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

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Acute Hepatitis C Management and New Epidemiology

• Daniel S. Fierer, M.D.
• Division of Infectious Diseases
• Mount Sinai School of Medicine

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• 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

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• 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

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• 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

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• 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

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

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• liver biopsy performed 8 weeks after first noted
  ALT elevation

Diagnosis stage 2 of 4 fibrosis, consistent
with chronic hepatitis C
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• 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

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• 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

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• Acute HCV Infection
• first 6 months of infection
• no specific diagnostic test
• spontaneous clearance can occur
• treatment highlyeffective

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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

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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
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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

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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

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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)

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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

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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
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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

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Fibrosis During Acute HCV Infection in HIV Men

• The only factors common to ALL
• male sex
• HIV infection
• acute HCV infection

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Virology HCV Genotype Distribution

• 28 genotype 1
• 25 genotype 1a
• 3 genotype 1b
• 3 genotype unknown (VL too low)

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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)
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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

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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

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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

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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

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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