Yimer G., Gry M., Amogne W., Makonnen E., Habtewold A., Petros Z., Aderaye G., Schuppe-Koistinen I., Lindquist L., Aklillu E.
Department of Laboratory Medicine, Karolinska University Hospital Huddinge C1:68, Karolinska Institutet, Stockholm, Sweden; Department of Pharmacology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; AstraZeneca R and D, Global Safety Assessment, Molecular Toxicology, Södertälje, Sweden; Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; AstraZeneca Innovative Medicines Personalised Healthcare and Biomarkers, Science for Life Laboratory, Solna, Sweden; Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge I:73, Stockholm, Sweden
Yimer, G., Department of Laboratory Medicine, Karolinska University Hospital Huddinge C1:68, Karolinska Institutet, Stockholm, Sweden, Department of Pharmacology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Gry, M., AstraZeneca R and D, Global Safety Assessment, Molecular Toxicology, Södertälje, Sweden; Amogne, W., Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia, Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge I:73, Stockholm, Sweden; Makonnen, E., Department of Pharmacology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Habtewold, A., Department of Laboratory Medicine, Karolinska University Hospital Huddinge C1:68, Karolinska Institutet, Stockholm, Sweden, Department of Pharmacology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Petros, Z., Department of Pharmacology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Aderaye, G., Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; Schuppe-Koistinen, I., AstraZeneca Innovative Medicines Personalised Healthcare and Biomarkers, Science for Life Laboratory, Solna, Sweden; Lindquist, L., Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge I:73, Stockholm, Sweden; Aklillu, E., Department of Laboratory Medicine, Karolinska University Hospital Huddinge C1:68, Karolinska Institutet, Stockholm, Sweden
Objectives: To evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI). Methods: A total of 1,060 treatment naive patients were prospectively enrolled into four treatment groups: HIV patients receiving efavirenz based HAART alone (Arm-1); TB-HIV co-infected patients with CD4≤200 cells/μL, receiving concomitant rifampicin based anti-TB and efavirenz based HAART (Arm-2); TB-HIV co-infected patients with CD4>200 cells/μL, receiving anti-TB alone (Arm-3); TB patients taking rifampicin based anti-TB alone (Arm-4). Liver enzyme levels were monitored at baseline, 1st, 2nd, 4th, 8th, 12th and 24th weeks during treatment. CD4 and HIV viral load was measured at baseline, 24th and 48th weeks. Data were analyzed using multivariate Cox Proportional Hazards Model. Results: A total of 159 patients (15%) developed DILI with severity grades 1, 2, 3 and 4 of 53.5%, 32.7%, 11.3% and 2.5% respectively. The incidence of cholestatic, hepatocellular or mixed pattern was 61%, 15% and 24%, respectively. Incidence of DILI was highest in Arm-2 (24.2%)>Arm-3 (10.8%)>Arm-1 (8.8%)>Arm-4 (2.9%). Concomitant anti-TB-HIV therapy increased the risk of DILI by 10-fold than anti-TB alone (p<0.0001). HIV co-infection increased the risk of anti-TB DILI by 4-fold (p = 0.004). HAART associated DILI was 3-fold higher than anti-TB alone, (p = 0.02). HAART was associated with cholestatic and grade 1 DILI whereas anti-TB therapy was associated with hepatocellular and grade ≥ 2. Treatment type, lower CD4, platelet, hemoglobin, higher serum AST and direct bilirubin levels at baseline were significant DILI predictors. There was no effect of DILI on immunologic recovery or virologic suppression rate of HAART. Conclusion: HAART associated DILI is mainly cholestatic and mild whereas hepatocellular or mixed pattern with high severity grade is more common in anti-tuberculosis DILI. TB-HIV co-infection, disease severity and concomitant treatment exacerbates the risk of DILI. © 2014 Yimer et al.