAThe Netherlands European Reference Network RARE-LIVER HamburgGermany Liver and Internal Medicine Unit Medical University of WarsawWarsaw 02-091Poland Translational Medicine Group Pomeranian Medical UniversitySzczecin 70-204Poland First Department of Medicine University Medical Center Hamburg EppendorfHamburg 20246Germany Martin Zeitz Center for Rare Diseases and Hamburg Center for Translational Immunology(HCTI) University Medical Center Hamburg EppendorfHamburg 20246Germany Division of Gastroenterology and Hepatology Maastricht University Medical CenterMaastricht 6229HXThe Netherlands

Autoimmune hepatitis(AIH)is a severe chronic autoimmune disease and has a significant impact on the patient’s quality of life,in particular regarding psychological problems such as anxiety and depression.Consistent evidence on which patient-related,disease-related or physician-related factors cause health-related quality of life(HRQoL)impairment in patients with AIH is lacking.Current studies on HRQoL in AIH are mainly single-centered,comprising small numbers of patients,and difficult to compare because of the use of different questionnaires,patient populations,and cutoff values.Literature in the pediatric field is sparse,but suggests that children/adolescents with AIH have a lower HRQoL.Knowledge of HRQoL and cohesive factors in AIH are important to improve healthcare for AIH patients,for example by developing an AIH-specific chronic healthcare model.By recognizing the importance of quality of life beyond the concept of biochemical and histological remission,clinicians allow us to seek enhancements and possible interventions in the management of AIH,aiming at improved health.

关键词： Autoimmune hepatitis Quality of life Depression Anxiety Corticosteroids

Pathogenesis of Autoimmune hepatitis

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World Journal of Hepatology 2021年第8期13卷 879-886页

作者： Jun-Hua Fan Geng-Feng Liu Xiao-Dan Lv Rui-Zhi Zeng Ling-Ling Zhan Xiao-Ping Lv Department of Gastroenterology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Clinical Experimental Medicine The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

Autoimmune hepatitis(AIH)is a chronic progressive liver disease whose etiology and pathogenesis are not yet clear.It is currently believed that the occurrence of AIH is closely related to genetic susceptibility and immune abnormalities,and other factors such as environment,viral infection and drugs that may cause immune dysfunction.This article reviews the pathogenesis of AIH and describes the latest research results in the past 5 years.

关键词： Autoimmune hepatitis Genetic susceptibility environmental factors Immunomodulation Drug-induced liver injury Intestinal microbes