Clinicopathological Study of Autoimmune Hepatitis Cases That Were Difficult to Differentiate from Drug-Induced Liver Injury

Tsutsui, Akemi; Harada, Kenichi; Tsuneyama, Koichi; Senoh, Tomonori; Nagano, Takuya; Takaguchi, Koichi; Ando, Masayuki; Nakamura, Satoko; Mizobuchi, Koichi; Kudo, Masatoshi

doi:10.1159/000480139

Cited by 11 publications

(5 citation statements)

References 30 publications

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“…In addition, there was a tendency, albeit not significant, towards a higher frequency of eosinophils in AIH patients. Both of those findings are in line with previous data . However, regarding the type and intensity of cellular infiltrates and of cholestasis no other distinguishing feature was found that could have helped to accurately direct diagnosis towards DILI or AIH.…”

Section: Discussionsupporting

confidence: 90%

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

Weber¹,

Benesic²,

Rotter³

et al. 2019

Liver International

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Background Drug‐induced liver injury (DILI) and idiopathic autoimmune hepatitis (AIH) are competing diagnoses in patients with acute liver injury (ALI) and drug intake. In absence of unequivocal markers, scores like RUCAM and AIH are used to distinguish both entities. However, in some cases the diagnosis remains ambiguous. Our aim was to identify a simple parameter to discriminate DILI and AIH shortly after starting corticosteroid treatment. Methods For the current analysis, 44 patients with ALI who took at least one drug and who received corticosteroids were included and comprised 22 DILI and 22 AIH cases. Scores of AIH and RUCAM were calculated at initial presentation, the final diagnosis was made from analysing the course of disease. Changes in the serum alanine aminotransferase (ALT) concentrations after starting corticosteroid treatment were determined and compared between the DILI and AIH groups. Results Fifty‐nine per cent of patients (n = 26) were correctly classified at presentation by AIH score and RUCAM respectively. However, in one‐third (n = 13) of the 44 patients, results were inconclusive and five other patients were misclassified. The decrease in ALT levels 1 week after the initiation of steroid therapy was significantly more pronounced in patients with the final diagnosis of DILI than in AIH patients (accuracy 77%). This difference was also observed in the 18 initially misclassified or inconclusive cases (accuracy 83%). Conclusion Short‐term response of ALT to corticosteroid therapy helps to differentiate DILI and AIH. This finding may be helpful in treatment decision for patients with inconclusive diagnostic scores.

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Section: Discussionsupporting

confidence: 90%

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

Weber¹,

Benesic²,

Rotter³

et al. 2019

Liver International

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“…It is conceivable that the more severe feature of cobblestone appearance of hepatocytes could be a characteristic of AP-AIH and thus useful for distinguishing from DILI, which has also been noted in previous studies. 43,52 In a study that compared AIH with DILI, Suzuki et al noted that the main findings of chronic hepatitis pattern, interface hepatitis, portal inflammation, and focal necrosis were present in all of their evaluated cases, although more severe in AIH. 17 Similar results were obtained in the present study.…”

Section: Discussionmentioning

confidence: 99%

Histopathological analysis of autoimmune hepatitis with “acute” presentation: Differentiation from drug‐induced liver injury

Tsutsui

Harada

Tsuneyama

et al. 2020

Hepatology Research

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Aim Presently, no standardized definition or acceptable diagnostic criteria have been established for acute presentation of autoimmune hepatitis (AP‐AIH), making it difficult to differentiate that condition from drug‐induced liver injury (DILI). This study aimed to characterize clinical and histological features for distinguishing between AP‐AIH and DILI. Methods Clinical, biochemical, and histological characteristics of AP‐AIH and DILI in clinically well‐characterized cases were compared in a standardized manner to clarify differences. Results In clinical evaluations, immunoglobulin G level and rate of anti‐nuclear antibody positivity were greater in AP‐AIH than DILI cases. As for diagnosis of each condition, significant (P < 0.01) differences were found for 10 features: lobular necrosis/inflammation, cobblestone appearance of hepatocytes, plasma cell infiltration in liver parenchyma, centrilobular fibrosis, hepatic rosette formation in areas with cobblestone appearance, portal inflammation, interface hepatitis, prominent plasma cells in portal areas, bile duct injury, and hepatic rosette formation in periportal areas. The area under the curve and cut‐off values for the combination of these 10 features were 0.95 and 9 (sensitivity 86%, specificity 90%), respectively. Conclusion Combinations of histological features were found to be helpful for differentiating AP‐AIH from DILI, but we were not able to statistically identify an individual feature as definitive.

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“…However, a new diagnostic scale to facilitate the diagnosis of DILI in Japan, the Digestive Disease Week Japan 2004 (DDW‐J) scale, which is highly sensitive and specific, was developed by modifying the Council for International Organizations of Medical Sciences/the Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale . Recently, Akemi Tsutsui et al . demonstrated that the DDW‐J scale was useful for differentiating AIH from DILI in cases with a DDW‐J scale score of ≥5 in 20 patients in whom it was difficult to differentiate autoimmune liver disease from DILI.…”

Section: Discussionmentioning

confidence: 99%

Differential characteristics in drug‐induced autoimmune hepatitis

et al. 2018

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Background and AimDrug‐induced autoimmune hepatitis (DIAIH) is an adverse effect associated with several drugs that usually occurs acutely, with variable latency, and it may potentially be mortal. There are a few reports and studies about DIAIH.MethodsThis was an analytical study of a retrospective cohort of patients, discriminated according to idiopathic or drug‐induced etiology, followed up for a 7‐year period until 31 December 2016.ResultsA total of 190 patients were selected for the analysis, 12 (6.3%) with DIAIH. The two main drugs related to DIAIH were nitrofurantoin, n = 8 (67%), and NSAID, n = 2 (17%), constituting 84% of the cases. There were no significant differences in seropositivity between AIH with DIAIH in antinuclear antibodies (ANA) and anti‐smooth muscle antibodies (ASMA) antibodies, with 82.6% versus 82.6% and 34% versus 16%, respectively. The fibrosis stages were similar, except for the F4 stage, in a greater proportion in AIH. None of the patients with DIAIH had cirrhosis or developed it during follow‐up, but it was present in 42.1% of the AIH cases at diagnosis (P = 0.003). Biochemical remission with management was higher in DIAIH but not significant (91.7% vs 80.9%, P = 0.35). The definitive interruption of immunosuppression was successfully performed in 25% of those with DIAIH without relapses but was only possible in 2.8% in AIH (P < 0.001) with 32 cases of relapses.ConclusionDIAIH constitutes a minor proportion of AIH. The clinical and histological characteristics may be similar; DIAIH patients have a greater chance of having treatment suspended with a low risk of relapse, progression to cirrhosis, or need for liver transplant.

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Clinicopathological Study of Autoimmune Hepatitis Cases That Were Difficult to Differentiate from Drug-Induced Liver Injury

Cited by 11 publications

References 30 publications

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug‐induced liver injury from autoimmune hepatitis

Histopathological analysis of autoimmune hepatitis with “acute” presentation: Differentiation from drug‐induced liver injury

Differential characteristics in drug‐induced autoimmune hepatitis

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