# Antinuclear antibody targets in autoimmune hepatitis and drug-induced liver injury: Diagnostic relevance of nucleosome antibodies

## TL;DR

The study shows that anti-nucleosome antibodies are more common in autoimmune hepatitis than in drug-induced liver injury, helping to distinguish between the two conditions.

## Contribution

The study identifies anti-nucleosome antibodies as a novel diagnostic marker for differentiating autoimmune hepatitis from drug-induced liver injury.

## Key findings

- Anti-nucleosome antibodies were present in 51.2% of autoimmune hepatitis patients and 15.4% of drug-induced liver injury patients.
- Anti-nucleosome antibodies showed high diagnostic accuracy (AUROC: 0.85) in differentiating autoimmune hepatitis from drug-induced liver injury.
- A homogeneous ANA pattern was more frequently observed in autoimmune hepatitis than in drug-induced liver injury.

## Abstract

Anti-nuclear antibodies (ANA) are detected in 70–100 % of patients with autoimmune hepatitis (AIH) and in 22–33 % of patients with drug-induced liver injury (DILI). However, little is known about the specific antigens which they bind to. This study aimed to investigate the antigen specificity of ANA in patients with AIH and DILI and to assess the diagnostic value of these antibodies in differentiating between the two diseases.

We performed a retrospective, cross-sectional analysis of ANA-positive patients with AIH or DILI treated at a tertiary referral center. ANA patterns were determined by indirect immunofluorescence, followed by antigen-specific characterization using ELISA.

A total of 81 patients were included (54 AIH, 27 DILI). A homogeneous ANA pattern was more frequently observed in AIH (75.9 %) than in DILI (48.1 %). Among patients with a homogeneous pattern, anti-nucleosome antibodies were present in 51.2 % of AIH patients and 15.4 % of DILI patients, yielding a specificity of 84.6 % (95 % confidence interval (CI) 54.6–98.1) and a sensitivity of 51.2 % (95 % CI: 35.1–67.1). Anti-nucleosome antibodies demonstrated the highest diagnostic accuracy in this subgroup (area under the curve (AUROC): 0.85; 95 % CI: 0.70–1.00), outperforming or equaling Immunoglobulin G (IgG) (AUROC: 0.85; 95 % CI: 0.74, 0.95), anti-F-actin antibodies (AUROC: 0.81; 95 % CI: 0.69, 0.93) and anti-smooth muscle antibodies (SMA) (AUROC: 0.80; 95 % CI: 0.67, 0.92).

In ANA-positive patients with a homogeneous ANA pattern, anti-nucleosome antibodies provide high diagnostic accuracy in distinguishing AIH from DILI. These findings suggest that anti-nucleosome antibodies may aid in the diagnostic workup of ANA-positive liver injury.

•Autoantibodies are an important hallmark in the diagnosis of autoimmune hepatitis (AIH).•ANA are positive in a notable proportion of patients with drug-induced liver injury (DILI).•Anti-nucleosome antibodies are significantly more prevalent in AIH than in DILI.•Anti-nucleosome antibodies may serve as a useful tool to differentiate AIH from DILI.

Autoantibodies are an important hallmark in the diagnosis of autoimmune hepatitis (AIH).

ANA are positive in a notable proportion of patients with drug-induced liver injury (DILI).

Anti-nucleosome antibodies are significantly more prevalent in AIH than in DILI.

Anti-nucleosome antibodies may serve as a useful tool to differentiate AIH from DILI.

Lay summary: Autoimmune hepatitis (AIH) is a condition in which the immune system mistakenly attacks the liver and typically requires long-term immunosuppressive therapy. In contrast, drug-induced liver injury (DILI) is caused by a reaction to a medication and usually improves after discontinuation of the offending drug, without the need of immunosuppression. Differentiating between these two liver diseases can be challenging, as they often present with similar features. In our study, we investigated whether the in-depth analysis of antinuclear antibodies (ANA) could help distinguish between AIH and DILI. We found that anti-nucleosome antibodies were clearly more frequently detected in patients with AIH than in those with DILI.