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Teker Düztaş D, Öztürk H, Eğritaş Gürkan Ö, Esendağlı G, Sarı S, Dalgıç B, Dalgıç A. Overview of the Etiology, Pathology, and Prognosis of Giant Cell Hepatitis. EXP CLIN TRANSPLANT 2024; 22:106-110. [PMID: 39498930 DOI: 10.6002/ect.pedsymp2024.o30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2024]
Abstract
OBJECTIVES Giant cell hepatitis is an important diagnostic consideration in early childhood, especially for patients who present with jaundice. Different diseases may play a role in their etiology. In this study, we presented pediatric patients in our center diagnosed with giant cell hepatitis. MATERIALS AND METHODS Liver biopsies performed in our hospital between January 2010 and December 2023 were retrospectively evaluated, and biopsies with histological giant cell formation were included in the study. Demographic, clinical, and histopathological characteristics of the patients were obtained from the medical records. RESULTS Our study included 31 cases of giant cell hepatitis. Twenty-four (90.3%) of the patients were male, and the median age was 4 months (range, 1-148 mo). The most common clinical findings were jaundice (93.5%). Among the 31 patients, idiopathic giant cell hepatitis was observed in 13 cases (41.9%), and etiology was elucidated in 18 patients. The most common diagnoses in these patients were progressive familial intrahepatic cholestasis, biliary atresia, and autoimmune hepatitis (22.6%, 19.4%, and 9.7%, respectively). The most common accompanying histopathologic findings were canalicular cholestasis (87.1%), lobular cholestasis (54.8%), and pericellular fibrosis (35.5%). Liver transplant was required in 10 patients (32.3%). Nine patients (29%) died from various reasons. Although follow-up of 13 patients (41.9%) are ongoing, 9 patients (29%) are no longer being followed. CONCLUSIONS Few studies in the pediatric age group on giant cell hepatitis have been conducted in the literature. Similar to our series, etiology could not be specified in most of the patients in these reports. Additional research is needed to improve our understanding of the disease process, uncover any other potential causes, and create specific treatment options.
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Affiliation(s)
- Demet Teker Düztaş
- From the Department of Pediatric Gastroenterology, Gazi University School of Medicine, Ankara, Turkey
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Maggiore G, Sciveres M. Giant cell hepatitis associated with autoimmune hemolytic anemia: More evidence for B-cell depletion therapy for a rare immune mediated disease of infancy. Clin Res Hepatol Gastroenterol 2024; 48:102435. [PMID: 39084551 DOI: 10.1016/j.clinre.2024.102435] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 07/28/2024] [Indexed: 08/02/2024]
Abstract
Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AHA) is a rare but severe disease of infancy defined by an acute liver injury, histologically characterized by a widespread giant cell transformation and by an autoimmune hemolysis. GCH-AHA is thought to be immune-mediated being however a distinct entity from juvenile autoimmune hepatitis. In particular, GCH-AHA displays a less favorable response to conventional immunosuppressive treatment compared to classical juvenile autoimmune hepatitis, carrying a higher risk of mortality. In fact, since his first description, conventional therapy with prednisone with azathioprine has been used as first line treatment, however with frequent relapses during tapering, as well as severe side effects related to its prolonged use at high doses in early age. Due to the frequent occurrence of relapse, several immunosuppressive drugs have been tried as second line therapy with doubtful success. In case of severe liver dysfunction and/or severe anemia, transitory remission has been achieved with intravenous immunoglobulins administration, however with temporary response. B-cell depletion treatment, mostly with chimeric anti-CD20 monoclonal antibody (rituximab; RTX) has been used since 2004 with encouraging results mostly in refractory cases as second-line therapy. In this issue, the report of a series of 20 children with GCH-AHA from Shanghai, China, confirms the previous treatment experiences of a greater efficacy in obtaining complete remission of RTX or RTX treatment regimens compared to conventional regimens, with a good safety. To date, published experience with this rare disease suggests that RTX should be considered the cornerstone of treatment for complicated or relapsing cases of GCH-AHA and given the increasing evidence on its efficacy and safety, RTX might be even an acceptable option as first line therapy beside conventional treatment, to drastically reduce the cumulative steroids exposure and its side effects.
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Affiliation(s)
- Giuseppe Maggiore
- Hepatology and Liver Transplant Unit IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
| | - Marco Sciveres
- Hepatology and Liver Transplant Unit IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy.
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Zhang XY, Gong JY, Wang JS, Feng JY, Chen L, Xie XB, Lu Y. Efficacy of rituximab-containing regimens used as first-line and rescue therapy for giant cell hepatitis with autoimmune hemolytic anemia a retrospective study. Clin Res Hepatol Gastroenterol 2024; 48:102392. [PMID: 38897557 DOI: 10.1016/j.clinre.2024.102392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 05/27/2024] [Accepted: 06/05/2024] [Indexed: 06/21/2024]
Abstract
OBJECTIVE To evaluate the efficacy of rituximab (RTX)-containing therapy as first-line as well as rescue treatment for giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA). METHODS This retrospective study recruited patients diagnosed with GCH-AHA and treated with conventional immunosuppressor regimens consisting of prednisone or RTX-containing regimes consisting of RTX and prednisone, with or without another immunosuppressor. The primary outcomes were the complete remission (CR) rate and time-period required for CR. The secondary outcomes included relapses and adverse events. RESULTS Twenty patients (8 females and 12 males; age range 1-26 months), 15 receiving conventional regimens and 5 receiving RTX-containing regimens, were included. The CR rates were 73.3 % (11/15) and 100 % (5/5) in the conventional and RTX-containing groups, respectively. The time-period required for CR was significantly shorter in the RTX-containing group than in the conventional group (6 (3-8) versus 14 (5-25) months, P = 0.015). Relapses occurred in 30.8 % (4/13) of patients in the conventional group; all achieved CR after adding RTX. Relapses occurred in 40.0 % (2/5) of patients in the RTX-containing group; both achieved CR after adding intravenous immune globulins or tacrolimus. Transient low immunoglobulin and infections were recorded in both groups. Treatment withdrawal was achieved in 73.3 % (11/15) and 60.0 % (3/5) of patients receiving conventional and RTX-containing regimens after 36 (2-101) and 22 (4-41) months, respectively. Two patients in conventional group died of disease progression and infection. CONCLUSIONS RTX-containing first-line therapy achieves CR of GCH-AHA more quickly than the conventional therapy. RTX is efficacious when added to rescue therapy.
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Affiliation(s)
- Xue-Yuan Zhang
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China
| | - Jing-Yu Gong
- Department of Pediatrics, Jinshan Hospital of Fudan University, Shanghai, China
| | - Jian-She Wang
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China
| | - Jia-Yan Feng
- Department of Pathology, Children's Hospital of Fudan University, Shanghai, China
| | - Lian Chen
- Department of Pathology, Children's Hospital of Fudan University, Shanghai, China
| | - Xin-Bao Xie
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China
| | - Yi Lu
- The Center for Pediatric Liver Diseases, Children's Hospital of Fudan University, Shanghai, China.
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4
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Quaglia A, Roberts EA, Torbenson M. Developmental and Inherited Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:122-294. [DOI: 10.1016/b978-0-7020-8228-3.00003-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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5
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Poddighe D, Madiyeva A, Talipova D, Umirbekova B. Infantile giant cell hepatitis with autoimmune hemolytic anemia. World J Hepatol 2021; 13:411-420. [PMID: 33959224 PMCID: PMC8080548 DOI: 10.4254/wjh.v13.i4.411] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/26/2021] [Accepted: 03/09/2021] [Indexed: 02/06/2023] Open
Abstract
Giant cell hepatitis (GCH) is characterized by large and multinucleated (syncytial) hepatocytes in the context of liver inflammation. Infantile GCH is typically associated with autoimmune hemolytic anemia in the absence of any other systemic or organ-specific autoimmune comorbidity. The etiology is unknown; concomitant viral infections (as potential trigger factors) have been identified in a few patients. The pathogenesis reportedly relies upon immune-mediated/ autoimmune mechanisms. This condition should be considered in any infant developing Coombs-positive anemia; indeed, anemia usually precedes the development of hepatitis. The clinical course is usually aggressive without the appropriate immunosuppressive therapy, which may include steroids, conventional immunosuppressors (e.g., azathioprine and cyclophosphamide as first-line treatments), intravenous immunoglobulin, and biologics (rituximab). Improvements in medical management (including the availability of rituximab) have significantly reduced the mortality of this condition in the last decade.
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Affiliation(s)
- Dimitri Poddighe
- Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
- Department of Pediatrics, National Research Center for Maternal and Child Health, Nur-Sultan 010000, Kazakhstan
| | - Aidana Madiyeva
- Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
| | - Diana Talipova
- Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
| | - Balzhan Umirbekova
- Department of Pediatrics, National Research Center for Maternal and Child Health, Nur-Sultan 010000, Kazakhstan
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Nastasio S, Matarazzo L, Sciveres M, Maggiore G. Giant cell hepatitis associated with autoimmune hemolytic anemia: an update. Transl Gastroenterol Hepatol 2021; 6:25. [PMID: 33824929 DOI: 10.21037/tgh.2020.03.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 03/02/2020] [Indexed: 11/06/2022] Open
Abstract
Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AHA) is a rare and severe disease characterized by autoimmune hemolysis associated with acute liver injury, histologically defined by widespread giant cell transformation. It occurs after the neonatal period, most commonly in the first year of life and uniquely affects pediatric patients. It is still poorly understood and likely underdiagnosed, although in recent years there have been advances in the understanding of its pathogenesis and the liver injury is now hypothesized to be secondary to a humoral immune mechanism. Although no laboratory test specific for the diagnosis currently exists, given its severity, it is fundamental to rule out GCH-AHA when evaluating a patient in the first year of life presenting with AHA and/or with acute liver disease of unknown etiology. While GCH-AHA is progressive in nature as other autoimmune liver disorders, it differs significantly from juvenile autoimmune hepatitis (JAIH) in that a cure can be achieved after several years of intensive treatment in a portion of patients. Conventional first line therapy consist of prednisone/prednisolone combined with azathioprine, however, several immunosuppressive drugs, commonly used in the treatment of JAIH have been tried as second line therapy, including cyclosporine, cyclophosphamide, mycophenolate mofetil, 6-mercaptopurine, calcineurin inhibitors, and sirolimus. Intravenous immunoglobulins have also been used in cases of severe liver dysfunction and/or severe anemia allowing for transitory remission. More recently treatment with B-cell depletion has been attempted in some patients and encouraging results have been reported in refractory cases. Although what constitutes optimal treatment has yet to be determined, the recent progress in the understanding of the pathogenetic mechanisms of GCH-AHA have made positive strides, cautiously pointing toward a hopeful prognosis for some of these patients.
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Affiliation(s)
- Silvia Nastasio
- Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Lorenza Matarazzo
- Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy
| | - Marco Sciveres
- Pediatric Hepatology and Pediatric Liver Transplantation, ISMETT, University of Pittsburgh Medical Center Italy, Palermo, Italy
| | - Giuseppe Maggiore
- Pediatric Hepatology and Pediatric Liver Transplantation, ISMETT, University of Pittsburgh Medical Center Italy, Palermo, Italy.,Department of Medical Sciences, University of Ferrara, Ferrara, Italy.,Division of Gastroenterology, Hepatology and Nutrition, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
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7
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Autoimmune Hemolytic Anemia in the Pediatric Setting. J Clin Med 2021; 10:jcm10020216. [PMID: 33435309 PMCID: PMC7828053 DOI: 10.3390/jcm10020216] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 01/04/2021] [Accepted: 01/05/2021] [Indexed: 12/21/2022] Open
Abstract
Autoimmune hemolytic anemia (AIHA) is a rare disease in children, presenting with variable severity. Most commonly, warm-reactive IgG antibodies bind erythrocytes at 37 °C and induce opsonization and phagocytosis mainly by the splenic macrophages, causing warm AIHA (w-AIHA). Post-infectious cold-reactive antibodies can also lead to hemolysis following the patient’s exposure to cold temperatures, causing cold agglutinin syndrome (CAS) due to IgM autoantibodies, or paroxysmal cold hemoglobinuria (PCH) due to atypical IgG autoantibodies which bind their target RBC antigen and fix complement at 4 °C. Cold-reactive antibodies mainly induce intravascular hemolysis after complement activation. Direct antiglobulin test (DAT) is the gold standard for AIHA diagnosis; however, DAT negative results are seen in up to 11% of warm AIHA, highlighting the need to pursue further evaluation in cases with a phenotype compatible with immune-mediated hemolytic anemia despite negative DAT. Prompt supportive care, initiation of treatment with steroids for w-AIHA, and transfusion if necessary for symptomatic or fast-evolving anemia is crucial for a positive outcome. w-AIHA in children is often secondary to underlying immune dysregulation syndromes and thus, screening for such disorders is recommended at presentation, before initiating treatment with immunosuppressants, to determine prognosis and optimize long-term management potentially with novel targeted medications.
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Kim YH, Kim JW, Lee EJ, Kang GH, Kang HJ, Moon JS, Ko JS. Successful Treatment of a Korean Infant with Giant Cell Hepatitis with Autoimmune Hemolytic Anemia Using Rituximab. Pediatr Gastroenterol Hepatol Nutr 2020; 23:180-187. [PMID: 32206631 PMCID: PMC7073370 DOI: 10.5223/pghn.2020.23.2.180] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 01/28/2020] [Indexed: 12/13/2022] Open
Abstract
Giant cell hepatitis with autoimmune hemolytic anemia (AHA) is a rare disease of infancy characterized by the presence of both Coombs-positive hemolytic anemia and progressive liver disease with giant cell transformation of hepatocytes. Here, we report a case involving a seven-month-old male infant who presented with AHA followed by cholestatic hepatitis. The clinical features included jaundice, pallor, and red urine. Physical examination showed generalized icterus and splenomegaly. The laboratory findings suggested warm-type AHA with cholestatic hepatitis. Liver biopsy revealed giant cell transformation of hepatocytes and moderate lobular inflammation. The patient was successfully treated with four doses of rituximab. Early relapse of hemolytic anemia and hepatitis was observed, which prompted the use of an additional salvage dose of rituximab. He is currently in clinical remission.
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Affiliation(s)
- Young Ho Kim
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Ju Whi Kim
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Eun Joo Lee
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Gyeong Hoon Kang
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Hyoung Jin Kang
- Department of Pediatrics, Seoul National University College of Medicine, Seoul National University Cancer Research Institute, Seoul National University Children's Hospital, Seoul, Korea
| | - Jin Soo Moon
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Jae Sung Ko
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
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Matarazzo L, Di Chio T, Nastasio S, Tommasini A, Ventura A, Maggiore G. B-cell depletion induces prolonged remission in patients with giant cell hepatitis and autoimmune hemolytic anemia. Clin Res Hepatol Gastroenterol 2020; 44:66-72. [PMID: 31076361 DOI: 10.1016/j.clinre.2019.03.010] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 03/17/2019] [Accepted: 03/19/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare and severe immune-mediated disorder. Despite aggressive immunosuppressive treatments, the mortality is high. Prednisone has been effectively employed to achieve remission, but with a risk of relapse, if discontinued, and with severe side effects. A possible causative role of humoral immune response has paved the way to anti CD-20 monoclonal antibody (rituximab; RTX). Nevertheless, data about timing of remission and long-term side effects are sparse. METHODS AND MATHERIALS We have retrospectively evaluated 3 refractory GCH-AHA patients in whom a prolonged remission has been achieved with RTX. In all patients, response to first and second line therapy was incomplete or transitory and severe steroid side effects occurred. RESULTS A stable and sustained remission was achieved after multiple doses of RTX allowing withdrawing all the other treatments. No life-threatening infections have been recorded, however two patients developed persistent, paucisymptomatic hypogammaglobulinaemia. The only patient who did not develop hypogammaglobulinemia received IgG replacement during RTX. CONCLUSION RTX induced complete and long-lasting remission allowing discontinuing all the other immunosuppressive drugs. A persistent, paucisymptomatic hypogammaglobulinaemia has been the unique side effect. Although further studies need to replicate our data, RTX can be considered as an effective and safe therapy for sustained remission in patients with severe refractory GCH-AHA.
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Affiliation(s)
- Lorenza Matarazzo
- Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy.
| | - Teresa Di Chio
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Silvia Nastasio
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, USA
| | - Alberto Tommasini
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo" Trieste, Trieste, Italy
| | - Alessando Ventura
- Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy; Institute for Maternal and Child Health, IRCCS "Burlo Garofolo" Trieste, Trieste, Italy
| | - Giuseppe Maggiore
- Section of Pediatrics, Department of Medical Sciences University of Ferrara, Ferrara, Italy
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Marks RA, Saxena R. Liver Diseases of Childhood. PRACTICAL HEPATIC PATHOLOGY: A DIAGNOSTIC APPROACH 2018:69-87. [DOI: 10.1016/b978-0-323-42873-6.00005-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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11
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Quaglia A, Roberts EA, Torbenson M. Developmental and Inherited Liver Disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2018:111-274. [DOI: 10.1016/b978-0-7020-6697-9.00003-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Velho PENF, Bellomo-Brandão MÂ, Drummond MR, Magalhães RF, Hessel G, Barjas-Castro MDL, Escanhoela CAF, Del Negro GMB, Okay TS. Bartonella henselae AS A PUTATIVE CAUSE OF CONGENITAL CHOLESTASIS. Rev Inst Med Trop Sao Paulo 2017; 58:56. [PMID: 27410916 PMCID: PMC4964325 DOI: 10.1590/s1678-9946201658056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 02/26/2016] [Indexed: 05/29/2023] Open
Abstract
Severe anemia and cholestatic hepatitis are associated with bartonella infections. A putative vertical Bartonella henselae infection was defined on the basis of ultrastructural and molecular analyses in a three-year-old child with anemia, jaundice and hepatosplenomegaly since birth. Physicians should consider bartonellosis in patients with anemia and hepatitis of unknown origin.
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Affiliation(s)
| | | | - Marina Rovani Drummond
- University of Campinas (UNICAMP) Medical Science School, Department of Medicine, Campinas, SP, Brazil
| | - Renata Ferreira Magalhães
- University of Campinas (UNICAMP) Medical Science School, Department of Medicine, Campinas, SP, Brazil
| | - Gabriel Hessel
- University of Campinas (UNICAMP) Medical Science School, Department of Pediatrics, Campinas, SP, Brazil
| | | | | | - Gilda Maria Barbaro Del Negro
- University of Sao Paulo (USP), School of Medicine and Institute of Tropical Medicine, Clinical Hospital, Division of Clinical Dermatology, Laboratory of Medical Mycology (LIM-53). Sao Paulo, SP, Brazil
| | - Thelma Suely Okay
- University of Sao Paulo (USP), Institute of Tropical Medicine, Laboratory of Seroepidemiology and Immunobiology. Sao Paulo, SP, Brazil
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Marsalli G, Nastasio S, Sciveres M, Calvo PL, Ramenghi U, Gatti S, Albano V, Lega S, Ventura A, Maggiore G. Efficacy of intravenous immunoglobulin therapy in giant cell hepatitis with autoimmune hemolytic anemia: A multicenter study. Clin Res Hepatol Gastroenterol 2016; 40:83-9. [PMID: 26138133 DOI: 10.1016/j.clinre.2015.03.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2014] [Revised: 02/03/2015] [Accepted: 03/26/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVE Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare disease of infancy, of possible autoimmune mechanism with poor prognosis due to its scarce response to immunosuppressive drugs. The aim of this retrospective multicenter study was to evaluate the efficacy and safety of intravenous immunoglobulin (IVIg) treatment in inducing and maintaining remission of the liver disease, in patients with GCH-AHA. METHODS Seven children with GCH-AHA, four newly diagnosed, and three in relapse, being treated with different therapies, received one to three IVIg infusions (0.5 to 2g/kg) in association with other immunosuppressive drugs. Subsequently five of them received monthly sequential IVIg infusions (mean 13.4, range 7-24). RESULTS IVIg infusions as first-line therapy associated with prednisone and other immunosuppressive drugs significantly (P=0.04) reduced the aminotransferase activity in all patients and normalized prothrombin activity in the only patient with severe liver dysfunction. Sequential monthly IVIg infusions determined a steroid-sparing effect and allowed a complete or partial remission in all patients, although with temporary efficacy, since relapse of the hemolytic anemia and/or of liver disease occurred in all patients. IVIg infusions were associated with mild side effects in two patients. CONCLUSIONS IVIg infusion can be safely and effectively administered in patients with severe GCH-AHA at diagnosis, or in case of relapse, in association with other immunosuppressive drugs. Repeated IVIg infusions may help maintain remission, however, due to their temporary efficacy, they should not be routinely employed.
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Affiliation(s)
- Giulia Marsalli
- Department of Clinical and Experimental Medicine, University of Pisa, Pediatric Gastroenterology Unit; University Hospital Santa Chiara, Pisa, Italy.
| | - Silvia Nastasio
- Department of Clinical and Experimental Medicine, University of Pisa, Pediatric Gastroenterology Unit; University Hospital Santa Chiara, Pisa, Italy
| | - Marco Sciveres
- Paediatric Hepatology and Liver Transplant Unit, UPMC-IsMett, Palermo, Italy
| | - Pier Luigi Calvo
- Department of Paediatric and Public Health Sciences, University of Torino, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy
| | - Ugo Ramenghi
- Department of Paediatric and Public Health Sciences, University of Torino, Azienda Ospedaliera Città della Salute e della Scienza, Torino, Italy
| | - Simona Gatti
- Department of Paediatrics, Università Politecnica delle Marche, Ancona, Italy
| | - Veronica Albano
- Department of Paediatrics, Università Politecnica delle Marche, Ancona, Italy
| | - Sara Lega
- Institute for Maternal and Child Health, University of Trieste, Trieste, Italy; IRCCS Burlo Garofolo, Trieste, Italy
| | - Alessandro Ventura
- Institute for Maternal and Child Health, University of Trieste, Trieste, Italy; IRCCS Burlo Garofolo, Trieste, Italy
| | - Giuseppe Maggiore
- Department of Clinical and Experimental Medicine, University of Pisa, Pediatric Gastroenterology Unit; University Hospital Santa Chiara, Pisa, Italy
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Paganelli M, Patey N, Bass LM, Alvarez F. Anti-CD20 treatment of giant cell hepatitis with autoimmune hemolytic anemia. Pediatrics 2014; 134:e1206-10. [PMID: 25201797 DOI: 10.1542/peds.2014-0032] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare autoimmune disease of infancy characterized by severe liver disease associated with Coombs-positive hemolytic anemia. We recently showed that GCH-AHA is probably caused by a humoral immune mechanism. Such data support the use of rituximab, an anti-CD-20 monoclonal antibody specifically targeting B lymphocytes, as a treatment for GCH-AHA. We describe here the detailed clinical evolution of 4 children with GCH-AHA who showed a complete response to rituximab. All patients shared a severe course of the disease with poor control on standard and aggressive immunosuppression. Rituximab was well tolerated, and no side effects or infections were registered. Several doses were needed to induce remission, and 5 to 11 additional maintenance injections were necessary in the 2 more severe cases. Weaning from corticosteroids was achieved in all subjects. A steroid-sparing effect was noted in the 3 children who started rituximab early in the course of the disease. Overall, we show here that there is a strong rationale for treating GCH-AHA with rituximab. Early treatment could reduce the use of corticosteroids. Nevertheless, short-term steroids should be initially associated with rituximab to account for autoantibodies' half-life. Repeated injections are needed to treat and prevent relapses, but the best frequency and duration of treatment remain to be defined.
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Affiliation(s)
| | - Natacha Patey
- Pathology, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montreal (QC), Canada
| | - Lee M Bass
- Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois; and Department of Pediatrics, Feinberg Medical School of Northwestern University, Chicago, Illinois
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15
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Maggiore G, Nastasio S, Sciveres M. Juvenile autoimmune hepatitis: Spectrum of the disease. World J Hepatol 2014; 6:464-476. [PMID: 25067998 PMCID: PMC4110538 DOI: 10.4254/wjh.v6.i7.464] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2013] [Revised: 03/19/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Juvenile autoimmune hepatitis (JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific and organ-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoantibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature.
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Giant cell hepatitis with autoimmune hemolytic anemia in children: proposal for therapeutic approach. J Pediatr Gastroenterol Nutr 2014; 58:669-73. [PMID: 24792633 DOI: 10.1097/mpg.0000000000000270] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVE Giant cell hepatitis (GCH) with autoimmune hemolytic anemia (AIHA) is a rare, progressive disorder in infants and young children. The disease is aggressive and may lead to liver or multiorgan failure with fatal prognosis. Therapy with anti-CD20 monoclonal antibody, rituximab (Rtx), proved effective. The primary objective of the study was to evaluate therapy for severe GCH with AIHA. METHODS We report on 5 cases of severe GCH with AIHA treated in our department between 2006 and 2011. RESULTS The median age of the children was 7 months (2-12 months), follow-up lasted 44 months (12-78 months), median (min-max), and the main observed symptoms were jaundice and hepatosplenomegaly. All of the children had positive direct Coombs test and biopsy-proven giant cell transformation of hepatocytes. Liver failure was observed in 3 children. First-line therapy (prednisone, azathioprine) proved ineffective in all but 1 of the patients, who initially responded to the treatment but relapsed after 4 months. The child subsequently developed hemophagocytic lymphohistiocytosis and died 2 months after hemopoietic stem cell transplantation. Four remaining patients finally achieved complete remission after 4 to 6 doses of Rtx. CONCLUSIONS We propose Rtx as the treatment of choice for severe GCH with AIHA in the early stages of the disease, provided steroids and azathioprine are ineffective.
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Humoral immune mechanism of liver injury in giant cell hepatitis with autoimmune hemolytic anemia. J Pediatr Gastroenterol Nutr 2014; 58:74-80. [PMID: 23969541 DOI: 10.1097/mpg.0b013e3182a98dbe] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is presumed to be an autoimmune disease, but the mechanism of liver injury is unknown. We proposed that in CGH-AHA, the humoral limb of autoimmunity is the dominant force driving progressive liver injury. METHODS We studied 6 cases of GCH-AHA and 6 cases of autoimmune hepatitis (AIH) with early childhood onset (3 type 1 and 3 type 2). Liver biopsies were graded for portal and periportal inflammation and for giant cells. Immunohistochemistry characterized cellular inflammation and complement involvement in injury by showing C5b-9 complex in hepatocytes. RESULTS Clinical and biochemical features at presentation were generally similar; however, the absence of autoantibodies and the presence of Coombs positivity did distinguish GCH-AHA from early-onset AIH. Liver biopsy pathology in CGH-AHA showed giant cells and little inflammation, whereas AIH showed the opposite. C5b-9 staining showed high-grade complement-mediated pan-lobular hepatocyte injury in all of the cases with GCH-AHA, whereas little C5b-9 was seen in hepatocytes in cases with AIH. Inflammation in GCH-AHA comprised mainly lobular macrophages and neutrophils, whereas portal and periportal T-cell and B-cell inflammation characterized cases with AIH. Most cases with AIH responded to therapy with prednisone and azathioprine, whereas most cases with GCH-AHA responded only to rituximab. CONCLUSIONS Widespread complement-mediated hepatocyte injury and typical C3a and C5a complement-driven liver inflammation along with Coombs-positive hemolytic anemia in GCH-AHA provide convincing evidence that systemic B-cell autoimmunity plays a central pathologic mechanism in the disease. Our findings support B-cell-directed immunotherapy as a first-line treatment of GCH-AHA.
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Lega S, Maschio M, Taddio A, Maggiore G, Ventura A. Giant cell hepatitis with Coombs-positive haemolytic anaemia: steroid sparing with high-dose intravenous immunoglobulin and cyclosporine. Acta Paediatr 2013. [PMID: 23205764 DOI: 10.1111/apa.12114] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Sara Lega
- Institute for Maternal and Child Health IRCCS ‘Burlo Garofolo’; University of Trieste; Trieste; Italy
| | - Massimo Maschio
- Institute for Maternal and Child Health IRCCS ‘Burlo Garofolo’; Trieste; Italy
| | - Andrea Taddio
- Institute for Maternal and Child Health IRCCS ‘Burlo Garofolo’; Trieste; Italy
| | - Giuseppe Maggiore
- Department of Pediatrics; University Hospital Santa Chiara; Pisa; Italy
| | - Alessandro Ventura
- Institute for Maternal and Child Health IRCCS ‘Burlo Garofolo’; University of Trieste; Trieste; Italy
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Maggiore G, Sciveres M, Fabre M, Gori L, Pacifico L, Resti M, Choulot JJ, Jacquemin E, Bernard O. Giant cell hepatitis with autoimmune hemolytic anemia in early childhood: long-term outcome in 16 children. J Pediatr 2011; 159:127-132.e1. [PMID: 21349541 DOI: 10.1016/j.jpeds.2010.12.050] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2010] [Revised: 11/29/2010] [Accepted: 12/30/2010] [Indexed: 12/27/2022]
Abstract
OBJECTIVE To assess the outcome of giant cell hepatitis combined with autoimmune hemolytic anemia in early childhood. STUDY DESIGN We report on 16 children with this disease evaluated over a 28-year period. RESULTS Children (nine boys; median age, 6 months) presented with jaundice, hepatomegaly, elevated aminotransferases, a positive Coombs test, and diffuse giant-cell transformation of hepatocytes on histology. Treatment with prednisone and azathioprine, plus, in three children, cyclosporine, resulted in complete remission in eight, partial remission in six, and failure in two. Relapses of hepatitis and/or anemia occurred in 11 and 10 children, respectively, requiring prolonged high levels of immunosuppression, and splenectomy or Rituximab, respectively. Treatment was stopped after a mean duration of 6 years, with no relapse, in seven children, with a median follow-up of 14 years. One child is alive 9 years after liver transplantation. Four children died of sepsis or multiple organ failure. CONCLUSIONS Giant cell hepatitis combined with autoimmune hemolytic anemia requires rigorous treatment. Immunosuppressive therapy results in remission in most cases. A complete cure can be expected after several years of intensive treatment. Liver transplantation may be associated with prolonged survival.
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Affiliation(s)
- Giuseppe Maggiore
- Department of Pediatrics and Division of Pediatric Gastroenterology and Hepatology, University Hospital Santa Chiara, Pisa, Italy
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Aladjidi N, Leverger G, Leblanc T, Picat MQ, Michel G, Bertrand Y, Bader-Meunier B, Robert A, Nelken B, Gandemer V, Savel H, Stephan JL, Fouyssac F, Jeanpetit J, Thomas C, Rohrlich P, Baruchel A, Fischer A, Chêne G, Perel Y. New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children. Haematologica 2011; 96:655-63. [PMID: 21228033 DOI: 10.3324/haematol.2010.036053] [Citation(s) in RCA: 151] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Autoimmune hemolytic anemia is a rare condition in children. Little is known about its initial presentation and the subsequent progression of the disease. DESIGN AND METHODS Since 2004, a national observational study has been aiming to thoroughly describe cases and identify prognostic factors. Patients from all French hematologic pediatric units have been included if they had a hemoglobin concentration less than 11 g/dL, a positive direct antiglobulin test and hemolysis. Evans' syndrome was defined by the association of autoimmune hemolytic anemia and immunological thrombocytopenic purpura. Data from patients' medical records were registered from birth to last follow-up. Autoimmune hemolytic anemia was classified as primary or secondary. Remission criteria, qualifying the status of anemia at last follow-up, were used with the aim of identifying a subgroup with a favorable prognosis in continuous complete remission. RESULTS The first 265 patients had a median age of 3.8 years at diagnosis. In 74% of cases the direct antiglobulin test was IgG/IgG+C3d. Consanguinity was reported in 8% of cases and first degree familial immunological diseases in 15% of cases. Evans' syndrome was diagnosed in 37% of cases. Autoimmune hemolytic anemia was post-infectious in 10%, immunological in 53% and primary in 37% of cases. After a median follow-up of 3 years, 4% of children had died, 28% were still treatment-dependent and 39% were in continuous complete remission. In multivariate analysis, IgG and IgG+C3d direct antiglobulin tests were associated with a lower rate of survival with continuous complete remission (adjusted hazard ratio, 0.43; 95% confidence interval, 0.21-0.86). CONCLUSIONS This nationwide French cohort is the largest reported study of childhood autoimmune hemolytic anemia. The rarity of this condition is confirmed. Subgroups with genetic predisposition and underlying immune disorders were identified.
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Affiliation(s)
- Nathalie Aladjidi
- Pediatric Hematology Unit, Centre de Référence National des Cytopénies Auto-immunes de l'Enfant (CEREVANCE) Hôpital des Enfants, Hôpital Pellegrin, CHU Bordeaux, Place Amelie Raba Leon, 33 000 Bordeaux, France.
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Suzuki M, Murohisa T, Arai D, Majima Y, Kuniyoshi T, Kojima K, Tamano M, Iijima M, Sugaya H, Hiraishi H. A case of autoimmune hepatitis presents giant cell hepatitis on liver histology. KANZO 2009; 50:65-70. [DOI: 10.2957/kanzo.50.65] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/12/2023]
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Yokoyama S, Kasahara M, Fukuda A, Morioka D, Mori T, Nakagawa S, Shimizu N, Saito O, Nakagawa A. Evans syndrome after successful living-donor liver transplantation for neonatal giant cell hepatitis. Transplantation 2007; 84:798-9. [PMID: 17893616 DOI: 10.1097/01.tp.0000280544.06865.07] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
MESH Headings
- Anemia, Hemolytic, Autoimmune/diagnosis
- Anemia, Hemolytic, Autoimmune/therapy
- Anemia, Hemolytic, Autoimmune/virology
- DNA, Viral/blood
- Epstein-Barr Virus Infections/complications
- Epstein-Barr Virus Infections/diagnosis
- Giant Cells/pathology
- Hepatitis/pathology
- Hepatitis/surgery
- Herpesvirus 4, Human/isolation & purification
- Humans
- Immune Tolerance/drug effects
- Infant
- Liver Transplantation
- Living Donors
- Male
- Postoperative Complications/diagnosis
- Postoperative Complications/therapy
- Postoperative Complications/virology
- Purpura, Thrombocytopenic, Idiopathic/diagnosis
- Purpura, Thrombocytopenic, Idiopathic/therapy
- Purpura, Thrombocytopenic, Idiopathic/virology
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Vajro P, Migliaro F, Ruggeri C, Di Cosmo N, Crispino G, Caropreso M, Vecchione R. Life saving cyclophosphamide treatment in a girl with giant cell hepatitis and autoimmune haemolytic anaemia: case report and up-to-date on therapeutical options. Dig Liver Dis 2006; 38:846-50. [PMID: 16266839 DOI: 10.1016/j.dld.2005.09.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2005] [Revised: 09/05/2005] [Accepted: 09/15/2005] [Indexed: 12/11/2022]
Abstract
We report the case of a girl affected by giant cell hepatitis associated with autoimmune haemolytic anaemia. Both conditions were severe with a number of life-threatening episodes of liver failure and anaemia unresponsive to several immunosuppressant drugs but cyclophosphamide. After a low-dose long-term treatment with this drug the patient is stably well without any therapy. A review of therapeutical options in this condition is also presented.
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Affiliation(s)
- P Vajro
- Department of Pediatrics, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy.
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24
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Kerkar N, Cohen S, Dugan C, Morotti RA, Phelps RG, Herold B, Shneider B, Emre S. Bullous pemphigoid after liver transplantation for liver failure. Liver Transpl 2006; 12:1705-10. [PMID: 17058253 DOI: 10.1002/lt.20930] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Coomb's positive autoimmune hemolytic anemia with giant cell hepatitis (GCH) is a rare cause of liver failure and is usually associated with poor prognosis. A child with liver kidney microsomal (LKM) antibody positivity underwent successful liver transplantation for liver failure secondary to GCH with Coomb's positive hemolytic anemia. Autoimmune neutropenia developed ten months after transplant. Four months later, pemphigoid skin lesions developed. The diagnosis of bullous pemphigoid (BP) was made on the basis of skin biopsy, direct and indirect immunofluorescence test results. Treatment was with immunosuppressants - prednisone and azathioprine/rapamycin, with addition of dapsone when lesions persisted. This child is unique in that his liver function and hemolytic anemia appeared to normalize after liver transplant, but neutropenia and BP both thought to be autoimmune in etiology, developed more than a year post-transplant.
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Affiliation(s)
- Nanda Kerkar
- Division of Pediatric Hepatology, Department of Pediatrics, Mount Sinai School of Medicine, New York, NY, USA.
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25
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Watanabe N, Takashimizu S, Shiraishi K, Kagawa T, Nishizaki Y, Mine T, Akatsuka A, Selmi C, Gershwin ME. Primary biliary cirrhosis with multinucleated hepatocellular giant cells: implications for pathogenesis of primary biliary cirrhosis. Eur J Gastroenterol Hepatol 2006; 18:1023-7. [PMID: 16894319 DOI: 10.1097/01.meg.0000230082.60921.be] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Histological and clinical features of syncytial giant cell hepatitis (GCH) are rarely observed in adults, and the disease has been associated with several autoimmune disorders and drug reactions. We describe here the case of a 62-year-old woman who presented with evidence of severe acute hepatocellular injury and cholestasis. Serum work-up demonstrated antimitochondrial antibodies specific for primary biliary cirrhosis (PBC) autoantigens, whereas markers of viral infection including hepatitis viruses, paramyxovirus and measles virus were negative. Liver histology revealed the presence of multinucleated hepatocellular giant cells in the parenchymal areas surrounding bridging necrosis. Importantly, damaged interlobular bile ducts were also observed within the lymphocyte-infiltrated portal tracts. Further study using transmission electron microscopy demonstrated the presence of filamentous strands and particles resembling paramyxovirus nucleocapsids in the cytoplasm of syncytial giant cells. To our knowledge, this is the first case of PBC with histological and clinical evidence of syncytial GCH in an adult, and we submit that it might provide novel clues in the enigma of PBC pathogenesis.
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Affiliation(s)
- Norihito Watanabe
- Division of Gastroenterology, Department of Internal Medicine, University School of Medicine, Kanagawa, Japan.
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26
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Kashyap R, Sarangi JN, Choudhry VP. Autoimmune hemolytic anemia in an infant with giant cell hepatitis. Am J Hematol 2006; 81:199-201. [PMID: 16493610 DOI: 10.1002/ajh.20414] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Autoimmune hemolytic anemia (AIHA) associated with giant cell hepatitis (GCH) is a rare disorder in infants. AIHA usually precedes the development of liver disease by months to years. Early recognition of the disease and prompt institution of immunosuppressive therapy results in clinical remission and prevents liver disease progression.
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Affiliation(s)
- Rajesh Kashyap
- Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
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27
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Kim MJ, Lee JJ, Park KS, Kim SY, Kil HR. A Case of Chronic Active Epstein-Barr Virus Infection with Autoimmnune Hepatitis and a Coronary Aneurysm. THE KOREAN JOURNAL OF HEMATOLOGY 2006. [DOI: 10.5045/kjh.2006.41.4.311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
- Mi Jin Kim
- Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea
| | - Ji Joung Lee
- Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea
| | - Kyoung Soo Park
- Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea
| | - Sun Young Kim
- Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea
| | - Hong Ryang Kil
- Department of Pediatrics, College of Medicine, Chungnam National University, Daejeon, Korea
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28
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Akyildiz M, Karasu Z, Arikan C, Nart D, Kilic M. Successful liver transplantation for giant cell hepatitis and Coombs-positive hemolytic anemia: a case report. Pediatr Transplant 2005; 9:630-3. [PMID: 16176422 DOI: 10.1111/j.1399-3046.2005.00346.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Giant cell hepatitis (GCH) with autoimmune hemolytic anemia (AHA) is a distinct entity with an aggressive course. Drugs, autoimmunity, and viruses have been implicated in its etiology. Without treatment, liver dysfunction is progressive and fatal. Although successful immunosuppressive treatment has been reported, a few patients have undergone liver transplantation with recurrence of the primary disease in the allograft. We report, an 18-year-old boy with progressive GCH with AHA without recurrence in the allograft following deceased donor (DD) liver transplantation.
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Affiliation(s)
- Murat Akyildiz
- Department of Gastroenterology and Hepatology, Ege University Organ Transplant and Research Center, Izmir, Turkey
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Sciveres M, Caprai S, Palla G, Ughi C, Maggiore G. Effectiveness and safety of ciclosporin as therapy for autoimmune diseases of the liver in children and adolescents. Aliment Pharmacol Ther 2004; 19:209-17. [PMID: 14723612 DOI: 10.1046/j.1365-2036.2003.01754.x] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Conventional treatment for autoimmune hepatitis results in a significant percentage of failures and several, poorly tolerated, side-effects. Therapy for autoimmune cholangitis and giant cell hepatitis associated with autoimmune haemolysis is poorly documented. Ciclosporin is a promising treatment for all of these diseases. METHODS We reviewed the records of 12 patients treated in our unit between 1987 and 2001. Eight had autoimmune hepatitis, two had autoimmune cholangitis and two had giant cell hepatitis. Indications for ciclosporin were treatment failure (four patients) and contraindications to/refusal of steroids (eight patients). Ciclosporin was administered in five untreated cases and in seven patients during relapse. The mean duration of ciclosporin administration was 35.6 months (8-89 months). The median follow-up was 6.5 years (1.5-15 years). RESULTS All patients achieved complete remission in a median period of 4.5 weeks (2-12 weeks). No treatment withdrawal due to side-effects occurred. Three patients required a combination of ciclosporin with conventional treatment due to severe liver function impairment. Tolerance to ciclosporin was excellent. A 20% transient elevation of serum creatinine occurred in one case, gingival hypertrophy in two and moderate hypertrichosis in two. CONCLUSIONS Ciclosporin may be considered as a safe treatment for all autoimmune liver diseases and as an effective alternative for front-line therapy.
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Affiliation(s)
- M Sciveres
- Gastroenterologia ed Epatologia Pediatrica, Dipartimento di Medicina della Procreazione e della Età Evolutiva, Università di Pisa, Pisa, Italy.
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Alexopoulou A, Deutsch M, Ageletopoulou J, Delladetsima JK, Marinos E, Kapranos N, Dourakis SP. A fatal case of postinfantile giant cell hepatitis in a patient with chronic lymphocytic leukaemia. Eur J Gastroenterol Hepatol 2003; 15:551-5. [PMID: 12702915 DOI: 10.1097/01.meg.0000050026.34359.7c] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Postinfantile giant cell hepatitis has been associated with various aetiologies, including drug taking, autoimmune diseases and viral infections. We present a fatal case of giant cell hepatitis in a patient with chronic lymphocytic leukaemia. No liver biopsy was available ante-mortem. The patient was treated with corticosteroids and aciclovir for suspected autoimmune hepatitis and reactivation of Epstein-Barr virus in the context of his haematological malignancy. Post-mortem liver biopsy showed severe giant cell hepatitis while the study of liver tissue by electron microscopy revealed paramyxo-like viral particles in the cytoplasm of the affected hepatocytes similar to those observed in previous reports of giant cell hepatitis. This case illustrates that the diagnosis of the underlying cause of giant cell hepatitis may be complicated because a heterogeneous group of different aetiologies needs to be investigated. The identification of the causative agent is essential before commencing any kind of therapy. A few sporadic case reports of paramyxo-like virus related, postinfantile giant cell hepatitis have shown that ribavirin was quite effective treatment but further clinical evaluation is needed.
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Abstract
BACKGROUND AND AIM Autoimmune hepatitis (AIH) is a chronic disease of unknown etiology, which usually progresses to cirrhosis if not diagnosed and treated promptly. Data on long-term follow up in children with AIH are scant. The aim of this study is to assess the long-term outcome of autoimmune hepatitis in children with respect to clinical and laboratory features at presentation. METHODS Data were extracted from the medical records of patients presenting over a 28-year period (1972-2000) to the Royal Children's Hospital, Melbourne, Australia. Additional information was obtained by interviewing patients, and their current physicians. Of the 30 patients (22 females, mean age 9 years) identified, 18 had type I, three had type II, four had autoimmune-polyendocrinopathy syndrome type 1, one had infantile giant-cell hepatitis associated with Coomb's-positive hemolytic anemia, and four were seronegative (antinuclear antibody (ANA), smooth muscle antibody (SMA) and liver-kidney microsomal antibody (LKM)). RESULTS Clinical features at presentation included hepatomegaly (86%), jaundice (66%) and splenomegaly (50%). Initial investigations revealed a median serum bilirubin level of 55 micromol/L (range 6-425), median aspartate aminotransferase level of 678 IU (range 70-2548), and abnormal clotting in 33% of patients. Liver biopsies were performed on all patients at presentation and 11 showed cirrhosis (36%). The mean follow-up period was 10.0 +/- 7.8 years with 43% being followed for > 10 years. Only two patients died and one required transplantation. Fourteen (50%) patients continue to be on low dose prednisolone with azathioprine, two (7%) are on prednisolone alone, and six (21%) are on no therapy. When the cirrhotic and non-cirrhotic patients were compared, the albumin level at presentation was significantly lower in the cirrhotic group (P=0.01). Of the patients who were cirrhotic at presentation, six (54%) remain compensated with a mean follow-up period of 8 years. All 24 patients currently under follow up are engaged in age-appropriate activities including school, part- or full-time work. CONCLUSION Autoimmune hepatitis has a favorable long-term outcome with a transplant-free survival rate of 90% over a mean period of 10.0 +/- 7.8 years (range: 0.5-23), and a normal or near-normal lifestyle irrespective of presenting clinical, laboratory or histological features.
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Affiliation(s)
- O I Saadah
- Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Melbourne, Victoria, Australia
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Hartman C, Berkowitz D, Brik R, Arad A, Elhasid R, Shamir R. Giant cell hepatitis with autoimmune hemolytic anemia and hemophagocytosis. J Pediatr Gastroenterol Nutr 2001; 32:330-4. [PMID: 11345187 DOI: 10.1097/00005176-200103000-00020] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- C Hartman
- Division of Pediatric Gastroenterology and Nutrition, Rambam Medical Center, Bruce Rappaport School of Medicine, Technion-lsrael Institute of Technology, Haifa
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Ben-Ari Z, Broida E, Monselise Y, Kazatsker A, Baruch J, Pappo O, Skappa E, Tur-Kaspa R. Syncytial giant-cell hepatitis due to autoimmune hepatitis type II (LKM1+) presenting as subfulminant hepatitis. Am J Gastroenterol 2000; 95:799-801. [PMID: 10710079 DOI: 10.1111/j.1572-0241.2000.01863.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Giant cell hepatitis (GCH) in adults is a rare event. The diagnosis of GCH is based on findings of syncytial giant hepatocytes. It is commonly associated with either viral infection or autoimmune hepatitis type I. A patient with GCH due to autoimmune hepatitis type II (LKM1+) is described, a combination that has not been previously reported. Corticosteroid therapy was effective in decreasing serum liver enzymes; however, the patient deteriorated rapidly and developed subfulminant hepatic failure. Although an emergency orthotopic liver transplantation was performed, the patient died because of reperfusion injury. Interestingly, only a few giant hepatocytes were noted in the explanted liver. This case stresses the association of GCH with autoimmune disorders, the possible immune mechanism involved in the formation of giant cell hepatocytes, and illustrates the rapidly progressive course and unfavorable prognosis that these patients can develop.
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Affiliation(s)
- Z Ben-Ari
- Liver Institute, Department of Medicine D, Rabin Medical Center, Petah Tiqva, Israel
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Abstract
The general histopathologic changes of chronic hepatitis and those related to the various causes are reviewed. Consideration also is given to underlying or associated diseases and to mixed infections in chronic viral hepatitis. Changes occurring in exacerbations or relapses are described. Selected histopathologic changes are illustrated. The nomenclature is reviewed briefly, with emphasis on separation of activity from stage of disease.
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Affiliation(s)
- K G Ishak
- Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA
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35
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Melendez HV, Rela M, Baker AJ, Ball C, Portmann B, Mieli-Vergani G, Heaton ND. Liver transplant for giant cell hepatitis with autoimmune haemolytic anaemia. Arch Dis Child 1997; 77:249-51. [PMID: 9370907 PMCID: PMC1717324 DOI: 10.1136/adc.77.3.249] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Giant cell hepatitis (CGH) with autoimmune haemolytic anaemia (AHA) is a distinct entity with an aggressive course. Immunosuppression may help early disease. A case is reported of a child with GCH and AHA with early disease recurrence after liver transplantation for end stage liver disease.
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Affiliation(s)
- H V Melendez
- Liver Transplant Surgical Service, King's College Hospital, London
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36
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Durand F, Degott C, Sauvanet A, Molas G, Sicot C, Marcellin P, Belghiti J, Erlinger S, Benhamou JP, Bernuau J. Subfulminant syncytial giant cell hepatitis: recurrence after liver transplantation treated with ribavirin. J Hepatol 1997; 26:722-6. [PMID: 9075682 DOI: 10.1016/s0168-8278(97)80440-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
We report the case of an adult patient affected by acute syncytial giant cell hepatitis which had a subfulminant course leading to liver transplantation. Syncytial giant cell hepatitis recurred after transplantation and was efficiently treated with ribavirin. In this patient, the recurrence of the disease, the presence of filamentous strands on electron microscopy during both bouts of hepatitis and the efficacy of ribavirin on post-transplantation hepatitis suggest that the disease was caused by an original virus. This observation also suggests that early administration of ribavirin in patients affected by acute syncytia; giant cell hepatitis of unknown origin could avoid liver transplantation.
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Affiliation(s)
- F Durand
- Service d'Hépatologie and INSERM U24, Hôpital Beaujon, Clichy, France
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37
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Choulot JJ, Parent Y, Etcharry F, Saint-Martin J, Mensire A. [Giant cell hepatitis and autoimmune hemolytic anemia: efficacy of splenectomy on hemolysis]. Arch Pediatr 1996; 3:789-91. [PMID: 8998533 DOI: 10.1016/0929-693x(96)82162-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND The previously reported cases of giant cell hepatitis with autoimmune hemolytic anemia were improved by prednisone plus azathioprine. CASE REPORT A 14-month-old boy suffered from giant cell hepatitis with auto-immune hemolytic anemia and positive direct Coombs test. Prednisone and azathioprine administration improved the liver disease but failed to control hemolysis so that repeated blood transfusions were necessary. Persistance of severe degree of hemolysis required splenectomy that was promptly and definitively effective. Azathioprine and prednisone were pursued for a total duration of five years. Twelve years after the onset of the disease, the child is well without any treatment. CONCLUSION This is the first reported case of such an association in which poorly controlled auto-immune hemolytic anemia benefited from splenectomy.
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Affiliation(s)
- J J Choulot
- Service de pédiatrie, centre hospitalier général, Pau, France
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38
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Lachaux A, Bertrand Y, Bouvier R, Dumont C, Pinzaru M, Hermier M. Intravenous immunoglobulin therapy in an infant with autoimmune hemolytic anemia associated with necrotic hepatitis and peliosis. J Pediatr Gastroenterol Nutr 1996; 22:99-102. [PMID: 8788295 DOI: 10.1097/00005176-199601000-00016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Affiliation(s)
- A Lachaux
- Service d'Hépatogastroentérologie et Nutrition Pédiatriques, CHG de Vienne, France
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39
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Kimura A, Ushijima K, Suzuki M, Tohma M, Inokuchi T, Kato H. Profile of urinary bile acids in familial intrahepatic cholestasis with Coombs' negative haemolytic anaemia. Acta Paediatr 1995; 84:1119-24. [PMID: 8563222 DOI: 10.1111/j.1651-2227.1995.tb13509.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
We present two male siblings with intrahepatic cholestasis and prolonged indirect hyperbilirubinaemia. Their familial intrahepatic cholestasis syndrome was characterized by Coombs' negative haemolytic anaemia, without giant cell transformation of hepatocytes and high concentrations of serum gamma-glutamyl transpeptidase and cholesterol. By gas chromatography-mass spectrometry, we detected large amounts of 1 beta-hydroxylated bile acids, especially 1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholan-24-oic acid (25.5-67.9% of total urine bile acids) in the urine during phenobarbital therapy. However, the amount of urinary 1 beta-hydroxylated bile acids gradually decreased as the disease progressed. At the end-stage, we detected large amounts of 7 alpha,12 alpha-dihydroxy-3-oxochol-4-en-24-oic acid (19.6% of total urine bile acids). The ratio of 7 alpha,12 alpha-dihydroxy-3-oxochol-4-en-24-oic acid to cholic acid in the urine was 0.8. We conclude that in infants with end-stage liver failure, the microsomal hydroxylation of bile acids is impaired and the excretion of delta 4-3-oxo bile acids is increased.
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Affiliation(s)
- A Kimura
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Japan
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40
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Horsmans Y, Galant C, Nicholas ML, Lamy M, Geubel AP. Failure of ribavarin or immunosuppressive therapy to alter the course of post-infantile giant-cell hepatitis. J Hepatol 1995; 22:382. [PMID: 7608496 DOI: 10.1016/0168-8278(95)80298-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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41
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Rabinovitz M, Demetris AJ. Postinfantile giant cell hepatitis associated with anti-M2 mitochondrial antibodies. Gastroenterology 1994; 107:1162-4. [PMID: 7926464 DOI: 10.1016/0016-5085(94)90242-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Whereas giant cell hepatitis (GCH) is a common diagnosis made in neonates, it is rare in the adult population. The diagnosis of GCH is based on the presence of giant cell transformation of hepatocytes. It is commonly associated with either viral hepatitis or autoimmune disorders. A patient with GCH who had anti-M2 mitochondrial antibodies is described. This combination, which has not been previously reported, underscores the association of GCH with autoimmune disorders and stresses the importance of corticosteroids as an empirical initial therapy.
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Affiliation(s)
- M Rabinovitz
- Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania
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42
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Perez-Atayde AR, Sirlin SM, Jonas M. Coombs-positive autoimmune hemolytic anemia and postinfantile giant cell hepatitis in children. PEDIATRIC PATHOLOGY 1994; 14:69-77. [PMID: 8159622 DOI: 10.3109/15513819409022027] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
We report a 23-month-old girl and a 9-month-old boy who presented with autoimmune hemolytic anemia followed by recurrent episodes of severe hepatitis. The first episode of hepatitis occurred 1 week and 15 months after presentation, respectively. Histologically, the livers showed loss of lobular architecture with diffuse giant cell transformation of hepatocytes and portal and pericellular fibrosis. The first patient died at 4 1/2 months after her initial presentation with a well-established micronodular cirrhosis. The second patient responded to steroid therapy and the hepatitis recurred when steroids were tapered. Postinfantile giant cell hepatitis may occur in association with Coombs-positive hemolytic anemia, it is thought to have an autoimmune mechanism, and early and sustained immunosuppression may control the progressive hepatocellular damage and prevent cirrhosis.
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Affiliation(s)
- A R Perez-Atayde
- Department of Pathology, Children's Hospital, Boston, Massachusetts 02115
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43
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Abstract
Giant-cell hepatitis is a frequent pattern of liver injury in the neonate, but it is rare after infancy. Such cases have been attributed to autoimmune disease, to non-A, non-B hepatitis and, most recently, to paramyxovirus infection. To better define the entity of postinfantile (syncytial) giant-cell hepatitis, we reviewed 24 biopsy specimens from 20 patients with this finding, either alone or in combination with other diagnoses. The number of multinucleated giant cells varied greatly from one specimen to another. Varying degrees of portal inflammation appeared in all but one of the patients, and all had hepatitislike acinar inflammation associated with hepatocellular injury. Fibrosis was a common finding, varying from mild periportal fibrosis to established cirrhosis (33%). The changes were interpreted as acute giant-cell hepatitis in 25%, as CAH in 42% and as active cirrhosis in the remainder. The patients ranged in age from 2 to 80 yr, with a mean of 35 yr and a male/female ratio of approximately 1:1. The signs and symptoms of liver disease were present for more than 1 mo in most patients. A positive antinuclear antibody titer was found in seven of the patients. Three patients had a direct Coombs reaction and anemia. Overall, evidence of autoimmune disease was found in 40% of the patients. One patient had non-Hodgkin's lymphoma involving the liver. Only one patient had a history of blood transfusion or risk factors for hepatitis C. No patient underwent serological study for paramyxovirus antibodies. Liver tissue from one patient was examined ultrastructurally, but no viral particles could be identified.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- K Devaney
- Department of Hepatic and Gastrointestinal Pathology Armed Forces Institute of Pathology, Washington, D.C. 20306
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44
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Lau JY, Koukoulis G, Mieli-Vergani G, Portmann BC, Williams R. Syncytial giant-cell hepatitis--a specific disease entity? J Hepatol 1992; 15:216-9. [PMID: 1506641 DOI: 10.1016/0168-8278(92)90039-r] [Citation(s) in RCA: 64] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Syncytial giant-cell hepatitis was recently reported to be related to a paramyxovirus and carried a poor prognosis. Twelve patients with syncytial giant-cell hepatitis seen in an 8 1/2-year period in our institute were reviewed. Seven patients had an identifiable aetiological cause: two had autoimmune chronic active hepatitis, one had primary sclerosing cholangitis and autoimmune chronic active hepatitis, two presented with prolonged jaundice after acute hepatitis A and B, one had chronic Epstein-Barr virus infection and the remaining patient was seropositive for antibody to hepatitis C virus. One patient with autoimmune chronic active hepatitis who had frequent syncytial giant cells in the liver responded promptly to corticosteroid treatment and a repeated biopsy 3 years later showed histological improvement with a marked decrease in the number of syncytial giant cells. Of the remaining five patients, three ran a clinical course of fulminant hepatic failure and two had severe chronic active hepatitis. These data indicate that syncytial giant-cell hepatitis is unlikely to be related to only one single aetiological agent and that syncytial giant-cell hepatitis does not always carry an ominous prognosis.
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Affiliation(s)
- J Y Lau
- Institute of Liver Studies, King's College Hospital School of Medicine and Dentistry, London, United Kingdom
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45
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Brichard B, Sokal E, Gosseye S, Buts JP, Gadisseux JF, Cornu G. Coombs-positive giant cell hepatitis of infancy: effect of steroids and azathioprine therapy. Eur J Pediatr 1991; 150:314-7. [PMID: 2044600 DOI: 10.1007/bf01955929] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
An 8-month-old boy and a 7-month-old girl presented with an acute, Coombs-positive auto-immune haemolytic anaemia and severe hepatitis. The clinical manifestations were pallor, jaundice and hepatomegaly. The liver histology revealed diffuse giant cell transformation and extensive necrosis with central-portal bridging. Combined immunosuppressive regimen with steroids and azathioprine led to prolonged clinical and biological remission with a respective 2 years and 7 months follow up. The girl, however, after 7 months developed a progressive encephalopathy of unknown aetiology, while liver and haematological disease were still under control. She died subsequently from severe recurrent seizures. We conclude that acute Coombs-positive giant cell hepatitis of infancy can be improved by sustained immunosuppressive therapy.
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Affiliation(s)
- B Brichard
- Department of Paediatrics, University of Louvain, Brussels, Belgium
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46
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Phillips MJ, Blendis LM, Poucell S, offterson J, Petric M, Roberts E, Levy GA, Superina RA, Greig PD, Cameron R. Syncytial giant-cell hepatitis. Sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features. N Engl J Med 1991; 324:455-60. [PMID: 1988831 DOI: 10.1056/nejm199102143240705] [Citation(s) in RCA: 177] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND METHODS We describe a new form of hepatitis, occurring in 10 patients over a period of six years, characterized clinically by manifestations of severe hepatitis, histologically by large syncytial giant hepatocytes, and ultrastructurally by intracytoplasmic structures consistent with paramyxoviral nucleocapsids. RESULTS The patients ranged in age from 5 months to 41 years. The tentative clinical diagnosis before biopsy was non-A, non-B hepatitis in five patients and autoimmune chronic active hepatitis in the others. Five patients underwent liver transplantation; the others died. The diagnosis of syncytial giant-cell hepatitis was established pathologically. The liver cords were replaced in all 10 patients by syncytial giant cells with up to 30 nuclei. In 8 of the 10 the cytoplasm contained pleomorphic particles of 150 to 250 microns, filamentous strands, and particles of 14 to 17 nm with peripherally disposed spikes resembling paramyxoviral nucleocapsids. Structures resembling degenerated forms were found in the other two patients. One of two chimpanzees injected with a liver homogenate from the index patient had an increase in the titer of paramyxoviral antibodies, probably an anamnestic reaction to previous paramyxoviral infection, suggesting that a paramyxoviral antigen but not viable virus was present in the liver homogenate. CONCLUSIONS Although further virologic studies will be required for precise classification, we believe that paramyxoviruses should be considered in patients with severe sporadic hepatitis.
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Affiliation(s)
- M J Phillips
- Department of Pathology, Hospital for Sick Children, Toronto, ON, Canada
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47
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Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 34-1988. Progressive pulmonary consolidations in a 10-year-old boy with Evans' syndrome. N Engl J Med 1988; 319:495-509. [PMID: 3405256 DOI: 10.1056/nejm198808253190807] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
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48
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Abstract
Autoimmune hemolysis is defined as a shortening of erythrocyte lifespan due to antibodies directed against the individuals own red cells. This autoantibody production (by B lymphocytes) is thought to result from deficient activity of suppressor T lymphocytes. The rate of erythrocyte destruction depends on the properties of the autoantibodies and on the activities of the complement and mononuclear phagocyte systems: anemia results when destruction outweighs marrow production. Autoimmune hemolysis, which may be primary or secondary, is classified into "warm," "cold," and "mixed" types. The hemolysis associated with pregnancy. Donath-Landsteiner antibodies, of mixed type, and in children, is treated in detail. Current treatment is with immunosuppressive drugs, surgery, and plasma exchange, though immunomanipulation may become important in the future; blood transfusion may be a life-saving adjunct to other therapy.
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49
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Vajro P, Romano A, Fontanello A, Oggero V, Vecchione R, Shmerling DH. Aagenaes's syndrome in an Italian child. ACTA PAEDIATRICA SCANDINAVICA 1984; 73:695-6. [PMID: 6485790 DOI: 10.1111/j.1651-2227.1984.tb09998.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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50
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Scotto J, Hadchouel M, Hery C, Alvarez F, Yvart J, Tiollais P, Bernard O, Brechot C. Hepatitis B virus DNA in children's liver diseases: detection by blot hybridisation in liver and serum. Gut 1983; 24:618-24. [PMID: 6862285 PMCID: PMC1420040 DOI: 10.1136/gut.24.7.618] [Citation(s) in RCA: 48] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Molecular hybridisation using cloned hepatitis B virus DNA (HBV DNA) was applied to liver and serum samples from 46 children (39 with liver diseases and seven controls) for detection of HBV DNA sequences, free and integrated into the liver cell genome. HBV DNA integration was observed in 10 children. The young age of some of these cases indicates that such integration can occur early in liver disease and is not related to the duration of viral infection. Thirteen children exhibited serological evidence of active viral multiplication. All but one had free HBV DNA in liver tissue and integrated HBV DNA sequences were found in four cases. Integrated HBV DNA sequences alone were also detected in three children with neither HBV-antigens nor HBV DNA in serum. One had inactive cirrhosis, and the two others, chronic active hepatitis. Consequently DNA hybridisation may be useful for diagnosis, in the absence of serological signs of HBV infection; its specificity was enhanced in the present investigation by negative results in six children with autoimmune chronic active hepatitis. Taken together, the above results imply that HBV-DNA integration can occur in both active and inactive liver disease. Integrated HBV DNA was also observed in the liver of three children with fatal hepatic failure who presented with antibodies to HBsAg and/or to hepatitis B core antigen in the serum. This finding raises the question of the relationship between the host immune factors and the state of HBV DNA.
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