Title: Acute%20Hepatitis%20C:%20Management%20and%20New%20Epidemiology
1Acute 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
11Cohort 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
12Acute 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
13Acute 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
14Risk 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
15Risk 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)
16Risk 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
17Fibrosis 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
18Fibrosis 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
19Fibrosis During Acute HCV Infection in HIV Men
- The only factors common to ALL
- male sex
- HIV infection
- acute HCV infection
20Virology HCV Genotype Distribution
- 28 genotype 1
- 25 genotype 1a
- 3 genotype 1b
- 3 genotype unknown (VL too low)
21Virology 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)
22Treatment 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
23Treatment 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
24Acute 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
25Acute 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
26Acknowledgements
- 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