Acute Hepatitis C Virus Infection: Epidemiology, Clinical...
Transcript of Acute Hepatitis C Virus Infection: Epidemiology, Clinical...
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Hepatitis web study
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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Disclosure Information
• No disclosures to report
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Hepatitis web study
Hepatitis web study
Acute Hepatitis C: Epidemiology
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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
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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
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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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Hepatitis web study
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
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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
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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
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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
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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
(%)
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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
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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
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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
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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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