Screening for Hepatitis C Virus Infection

1
Screening for Hepatitis C Virus Infection

• Prepared for
• Agency for Healthcare Research and Quality (AHRQ)
• www.ahrq.gov

2
Outline of Material

• Introduction to the epidemiology of and screening
  for hepatitis C virus (HCV) infection
• Systematic review methods
• The clinical questions addressed by the
  comparative effectiveness review
• Results of studies and evidence-based conclusions
  about the benefits and adverse effects of
  screening for HCV infection
• Updated recommendations from the U.S. Preventive
  Services Task Force and the Centers for Disease
  Control and Prevention for screening for HCV
  infection
• What to discuss with patients and their caregivers

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

3
BackgroundPrevalence of Hepatitis C Virus
Infection

• The hepatitis C virus (HCV) is the most common
  chronic blood-borne pathogen in the United
  States.
• About 78 percent of individuals who test positive
  for anti-HCV antibody have detectable hepatitis C
  virus in their blood, indicating chronic
  infection.
• The Centers for Disease Control and Prevention
  estimated that there were 16,000 new cases of
  acute HCV infection in the United States in 2009.
  
• HCV infection was associated with an estimated
  15,000 deaths in 2007.

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

4
BackgroundRisk Factors for Hepatitis C Virus
Infection

• The strongest risk factor for infection with the
  hepatitis C virus (HCV) is injection drug use.
• Transfusions received before 1992 are also a risk
  factor for HCV infection.
• Blood transfusions are no longer an important
  source of infection because of the implementation
  of effective screening programs for donated
  blood.
• People born between 1945 and 1965 are at
  particular risk.
• About 75 percent of patients with HCV infection
  were born between the years 1945 and 1965, with
  the highest prevalence (4.3) in people 40 to 49
  years of age in 19992002.

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

5
Background Clinical Consequences ofHepatitis C
Virus Infection

• Infection with the hepatitis C virus (HCV) is a
  leading cause of complications from chronic liver
  disease including cirrhosis, hepatic failure,
  hepatocellular cancer, and death.
• Although the incidence of HCV infection has been
  declining over the last two decades, the rates of
  cirrhosis, hepatic failure, and hepatocellular
  cancer are expected to rise in the next 10 to 20
  years.
• This rise is expected because of the long lag
  time between infection with HCV and the
  development of complications.

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

6
Background Importance of Screening for Hepatitis
C Virus Infection

• Screening for hepatitis C virus (HCV) infection
  in asymptomatic adults without a history of liver
  disease or liver enzyme abnormalities may
  identify infected patients early, before they
  develop serious liver damage.
• Data from the Centers for Disease Control and
  Prevention suggest that out of every 100 people
  infected with HCV
• About 75 to 85 will develop chronic HCV infection
• About 520 will develop cirrhosis over 2030
  years, with the rates increasing after 30 years
• HCV antibody testing with subsequent polymerase
  chain reaction testing was found to be accurate
  for identifying patients with HCV infection.

• Centers for Disease Control and Prevention.
  Available at www.cdc.gov. Accessed August 9,
  2013.
• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.
• U.S. Preventive Services Task Force. Ann Intern
  Med. 2004140(6)462-4. PMID 15023712.

7
BackgroundObjectives of This Systematic Review

• The authors of this review aimed to evaluate the
  evidence regarding
• The effects of screening for hepatitis C virus
  (HCV) infection on clinical outcomes in
  asymptomatic adults
• The relative effectiveness of various screening
  strategies for HCV infection
• The potential harms of screening for HCV
  infection
• The effects of counseling interventions on
  clinical and intermediate outcomes in patients
  with HCV infection
• The effects of labor-and-delivery practices and
  breastfeeding on mother-to-child transmission of
  HCV infection
• This review has also been used by the U.S.
  Preventive Services Task Force to update its
  recommendations on HCV screening.

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

8
Agency for Healthcare Research and Quality (AHRQ)
Comparative Effectiveness Review (CER) Development

• Topics are nominated through a public process,
  which includes submissions from health care
  professionals, professional organizations, the
  private sector, policymakers, members of the
  public, and others.
• A systematic review of all relevant clinical
  studies is conducted by independent researchers,
  funded by AHRQ, to synthesize the evidence in a
  report summarizing what is known and not known
  about the select clinical issue. The research
  questions and the results of the report are
  subject to expert input, peer review, and public
  comment.
• The results of these reviews are summarized into
  Clinician Research Summaries and Consumer
  Research Summaries for use in decisionmaking and
  in discussions with patients.
• The Research Summaries and the full report, with
  references for included and excluded studies, are
  available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at http//www.effectivehealthcare.ahrq.g
  ov/hepatitis-c-screening.cfm.

9
Clinical Questions Addressed by This Comparative
Effectiveness Review (1 of 4)

• Key Question 1a. Does screening for hepatitis C
  virus (HCV) infection in nonpregnant adults
  without known abnormal liver enzymes reduce
  mortality and morbidity due to HCV infection
  affect quality of life or reduce incidence of HCV
  infection?
• Key Question 1b. Does screening for HCV infection
  during pregnancy reduce vertical transmission of
  HCV or improve mortality or morbidity for the
  mother or child?

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

10
Clinical Questions Addressed by This Comparative
Effectiveness Review (2 of 4)

• Key Question 2a. What is the effectiveness of
  different risk-based or prevalence-based methods
  for screening for HCV infection in improving
  clinical outcomes?
• Key Question 2b. What is the sensitivity and
  number needed to screen to identify one case of
  HCV infection of different risk-based or
  prevalence-based methods for screening for HCV
  infection?
• Key Question 3. What are the harms associated
  with screening for HCV infection, including
  adverse effects such as anxiety, labeling, and
  impact on relationships?

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

11
Clinical Questions Addressed by This Comparative
Effectiveness Review (3 of 4)

• Key Question 4a. What are the comparative
  effectiveness and comparative diagnostic accuracy
  of various tests and strategies for the workup to
  guide treatment decisions in patients who test
  positive for HCV infection?
• Key Question 4b. What proportion of patients with
  screen-detected HCV infection receives treatment?
  
• Key Question 5. What are the harms associated
  with the workup for guiding treatment decisions?

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

12
Clinical Questions Addressed by This Comparative
Effectiveness Review (4 of 4)

• Key Question 6a. How effective is counseling or
  immunization of patients with hepatitis C virus
  (HCV) infection at improving health outcomes or
  reducing the spread of HCV?
• Key Question 6b. Does becoming aware of a
  positive serostatus for HCV infection decrease
  high-risk behaviors?
• Key Question 6c. How effective is counseling or
  immunization of patients with HCV infection at
  improving intermediate outcomes, including change
  in high-risk behaviors?
• Key Question 7. Do any interventions decrease or
  increase the risk of vertical transmission of HCV
  during delivery or in the perinatal period?

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

13
Rating the Strength of Evidence From the
Comparative Effectiveness Review

• The strength of evidence was classified into four
  broad categories

High Further research is very unlikely to change the confidence in the estimate of effect.
Moderate Further research may change the confidence in the estimate of effect and may change the estimate.
Low Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
Insufficient Evidence either is unavailable or does not permit estimation of an effect.

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

14
Evidence for the Clinical Benefits and Harms of
HCVScreening in Nonpregnant and Pregnant
Asymptomatic Adults

• There was no direct evidence of clinical benefits
  and limited evidence on harms associated with
  screening for hepatitis C virus infection, when
  compared with no screening or between different
  screening approaches, in nonpregnant and pregnant
  adults.
• Strength of Evidence Insufficient

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

15
Sensitivity of Different Strategies for
Hepatitis C Virus Screening

• Targeted screening strategies based on multiple
  risk factors were associated with sensitivities
  of more than 90 percent and with numbers needed
  to screen to identify one case of hepatitis C
  virus infection of less than 20.
• Strength of Evidence Low
• The more narrowly targeted screening strategies
  were associated with numbers needed to screen of
  less than two but with the trade-off of missing
  up to two-thirds of infected patients.
• Strength of Evidence Low

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

16
Evidence for the Clinical Benefits and Adverse
Effects Associated With Detection of Hepatitis C
Virus Infection

• Biopsy-related adverse effects appeared to be
  small, with a risk of death of less than 0.2
  percent and a risk of serious complications
  (primarily bleeding and severe pain) of about 1
  percent.
• Strength of Evidence Moderate

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

17
Evidence for the Clinical Benefits and Adverse
Effects Associated With Treatment of HCV
Infection (1 of 2)

• From 15 to 33 percent of patients with
  screen-detected chronic hepatitis C virus (HCV)
  infection received treatment however, this
  varied according to the population assessed and
  the treatment eligibility criteria used.
• Strength of Evidence Moderate
• Treatment of HCV genotype 1 infection with triple
  and dual antiviral therapy regimens resulted in
  sustained virologic response (SVR) rates of 66 to
  80 percent and 43 to 52 percent, respectively.
• Strength of Evidence Moderate
• Evidence from cohort studies and meta-analyses
  suggested that achieving an SVR after antiviral
  therapy was associated with a lower risk of
  all-cause mortality, hepatocellular carcinoma,
  and cirrhosis when compared with not achieving an
  SVR.
• Strength of Evidence Moderate

For information on the effectiveness of
antiviral regimens in patients infected with HCV
of other genotypes, please refer to the
complementary review on treatment of HCV
infection referenced below.

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.
• Chou R, Hartung D, Rahman B, et al. AHRQ
  Comparative Effectiveness Review No. 76.
• Available at www.effectivehealthcare.ahrq.gov/hepc
  treatment.cfm.

18
Evidence for the Clinical Benefits and Adverse
Effects Associated With Treatment of HCV
Infection (2 of 2)

• Dual and triple antiviral therapy regimens for
  hepatitis C virus (HCV) infection have been shown
  to be associated with adverse effects such as
  fatigue, headache, flu-like symptoms, hematologic
  events, and rash.
• Strength of Evidence Moderate

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.
• Chou R, Hartung D, Rahman B, et al. AHRQ
  Comparative Effectiveness Review No. 76.
• Available at www.effectivehealthcare.ahrq.gov/hepc
  treatment.cfm.

19
Impact of Awareness of HCV Serostatus and
Counseling on Health Outcomes and Reduction in
the Spread of HCV Infection or High-Risk
Behaviors in HCV-Positive Patients

• Knowledge of hepatitis C virus (HCV) serostatus
  may reduce alcohol use in the short term, but the
  evidence indicates that any such behavior is not
  lasting.
• Strength of Evidence Low
• Evidence on the effects of counseling or
  immunizations for the hepatitis A and B viruses
  on health outcomes, reduction in the spread of
  HCV, or decrease in high-risk behaviors was
  limited.
• Strength of Evidence Insufficient

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

20
Risk of Vertical Transmission of Hepatitis C
Virus During Delivery or the Perinatal Period

• The risk of vertical transmission of hepatitis C
  virus (HCV) infection did not differ
  significantly between cesarean (elective or
  emergent) delivery and vaginal delivery.
• Strength of Evidence Moderate
• Prolonged labor (gt6 hours based on one study)
  after membrane rupture was associated with
  increased risk of vertical transmission of HCV
  infection.
• Strength of Evidence Low
• No significant association was found between
  breastfeeding and risk of transmitting HCV
  infection.
• Strength of Evidence Moderate

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

21
Additional Information

• New oral antiviral agents, some of which do not
  require interferon in the treatment regimen, are
  under development and have obtained fast-track
  status for review in the next few years by the
  U.S. Food and Drug Administration.
• Preliminary studies suggest that these agents may
  be more tolerable than currently available
  therapies.
• Clinical practice has evolved toward less routine
  use of biopsy. However, this comparative
  effectiveness review found no studies reporting
  the proportion of patients who undergo biopsy
  before treatment.
• Noninvasive diagnostic tests are being developed
  for the diagnosis of fibrosis and cirrhosis and
  for guiding treatment decisions in HCV-positive
  patients (see the full report).

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

22
U.S. Preventive Services Task Force 2013
Recommendations for HCV Infection Screening

• The USPSTF recommends screening for hepatitis C
  virus (HCV) infection in adults at high risk,
  including those with any history of intravenous
  drug use or blood transfusions before 1992.
• The USPSTF recommends that clinicians offer
  screening for HCV infection in adults born
  between 1945 and 1965.
• Grade B Recommendation

The USPSTF recommends this service. There is
moderate certainty that the net benefit is
moderate.

• U.S. Preventative Services Task Force. Available
  at www.uspreventiveservicestaskforce.org.
  Accessed June 26, 2013.

23
The Centers for Disease Control and Prevention
2012 Testing Recommendation for Chronic HCV
Infection

• In addition to the 1998 guidelines for testing
  for chronic HCV infection, the Centers for
  Disease Control and Prevention published the
  following recommendation in August 2012.
• People who should be tested once in their
  lifetime for hepatitis C virus (HCV) infection
  without ascertaining their risk factors include
• Adults born in the years 1945 through 1965

• The Centers for Disease Control and Prevention.
  Available at www.cdc.gov/hepatitis/hcv/guidelinesc
  .htm. Accessed August 9, 2013.

24
Conclusions (1 of 2)

• No direct evidence comparing clinical outcomes in
  patients screened with those not screened was
  available.
• However, several studies provided indirect
  evidence regarding the potential benefits of
  screening.
• Screening tests (hepatitis C virus HCV antibody
  testing with subsequent polymerase chain reaction
  testing) can accurately identify adults with
  chronic HCV infection.
• Targeted screening strategies resulted in numbers
  needed to screen to identify one case of HCV
  infection of less than 20 however, they missed a
  significant number of infected patients.
• In HCV-positive patients, treatment with
  antiviral regimens resulted in sustained
  virologic response rates of 4380 percent, which
  was associated with a reduction in hepatocellular
  carcinoma and mortality.

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.
• Chou R, Hartung D, Rahman B, et al. AHRQ
  Comparative Effectiveness Review No. 76.
• Available at www.effectivehealthcare.ahrq.gov/hepc
  treatment.cfm.
• U.S. Preventive Services Task Force. Ann Intern
  Med. 2004140(6)462-4. PMID 15023712.

25
Conclusions (2 of 2)

• The evidence was insufficient to determine the
  effectiveness of counseling in patients who were
  positive for hepatitis C virus or the
  effectiveness of immunizations for the hepatitis
  A and B viruses on clinical outcomes.
• Limited evidence suggests that for some patients,
  knowledge of hepatitis C status may be associated
  with reduction in high-risk behaviors such as
  alcohol use in the short term.
• Additional research is needed to understand
  effective interventions for preventing vertical
  transmission.

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

26
What To Discuss With Your Patients andTheir
Caregivers (1 of 2)

• The patients risk status for hepatitis C virus
  (HCV) infection
• That HCV infection is potentially curable
• ??The U.S. Preventive Services Task Force
  recommendations about screening for HCV infection
  
• The available diagnostic tests for HCV infection
  and their accuracy
• The potential emotional and social impact of
  being screened for HCV infection

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.

27
What To Discuss With Your Patients andTheir
Caregivers (2 of 2)

• The potential benefits and harms of diagnostic
  tests for hepatitis C virus (HCV) infection
• If the patient tests positive for HCV infection,
  the possibility that he/she might be referred to
  a liver specialist
• For HCV-positive patients
• The available tests and workup strategies to
  guide treatment decisions and the accuracy of the
  various tests
• The importance of monitoring for fibrosis,
  cirrhosis, and hepatocellular carcinoma
• The impact of various interventions in preventing
  vertical transmission of HCV during delivery or
  in the perinatal period

• Chou R, Barth Cottrell EB, Wasson N, et al. AHRQ
  Comparative Effectiveness Review No. 69.
• Available at www.effectivehealthcare.ahrq.gov/hepa
  titis-c-screening.cfm.