Outcomes in patients with autoimmune hepatitis with an index presentation of severe acute hepatitis.

Abstract

Background and Aim: Autoimmune hepatitis (AIH) is a heterogeneous disease, with index presentations varying from fulminant hepatitis with liver failure to subclinical mild liver enzyme derangement. The natural history and outcomes for patients are also widely variable.We examined a cohort of patients with AIH who presented with severe acute hepatitis to describe their natural history of disease, disease severity, treatment, and outcomes. Method(s): We performed a retrospective cohort study of patients presenting to a large metropolitan health network between 2011 and 2021 with an acute severe hepatitis (defined as an alanine aminotransferase [ALT] level > 10 times the upper limit of normal) attributed to AIH. Baseline data on patient demographics, routine biochemistry, auto-antibodies associated with AIH, liver histology, and simplified autoimmune hepatitis score were obtained. Study outcomes included mortality, presence of cirrhosis at diagnosis, duration of treatment with prednisolone and steroid-sparing agents, normalization of liver function test (LFT) results, and incidence of AIH flares (defined as the reintroduction or dose increase of steroids by a gastroenterologist in response to a clinical or biochemical change). Result(s): In total, 61 patients (median age, 50 years [IQR, 27-64]; 66% female) presenting with acute severe hepatitis secondary to AIH were identified during the study period. Three patients had a known history of liver disease from another etiology, and 13 (21%) had a history of non-liverrelated autoimmune disease. The median peak ALT level was 1191 IU/L (980-1527), bilirubin was 156 mumol/L (41-288), international normalized ratio (INR) was 1.3 (1.2-1.6), and IgG was 23.9 g/L (18.6-29.9). Positive autoantibodies were noted in 52 patients (85%): anti-nuclear antibody (75%), anti-smooth muscle antibody (48%), anti-liver-kidney microsomal antibody (2%), and anti-mitochondrial antibody (2%). The median simplified autoimmune hepatitis score was 7, with 33 (54%) and 13 (21.3%) patients classified as having likely and probable AIH, respectively. On liver biopsy, 29 patients (48%) had classical findings consistent with AIH, and 23 patients (38%) had findings compatible with AIH. Two patients presented with acute liver failure, and liver cirrhosis was diagnosed in a further two patients (3.3%) on the index presentation. Median hospital length of stay was 9 days (4-12). All patients were treated with corticosteroid therapy (hydrocortisone, 3; methylprednisolone, 1; oral budesonide, 5; and prednisolone, 52), and 58 patients (95%) subsequently commenced a thiopurine (azathioprine, 55; and 6-mercaptopurine, 3). The median time to ALT normalization after commencing treatment was 4 months (IQR, 2-7), with a median time to first complete steroid wean of 7 months (IQR, 5-10). Cumulatively, seven patients (11.5%) had an AIH flare at 6 months, 9 (14.8%) at 12 months, 14 (23%) at 24 months, and 21 (33.4%) at 36 months. At 36 months of follow-up, six patients (9.8%) had required readmission to hospital for disease- or treatment-related complications, and 13 (21.3%) remained on corticosteroids. Three deaths (4.9%) were recorded (two from liver failure and one from infection), with a median survival of 2.5 months after AIH diagnosis. Conclusion(s): AIH manifesting as severe hepatitis is a serious condition with a high prevalence of jaundice and a short-term mortality rate of 4.9% despite treatment. Most patients are steroid-sensitive, with a median time to ALT normalization of 4 months after initiation of treatment. Patients typically require prolonged steroid treatment, with a median initial duration of 7 months, and 21.3% of patients remained on steroids 36 months after diagnosis. A third of patients experienced a significant disease flare during the follow-up period, highlighting the need for long-term follow-up. Future studies focusing on severe AIH are required to further inform optimal management and outcomes in this cohort.