Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients
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{"title"=>"Pharmacogenetic & pharmacokinetic biomarker for efavirenz based ARV and rifampicin based anti-TB drug induced liver injury in TB-HIV infected patients", "type"=>"journal", "authors"=>[{"first_name"=>"Getnet", "last_name"=>"Yimer", "scopus_author_id"=>"24449522300"}, {"first_name"=>"Nobuhisa", "last_name"=>"Ueda", "scopus_author_id"=>"55318921200"}, {"first_name"=>"Abiy", "last_name"=>"Habtewold", "scopus_author_id"=>"47861724900"}, {"first_name"=>"Wondwossen", "last_name"=>"Amogne", "scopus_author_id"=>"6507123166"}, {"first_name"=>"Akira", "last_name"=>"Suda", "scopus_author_id"=>"35369184400"}, {"first_name"=>"Klaus Dieter", "last_name"=>"Riedel", "scopus_author_id"=>"7101773082"}, {"first_name"=>"Jürgen", "last_name"=>"Burhenne", "scopus_author_id"=>"6701565530"}, {"first_name"=>"Getachew", "last_name"=>"Aderaye", "scopus_author_id"=>"6602473171"}, {"first_name"=>"Lars", "last_name"=>"Lindquist", "scopus_author_id"=>"7006213302"}, {"first_name"=>"Eyasu", "last_name"=>"Makonnen", "scopus_author_id"=>"6602090569"}, {"first_name"=>"Eleni", "last_name"=>"Aklillu", "scopus_author_id"=>"6603381992"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"22162992", "scopus"=>"2-s2.0-82755165151", "doi"=>"10.1371/journal.pone.0027810", "sgr"=>"82755165151", "pui"=>"363035545"}, "id"=>"1f1e98d3-b987-3388-bc34-e0edbbe99d01", "abstract"=>"BACKGROUND: Implication 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 FINDINGS: Newly diagnosed treatment naive 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). CONCLUSION: We 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.", "link"=>"http://www.mendeley.com/research/pharmacogenetic-pharmacokinetic-biomarker-efavirenz-based-arv-rifampicin-based-antitb-drug-induced-l", "reader_count"=>63, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>13, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>5, "Student > Master"=>10, "Other"=>2, "Student > Bachelor"=>5, "Lecturer"=>5}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>13, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>15, "Student > Postgraduate"=>5, "Student > Master"=>10, "Other"=>2, "Student > Bachelor"=>5, "Lecturer"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>7, "Nursing and Health Professions"=>4, "Medicine and Dentistry"=>25, "Agricultural and Biological Sciences"=>15, "Design"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>5, "Chemistry"=>1, "Social Sciences"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>25}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Computer Science"=>{"Computer Science"=>1}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>5}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>2, "United Kingdom"=>1, "South Africa"=>2, "Indonesia"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/706253"], "description"=>"<p>Frequency distribution of <i>NAT2</i> genotype and alleles and deduced phenotype (according to the NAT-2 nomenclature; <a href=\"http://louisville.edu/medschool/pharmacology/NAT2.html\" target=\"_blank\">http://louisville.edu/medschool/pharmacology/NAT2.html</a>) between patients who developed concomitant efavirenz based ARV and rifampicin based anti-tuberculosis drug induced liver injury (DILI Yes) and who did not (DILI No).</p>", "links"=>[], "tags"=>["genotype", "alleles", "deduced", "phenotype", "nat-2", "patients", "developed", "concomitant", "efavirenz", "arv", "rifampicin", "anti-tuberculosis", "induced", "did"], "article_id"=>376581, "categories"=>["Biotechnology", "Cell Biology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Getnet Yimer", "Nobuhisa Ueda", "Abiy Habtewold", "Wondwossen Amogne", "Akira Suda", "Klaus-Dieter Riedel", "Jürgen Burhenne", "Getachew Aderaye", "Lars Lindquist", "Eyasu Makonnen", "Eleni Aklillu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027810.t004", "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Frequency_distribution_of_NAT2_genotype_and_alleles_and_deduced_phenotype_according_to_the_NAT_2_nomenclature_http_louisville_edu_medschool_pharmacology_NAT2_html_between_patients_who_developed_concomitant_efavirenz_based_ARV_and_rifampicin_based_anti_tu/376581", "title"=>"Frequency distribution of <i>NAT2</i> genotype and alleles and deduced phenotype (according to the NAT-2 nomenclature; http://louisville.edu/medschool/pharmacology/NAT2.html) between patients who developed concomitant efavirenz based ARV and rifampicin based anti-tuberculosis drug induced liver injury (DILI Yes) and who did not (DILI No).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 11:06:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/706416"], "description"=>"<p>*see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027810#pone-0027810-t004\" target=\"_blank\">table 4</a> for detail NAT-2 allele and genotype frequency distribution.</p><p>Contrast analysis within each genotype group was done using one of the genotype as indicator reference. For the <i>NAT2</i> genotypes, subjects were stratified into rapid (carrier of <i>NAT2*4, *12 or *13</i>) and slow (homozygous for <i>NAT2*5, *6, *</i>7 or combination there off) acetylators.</p>", "links"=>[], "tags"=>["abcb1", "genes", "concomitant", "anti-tb", "efavirenz", "induced", "cox", "regression"], "article_id"=>376759, "categories"=>["Biotechnology", "Cell Biology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Getnet Yimer", "Nobuhisa Ueda", "Abiy Habtewold", "Wondwossen Amogne", "Akira Suda", "Klaus-Dieter Riedel", "Jürgen Burhenne", "Getachew Aderaye", "Lars Lindquist", "Eyasu Makonnen", "Eleni Aklillu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027810.t003", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_CYP2B6_CYP3A5_NAT2_UGT2B7_SLCO1B1_and_ABCB1_genotype_haplotype_genes_with_development_of_concomitant_anti_TB_and_efavirenz_based_ART_induced_liver_injury_using_cox_regression_analysis_/376759", "title"=>"Association of <i>CYP2B6</i>, <i>CYP3A5</i>, <i>NAT2</i>, <i>UGT2B7</i>, <i>SLCO1B1</i> and ABCB1 genotype/haplotype genes with development of concomitant anti-TB and efavirenz based ART induced liver injury using cox regression analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 11:07:17"}
  • {"files"=>["https://ndownloader.figshare.com/files/706297"], "description"=>"<p>Association of socio demographic parameters of study participants and type of therapy with DILI.</p>", "links"=>[], "tags"=>["socio", "parameters"], "article_id"=>376651, "categories"=>["Biotechnology", "Cell Biology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Getnet Yimer", "Nobuhisa Ueda", "Abiy Habtewold", "Wondwossen Amogne", "Akira Suda", "Klaus-Dieter Riedel", "Jürgen Burhenne", "Getachew Aderaye", "Lars Lindquist", "Eyasu Makonnen", "Eleni Aklillu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027810.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Association_of_socio_demographic_parameters_of_study_participants_and_type_of_therapy_with_DILI_/376651", "title"=>"Association of socio demographic parameters of study participants and type of therapy with DILI.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 11:06:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/706364"], "description"=>"<p>Comparison of median and inter quartile range of pre-treatment biochemical variables, liver chemistry tests and efavirenz kinetics between TB/HIV co-infected patients who developed anti-TB and efavirenz based HAART induced sever liver injury and who did not using Cox regression analysis.</p>", "links"=>[], "tags"=>["median", "inter", "quartile", "pre-treatment", "biochemical", "efavirenz", "kinetics", "co-infected", "patients", "developed", "anti-tb", "haart", "induced", "sever", "did", "cox", "regression"], "article_id"=>376698, "categories"=>["Biotechnology", "Cell Biology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Getnet Yimer", "Nobuhisa Ueda", "Abiy Habtewold", "Wondwossen Amogne", "Akira Suda", "Klaus-Dieter Riedel", "Jürgen Burhenne", "Getachew Aderaye", "Lars Lindquist", "Eyasu Makonnen", "Eleni Aklillu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027810.t002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_median_and_inter_quartile_range_of_pre_treatment_biochemical_variables_liver_chemistry_tests_and_efavirenz_kinetics_between_TB_HIV_co_infected_patients_who_developed_anti_TB_and_efavirenz_based_HAART_induced_sever_liver_injury_and_who_did_n/376698", "title"=>"Comparison of median and inter quartile range of pre-treatment biochemical variables, liver chemistry tests and efavirenz kinetics between TB/HIV co-infected patients who developed anti-TB and efavirenz based HAART induced sever liver injury and who did not using Cox regression analysis.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 11:06:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/706147"], "description"=>"<p>8-hydroxyefavirenz (ng/mL) and efavirenz/8-hydroxyefavirenz ratio (MR) was compared between patients who developed concomitant efavirenz-based HAART and rifampicin based anti-tubercular drugs induced liver injury (cases) and those who did not (controls).</p>", "links"=>[], "tags"=>["efavirenz", "pharmacokinetics", "dili", "cases", "transformed", "plasma"], "article_id"=>376471, "categories"=>["Biotechnology", "Cell Biology", "Genetics", "Infectious Diseases", "Pharmacology"], "users"=>["Getnet Yimer", "Nobuhisa Ueda", "Abiy Habtewold", "Wondwossen Amogne", "Akira Suda", "Klaus-Dieter Riedel", "Jürgen Burhenne", "Getachew Aderaye", "Lars Lindquist", "Eyasu Makonnen", "Eleni Aklillu"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0027810.g001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_efavirenz_pharmacokinetics_between_DILI_cases_and_controls_mean_log_transformed_plasma_efavirenz_ng_mL_/376471", "title"=>"Comparison efavirenz pharmacokinetics between DILI cases and controls: mean log transformed plasma efavirenz (ng/mL).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 11:05:45"}

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Relative Metric

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