Jennifer Layden, MD, PhD - PowerPoint Presentation

Jennifer Layden, MD, PhD Assistant Professor of Medicine and Public Health Sciences Loyola University Health System

Review of Pilot dataDiscuss 2 pilot data sets Review basic epidemiologic data Discuss ongoing / planned analyses

Hepatitis Pilot Data from two source populations ff Aims: - chronic/recovered infection rates - immediate cases/controls for:-viral genotyping/sequencing-host genotyping Subjects enrolled in H3N study (B Tayo ) N: 200

Data Analysis PlanStored samples run in LUMC reference lab HCV: 4 th generation Ab HBV: Surface AgHIV: HIV-1/2 Ab Aminotransferase level (ALT)

METS Cohort Pilot Study (N=493)   Seroprevalence HIV (% HIV Ab positive)3.9% N=19 HCV (% HCV Ab positive) 5.9% N=29 HBV (% HBV Surface Antigen positive) 14.2% N=70 ALT Median (Range)   17 (5-95)

METS Pilot Study   HCV Ab Positive (N=29) HCV Ab Negative (N=461) P-value ALT (median) 19 17 NS HIV Ab positive 13.8% (4)3.8% (16)0.01HBsAg positive13.8% (4)14.1% (65)NS  HBsAg Positive(N=70)HBsAg Negative(N=423)P-valueALT (median)21160.001HIV Ab positive4.3% (3)5.9% (25)NSHCV positive5.8% (4)5.9% (25)NS Comparison of HCV Antibody Positive to Negative Population Comparison of HBV S Antigen Positive to Negative Population

Nigeria (H3N) Pilot Study (N=200)   Seroprevalence HIV (% HIV Ab positive)5.0% N=10 HCV (% HCV Ab positive) 3.0% N=6HBV(% HBV Surface Antigen positive)7.5%N=15ALT Median(Range) 13.8 (5-171)

Nigeria Pilot Results   HCV Ab Positive (N=6) HCV Ab Negative (N=194) P-value ALT 12.8 ± 5.6 13.8 ± 16.1 0.88 HIV Ab positive33.3% (2)4.1% (8)0.001HBsAg positive16.6% (1)7.2% (14) 0.4 HBsAg Positive(N=15)HBsAg Negative(N=185)P-valueALT24.5 ± 41.112.9 ± 11.530.006HIV Ab positive53.3% (8)1.1% (2)0.1HCV positive6.7% (1) 2.7% (5) 0.4 Comparison of HCV Antibody Positive to Negative Population Comparison of HBV S Antigen Positive to Negative Population

Logistic Regression:Association with HCV Seropositivity Univariable Analyses Variable OR 95% CI P-value HIV +6.7 2.7-16.9<0.001HBV S Ag+1.40.6-3.5 0.5

Logistic Regression: Association with HBV S Ag Seropositivity Univariable Analyses Variable OR 95% CIP-valueHIV +1.50.6-4.10.4HCV Ab + 1.4 0.6-3.5 0.5 ALT 1.03 1.01-1.040.001

Summary of Basic Analysis Overall higher than expected HCV Sero -positivity in Ghana and Nigeria Low mean ALT levels Overall low values No variation seen by HCV status Higher values in those with +S Ag HCV Seropositivity associated with: HIV + status (>6 OR’s) HBV S Ag + associated with: -higher ALT values

Ongoing AnalysesSamples to CDC: HCV / HBV v iral sequencing / genotypingViral load measurementsSamples to Duke:Genotyping of IL28B SNP’s Association of cleared vs chronic infectionOverall allelic variation

HBV S Antigen / S Gene Sequencing Concordancy Results S Ag positive: 85 individuals S Gene positive: 136 individuals S gene+ S gene - N HBV S Ag + 53 (7.6%)32 (4.6%)85HBV S Ag-83 (12.0%)525 (75.8%) 508 N 136 557 593

Factors Associated HbSAg and S gene Status S Ag+ Sag- Variable S Gene+ N=53 S Gene-N=32S Gene+N=83S Gene –N=525HIV Ab + 5.7% 6.2% 3.6% 4.0% HCV Ab+9.4%3.1%4.8%5.1%ALT22.722.916.816.3

Questions Arising from these results What contributes to the discordant results? Is there a high level of occult HBV? Significance? Can there be mutations within the SAg causing the low rate?

Current Progress of Pilot Data CDC based testing: HBV: Check HBV EAg and EAb, CoreAb, SAb and HBV DNA quant HCV: Finishing sequencing resultsAssess for chronic infection ratesDukeIL28B genotyping Allelic variation across SNPs

Kumasi Blood Bank ProtocolActive Enrollment Re-testing and survey administration to assess risk factors of acquistion

Investigators LUMC: N Mora, I Berzin , L Dugas, B Tayo, A LukeMETS: A Luke, PhD; J Plange-Rhule, MD, PhD Nigeria: B Tayo, PhD, B Salako, MD, A Akere , MD CDC: J Forbi, PhD, Y Khadanov, PhDDuke: T Urban, PhD, PharmD