Clinical and Molecular Risk Factors of Anti-tubercular Therapy Induced Hepatitis.

Background: This is a case-control study aimed at evaluating clinical as well as molecular risk factors for occurrence of ATT induced hepatitis in Northern Indian population.

Methods: 100 patients of tuberculosis were recruited from both Outdoor patient department and wards of Lok Nayak Hospital, New Delhi. 40 out of 100 patients who developed ATT induced hepatitis were taken as test group and 60 out of 100 patients who didn't develop liver dysfunction on ATT were taken as controls and studied and compared for clinical factors such as age, gender, nutritional status, HBsAg carrier, chronic hepatitis C and HIV infection. Molecular factors i.e. NAT2 acetylator status, GSTT1 and M1 null mutations were also determined in all of the patients in each group and compared.

Results: Mean body weight and serum albumin were significantly lower in the ATT induced hepatitis patients as compared to the control group. No preferential association was observed between age and gender with ATT induced hepatitis. HBsAg carrier (OR-6.5;  = 0.03), HIV infection (OR-5.1;  = 0.01), slow acetylator phenotype (OR-3.85;  = 0.02), GSTM1 null mutation (OR-2.72;  = 0.02) and GSTT1 null mutation (OR-3.12;  = 0.02) were found to be positively co-related to ATT induced hepatitis according to the univariate analysis. HBsAg carrier (OR-23.18;  = 0.01), HIV infection (OR-16.92;  = 0.02), Slow acetylator phenotype (OR-70.90;  = 0.001), GSTM1 null mutation (OR-37.03;  = 0.002) and GSTT1 null mutation (OR-8.19;  = 0.014) were also found to be independently increasing the risk of ATT induced hepatitis using multivariate analysis.

Conclusion: The present study established a positive co-relation between malnutrition, HBsAg carrier, HIV infection, NAT2 slow acetylators, GSTM1 null mutation, GSTT1 null mutation and ATT induced hepatitis.