Exploratory Study of Autoantibody Profiling in Drug‐Induced Liver Injury with an Autoimmune Phenotype

Abstract

Drug‐induced liver injury (DILI) sometimes presents with an autoimmune hepatitis‐like phenotype (AI‐DILI), and it is challenging to distinguish it from de novo autoimmune hepatitis (AIH). We conducted a study to identify autoantibodies unique to AI‐DILI by profiling serum autoantibodies. Autoantibodies were quantified using an autoantigen array containing 94 autoantigens from four groups: AI‐DILI (n = 65), DILI controls (n = 67), de novo AIH (n = 17), and healthy controls (HCs; n = 30). In 37 patients with AI‐DILI, samples were also collected 6 months after presentation. AI‐DILI and de novo AIH had similar anti‐neutrophil antibody and anti‐smooth muscle antibody prevalence. Compared to HCs, de novo AIH had an increase in many immunoglobulin G (IgG; 35 [46.1%]) and IgM (51 [70%]) autoantibodies, whereas AI‐DILI had an increase of IgM (40 [54.8%]) but not IgG autoantibodies. DILI controls had a similar IgG and IgM profile compared to HCs. Comparing de novo AIH to AI‐DILI identified 18 (23.7%) elevated IgG but only one (1.4%) IgM autoantibodies, indicating the unique IgG autoantibody profile in de novo AIH. Compared to DILI and HCs, increased IgM autoantibodies in AI‐DILI and de novo AIH were common; however, AI‐DILI induced by different drugs showed different frequencies of IgM autoantibodies, with nitrofurantoin‐related AI‐DILI showing a higher number of increased IgM autoantibodies. AI‐DILI autoantibody levels at diagnosis and at 6 months showed a significant decline in 37 IgM autoantibodies. A model with highly correlated IgG and IgM was fitted into multivariate logistic regression and revealed an area under the curve of 0.87 (95% confidence interval, 0.79‐0.95) to distinguish de novo AIH from AI‐DILI. Conclusion: The unique IgG and IgM autoantibody signature appears to be a promising biomarker for distinguishing AI‐DILI from de novo AIH.

Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis

“…However, this would be of special interest, because the distinction between AIH, DILI, and herbal-induced liver injury (HILI) or autoimmune-like DILI/HILI can be challenging. [18,31,32] Likewise, the discrimination between asAIH and nonautoimmune severe hepatitis with or without ALF can be difficult and clinically meaningful given that asAIH may benefit from rapid steroid therapy. [33][34][35] Unfortunately, we did not have a long-term follow-up of all patients to assure the clinical diagnosis of AIH or DILI by the clinical disease course (e.g., successful steroid withdrawal in DILI and relapse of AIH).…”

Anticardiolipin and other antiphospholipid antibodies in critically ill COVID-19 positive and negative patients

“…3 4 One of the salient features of COVID-19 is the development of thrombotic events associated with severe morbidity and mortality. [5][6][7][8] In the context of systemic inflammation and dysregulated immunity, 9 some reports have linked APLA to these thromboses, 10 11 severe COVID-19 6 12 and release of neutrophil extracellular traps. 6 However, APLAs are also described in a variety of other infectious diseases 13 and critically ill patients have high rates of thromboembolism that were not linked to APS or APLA 14 (critically reviewed in ref.…”

Liver Injury Following Tinospora Cordifolia Consumption: Drug-Induced AIH, or de novo AIH?

“…However, for many of these drugs, the documented evidence is very limited and consists of a single report and/or short follow-up, which makes it difficult to distinguish DI-AIH from AIH (19). It is well known that autoantibodies can found in patients with other liver diseases than AIH, such as in chronic liver diseases such fatty liver disease (20)(21), acute liver failure (22), DILI due to prescription agents or HDS (23,24). Unfortunately, there is still no consensus on the criteria for DI-AIH and the experts do not agree on the definitions (23)(24).…”

“…It is well known that autoantibodies can found in patients with other liver diseases than AIH, such as in chronic liver diseases such fatty liver disease (20)(21), acute liver failure (22), DILI due to prescription agents or HDS (23,24). Unfortunately, there is still no consensus on the criteria for DI-AIH and the experts do not agree on the definitions (23)(24).…”