Post-Infantile Giant Cell Hepatitis

Abstract

Purpose: Giant cell hepatitis (GCH), definded by the presence of multinucleated hepatocytes, is well known in children but rare in adults. The etiology and pathogenesis are still unclear, clinical course may be poor. Until today mainly case reports have been published, however. Aim: to analyse a cohort of patients with special attention to possible causative agents and outcome. Methods: Retrospective analysis of patients with post-infantile GCH from the past 15 years. Included were biopsies from patients above 20 years with at least two syncytial giant cells showing at least four nuclei in liver biopsy (each reviewed by two expert liver pathologists). Clinical records were reviewed. Patients with a follow-up of less than 6 months were excluded. Results: We included 25 of 46 patients (mean 47 yrs, range 25–75), 11 men, 14 women. Most patients presented with a mixed cholestatic-cytolytic pattern: Bilirubin 15 ×, ALAT 17 ×, GGT 6 × upper limit of normal. Serologic studies showed in 6 patients (24%) signs of acute viral infection (3 HAV, 1 HIV, 1 Rubeolavirus, 1 HSV, RSV + Paramyxovirus) and in 10 patients elevated autoantibodies (ANA 50%, SMA 30%, ANCA 28%, Anti-ds-DNA 6%, Anti-ASGP-R 6%, Anti-SLA 6%). One patient had a rheumatoid arthritis and 4 a primary sclerosing cholangitis. In 7 possible causative drugs were identified. In 8 no cause was found. Histology showed in 12 patients acute, in 6 subacute and in 6 chronic GCH. 52% had confluent necrosis. 13 patients received no specific treatment, 9 were treated by immunosuppression, 3 had UDCA. Follow-up was 3 yrs (0.5–14). In 17 patients complete recovery occurred, 5 had chronic disease (chronic hepatitis, 1 liver transplantation after 14yrs), 2 died due to hepatic failure (1 PSC, 1 HIV), 1 died from pneumonia. All 4 patients with PSC had a chronic course, all 7 patients with medication associated GCH recovered. Conclusions: We present the analysis of the largest cohort of patients with postinfantile GCH. GCH in adults seems to be an unspecific reaction of the liver to different noxious stimuli (viruses, medication, autoimmune disorders). The stimulus seems to define the clinical course. PSC possibly predisposes to GCH. The prognosis of medication induced GCH seems to be good. Because of the heterogenicity of etiologies a specific therapeutic approach cannot be recommended. Efforts must be taken to identify a causative agent.