Antiretroviral therapy-induced liver alterations

Walker, Ulrich A.

doi:10.1097/coh.0b013e328122dbaa

Cited by 17 publications

(14 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antiretroviral and anti-tuberculosis chemotherapy associated drug induced liver injury (DILI) is a common and challenging adverse event causing adherence problem leading to hospitalization and life-threatening events [1]–[4]. DILI can be fatal if therapy is not interrupted on time, and the subsequent adherence problem may cause treatment failure and relapse or drug resistance [5]–[7].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

et al. 2014

View full text Add to dashboard Cite

ObjectivesTo evaluate the incidence, type, severity and predictors of antiretroviral and/or anti-tuberculosis drugs induced liver injury (DILI).MethodsA 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.ResultsA 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.ConclusionHAART 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.

show abstract

Section: Introductionmentioning

confidence: 99%

“…All classes of antiretroviral drugs and some anti-TB drugs such as pyrazinamide, isoniazid and rifampicin are identified as potential cause of DILI [1], [3]. The type and incidence of DILI display wide differences between population and geographical location [14]–[16].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Although effective therapy is available for both TB and HIV, concurrent treatment is complicated due to adverse drug reactions [2]. Anti-tuberculosis and antiretroviral drug induced liver injury (DILI), a common serious adverse drug reaction, is one of the most challenging clinical problems, cause of hospitalization and life-threatening events [3], [4]. DILI can be fatal if therapy is not interrupted on time, and the subsequent adherence problem may cause treatment failure and, relapse or drug resistance [5]–[7].…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients

et al. 2011

View full text Add to dashboard Cite

BackgroundImplication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI) has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI) in HIV and tuberculosis (TB) co-infected patients.Methods and FindingsNewly diagnosed treatment naïve TB-HIV co-infected patients (n = 353) were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001), higher plasma efavirenz level (p = 0.009), efavirenz/8-hydroxyefavirenz ratio (p = 0.036), baseline AST (p = 0.022), ALT (p = 0.014), lower hemoglobin (p = 0.008), and serum albumin (p = 0.007), NAT2 slow-acetylator genotype (p = 0.039) and ABCB1 3435TT genotype (p = 0.001).ConclusionWe report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification of patients at risk of DILI.

show abstract

“…On the other hand, antiretroviral (ARV) treatment-associated hepatotoxicity is of increasing concern in the management of patients with HIV/AIDS ( Jones and Nunez, 2012;Reisler et al, 2003;Turkova et al, 2009;Ugiagbe et al, 2012;Walker, 2007).…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association and Replication Study of Hepatotoxicity Induced by Antiretrovirals Alone or with Concomitant Anti-Tuberculosis Drugs

Petros

Lee

Takahashi

et al. 2017

OMICS: A Journal of Integrative Biology

View full text Add to dashboard Cite

Drug-induced hepatotoxicity (DIH) is a common adverse event that is associated with both antiretroviral (ARV) and anti-tuberculosis drugs (ATD). Moreover, the genetic variations predisposing ARV-and ARV-ATDinduced liver toxicity in African populations are not well investigated, despite the two diseases being the major global health problems in sub-Saharan Africa. We performed a genome-wide association study (GWAS) and replication study to identify the genetic variants linked to the risk of developing DIH due to ARV drugs alone, and ARV-ATD co-treatment in Ethiopian HIV-positive patients. Treatment-naïve newly diagnosed HIV patients (n = 719) with or without tuberculosis (TB) co-infection were enrolled prospectively and received efavirenz-based ARV therapy with or without rifampicin-based short course ATD, respectively. Whole-genome genotyping was performed by using the Illumina Omni Express Exome Bead Chip genotyping array with 951,117 single nucleotide polymorphisms (SNPs) on a total of 41 cases of DIH, and 452 people without DIH (treatment tolerants). The replication study was carried out for 100 SNPs with the lowest p-values (top SNPs) by using an independent cohort consisting of 18 DIH cases and 208 treatment tolerants. We identified a missense SNP rs199650082 (2756G/A, R919Q, p = 1.4 · 10 -6 , odds ratio [OR] = 18.2, 95% confidence interval [CI] = 7.1-46.9) in an endoplasmic reticulum to the nucleus signaling-1 (ERN1) gene on chromosome 17 to be associated with DIH in the ARV-only cohort. In the ARV-ATD co-treatment groups, rs4842407, a long intergenic noncoding RNAs (lincRNAs) transcript variant on chromosome 12, was associated with DIH ( p = 5.3 · 10 -7, OR = 5.4, 95% CI = 2.8-10.3). These genetic variants that are putatively associated with DIH due to ARV drugs alone and ARV-ATD co-treatment establish a foundation for future personalized medicine in people with HIV and TB and call for larger studies in independent populations.

show abstract

Antiretroviral therapy-induced liver alterations

Abstract: Hepatotoxicity is associated with all classes of antiretroviral agents and continues to contribute to hospitalization.

Cited by 17 publications

References 56 publications

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

Evaluation of Patterns of Liver Toxicity in Patients on Antiretroviral and Anti-Tuberculosis Drugs: A Prospective Four Arm Observational Study in Ethiopian Patients

Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients

Genome-Wide Association and Replication Study of Hepatotoxicity Induced by Antiretrovirals Alone or with Concomitant Anti-Tuberculosis Drugs

Contact Info

Product

Resources

About