The clinical features of drug-induced liver injury observed through liver biopsy: focus on relevancy to autoimmune hepatitis

Abstract

Background/AimsAccurate diagnosis of drug-induced liver injury (DILI) is difficult without considering the possibility of underlying diseases, especially autoimmune hepatitis (AIH). We investigated the clinical patterns in patients with a history of medication, liver-function abnormalities, and in whom liver biopsy was conducted, focusing on accompaniment by AIH.MethodsThe clinical, serologic, and histologic findings of 29 patients were compared and analyzed. The patients were aged 46.2±12.8 years (mean±SD), and 72.4% of patient were female. The most common symptom and causal drug were jaundice (58.6%) and herbal medications (55.2%), respectively.ResultsAspartate aminotransferase (AST), alanine aminotransferase, total bilirubin, alkaline phosphatase, and γ-glutamyl transpeptidase levels were 662.2±574.8 U/L, 905.4±794.9 U/L, 12.9±10.8 mg/dL, 195.8±123.3 U/L, and 255.3±280.8 U/L, respectively. According to serologic and histologic findings, 21 cases were diagnosed with DILI and 8 with AIH. The AIH group exhibited significantly higher AST levels (537.1±519.1 vs. 1043.3±600.5 U/L), globulin levels (2.7±0.4 vs. 3.3±0.5 g/dL), and prothrombin time (12.9±2.4 vs. 15.2±3.9 s; P<0.05). Antinuclear antibody was positive in 7 of 21 cases of DILI and all 8 cases of AIH (P=0.002). The simplified AIH score was 3.7±0.9 in the DILI group and 6.5±0.9 in the AIH group (P<0.001).ConclusionsAccurate diagnosis is necessary for patients with a history of medication and visits for liver-function abnormalities; in particular, the possibility of AIH should be considered.

Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease

“…Ju et al [33] have studied the histological features of DILI patients in Korea, with special focus on relevancy of AIH. The study showed that characteristic histologic features of AIH, as interface hepatitis and lymphoplasmocytic infiltrates, were present in up to one third of DILI patients.…”

Autoimmune hepatitis

“…Viruses associated with the onset of AIH include: HAV, HCV, HEV, EBV, HSV and measles [3,24,27,28]. Drug-induced liver injury (DILI) can mimic, trigger or unmask AIH [29,30], and distinction between DILI and AIH can be challenging [30][31][32][33].…”

“…Since DILI can mimic, trigger or unmask AIH, distinction between DILI with features of AIH and true AIH requires scrutiny of clinical and histological differences [30][31][32][33]48,49].…”

“…While interface hepatitis is the key histological feature in AIH, it also occurs in HBV (with or without HDV), HCV and HEV infections, Wilson disease and drug-induced liver injury [33,46,76,77]. In contrast, central zonal necrosis and perivenulitis of the central vein ( Fig.…”

Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients

“…Although the exact mechanism of DILI is still largely unidentified, it seems to involve 2 pathways -direct liver toxicity and adverse immune reactions (Holt and Ju, 2006). DILIs from herbal medicines are generally idiosyncratic drug reactions, strongly suggesting a mainly immune response (Ju et al, 2012). Immune responses against foreign antigens and malignant cells are lower in the elderly, and most immune cells involved in innate immunity show decreased function with aging (Tajiri and Shimizu, 2013).…”