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Acute Hepatitis C: Management and New Epidemiology

Acute Hepatitis C: Management and New Epidemiology. Daniel S. Fierer, M.D. Division of Infectious Diseases Mount Sinai School of Medicine. 46 y.o. man with HIV infection acquired via sex with men CD4 count 427 (26%) cells/ μ L HIV viral load 26,168 copies/mL

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Acute Hepatitis C: Management and New Epidemiology

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  1. Acute Hepatitis C: Management and New Epidemiology • Daniel S. Fierer, M.D. • Division of Infectious Diseases • Mount Sinai School of Medicine

  2. 46 y.o. man with HIV infection acquired via sex with men • CD4 count 427 (26%) cells/μL • HIV viral load 26,168 copies/mL • hepatitis A Ab positive, hepatitis B immune (vaccinated), hepatitis C Ab negative • LFTs normal • no antiretroviral medications prescribed

  3. 3 months later, at routine check-up: • asymptomatic, exam unremarkable • had unprotected sex with many men • used crystal methamphetamine, cocaine, “ecstasy,” amyl nitrate, marijuana • denied injection use or sharing implements • Labs: • ALT 960, AST 760, total bili 1.0, alk phos 211

  4. His new hepatitis was caused by: • MDMA (“ecstasy”)-induced hepatitis • crystal meth-induced hepatitis • syphilitic hepatitis • acute hepatitis B infection • acute hepatitis C infection • mushrooms he picked on trip to Maine

  5. Follow-up studies: • hepatitis C antibody positive • hepatitis C viral load 5.9 log10 IU/mL • genotype 1a • RPR non-reactive • hepatitis B VL undetectable • didn’t actually eat the mushrooms

  6. Over the next 2 months: • HCV VL fluctuated between4.6 and 6.6 logs • ALT fluctuated between 1096 and 654 U/L • no spontaneousclearance

  7. liver biopsy performed 8 weeks after first noted ALT elevation Diagnosis: stage 2 of 4 fibrosis, consistent with chronic hepatitis C

  8. His hepatitis C infection is: • chronic, acquired through prior needle-sharing (he lied about his IDU) • acute, acquired through recent needle-sharing (he lied about his IDU) • acute, acquired via sex • chronic, I don’t know how he got it • acute, I don’t know how he got it

  9. How would you treat him? • observe, re-biopsy in 5 years, fibrosis is only stage 2 • IFN-alfa alone 3 times/week for 6 months • peg-IFN alone for 6 months • peg-IFN alone for 12 months • peg-IFN/RBV for 6 months • peg-IFN/RBV for 12 months

  10. Chronic HCV Infection • after 6 months of infection • less responsive to treatment • cause of almost all HCV-related liver damage • Acute HCV Infection • first 6 months of infection • no specific diagnostic test • spontaneous clearance can occur • treatment highlyeffective

  11. Cohort Case Definition for Acute HCV Infection • two of three: • seroconversion (prefer < 1 year) • marked elevation in ALT (> 10 x ULN) • wide fluctuations in HCV VL (> 1 log) • characteristic of acute HCV infection

  12. Acute HCV Infection:course • viremia detectable within 7 to 10 days • ALT elevation 2 to 8 weeks post-infection • antibody seroconversion 8 to 10 weeks • HCV VL fluctuations Sulkowski M, JAMA 2002

  13. Acute HCV in HIV+ MSM:Demographics • 31 HIV+ MSM with acute HCV infection enrolled from Jan’06 to Aug’08 • median age 41 years • 14 White, 13 Hispanic, 4 African American • HIV infection duration 0 months to 16 years • median CD4 count 527 cells/μL • 7 (22%) never received antiretrovirals

  14. Risk Factors for Acute HCV: Case-control Study • 21 cases were age-matched with 21 HIV-infected MSM without HCV infection • ethnicity, duration of HIV infection, CD4 count, HIV VL not significantly different (p > 0.05) • explicit questionnaire: sex and drugs, STI, and other HCV risk factors over prior 12 months • self-administered

  15. Risk Factors for Acute HCV: Case-control Study • unprotected receptive anal intercourse with (p = 0.04) or without (p = 0.03) ejaculation • unprotected receptive oral sex with ejaculation (p = 0.03) • use of sex toys (p = 0.03) • “sex while high” (p = 0.01) • use of marijuana (p = 0.04)

  16. Risk Factors for Acute HCV: Case-control Study • Not significant (p > 0.05): • insertive anal intercourse • insertive oral sex • fisting • use of injection drugs • sharing drug implements

  17. Fibrosis During Acute HCV Infection in HIV+ Men • 20 patients underwent liver biopsy • median 4 months after detection of ALT elevation (range 3 weeks to 4 1/3 years) • 17 (85%) had stage 2 of 4 fibrosis (Scheuer) • 2 had stage 1 • 1 had stage 0 Fierer et al, JID Sept 2008

  18. Fibrosis During Acute HCV Infection in HIV+ Men • None of usual risk factors for pre-existing fibrosis: • most with normal ALT over last year • some never received ARVs; rare “d-drug” use • alcohol intake low (<30 g/day) • some never used recreational drugs • normal BMI/fasting glucose • most without prior hepatitis B infection

  19. Fibrosis During Acute HCV Infection in HIV+ Men • The only factors common to ALL: • male sex • HIV infection • acute HCV infection

  20. Virology: HCV Genotype Distribution • 28 genotype 1 • 25 genotype 1a • 3 genotype 1b • 3 genotype unknown (VL too low)

  21. * * * * * Virology: Phylogenetic Analysis • nine genotype 1a isolates sequenced† • five were part of cluster: • bootstrap value 71.2%(at branch point of 22 sequences) • †region sequenced: 5’ UTR – E1 (868 bp) bootstrap value 71.2% K2P Distances, Neighbor Joining, bootstrapping (n=1000)

  22. Treatment of Acute HCV in HIV+ Men • 31 patients enrolled: • 4 spontaneously cleared within 6 months • 4 refused therapy and lost to follow-up • 2 still in evaluation period • 21 initiated therapy

  23. Treatment of Acute HCV in HIV+ Men • Treatment: pegIFN plus RBV • 10 treated during acute phase completed therapy and 6 month SVR evaluation: • 8 had SVR • 5 treated 24 weeks, 3 treated 48 weeks • 2 failed treatment • prior to 24 weeks

  24. Acute HCV Infection ofHIV+ MSM: Conclusions • Acute HCV infection of HIV+ men is a newly-described clinical syndrome: • route of transmission related to sex • moderately advanced fibrosis occurs within weeks to months and does not regress in years • Emerging infection in the US as well as in Europe

  25. Acute HCV Infection ofHIV+ MSM: Conclusions • Enhanced surveillance in HIV+ MSM should be performed to enable detection and curative treatment in the acute phase to prevent further progression of already significant liver fibrosis. • LFTs every 3 months, Ab every 6-12 months

  26. Acknowledgements • Andrea Branch & lab: • Arielle Klepper • Kristin Bateman • Sarah Fishman • Epidemiologist: • Stephanie Factor • Clinical team: • Alison Uriel • Damaris Carriero • Douglas Dieterich • Michael Mullen • Pathologists: • Swan Thung • Isabel Fiel

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