Pharmacogenetic Testing as a Tool to Prevent Isoniazid-Induced Hepatotoxicity in Pulmonary Tuberculosis Therapy: A Case Report

INTRODUCTION. Hepatotoxicity is the leading cause of isoniazid discontinuation, significantly reducing the efficacy of antituberculosis therapy, increasing the risk of disease relapse, and contributing to secondary drug resistance in Mycobacterium tuberculosis. The development of hepatotoxic reactions to isoniazid is associated with genetic variations in the activity of N-acetyltransferase 2 (NAT2), an enzyme responsible for hepatic biotransformation of the medicinal product. Dose reduction may prevent liver damage in slow acetylators. However, there is no unified algorithm for dosing this antituberculosis medicinal product based on the results of pharmacogenetic testing. CASE DESCRIPTION. A 35-year-old man, a Yakut, was diagnosed with A16.0 Focal tuberculosis in the upper lobes of both lungs (S1–2) at the stage of infiltration without isolation of Mycobacterium tuberculosis in 2022 and was treated in the respiratory tuberculosis department of the E.N. Andreev Phthisiology Research-Practice Center, Republic of Sakha (Yakutia). Diagnosis was confirmed via clinical, laboratory, and imaging findings. Initial therapy included a daily oral combination comprising isoniazid (500 mg), rifampicin (600 mg), pyrazinamide (1750 mg), and ethambutol (1200 mg). During the intensive of therapy, the patient developed moderate hepatocellular liver damage, which manifested as nausea, vomiting (one episode), weakness, and epigastric pain. Serum alanine transaminase (ALT) increased to 665.5 U/L and aspartate transaminase (AST) increased to 218.8 U/L. Ultrasound examination revealed hepatomegaly, diffuse hepatic and splenic parenchymal changes, chronic cholecystitis, and reactive pancreatitis. Pharmacogenetic testing identified NAT2 allelic variants ( *5 , *11 , *12 ) associated with slow isoniazid acetylation. When treatment continued, the dose of isoniazid was reduced to 300 mg/day; the patient took the other medicines at the same doses. The tolerability of antituberculosis therapy was satisfactory, and hepatotoxic reactions did not develop. The intensive phase of tuberculosis treatment was 64 days. Showing clinical and radiological improvement, the patient was discharged from the hospital. Therapy in the continuation phase included a combination of isoniazid (300 mg) and rifampicin (600 mg) once a day for 120 days. After completion of therapy, the patient was considered clinically cured and was transferred to group III of dispensary observation (regular follow-up visits). CONCLUSIONS. Individualisation of isoniazid dosing according to the results of pharmacogenetic testing allowed the medical team to continue treatment of the patient with drug-sensitive pulmonary tuberculosis and to avoid recurrent development of isoniazid-induced liver damage.