Post-infantile giant cell hepatitis

Costa Santos, Inês; Martins, Cláudio; Alves, Ana Luísa

doi:10.1016/j.medcle.2024.01.029

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Eosinophils are also noted (arrowhead) (H&E, 400×)." ] ] ] "textoCompleto" => "Giant cell hepatitis is commonly observed in pediatric hepatic diseases. Post-infantile giant cell hepatitis (PIGCH), the adult form, is rather rare, constituting merely 0.1–0.25% of adult liver diseases.<a class="elsevierStyleCrossRefs" href="#bib0030">1,2</a> We report a case of PIGCH with rapid progression to cirrhosis, featuring a potential new culprit.A 22-year-old male was referred for elevated liver enzymes on routine blood tests showing a cytolysis predominant pattern with aspartate aminotransferase of 139IU/L (normal range value [RV]<40IU/L), alanine aminotransferase of 476IU/L (RV<55IU/L), gamma-glutamyl transpeptidase of 135IU/L (RV<64IU/L), normal alkaline phosphatase and total bilirubin. He had no previous medical history, apart from Coronavirus disease 19 (COVID-19) two months prior to the laboratory assessment, which had a mild symptomatic course, not requiring medical care. Apart from this period, he was completely asymptomatic. He denied any chronic medication, recent introduction of drugs or herbal products, or any epidemiology suggestive of zoonotic diseases. Blood analyses from the previous year had normal liver values.The patient had a good general status, being physical examination unremarkable. Subsequent laboratory assessment, following two months, showed overlapping values of liver enzymes, with preserved liver function. An abdominal ultrasound and contrast-enhanced computed tomography identified mild steatotic hepatomegaly and slight splenomegaly, excluding focal lesions, biliary lithiasis, thrombosis or other complications of the portosplenomesenteric territory. An extensive blood work-up excluded hepatotropic infectious agents, metabolic causes, immune-mediated liver diseases, and systemic autoimmune diseases and hematological disorders with potential hepatic involvement (detailed in <a class="elsevierStyleCrossRef" href="#sec0020">Supplementary table</a>). Past infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was documented by serology and negative viral load.After 8 months of persistent liver cytolysis, mild thrombocytopenia (111×103/μL) and hyperbilirubinemia (1.8mg/dL) arose. Given the inconclusive etiological investigation, an ultrasound-guided percutaneous liver biopsy was undertaken, documenting liver cirrhosis. The remarkable presence of numerous multinucleated giant hepatocytes along with features of hepatitis, namely lymphocyte-predominant inflammatory infiltrate, mild interface hepatitis and focal hepatocellular necrosis, allowed the diagnosis of PIGCH, already in cirrhotic phase (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). No histopathological findings suggestive of an underlying etiology for PIGCH were noted.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The patient was referred to a liver transplant center, remaining asymptomatic, with no signs of hepatic decompensation at one year follow-up, despite continued elevation of liver enzymes.PIGCH has fewer than 200 cases reported in the literature.<a class="elsevierStyleCrossRefs" href="#bib0030">1,2</a> Immuno-mediated diseases, mainly autoimmune hepatitis, constitute the primary cause (30–40% of the cases). Less frequently, PIGCH has also been described in primary biliary and primary sclerosing cholangitis, ulcerative colitis, Sjogren's syndrome, systemic lupus erythematous, rheumatoid arthritis and polyarteritis nodosa.<a class="elsevierStyleCrossRefs" href="#bib0030">1,3,4</a> Hepatotropic viruses comprise 20% of the causes, such as hepatitis A, B, C and E viruses, cytomegalovirus, Epstein–Barr, herpes simplex and human herpes 6 viruses.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> In 10–12% of the cases, medications are found to be the causative agent. Methotrexate, 6-mercaptopurine, amitriptyline, chlorpromazine, diclofenac, androgenic analogs, as well as herbal remedies and dietary supplements, were reported in association with PIGCH.<a class="elsevierStyleCrossRefs" href="#bib0030">1,2,4</a> Hematological disorders, particularly chronic lymphocytic leukemia, but also lymphoma and autoimmune hemolytic anemia have been tied to the development of PIGCH (7–8% of the cases). While some patients may have more than one contributing etiology for PIGCH, no predisposing factor is found in 10–30% of the cases.<a class="elsevierStyleCrossRefs" href="#bib0030">1,3,4</a>Disease presentation is highly variable, ranging from mild asymptomatic elevations in liver enzymes to cirrhosis or acute liver failure, demanding liver transplantation.<a class="elsevierStyleCrossRef" href="#bib0040">3</a> Diagnosis of PIGCH requires liver biopsy with documentation of giant multinucleated hepatocytes along with features of hepatitis such as inflammation, lobular disarray, Kupffer cell hypertrophy or focal hepatocellular necrosis.<a class="elsevierStyleCrossRef" href="#bib0045">4</a>Management of PIGCH is still a matter of debate, but treatment of the underlying cause, especially if autoimmune or viral, can result in clinical stability.<a class="elsevierStyleCrossRefs" href="#bib0030">1,3</a> Idiopathic PIGCH has a poor prognosis, frequently requiring liver transplant. Unfortunately, post-transplant recurrence of PIGCH has been documented.<a class="elsevierStyleCrossRefs" href="#bib0040">3,4</a>Our case highlights a rare presentation, remaining idiopathic despite thorough investigation. Nevertheless, the lymphocyte-predominant infiltrate on liver biopsy, often suggestive of a viral etiology, and the temporal correlation between the elevation of liver enzymes and SARS-CoV-2 infection make it challenging to dismiss the potential contribution of this virus. A single case of fatal acute liver failure with presence of giant cell hepatitis in an infant with COVID-19-associated multisystem inflammatory syndrome has been reported.<a class="elsevierStyleCrossRef" href="#bib0050">5</a> To our knowledge, this is the first case reporting SARS-CoV-2 as a potential trigger of PIGCH.Ethical considerationsThe present publication upholds confidentiality by not providing any information regarding the patient's identity. Informed consent for this publication was obtained from the patient for publication of this case report and accompanying figures.FundingNo financial support was provided for this publication.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0025" ] ] ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1570 "Ancho" => 3175 "Tamanyo" => 981182 ] ] "descripcion" => array:1 [ "en" => "Liver biopsy histopathological examination: (a) Liver parenchyma with regenerative nodules with multinucleated giant hepatocytes (arrows), mainly in periseptal zones (H&E, 10×); (b) Masson's trichrome staining highlighting septal fibrosis (arrowheads), demarcating regenerative nodules, consistent with definitive cirrhosis (Ishak score 6); (c) Presence of septal and intralobular lymphocyte-predominant inflammatory infiltrate (arrows) and focal hepatocellular necrosis (dashed circle) (H&E, 100×); (d) Multinucleated giant hepatocytes (arrows) and mild interface hepatitis (asterisk) (H&E, 200×); (e) Multinucleated giant hepatocytes (arrows), having more than 4–5 nuclei, and the aforementioned features of hepatitis, allowing the diagnosis of PIGCH. Eosinophils are also noted (arrowhead) (H&E, 400×)." ] ] 1 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.doc" "ficheroTamanyo" => 540672 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoimmune post-infantile giant cell hepatitis: a case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "Y. Xiao" 1 => "Z.H. Gao" 2 => "M. Deschenes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3138/canlivj-2020-0024" "Revista" => array:6 [ "tituloSerie" => "Can Liver J" "fecha" => "2021" "volumen" => "4" "paginaInicial" => "104" "paginaFinal" => "109" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35991767" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Postinfantile giant cell hepatitis: an etiological and prognostic perspective" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Bihari" 1 => "A. Rastogi" 2 => "S.K. Sarin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2013/601290" "Revista" => array:5 [ "tituloSerie" => "Hepat Res Treat" "fecha" => "2013" "volumen" => "2013" "paginaInicial" => "601290" "itemHostRev" => array:3 [ "pii" => "S1556086420311072" "estado" => "S300" "issn" => "15560864" ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Post-infantile giant cell hepatitis: a literature review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J. Jiao" 1 => "X. Zhang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.14218/jctp.2022.00016" "Revista" => array:7 [ "tituloSerie" => "J Clin Transl Pathol" "fecha" => "2022" "volumen" => "2" "paginaInicial" => "100" "paginaFinal" => "107" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/37092012" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S1556086421021250" "estado" => "S300" "issn" => "15560864" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Post-infantile giant cell hepatitis: a single center's experience over 25 years" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B. Matta" 1 => "R. Cabello" 2 => "M. Rabinovitz" 3 => "M. Minervini" 4 => "S. Malik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4254/wjh.v11.i12.752" "Revista" => array:6 [ "tituloSerie" => "World J Hepatol" "fecha" => "2019" "volumen" => "11" "paginaInicial" => "752" "paginaFinal" => "760" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31966907" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Case report: fatal acute liver failure with giant cell transformation in a pediatric patient associated with MIS-C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Bonilla Gonzalez" 1 => "M. Hincapié Echeverría" 2 => "R. Plazas Pachón" 3 => "P. Mora Umaña" 4 => "B.L. Diaz Gómez" 5 => "N. Gualdron Barreto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fped.2021.780258" "Revista" => array:5 [ "tituloSerie" => "Front Pediatr" "fecha" => "2022" "volumen" => "9" "paginaInicial" => "780258" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/35127589" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000016300000002/v1_202407220832/S2387020624002894/v1_202407220832/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000016300000002/v1_202407220832/S2387020624002894/v1_202407220832/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020624002894?idApp=UINPBA00004N"]

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Vol. 163. Issue 2.

Pages 102-104 (July 2024)

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