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USPSTF issues draft recommendation
statement for HCV screening in adults
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Download the PDF here
Publish date: August 27, 2019 USPSTF Press Announcement
comment: https://www.uspreventiveservicestaskforce.org/Page/Name/us-preventive-services-task-force-opportunities-for-public-comment
HCV is the most common chronic bloodborne pathogen in the United States and a leading cause of complications from chronic liver disease.1 HCV infection is associated with more deaths than the top 60 other reportable infectious diseases combined, including HIV.2 The most important risk factor for HCV infection is past or current injection drug use.1 In the United States, an estimated 4.1 million persons have past or current HCV infection (i.e., tests positive for the anti-HCV antibody). Of these persons with antibodies, approximately 2.4 million have current infections based on testing with molecular assays for HCV RNA.1, 3-5 The estimated prevalence of chronic HCV infection is approximately 1.0% (2013 to 2016).6 An estimated 41,200 new HCV infections occurred in the United States in 2016.7 Cases of acute HCV infection have increased approximately 3.5-fold (2010 to 2016) over the last decade.7 The increase in acute HCV incidence has mostly affected young, white persons who inject drugs (PWID), especially those living in rural areas.8-10 There has also been an increase in the number of women ages 15 to 44 years with HCV infection.11, 12
Persons born between 1945 and 1965 are more likely to be diagnosed with HCV infection, possibly because they received blood transfusions before the introduction of screening in 1992 or have a history of other risk factors for exposure decades earlier2. Many persons with chronic HCV infection are unaware of their condition. A risk-based approach may miss detection of a substantial proportion of HCV-infected persons in the birth cohort because of a lack of patient disclosure or knowledge about prior risk status. As a result, 1-time screening for HCV infection in the birth cohort may identify infected patients at earlier stages of disease who could benefit from treatment before developing complications from liver damage.
The trials evaluated a variety of DAA regimens recommended in current guidelines. Treatment duration was 12 weeks in all but two trials, which allocated patients to either 8 or 12 weeks of treament. Eleven trials were of good quality and 22 were of fair quality. Forty-nine trials found DAA regimens associated with pooled SVR rates that ranged from 95.5% to 98.9% across genotypes. Evidence was greatest for genotype 1 infection (32 trials), the most frequent genotype in the United States.1 SVR rates were similar in trials that stratified patients according to age, sex, race/ethnicity, or treatment experience with non-DAA regimens.1
Although all adults ages 18 to 79 years should be screened, a number of risk factors increase risk. The most important risk factor for HCV infection is past or current injection drug use. In the United States, recent increases in HCV incidence have predominantly been among young persons who inject drugs (PWID).1, 14 Approximately one-third of PWID ages 18 to 30 years are infected with HCV, and 70% to 90% of older PWID are infected.14 Clinicians may want to consider screening in adolescents younger than age 18 years and in adults older than age 79 years who are at high risk.
Pregnant adults should be screened. HCV prevalence has doubled in women ages 15 to 44 years from 2006 to 2014.1, 11, 12 From 2011 to 2014, 0.73% of pregnant women tested had an HCV infection, with a 68% increase in the proportion of infants born to HCV-infected mothers.1, 11 Approximately 1,700 infected infants are born annually to 29,000 HCV-infected mothers.1, 12 Due to the increasing prevalence of HCV in women ages 15 to 44 years and in infants born to HCV-infected mothers, clinicians may want to consider screening pregnant persons younger than age 18 years.
An estimated 78% of persons who test positive for the anti-HCV antibody have detectable levels of HCV in the blood (viremia), reflecting chronic infection. Persons who have HCV and undetectable viremia are considered "cured," as demonstrated by the absence of serum HCV RNA1.
The USPSTF also considered that risk-based screening does not work well in identifying persons who are at increased risk for HCV infection.
The new studies provided evidence that the magnitude of the net benefit in the birth cohort is moderate, not small.
The USPSTF concludes with moderate certainty that there is a linkage between SVR and clinical outcomes (hepatocellular carcinoma and mortality) and that the overall net benefit of screening is moderate. The evidence supporting this linkage includes consistent associations between achieving SVR and improved clinical outcomes, with most studies reporting large effect sizes, as well as evidence from studies that controlled for several confounders and found an early mortality reduction among patients with all viral genotypes who achieved SVR and are probably similar to patients detected and eligible for treatment hrough U.S. screening programs. In addition, evidence showed that antiviral treatment results in improved clinical outcomes. A new modeling study showed that birth-cohort screening provided nearly twice the benefit of risk-based screening.
The USPSTF also reviewed a modeling study that informed the CDC's 2012 recommendation on screening for HCV and reported large estimated reductions in HCV-related mortality with a birth-cohort approach versus risk-based screening15. These estimates assumed a lifetime rate of progression to cirrhosis in untreated patients with HCV infection of 54% and a mortality rate from HCV infection of 22%. However, longitudinal studies with up to 20 years of follow-up report cirrhosis in 10% to 20% of HCV-infected patients, and the longest study reported HCV-related mortality in 5.9% of patients after 45 years. In addition, estimates of clinical benefit in the modeling study assumed that risk for cirrhosis and other complications of HCV infection in patients achieving SVR after antiviral therapy reverted to that of uninfected persons5. These assumptions relate to important uncertainties about the natural history of HCV infection. If progression to cirrhosis or mortality was lower than assumed, the benefit from screening and treatment would also be lower. A recent modeling study by Liu and colleagues16 evaluated risk factor–guided and birth-cohort screening strategies. Model assumptions seemed conservative and consistent with available data on the natural history of HCV and effectiveness of antiviral treatment. The study concluded that birth-cohort screening provides nearly twice the benefit of risk-based screening.
Overall, the review's conclusions on the association between SVR and decreased risk for hepatocellular carcinoma were consistent with the USPSTF review. The pooled adjusted HR estimates for hepatocellular carcinoma were 0.24 (95% CI, 0.18 to 0.31) in the general HCV population and 0.23 (95% CI, 0.16 to 0.35) in patients with advanced fibrosis or cirrhosis.
Benefits of Early Detection or Treatment
The USPSTF found no direct evidence on the benefits of HCV screening versus no screening on health outcomes or the effects of prenatal HCV screening on the risk of vertical transmission.1 Treatment studies focused on populations without cirrhosis who are more likely to be asymptomatic and identified by screening. Of the trials of DAA regimens (n=7,167; 26%-69% female; mean age, 45 to 62 years), 14 were multinational; 11 were conducted in the United States or Canada; and the remainder were conducted in New Zealand, Egypt, France, or Asia. In 29 trials, 60% to 100% of patients were white.1 The trials evaluated a variety of DAA regimens recommended in current guidelines. Treatment duration was 12 weeks in all but two trials, which allocated patients to either 8 or 12 weeks of treament. Eleven trials were of good quality and 22 were of fair quality. Forty-nine trials found DAA regimens associated with pooled SVR rates that ranged from 95.5% to 98.9% across genotypes. Evidence was greatest for genotype 1 infection (32 trials), the most frequent genotype in the United States.1 SVR rates were similar in trials that stratified patients according to age, sex, race/ethnicity, or treatment experience with non-DAA regimens.1
Direct evidence on the effects of current DAA regimens on health outcomes is limited.1 Pooled analysis from 10 trials found small, short-term improvements in quality of life scale scores after treatment with a DAA regimen compared with baseline scores.1 Trials reporting short-term mortality (<1 year) found few events and were not designed to detect differences in mortality rates. Twenty-one trials reported no deaths; in the other 10 trials, there were 17 deaths (0.4% [17/3,848] overall).1
The USPSTF review evaluated the linkage between achieving an SVR after antiviral therapy versus no SVR and health outcomes. SVR after antiviral therapy was consistently associated with decreased risk of all-cause mortality (13 studies; pooled hazard ratio [HR], 0.40 [95% confidence interval {CI}, 0.28 to 0.56]), liver mortality (4 studies; pooled HR, 0.11 [95% CI, 0.04 to 0.27]), cirrhosis (4 cohorts in 3 studies; pooled HR, 0.36 [95% CI, 0.33 to 0.40]), and hepatocellular carcinoma (20 studies; pooled HR, 0.29 [95% CI, 0.23 to 0.38]) versus no SVR, after adjustment for potential confounders.1
The USPSTF found that new evidence on the risk of vertical transmission is limited. Five observational studies found no clear association between risk of vertical transmission of HCV infection and the mode of delivery.1 One good-quality U.S. study showed that prolonged rupture of membranes (more than 6 hours) was associated with increased risk of HCV transmission in 189 mother-infant pairs compared with membrane rupture lasting less than 6 hours (adjusted odds ratio, 9.3 [95% CI, 1.5 to 180]).1, 22 One observational study in 188 mother-infant pairs found that internal fetal monitoring was associated with an increased risk of vertical transmission of HCV infection compared with external monitoring (adjusted odds ratio, 6.7 [95% CI, 1.1 to 35.9]).1, 22 Three observational studies did not find a clear association between breastfeeding and an increased risk of vertical transmission of HCV infection.1
In adolescents, the evidence is also limited. Seven trials (n=300) reported SVR rates in adolescents taking DAA regimens similar to those used in adults (97% to 100%).1 However, some of the trials evaluated regimens that are not approved by the U.S. Food and Drug Administration for use in adolescents.1 DAA regimens recommended and approved by the U.S. Food and Drug Administration for use in adolescents are ledipasvir/sofosbuvir, sofosbuvir/ribavirin, and glecaprevir/pibrentasvir.1 The evidence on antiviral treatment and health outcomes in adolescents is very limited. One post-hoc before-and-after analysis found that scores based on the Pediatric Quality of Life Inventory (i.e., school and social functioning) improved from baseline to 24 weeks after treatment with a DAA regimen.1
Modeling studies that compared screening of all persons age 18 years and older with birth cohort screening suggested that expanded screening strategies would be beneficial despite different assumptions regarding chronic HCV infection progression, costs of DAA therapy, and rates of linkage to care.1 One analysis of a hypothetical cohort of the U.S. population used more conservative assumptions and found that screening everyone age 18 years and older would identify 256,000 additional HCV cases and lead to 280,000 additional cures and 4,400 fewer cases of hepatocellular carcinoma over a lifetime.1, 23
U.S. Preventive Services Task Force Issues Draft Recommendation Statement on Screening for Hepatitis C Virus Infection in Adolescents and Adults
Clinicians should screen all adults for hepatitis C infection
"Today, more people are infected with hepatitis C than there were a decade ago, but there are now better treatments available," says Task Force chair Douglas K. Owens, M.D., M.S. "The evidence now shows more people can benefit from screening; therefore, we are recommending to screen all adults ages 18 to 79 for hepatitis C."
The Task Force also suggests that clinicians consider screening patients who are younger than age 18 and older than age 79 if they are at high risk for infection.
The Task Force's new recommendation expands the ages for screening to all adults. This change is based on new evidence that shows hepatitis C is affecting more people than it did previously—many of whom are younger. And, there are now newer antiviral medications that are more effective and safer in treating people with hepatitis C.
"It is concerning that we are seeing a significant increase in hepatitis C, and many people don't know they have it," says Task Force vice chair Alex H. Krist, M.D., M.P.H. "The good news is that we have newer treatments that are more effective and safer, and screening adults for hepatitis C can detect the infection earlier, before they have complications from the virus."
Draft Recommendation & Statement - The USPSTF recommends screening for hepatitis C virus (HCV) infection in adults ages 18 to 79 years.....open for public
comment: https://www.uspreventiveservicestaskforce.org/Page/Name/us-preventive-services-task-force-opportunities-for-public-comment
https://www.uspreventiveservicestaskforce.org/Page/Document/draft-recommendation-statement/hepatitis-c-screening1
Screening Intervals
Most adults need only be screened once. Persons with continued risk for HCV infection (e.g., PWID) should be screened periodically. There is limited information about the specific screening interval that should occur in persons who continue to be at risk for new HCV infection.
Screening Implementation
The USPSTF believes that screening should be voluntary and undertaken only with the patient's knowledge and understanding that HCV screening is planned.
Treatment
The purpose of antiviral treatment regimens for HCV infection is to prevent long-term health complications of chronic HCV infection (such as cirrhosis, liver failure, and hepatocellular carcinoma).
Currently, all oral direct-acting antiviral (DAA) regimens without interferon have been accepted as the standard treatment of chronic HCV infection. Antiviral therapy is not generally considered during pregnancy because of the lack of data on the safety of newer DAA regimens during pregnancy and breastfeeding.16, 17
Other Related USPSTF Recommendations
The USPSTF has made recommendations on screening for hepatitis B virus infection in pregnant persons, screening for hepatitis B virus infection in adults, and screening for HIV infection.18-20
Draft: Importance
HCV is the most common chronic bloodborne pathogen in the United States and a leading cause of complications from chronic liver disease.1 HCV infection is associated with more deaths than the top 60 other reportable infectious diseases combined, including HIV.2 The most important risk factor for HCV infection is past or current injection drug use.1 In the United States, an estimated 4.1 million persons have past or current HCV infection (i.e., tests positive for the anti-HCV antibody). Of these persons with antibodies, approximately 2.4 million have current infections based on testing with molecular assays for HCV RNA.1, 3-5 The estimated prevalence of chronic HCV infection is approximately 1.0% (2013 to 2016).6 An estimated 41,200 new HCV infections occurred in the United States in 2016.7 Cases of acute HCV infection have increased approximately 3.5-fold (2010 to 2016) over the last decade.7 The increase in acute HCV incidence has mostly affected young, white persons who inject drugs (PWID), especially those living in rural areas.8-10 There has also been an increase in the number of women ages 15 to 44 years with HCV infection.11, 12
Opportunity for Public Comment.....https://www.uspreventiveservicestaskforce.org/Page/Name/us-preventive-services-task-force-opportunities-for-public-comment
In an effort to make the U.S. Preventive Services Task Force (USPSTF) recommendations clearer and its processes more transparent, the Task Force started posting draft Recommendation Statements online for public comment in 2009. To further enhance its work, the Task Force began inviting public comment on all its draft Research Plans in December 2011 and its draft Evidence Reviews in March 2013.
To learn more about and comment on USPSTF draft Research Plans, Evidence Reviews, or Recommendation Statements, continue reading below.
•There is no direct evidence on the benefit of screening for HCV infection in asymptomatic adults on health outcomes. There is inadequate direct evidence on the effect of treatment on health outcomes in adults and adolescents. However, there is convincing evidence that the newer DAA regimens result in SVR in a very high proportion (>95%) of adults ages 18 to 79 years and adequate evidence of SVR in adolescents.
•There is adequate evidence of a consistent association between SVR after antiviral therapy and improved health outcomes (decreased risk of all-cause mortality, mortality due to liver disease, cirrhosis, and hepatocellular carcinoma).
•Given the accuracy of the screening test and the availability of effective interventions for HCV infection, the USPSTF determined that the indirect evidence is adequate that the magnitude of the benefit of screening and treatment is substantial for adults ages 18 to 79 years.
•Potential harms of screening include anxiety, patient labeling, and feelings of stigmatization. There is inadequate direct evidence on the harms of screening for HCV infection.
•Currently recommended DAA regimens are associated with fewer harms than older interferon-containing therapies, and treatment duration is shorter at 8 to 12 weeks. There is adequate evidence that DAA regimens are associated with low rates of serious adverse effects and withdrawal due to adverse effects.
•There is adequate evidence to bound the overall harms of screening and treatment as small based on the known harms of treatment, the high accuracy of screening, and the low likelihood of harms from a blood draw.
The USPSTF concludes with moderate certainty that screening for HCV infection in adults ages 18 to 79 years has substantial net benefit.
Draft: Research Needs and Gaps
There are several key research gaps that could help inform the benefit of screening for HCV infection in U.S.-based populations:
•Research is needed on the yield of repeat versus one-time screening for HCV and different repeat screening intervals to inform recommendations on optimal screening intervals.
•Research is needed to identify labor management practices (e.g., prolonged rupture of membranes or use of internal fetal monitoring) and treatment of HCV infection prior to pregnancy to reduce the risk of mother-to-child transmission.
•Trials and cohort studies that measure effects on quality of life, function, and extrahepatic effects of HCV infection (e.g., renal function, cardiovascular effects, or diabetes) would be helpful for evaluating the impact of DAA regimens on short-term health outcomes.
•Additional studies are needed to examine the epidemiology of HCV infection and the effectiveness of DAA regimens in adolescents.
Draft: Recommendations of Others
The Centers for Disease Control and Prevention recommends screening in high-risk patients and age cohort–based screening for HCV in all persons born between 1945 and 1965.25 The CDC and the American College of Obstetricians and Gynecologists recommend offering HCV screening to pregnant persons with risk factors.26, 27 The American Association for the Study of Liver Diseases, the Infectious Diseases Society of America, and the American College of Gastroenterology recommend screening for HCV infection in higher-risk patients.28, 29
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