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HEPATITIS WEB STUDY

H. Nina Kim, MD Assistant Professor of Medicine Division of Infectious Diseases University of Washington School of Medicine

Acute Hepatitis C Virus Infection: Epidemiology, Clinical Features, and Diagnosis

March 11, 2013

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•  No disclosures to report

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Acute Hepatitis C: Epidemiology

Hepatitis web study Source: CDC Division of Viral Hepatitis. Statistics and Surveillance.

Incidence of Acute Hepatitis C, by year United States, 1982-2010

0

10,000

20,000

30,000

40,000

50,000

60,000

Est

imat

ed N

umbe

r of C

ases

Hepatitis web study Source: National Notifiable Diseases Surveillance System (NNDSS)

Reported Number of Acute HCV Cases United States, 2000-2010

0

500

1,000

1,500

2,000

2,500

3,000

3,500

2000 2002 2004 2006 2008 2010

Num

ber o

f Cas

es

Year

Hepatitis web study Source: CDC Division of Viral Hepatitis. Statistics and Surveillance.

Hepatitis C Incident Cases in 2010

17,000 estimated new HCV infections per year in U.S.

2,800 cases with symptomatic acute HCV

853 cases of acute HCV actually reported

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Rationale for Identifying Patients with Acute HCV

•  Provide risk reduction counseling and linkage to care

•  Shift dynamics of natural history of HCV disease

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Hepatitis C Transmission

•  Bloodborne transmission is the most common route

•  Sexual transmission in general population considered rare

-  Among cohort of 895 heterosexual HCV-serodiscordant couples, only 3 transmissions occurred à incidence 0.37/1000 person-years

-  Strain analysis did not support sexual transmission

•  Increasing reports of HIV-infected men who have sex with men with sexually-acquired acute HCV infection in Europe, Australia, and U.S.

Source: Vandelli C, et al. Am J Gastroenterol. 2004;99:855-9.

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List of Potential Hepatitis C Exposures

Potential Source of Exposure to Hepatitis C Virus

Recent injection drug use

Needle stick injury

Procedures involving potentially reused needles: tattooing, body-piercing, acupuncture

Exposure to re-used sharp objects or re-used vials of injectable materials

Nosocomial exposure to contaminated equipment, or potential direct exposure to blood

High risk sexual practices: fisting, bleeding during sex, use of sharp objects during sex

Sexual contact with a known HCV-infected partner

Sexual contact with known HIV positive partner

Sexual contact with known sexually transmitted infections in patient or their partner

Blood transfusion or unsafe therapeutic procedures during travel in a developing country

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Diagnosis

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Diagnosis of Acute Hepatitis C

•  Acute HCV = first 6 months of infection

•  Diagnosis of acute HCV can be challenging: - Most cases asymptomatic - No reliable or specific IgM-based HCV antibody test

Hepatitis web study Source: CDC and Prevention

Acute Hepatitis C: 2012 CDC Case Definition

Acute Hepatitis C: 2012 Case Definition

Clinical Presentation An acute illness consistent with acute viral hepatitis AND Jaundice/dark urine or ALT greater than 400 IU/L

Laboratory Criteria for Diagnosis

Meets 1 of the following 3 criteria: • HCV EIA positive, OR • HCV RIBA positive, OR • HCV RNA positive AND • Negative HAV IgM AND negative HBV IgM anti-HBc

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Diagnosis of Acute Hepatitis C

•  Hepatitis C RNA – quantitative (or qualitative) assay - Can detect HCR RNA as early as 1 week from time of infection - Most sensitive early test - Levels can fluctuate widely in acute infection - Best to use assay with low limit of detection (<10-15 IU/mL)

•  Serum ALT - Elevated in range of 400-800 U/L for symptomatic patients - Any new elevation (typically >7X ULN)

•  Hepatitis C antibody (by standard EIA) - Lags behind HCV RNA - In most patients, detected x 2-4 months from time of infection - Not as sensitive: only 50-70% acutely infected are HCV Ab (+) - Helpful if seroconversion has occurred

Hepatitis web study Source: www.hepwebstudy.org

Spontaneous Clearance of HCV after Acute Infection

+/- Symptoms

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Weeks

HCV RNA

ALT

Anti-HCV

HCV Infection

Hepatitis web study Source: www.hepwebstudy.org

HCV Persistence after Acute Infection

+/- Symptoms

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Weeks

HCV RNA

ALT

Anti-HCV

HCV Infection

Hepatitis web study Source: McGovern BH, et al. Clin Infect Dis. 2009;49:1051-60.

Distribution of HCV RNA Levels for Acute versus Chronic HCV

16.0

8.0

13.0

25.0

20.0

11.0

7.0

0.0 1.3 1.9 1.9

7.9

16.5

26.1

30.2

14.3

0

10

20

30

40

<3.5 4.0 4.5 5.0 5.5 6.0 6.5 >6.5

Perc

ent o

f All

Patie

nts

(%)

Baseline HCV RNA concentration, log10 IU/ml

Acute Chronic

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Clinical Features & Natural History

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Acute Hepatitis C

Clinical Features Among 51 Patients with Acute HCV Infection

Source: Gerlach JT, et al. Gastroenterology. 2003;125:80-8.

68

55

39 34

25

0

20

40

60

80

100

Jaundice Flu-Like Symptoms

Dark Urine & White Stool

Nausea Abdominal Pain

Patie

nts

(%)

Hepatitis web study

Acute Hepatitis C

Clinical Features Among 24 Patients with Acute HCV Infection

Source: Santantonio T, et al. Dig Liver Dis. 2003;35:104-13.

63

50

38

17

0

20

40

60

80

100

Fatigue Jaundice Dyspepsia Abdominal Pain

Patie

nts

(%)

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Natural History of Acute HCV Infection

•  Incubation period = 4-14 weeks - Most with acute HCV are asymptomatic or minimally symptomatic - Only 10-20% have a distinct clinical illness

•  If clinical illness occurs, hepatitis is rarely fulminant - ALT typically 400-1000 U/L - Bilirubin rarely >12 mg/dl

•  Two possible outcomes: - Spontaneous clearance: estimated at 20-25% (may be lower in HIV-infected)

- Persistent chronic HCV infection.

Source: Low, et. al. AIDS Reviews 2008; 10:245-53.

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Predictors of Spontaneous HCV Clearance

•  Lower peak HCV RNA levels •  Rapid early decline in HCV viral level •  High ALT •  Presence of jaundice •  Female gender •  Younger age •  Non-black race •  Coinfection with chronic hep B (+HBsAg) •  IL28B CC homozygous genotype

Hepatitis web study Source: Thomas DT, et al. Nature. 2009;461:798-802.

Genetic Variation in IL28-B and Spontaneous HCV Clearance

23.4 29.5

53.0

0

20

40

60

80

100

T/T C/T C/C

Spon

tane

ous

Cle

aran

ce o

f HC

V (%

)

Genotype

Hepatitis web study Source: Thomas DT, et al. Nature. 2009;461:798-802.

Genetic Variation in IL28-B and Spontaneous HCV Clearance

0

20

40

60

80

100

All European Ancestry African Ancestry

Cle

aran

ce (%

)

T/T C/T C/C

P = 4 x 10-7 P = 0.04 P = 3 x 10-7

Hepatitis web study

Hepatitis web study

§  Often a missed diagnosis!

§  Contaminated blood exposure is the most common but sexual transmission can occur

§  Confirmation of acute hepatitis C can be challenging since minority (10-20%) of patients have clinical symptoms

§  HCV RNA, serum ALT and HCV antibody testing remain the cornerstone of acute HCV diagnosis

§  Spontaneous clearance can occur in some acutely infected patients but the majority (75%) will go onto chronic infection if untreated.

Acute Hepatitis C: Summary

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End

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