Autoantibody-Negative Autoimmune Hepatitis

Abstract

Autoimmune hepatitis has a variable clinical phenotype, and the absence of conventional autoantibodies does not preclude its diagnosis or need for treatment. The goals of this review are to describe the frequency and nature of autoantibody-negative autoimmune hepatitis, indicate its outcome after corticosteroid treatment, and increase awareness of the diagnosis in patients with unexplained acute and chronic hepatitis. The frequency of presumed autoantibody-negative autoimmune hepatitis in patients with acute and acute severe presentations is ≤7%, and its frequency in patients with chronic presentations is 1-34%. Patients with acute presentations can have normal serum γ-globulin levels, centrilobular zone 3 necrosis, and low pre-treatment international diagnostic scores. Liver tissue examination is essential for the diagnosis, and hepatic steatosis can be a co-morbid feature. The comprehensive international scoring system can support but never override the clinical diagnosis pre-treatment, and non-standard serological markers should be sought if the clinical diagnosis is uncertain or the diagnostic score is low. A 3-month treatment trial with corticosteroids should be considered in all patients, regardless of the serological findings, and improvements have occurred in 67-87% of cases. Autoantibody-negative autoimmune hepatitis may be associated with an autoantibody outside the conventional battery; it may have a signature autoantibody that is still undiscovered, or its characteristic autoantibodies may have been suppressed or have a delayed expression. The pathogenic mechanisms are presumed to be identical to those of classical disease. Autoantibody-negative autoimmune hepatitis is an infrequent but treatable disease that must be considered in unexplained acute and chronic hepatitis.

Clinical Presentation, Treatment Outcome and Predictors of Severity in Autoimmune Hepatitis: A Retrospective, Multicenter Experience

“…Autoimmune hepatitis is a complex disease that represents a challenge in diagnosis and management due to the diversity of the clinical presentation, wide spectrum of the disease and variable response to treatment [15] . AIH can affect different age groups and although recognized by the presence of auto-antibodies and elevated immunoglobulins, these markers are absent in a significant proportion of patients that may reach 30% [16] . The quiescent course of the disease especially at early stage is another challenge since disease can progress slowly and evolve to cirrhosis without significant symptoms [17] .…”

Role of Histopathology in Autoimmune Hepatitis

“…'Autoantibody-negative' AIH resembles type I AIH in all respects, including histology, aside from serological marker profile. This includes a good response to treatment with steroids [39] . Liver histology is required for the diagnosis of 'autoantibody-negative' AIH.…”

“…In acute presentation, centrilobular necrosis and a plasma-cell-rich inflammatory infiltrate supports the diagnosis. In chronic disease, the presence of interface hepatitis and absence of findings of other chronic liver disease, such as steatosis, granulomas, biliary injury and siderosis are compatible with AIH [39] .…”

Autoimmune hepatitis

“…A minority of patients express only these autoantibodies [62]. If all autoantibodies are absent but the RDC are compatible with the diagnosis of AIH, empiric treatment with steroids should be considered and the RDC score should be recalculated on the basis of the response to immunosuppression [64].…”