Presence of multilobular necrosis on liver biopsy identifies corticosteroid responsiveness in acute indeterminate hepatitis.

Su Lin,Mohsin Hassan,Andrew Hall,Alberto Quaglia,Cornelius Engelmann,Catarina Araujo,Rahul Kumar,Alexandra Phillips,Rajiv Jalan

doi:10.1111/liv.15144

Abstract

Treatment of patients with severe indeterminate hepatitis (IAH) is an unmet need. Corticosteroids are often used in the management of these patients but criteria for the selection of patients for this intervention are arbitrary. The aims of this study were to analyse the clinical and pathological features of patients with IAH to define predictors of corticosteroid responsiveness. This study included consecutive patients with acute indeterminate hepatitis admitted to a single hospital and underwent a liver biopsy. The clinical manifestation and histopathological features of steroid and non-steroid groups were compared and their relationship with corticosteroids response was evaluated. Forty-eight patients were included, 24 (50%) recovered and the other half underwent liver transplantation or died within 3-months. Of the 48 cases, 24 received corticosteroids (initial dose of 45±12mg prednisolone). Corticosteroids were initiated 2.7±3.8days after admission. Liver biopsy was performed 2-days (median, IQR 1-3) after admission. Fifteen (62.5%) patients receiving corticosteroids survived without transplantation compared with 9 (37.5%) that did not receive steroids (P=.149). In those with multilobular necrosis, 50% reduction in the death/transplantation rate was observed after steroid treatment (P=.018). In patients without multilobular necrosis and with or without perivenulitis, corticosteroids did not impact the outcome. Response to corticosteroids was independent of the MELD score. The presence of multilobular necrosis on liver biopsy helps identify a subgroup of IAH cases who may benefit from the administration of corticosteroids.

Highlights

Indeterminate acute hepatitis (IAH) refers to an acute hepatitis illness in which the aetiology cannot be determined despite an exhaustive search for the cause
This study focused on the role of liver histopathology in the guidance of corticosteroid therapy in patients with IAH
In post hoc analyses, the results showed a reduction of 50% in the death/transplantation rate after treatment with corticosteroids in IAH patients with multilobular necrosis

Summary

| INTRODUCTION

Indeterminate acute hepatitis (IAH) refers to an acute hepatitis illness in which the aetiology cannot be determined despite an exhaustive search for the cause. This condition has been referred to as ‘non A, non B, non C’, ‘non A-E’, or ‘seronegative’ acute hepatitis.[1] IAH is clinically challenging due to its inherent complexity, lack of diagnostic criteria, poor prognosis and its treatment is an unmet need. There are no criteria that define which patients with IAH may benefit from the administration of corticosteroids. We explored the clinical and pathological features that may be used to select patients with IAH that may benefit from corticosteroids

| METHODS

| RESULTS

Findings

| DISCUSSION