Oral Presentations - Pathology and Laboratory Medicine - University ...

Graduate StudentAbstract # 14Rachel E Wade 1 , Mark Hull 2 , Valentina Montessori 2 , Julio Montaner 2 , MarianneHarris 2 , Marissa Jitratkosol 1 , Izabelle Gadawski 1 , Hélène Côté 11University of British Columbia, Department of Pathology and Laboratory Medicine,2BC Centre for Excellence in HIV/AIDSRachel Wadeishak-knodell pathology score, mitochondrial dnacontent and mitochondrial gene expression in liverfrom patients co-infected with hiv and hepatitis cvirusBackround/ObjectivesHepatic mitochondrial toxicity is a concern for HIV/Hepatitis C Virus (HCV) co-infected patients and may beassociated with altered mitochondrial DNA (mtDNA) content and mitochondrial gene expression (mt-mRNA) dueto viral effects or associated therapies. We investigated the relationships between liver biopsy Ishak-Knodell (IK)pathology scores, liver mtDNA and mt-mRNA levels, in patients ON and OFF-highly active antiretroviral therapy(HAART).MethodsIn this observational cohort study, HIV/HCV co-infected patients (N=34 ON-HAART; N=18 OFF-HAART)underwent a double liver biopsy during pre-HCV therapy assessment. IK scores were recorded from patientcharts. MtDNA/nDNA and mt-mRNA/beta-actin mRNA were quantified in the second biopsy sample by qPCR.Comparisons were performed using the Mann-Whitney test.ResultsThere was high inter-individual variability in mtDNA and mt-mRNA, notably in the ON-HAART group (CV=92and 103% respectively vs. 59 and 62% for OFF-HAART). The ON and OFF-HAART groups did not differsignificantly in median[IQR] IK score (N=32, 7.5[4.8-9.0] vs. N=16, 7.0[4.0-8.3], p=0.84), mtDNA content (N=32,368[315-545] vs. N=18, 399[312-623], p=0.81) or mt-mRNA (N=24, 28[19-36] vs. N=15, 27[21-30], p=0.92).No differences were seen between ON-HAART patients on protease inhibitors (PI) versus non-nucleoside reversetrancscriptase inhibitors (NNRTI) with respect to IK scores (N=17, 8.0[4.0-9.0] vs. N=6, 6.0[4.3-8.5], p=0.74) ormtDNA (N=17, 391[305-538] vs. N=7, 320[242-394], p=0.19). However, mt-mRNA was higher in patients on PIcompared to NNRTI (N=13, 34[26-39] vs. N=4, 17[15-20], p=0.015). Patients on dideoxynucleoside (D-drugs:d4T, ddI) versus other nucleoside reverse transcriptase inhibitors (NRTIs) did not differ in IK scores (N=6, 8.5[5.0-9.0] vs. N=24, 6.0[4.8-9.0], p=0.97), mtDNA (N=6, 357[302-502] vs. N=25, 370[320-625], p=0.68) or mt-mRNA(N=5, 35[21-39] vs. N=17, 27[20-34], p=0.54).ConclusionThe lack of differences between the ON and OFF-HAART groups supports previous observations that HAART is notassociated with increased hepatic mitochondrial toxicity amongst HIV/HCV co-infected patients. Although limitedby small sample size, the results fail to associate drug classes (PI versus NNRTI; D-drug versus other NRTI) withtoxicity. These findings may inform management of HIV/HCV co-infected patients.24 2 0 1 0 * O r a l P r e s e n t a t i o n s