Liver Fibrosis Helps to Distinguish Autoimmune Hepatitis from DILI with Autoimmune Features: A Review of Twenty Cases

Abstract

Background and Aims: Drug-induced liver injury with autoimmune features (AI-DILI) mimics the clinical presentation, and laboratory and pathologic features of idiopathic autoimmune hepatitis (AIH). We aimed to identify histopathologic hallmarks to differentiate these entities. Methods: All liver biopsies archived for the past 10 years were reviewed retrospectively to identify cases of recently detected liver injury associated with predominantly lymphoplasmacytic interphase hepatitis, positive markers for liver autoimmunity, and negative tests for viral hepatitis. Twenty cases were divided into AIH ( n = 12) or AI-DILI ( n = 8) groups. Blind qualitative evaluation of necroinflammatory changes and liver fibrosis were performed according to the Scheuer scoring system. Cellular densities were determined using ImageJ (V1.51t, National Institutes of Health, Bethesda, MD, USA). Fibrosis was assessed on Masson trichrome-stained slides, and collagen deposition was estimated following a protocol of color deconvolution. Results: Necroinflammatory changes as well as densities (portal and lobular) of neutrophils and eosinophils, intracellular cholestasis, and regenerative changes did not differ between the two groups ( P ≥ 0.05). Neutrophil densities but not eosinophils showed a positive correlation with the severity of hepatocellular damage ( r = 0.6 and 0.58, vs. alanine aminotransferase, P < 0.05). Ceroid-laden macrophages but not histiocytic aggregates appeared to be more common in AI-DILI ( P < 0.05). AIH patients presented more often with evidence of chronic damage, including higher scores of fibrosis and collagen deposition, in comparison to AI-DILI ( P < 0.05). Conclusions: Although there is no histologic feature pathognomonic for AI-DILI or AIH, advanced stages of liver fibrosis can be used to support the diagnosis of AIH in some cases. Definitive diagnosis of AI-DILI requires follow-up and demonstration of complete remission after drug withdrawal with no need for immunosuppression.

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“…For staining quantification, a method based on previously published quantification techniques was used. 69 , 70 The image analyzing software Fiji was used. 71 Magnified images (40×) with areas of the exact same sizes of 4 randomly chosen areas per sample were taken.…”

Immune Boosting Gone Wrong? A COVID-Concoction-Conundrum

“…To add to the challenge, unless there is presence of extensive background fibrosis, there are no absolute differentiating points on histopathology. 4 In this context, we re-enforce the need for a detailed mechanistic, toxicological and botanical analysis of such cases in conjunction with public awareness about the potential association.…”

Red Blood Cell Distribution Width-to-Platelet Ratio and Other Laboratory Indices Associated with Severity of Histological Hepatic Fibrosis in Patients with Autoimmune Hepatitis: A Retrospective Study at a Single Center

“…For the most part, the etiology of this severe liver disease is unknown. The diagnosis of AIH is made based on blood test and pathology results, including increased serum transaminase and immunoglobulin G (IgG) levels, autoantibodies, and interface hepatitis [ 1 , 2 ]. However, liver autoantibodies can also be detected in patients with infectious hepatitis.…”

“…This finding suggests these indicators are nonspecific and must be used carefully for the diagnosis of AIH. There are also reports of drug-induced hepatotoxicity accompanied by an autoimmune response [ 1 , 3 ]. Therefore, because the clinical signs of both conditions overlap [ 4 ], diagnosis of idiopathic AIH versus drug-induced liver injury (DILI) can be challenging [ 1 , 4 – 7 ].…”

“…There are also reports of drug-induced hepatotoxicity accompanied by an autoimmune response [ 1 , 3 ]. Therefore, because the clinical signs of both conditions overlap [ 4 ], diagnosis of idiopathic AIH versus drug-induced liver injury (DILI) can be challenging [ 1 , 4 – 7 ]. The American Association for the Study of Liver Disease [ 8 ] gives a conditional recommendation (low certainty) for the use of budesonide and azathioprine or prednisone/prednisolone and azathioprine as initial treatments for patients who present with AIH without cirrhosis, if it is not acute severe AIH.…”