R. T. Schooley, MD Slide 1 of 29
Case 1: Acute Hepatitis C Virus (HCV) Infection Robert T. Schooley, MD Professor and Vice Chair of Medicine University of California San Diego
IAS–USA
FORMATTED: 04-18-13
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Learning Objectives After attending this presentation, learners will be able to: • Describe the factors associated with transmission of HCV transmission among sexually active MSMs in the US and Europe. • Describe the natural history of acute HCV infection. • Understand the current approach to therapeutic intervention in acute HCV infection.
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Case 1: Chief Complaint • A 26‐year‐old Caucasian man in his first year of TDF/FTC/efavirenz is referred to you when he is found to have a positive ELISA for HCV. He had been HCV f h db seronegative when he was initially evaluated for his recently diagnosed HIV infection earlier in the year. He is asymptomatic.
IAS–USA
April 23, 2013 1
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Past Medical History • Previously healthy MSM found to be HIV‐1 infected at a community testing site 1 year ago • CD4 cell count: 236 cells/mm3; HIV‐1 RNA level: p / ; g yp yp 106 copies/mL; viral genotype: wild type. • Refused additional evaluation except for hepatitis A, B and C serologies ‐ all were negative • Begun on TDF/FTC/efavirenz – Tolerated regimen well – VL undetectable within 2 months – CD4 cell count 350 cells/mm3 at 3 months
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Family and Social History • Family history: unremarkable • Social history – Caucasian – Works as a travel agent; lives alone – Sexually active • Binge weekend unprotected serosorted sex
– Drinks 2 – 3 beers/day; meth on weekends – No tattoos – No IDU
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Physical Exam Gen: WDWN WM nad HEENT: Sclerae non‐icteric Chest: Clear to A & P CV: No murmurs, gallops or rubs Abd: Mild RUQ tenderness; liver edge 1 cm below RCM; no splenomegaly • Neuro: Normal • Skin: No rash, petechiae or jaundice
• • • • •
IAS–USA
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Initial Laboratory Exam • CBC: WBC 6700, normal differential count; Hct 45; Plts 180,000 • Serum electrolytes: Normal • LFTs – AST, ALT ~ 2.5x ULN – Total bilirubin: 1.3
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What Would You do Now? 1. Order serological studies for hepatitis A, B and C 2. Order a HCV RNA test 3. Refer for a liver biopsy 4. Order a heterophile antibody test 5. Order an anti-CMV antibody test
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Initial Laboratory Findings • HAV IgG ELISA negative • HBsAg, HBeAg negative; HBcAb, HBsAb negative • HCV antibody ELISA positive • Heterophile antibody test negative • CMV IgG positive, IgM negative
IAS–USA
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What Would You do Now? 1. 2. 3 3. 4.
Order plasma HCV RNA level Order plasma HBV DNA level O d IL28B Order IL28B genotype t Order HCV RNA level and genotype
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Recommended Testing Sequence for Identifying Current HCV Infection HCV ANTIBODY
NON-REACTIVE
REACTIVE
HCV RNA
NOT DETECTED
DETECTED
STOP*
*Repeat HCV Ab testing if HCV exposure within past 6 months.
CURRENT HCV INFECTION
NO CURRENT HCV INFECTION
Link to Care
**Repeat HCV RNA testing if HCV exposure within past 6 months or recent HCV infection or has clinical evidence of HCV disease.
CDC Division of Viral Hepatitis, 2013
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Two Weeks Later • • • • •
Still feels tired and has reduced appetite HCV RNA level 108 IU/mL HCV genotype 1a g yp IL28b genotype: C‐C AST, ALT 4x normal
IAS–USA
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HCV Is Cleared in Acute Infection in a Subset of Patients Acute Hepatitis C
Resolved
15-30% 15-
Stable
Stable
Chronic Hepatitis
Cirrhosis 20%‐50%
Chronic HCV Infection 65 – 85% of Infections
4 6 Months
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Spontaneous Clearance of HCV in Symptomatic Patients
Gerlach, Gastroenterology, 2003
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Resolution of Acute HCV Infection with PEG‐‐IFNа with PEG IFNа/RBV /RBV
Average time from infection ->therapy: 89 days Interferon alpha – 5 mU qd x 4 weeks, then 5 mU three times weekly for 24 weeks
Jaekel, NEJM, 2001
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Treatment of Acute HCV in HIV+ MSM Study
Rx
Duration (wk)
SVR rate
Gilleece 2005, London
pIFN+RBV
24
16/27 (59%)
Vogel 2006, Germany
pIFN+RBV
24-48
22/36 (61%)
Dominguez 2006, France
pIFN+RBV
24
10/14 (71%)
Matthews 2009, 2009 Australia
pIFN+RBV
24
16/22 (73%)
Piroth 2010, France
pIFN+RBV
24-48
32/39 (82%)
Lambers 2011, Amsterdam
pIFN+RBV
24-48
38/50 (76%)
Obermeier 2011, Germany pIFN+RBV
24-48
93/175 (53%)
Fierer 2013, (unpublished) pIFN+RBV New York City
24-48
29/46 (63%)
TOTAL:
24-48
256/409 (63%)
pIFN+RBV
Fierer, CROI 2013
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Acute HCV in HIV+ MSM: TVR Treatment Results ETR
SVR 4 SVR 8 SVR 12 SVR 24
17/20
17/20
16/19
14/17
11/14
Success 85% Rate
85%
84%
82%
79%
Total
Fierer, CROI 2013
IAS–USA
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IL28B C‐C Allele is Associated with HCV Clearance in Acute Infection
Thomas, Nature, 2009
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Clinical Course • He opts to defer therapy • LFTs fall over 12 weeks • HCV RNA becomes undetectable 2 weeks later
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He Asks You Whether He Should Worry about Getting HCV Infected Again How should you respond? 1. Don’t worry about HCV; you are now immune because y you have antibodies to the virus. 2. You can get it again if you are re-exposed 3. Get another antibody test in a year if you continue to engage in risky behaviors 4. Get another HCV RNA test every 6 months if you continue to engage in risky behaviors
IAS–USA
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HCV Sexual Transmission Networks England Netherlands Germany France Australia
Van de Lar, Gastroenterology, 2009
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