Acute%20Hepatitis%20C:%20Management%20and%20New%20Epidemiology - PowerPoint PPT Presentation

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Acute%20Hepatitis%20C:%20Management%20and%20New%20Epidemiology

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HIV viral load 26,168 copies/mL ... Arielle Klepper. Kristin Bateman. Sarah Fishman. Epidemiologist: Stephanie Factor. Clinical team: ... – PowerPoint PPT presentation

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Title: Acute%20Hepatitis%20C:%20Management%20and%20New%20Epidemiology


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
  • didnt 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 dont know how he got it
  • acute, I dont 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
  • 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 lt 1 year)
  • marked elevation in ALT (gt 10 x ULN)
  • wide fluctuations in HCV VL (gt 1 log)
  • characteristic of acute HCV infection

12
Acute HCV Infectioncourse
  • 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 MSMDemographics
  • 31 HIV MSM with acute HCV infection enrolled
    from Jan06 to Aug08
  • 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 gt 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 gt 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 (lt30 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
(n1000)
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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