Drug-induced liver injury (DILI) is one of the main causes of acute liver failure in children. Its incidence is probably underestimated, as specific diagnostic tools are currently lacking. Over 1000 known drugs cause DILI, and the list is expanding. The aim of this review is to describe DILI pathogenesis and emphasize the drugs accountable for child DILI in order to aid its recognition. Intrinsic DILI is well described in terms of mechanism, incriminated drugs, and toxic dose. Conversely, idiosyncratic DILI (iDILI) is unpredictable, occurring as a result of a particular response to drug administration, and its occurrence cannot be foreseen in clinical studies. Half of pediatric iDILI cases are linked to antibiotics, mostly amoxicillin–clavulanate, in the immune-allergic group, while autoimmune DILI is the hallmark of minocycline and nitrofurantoin. Secondly, antiepileptics are responsible for 20% of pediatric iDILI cases, children being more prone to iDILI caused by these agents than adults. A similar tendency was observed in anti-tuberculosis drugs, higher incidences being reported in children below three years old. Current data show growing cases of iDILI related to antineoplastic agents, atomoxetine, and albendazole, so that it is advisable for clinicians to maintain a high index of suspicion regarding iDILI.

Drug-induced liver injury (DILI) remains one of the most challenging adverse drug reactions in clinical practice, particularly in its idiosyncratic form, which is not dose-dependent and is largely driven by host-specific immune and genetic factors. Recent genomic studies have revealed strong associations between certain human leukocyte antigen (HLA) alleles and susceptibility to DILI, supporting an immunogenetic mechanism in which drug or metabolite–protein adducts act as neoantigens, triggering aberrant T-cell activation and hepatocellular injury. This review summarizes current evidence on the contribution of HLA polymorphisms to the pathogenesis of idiosyncratic DILI, highlighting allele-specific risk patterns, such as HLA-B*57:01 associated with flucloxacillin, HLA-DRB1*15:01–DQB1*06:02 in amoxicillin–clavulanate, and HLA-B*35:02 in minocycline-induced liver injury. Furthermore, ethnic variability and allele-haplotype interactions are discussed as potential modulators of susceptibility and clinical phenotype. By integrating genetic and immunological insights, the identification of HLA signatures offers promising tools for precision medicine, enabling earlier identification of at-risk individuals and improved prevention of severe hepatotoxic reactions.

Background. Autoimmune sclerosing cholangitis (ASC) is a rare clinical entity characterized by overlapping features of autoimmune hepatitis and primary sclerosing cholangitis. It predominantly affects pediatric patients. Therapeutic management is often complex, requiring a multidisciplinary and individualized approach, especially in the context of associated autoimmune diseases. Case presentation. We present the case of a female patient diagnosed at the age of 10 with ASC, for which immunosuppressive therapy with prednisone, azathioprine (AZA), and ursodeoxycholic acid (UDCA) was initiated, with an initially favorable course. One year later, following a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, the patient experienced reactivation of liver disease and subsequently developed ulcerative pancolitis (UC), for which 5-aminosalicylic acid (5-ASA) therapy was initiated. Due to repeated hepatic flares and/or colitis relapses, therapy was escalated successively to mycophenolate mofetil, tacrolimus, and eventually infliximab (IFX). Despite treatment, the liver disease progressed, culminating in liver cirrhosis. Our patient developed portal hypertension and esophageal varices, with two episodes of upper gastrointestinal bleeding requiring endoscopic band ligation. At the age of 14, the patient developed recurrent episodes of non-infectious ulcerative stomatitis. Biopsy of the lesions revealed non-specific chronic inflammation, unrelated to colitis activity (confirmed microscopic remission of UC). By exclusion, an adverse drug reaction was suspected, with AZA being the most likely cause. Following its discontinuation, the lesions resolved. Beyond the physiological and therapeutic aspects, the patient displays marked emotional fragility due to prolonged and repeated hospitalizations (18 out of 60 months), which have impacted treatment adherence. Conclusions. This case highlights the complexity of managing pediatric patients with multiple autoimmune diseases. The necessary combination of immunosuppressive therapies may lead to significant adverse effects and further complicate disease progression. Moreover, psychological components play a crucial role in treatment compliance and therapeutic success, emphasizing the need for an integrated approach that includes specialized psychological support.

Autoimmune liver diseases (AILD), including autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC), are rare but important causes of chronic liver disease in children. Although HLA-DRB1 alleles have been associated with disease susceptibility, their role in modulating the clinical phenotype and long-term outcome of pediatric AILDs remains incompletely understood. We aimed to characterize the distribution of HLA-DRB1 alleles and genotype combinations and describe the accompanying clinical features in a pediatric AILD cohort. Thirty children diagnosed with AIH-1 (n = 14), AIH-2 (n = 6), or ASC (n = 10) underwent HLA-DRB1 genotyping. Clinical presentation, fibrosis stage, treatment response, and associated autoimmune diseases were retrospectively analyzed. The most frequent alleles copies were HLA-DRB1*03 (n = 15), predominantly identified in AIH, and HLA-DRB1*13 (n = 14), identified in both AIH and ASC. Genotype combinations involving these alleles were observed across a broad spectrum of clinical presentations, fibrosis stages, treatment responses, and extrahepatic autoimmune manifestations. In this small cohort, HLA-DRB1*14-containing genotypes were observed in several patients with severe disease features, including advanced fibrosis, cirrhosis, treatment-refractory disease, and ulcerative colitis. Patients carrying HLA-DRB1*11, HLA-DRB1*15, or HLA-DRB1*16 had favorable hepatic outcomes despite severe initial presentation or associated extrahepatic autoimmune manifestations; however, the number of carriers was small. Clinical features varied among patients carrying different genotype combinations; however, the independent contribution of the accompanying allele could not be assessed. Our findings illustrate marked clinical heterogeneity among children carrying different HLA-DRB1 alleles and genotype combinations. In this exploratory cohort, selected HLA-DRB1 combinations co-occurred with distinct clinical patterns. HLA profiling may have a role in future risk stratification and individualized follow-up of children with AILD, but these observations are hypothesis-generating, they do not support genotype-based clinical management and require validation in larger, multicenter cohorts.