Case 1: Acute Hepatitis C Virus (HCV) Infection. Learning Objectives. Case 1: Chief Complaint

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 Universi...
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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

April 23, 2013 2

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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

April 23, 2013 3

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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

April 23, 2013 4

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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

IAS–USA

April 23, 2013 5

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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

April 23, 2013 6

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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

April 23, 2013 7

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HCV Sexual Transmission Networks  England Netherlands Germany France Australia

Van de Lar, Gastroenterology, 2009

IAS–USA

April 23, 2013 8

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