Association of human leukocyte antigen‐B*13:01 with dapsone‐induced liver injury

Abstract

Human leukocyte antigens (HLA) have been linked to adverse drug reactions. Generally, HLA association is phenotype specific and is related to either liver or skin injury.HLA-A*13:01 has been linked to dapsone-induced severe cutaneous drug reactions and its role in drug-induced liver injury (DILI) is unclear. In our series, all of the four patients with immunoallergic dapsone DILI were carrying HLA-B*13:01 compared to its prevalence of 1-12% among Indians. HLA-B*13:01 plays a role not only in dapsone-induced severe cutaneous adverse reaction (SCAR) but also in dapsoneinduced liver injury with immunoallergic features and highlights the role of adaptive immune response in the pathogenesis of both liver and skin injury and associated other organ involvement.

Human Leucocyte Antigen Genetics in Idiosyncratic Drug-Induced Liver Injury with Evidence Based on the Roussel Uclaf Causality Assessment Method

“…The HLA genetics were verified for 19 drugs and 1 drug class in a total of 900 cases of iDILI with evidence based on the RUCAM for the causality assessment, as reported in 16 publications (Table 1) [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. In 683/900 iDILI cases (76%), the RUCAM-based final scores or causality gradings were presented, ranging from possible to highly probable causality gradings in most study cohorts.…”

“…HLA gene analysis of iDILI cases with a firm diagnosis as evidence based on the RUCAM indicates a genetic association with the injury caused by 19 drugs and 1 drug class, but there is variability in the HLA allele genes responsible for individual drugs triggering the liver injury (Table 1) [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. This association could not be firmly established in iDILI cases lacking a robust causality assessment (Table 2) [60][61][62][63][64][65][66][67][68][69][70].…”

“…Much of the efforts focused on the role of the human leucocyte antigen (HLA) alleles associated with iDILI are based on specific drugs or ethnicities [6]. The quality of reports on HLA's association with iDILI is variable: many reports used the RUCAM for the causality assessment, some reports included final RUCAM-based causality rankings [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59], but other reports used no causality assessment method (CAM) at all or a non-validated method based on vague opinion only [60][61][62][63][64][65][66][67][68][69][70].…”

Idiosyncratic DILI: Immunology in Cases with Evidence Based on RUCAM

“…Genetic human leucocyte antigen (HLA) alleles are associated with RUCAM based iDILI by drugs like amoxicillin-clavulanate [82][83][84][85], carbamazepine [82], dapsone [85], enalapril [86], erythromycin [86], fenofibrate [86], flucloxacillin [82,[87][88][89], flupirtine [90], infliximab [91], isoxazolyl penicillins [82], methimazole [92], methyldopa [86], minocycline [93], nitrofurantoin [94], sertaline [86], terbinafine [86], ticlopidine [86], and trimethoprim-sulfamethoxazole [95]. Despite this overt association, a firm causal relationship between HLA alleles and immunity of iDILI has not yet clearly been established and await further studies.…”

Newly identified genetic variants associated with idiosyncratic drug-induced liver injury

“…As minocycline was shown to directly bind to this specific HLA allele, this interaction may be a potential initiating event in minocycline DILI [27]. Another antibiotic with a recent HLA association is dapsone, identified in an Indian population, who presented with acute liver injury with immune-allergic features [28]. HLA-B ∗ 13:01 was identified in all four patients as compared with 1–12% in the control population and this same allele was associated with severe cutaneous adverse event with Dapsone.…”