Screening for Hepatitis C Virus Infection in Adolescents and Adults: A Systematic Review Update for the U.S. Preventive Services Task Force [Entered Retrospectively]

Project Summary Title and Description

Title
Screening for Hepatitis C Virus Infection in Adolescents and Adults: A Systematic Review Update for the U.S. Preventive Services Task Force [Entered Retrospectively]
Description
Background: Prior reviews on hepatitis C (HCV) infection screening and treatment used by the U.S. Preventive Services Task Force (USPSTF) to inform its 2013 recommendation found interferon-containing antiviral therapies associated with sustained virologic response (SVR) rates of 68 percent to 78 percent and an association between SVR after antiviral therapy and improved clinical outcomes. Interferon-containing regimens were associated with a high rate of harms. Since the prior reviews, interferon-containing antiviral therapies have been replaced by all-oral direct acting antiviral (DAA) regimens. Purpose: To systematically review the evidence on screening for HCV infection in asymptomatic adults and adolescents, including effects of DAA regimens and interventions to prevent mother-to-child transmission. Data Sources: We searched the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Ovid MEDLINE and ClinicalTrials.gov through February 2019, manually reviewed reference lists, and conducted literature surveillance through November 22, 2019. Study Selection: Randomized controlled trials (RCTs), non-randomized trials, and cohort studies of HCV screening, antiviral therapy, and interventions to prevent mother-to-child transmission of HCV infection on SVR and clinical outcomes; and cohort studies on the association between an SVR after antiviral therapy versus no SVR and clinical outcomes. Treatment studies focused on populations without cirrhosis who are more likely to be asymptomatic and identified by screening. Data Extraction: One investigator abstracted data, and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): No study evaluated the benefits of HCV screening versus no screening, or the yield of repeat versus one-time screening. Previously reviewed studies found that HCV screening might be associated with negative psychological and social consequences, but had important methodological limitations; no new studies were identified. One new study found similar diagnostic yield of risk-based and birth cohort screening, but it was retrospective and assumed perfect implementation of risk-based screening. Ten trials reported improvements in some quality of life and functional outcomes following DAA treatment compared with prior to treatment, but differences were small, studies were open-label, and there was no non-DAA comparison group. Forty-nine trials found DAA regimens associated with pooled SVR rates that ranged from 95.5 percent to 98.9 percent across genotypes; rates of serious adverse events (1.9%) and withdrawal due to adverse events (0.4%) were low. Seven trials reported SVR rates in adolescents with DAA therapy similar to those observed in adults. An SVR after antiviral therapy was 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. New evidence on interventions to reduce the risk of mother-to-infant transmission was limited and did not change the conclusion from the prior review that no intervention has been clearly demonstrated to reduce risk. Limitations: Most DAA trials were not randomized and did not have a non-DAA comparison group, almost all DAA trials relied on SVR as the main efficacy outcome, observational studies varied in how well they adjusted for confounders, and few studies evaluated the effectiveness of DAA regimens in adolescents. Conclusions: The USPSTF previously determined that HCV screening is highly accurate. Currently recommended all-oral DAA regimens are associated with very high SVR rates (95.5% to 98.9% across genotypes) and few harms relative to older antiviral therapies. An SVR after antiviral therapy is associated with improved clinical outcomes compared with no SVR, after adjusting for potential confounders. Direct evidence on the benefits of HCV screening remains unavailable, and direct evidence on the effects of antiviral therapy on clinical outcomes remains limited but indicates improved long-term outcomes.
Attribution
N/A
Authors of Report
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Methodology description
Study Selection: Randomized controlled trials (RCTs), non-randomized trials, and cohort studies of HCV screening, antiviral therapy, and interventions to prevent mother-to-child transmission of HCV infection on SVR and clinical outcomes; and cohort studies on the association between an SVR after antiviral therapy versus no SVR and clinical outcomes. Treatment studies focused on populations without cirrhosis who are more likely to be asymptomatic and identified by screening. Data Extraction: One investigator abstracted data, and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.
PROSPERO
N/A
DOI
N/A
Notes
Data was entered retrospectively via the upload of the evidence and quality tables in Word. The files uploaded for this project include: Appendix Table 1. Study Characteristics of Interventions to Prevent Mother-to-Infant Transmission of HCV Infection Appendix Table 2. Transmission Outcomes of Interventions to Prevent Mother-to-Infant Transmission of HCV Infection Appendix Table 3. Additional Outcomes of Interventions to Prevent Mother-to-Infant Transmission of HCV Infection Appendix Table 4. Quality Assessment of Studies of Interventions to Prevent Mother-to-Infant Transmission of HCV Infection Appendix Table 5. Evidence Table of Observational Studies of Direct Acting Antiviral Therapy on Health Outcomes in Adults Appendix Table 6. Quality Assessment of Observational Studies of Direct Acting Antiviral Therapy on Health Outcomes in Adults Appendix Table 7. Study Characteristics of Direct Acting Antiviral Therapy in Adolescents Appendix Table 8. Studies of Direct Acting Antiviral Therapy in Adolescents – Effectiveness and Harms Appendix Table 9. Quality Assessment of Studies of Direct Acting Antiviral Therapy in Adolescents Appendix Table 10. Study Characteristics of Direct Acting Antiviral Therapy in Adults Appendix Table 11. Studies of Direct Acting Antiviral Therapy in Adults – Sustained Virologic Response Outcomes Appendix Table 12. Studies of Direct Acting Antiviral Therapy in Adults – Clinical Outcomes and Adverse Events Appendix Table 13. Quality Assessment of Studies of Direct Acting Antiviral Therapy in Adults Appendix Table 14. Studies of the Association Between Sustained Virologic Response and Clinical Outcomes – Study Characteristics Appendix Table 15. Studies of the Association Between Sustained Virologic Response and Clinical Outcomes – Intervention Characteristics and Results Appendix Table 16. Quality Assessment of Studies of the Association Between Sustained Virologic Response After Antiviral Therapy and Clinical Outcomes
Funding Source
This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA 290201500009I, Task Order No. 7)

Key Questions

1. Key Question 1a. Does screening for HCV infection in pregnant and nonpregnant adolescents and adults without known abnormal liver enzyme levels reduce HCV-related mortality and morbidity or affect quality of life? Key Question 1b. Does prenatal screening for HCV infection reduce risk of vertical transmission of HCV infection?
2. Key Question 2. What is the effectiveness of different risk- or prevalence-based methods for screening for HCV infection on clinical outcomes?
3. Key Question 3. What is the yield (number of new diagnoses per tests performed) of one-time versus repeat screening or alternative screening strategies for HCV infection, and how does the screening yield vary in different risk groups?
4. Key Question 4. What are the harms of screening for HCV infection (e.g., anxiety and labeling)?
5. Key Question 5. What are the effects of interventions during labor and delivery or the perinatal period on risk of vertical transmission of HCV infection?
6. Key Question 6. What is the effectiveness of currently recommended antiviral treatments in improving health outcomes in patients with HCV infection?
7. Key Question 7. What is the effectiveness of currently recommended antiviral treatments in achieving a SVR in patients with HCV infection?
8. Key Question 8. What are the harms of currently recommended antiviral treatments?
9. Key Question 9. What is the association between experiencing SVR following antiviral treatment and reduction in risk of HCV-related adverse health outcomes?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Comparison of current US risk strategy to screen for hepatitis C virus with a hypothetical targeted birth cohort strategy.2012
Vertical transmission of hepatitis C virus in a cohort of 2,447 HIV-seronegative pregnant women: a 24-month prospective study.2001
Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission.2000
Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy.
Maternal drug use is a preeminent risk factor for mother-to-child hepatitis C virus transmission: results from a multicenter study of 1372 mother-infant pairs.2002
A significant sex--but not elective cesarean section--effect on mother-to-child transmission of hepatitis C virus infection.2005
Efficacy and safety of glecaprevir/pibrentasvir in patients with chronic hepatitis C virus genotype 5 or 6 infection (ENDURANCE-5,6): an open-label, multicentre, phase 3b trial.2019
Efficacy and safety of 12 weeks of elbasvir ± grazoprevir ± ribavirin in participants with hepatitis C virus genotype 2, 4, 5 or 6 infection: The C-SCAPE study.2018
Direct-Acting Antiviral Therapy for HCV Infection Is Associated With a Reduced Risk of Cardiovascular Disease Events.2019
Paritaprevir, ritonavir, ombitasvir, and dasabuvir with and without ribavirin in people with HCV genotype 1 and recent injecting drug use or receiving opioid substitution therapy.2018
Sofosbuvir and velpatasvir for hepatitis C virus infection in people with recent injection drug use (SIMPLIFY): an open-label, single-arm, phase 4, multicentre trial.2018
The short-term incidence of hepatocellular carcinoma is not increased after hepatitis C treatment with direct-acting antivirals: An ERCHIVES study.2018
Sofosbuvir in combination with daclatasvir or simeprevir for 12 weeks in noncirrhotic subjects chronically infected with hepatitis C virus genotype 1: a randomized clinical trial.2019
Efficacy and safety of elbasvir/grazoprevir in participants with hepatitis C virus genotype 1, 4, or 6 infection from the Asia-Pacific region and Russia: Final results from the randomized C-CORAL study.2019
Sofosbuvir-velpatasvir for treatment of chronic hepatitis C virus infection in Asia: a single-arm, open-label, phase 3 trial.2019
Ledipasvir/sofosbuvir for treatment-naive and treatment-experienced Chinese patients with genotype 1 HCV: an open-label, phase 3b study.2018
Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection.2018
Sofosbuvir and Velpatasvir Combination Improves Patient-reported Outcomes for Patients With HCV Infection, Without or With Compensated or Decompensated Cirrhosis.2017
Improvement of health-related quality of life and work productivity in chronic hepatitis C patients with early and advanced fibrosis treated with ledipasvir and sofosbuvir.
A phase IIIb study of ledipasvir/sofosbuvir fixed-dose combination tablet in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 hepatitis C virus.2016
Sofosbuvir Plus Velpatasvir Combination Therapy for Treatment-Experienced Patients With Genotype 1 or 3 Hepatitis C Virus Infection: A Randomized Trial.
Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection.
Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection.2015
Randomized phase 3 trial of ombitasvir/paritaprevir/ritonavir for hepatitis C virus genotype 1b-infected Japanese patients with or without cirrhosis.2015
Sofosbuvir With Velpatasvir in Treatment-Naive Noncirrhotic Patients With Genotype 1 to 6 Hepatitis C Virus Infection: A Randomized Trial.2015
Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials.2016
Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection.2015
Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection.
Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial.2016
All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study.2015
Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial.2015
Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial.2015
Simeprevir plus sofosbuvir (12 and 8 weeks) in hepatitis C virus genotype 1-infected patients without cirrhosis: OPTIMIST-1, a phase 3, randomized study.2016
Efficacy and Safety of Ombitasvir, Paritaprevir, and Ritonavir in an Open-Label Study of Patients With Genotype 1b Chronic Hepatitis C Virus Infection With and Without Cirrhosis.2015
Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study.2016
Ledipasvir plus sofosbuvir for 12 weeks in patients with hepatitis C genotype 4 infection.2016
Ledipasvir/sofosbuvir fixed-dose combination tablet in Taiwanese patients with chronic genotype 1 hepatitis C virus.2016
The combination of elbasvir and grazoprevir for the treatment of chronic HCV infection in Japanese patients: a randomized phase II/III study.2017
Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study.
Patient-reported outcomes in individuals with hepatitis C virus infection treated with elbasvir/grazoprevir.2018
Clinical outcomes in patients with chronic hepatitis C after direct-acting antiviral treatment: a prospective cohort study.2019
Safety and efficacy of combined sofosbuvir/daclatasvir treatment of children and adolescents with chronic hepatitis C Genotype 4.2019
Efficacy and safety of sofosbuvir-ledipasvir for treatment of a cohort of Egyptian patients with chronic hepatitis C genotype 4 infection.2018
Sustained Viral Response in Genotype 4 Chronic Hepatitis C Virus-infected Children and Adolescents Treated With Sofosbuvir/Ledipasvir.2018
Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1.2014
Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine.2015
Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study.2014
Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.
Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis.2014
Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial.2014
Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment.
Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial.2015
ABT-450, ritonavir, ombitasvir, and dasabuvir achieves 97% and 100% sustained virologic response with or without ribavirin in treatment-experienced patients with HCV genotype 1b infection.2014
ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV.2014
Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.2014
Health-related Quality of Life in Adolescent Patients With Hepatitis C Genotype 1 Treated With Sofosbuvir and Ledipasvir.2018
Long-term outcome after interferon therapy in elderly patients with chronic hepatitis C.2007
Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection.2010
A sustained virologic response reduces risk of all-cause mortality in patients with hepatitis C.2011
Effect of Paritaprevir/Ritonavir/Ombitasvir/Dasabuvir and Ledipasvir/Sofosbuvir Regimens on Survival Compared With Untreated Hepatitis C Virus-Infected Persons: Results From ERCHIVES.2017
Nonresponse to interferon-α based treatment for chronic hepatitis C infection is associated with increased hazard of cirrhosis.
All-cause mortality and liver-related outcomes following successful antiviral treatment for chronic hepatitis C.2014
The incidence and risk factors for the development of hepatocellular carcinoma after peginterferon plus ribavirin therapy for chronic hepatitis C.-- Not Found --
Racial differences in the progression to cirrhosis and hepatocellular carcinoma in HCV-infected veterans.2014
Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: A long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis.1999
Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Osaka Hepatocellular Carcinoma Prevention Study Group.1998
Favorable prognosis of chronic hepatitis C after interferon therapy by long-term cohort study.2003
Excess liver-related morbidity of chronic hepatitis C patients, who achieve a sustained viral response, and are discharged from care.2011
HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma.2017
Development of hepatocellular carcinoma after interferon therapy in chronic hepatitis C. Is it possible to reduce the incidence by ribanirin and IFN combination therapy?2005
Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group.1998
Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death.2004
Effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with chronic hepatitis.2009
Assessment of hepatocellular carcinoma risk based on peg-interferon plus ribavirin treatment experience in this new era of highly effective oral antiviral drugs.2017
Long-term cohort study of chronic hepatitis C according to interferon efficacy.2012
Transient biochemical response in interferon therapy decreases the development of hepatocellular carcinoma for five years and improves the long-term survival of chronic hepatitis C patients.2002
Decrease in alpha-fetoprotein levels predicts reduced incidence of hepatocellular carcinoma in patients with hepatitis C virus infection receiving interferon therapy: a single center study.2012
Long-term benefit of hepatitis C therapy in a safety net hospital system: a cross-sectional study with median 5-year follow-up.2013
Disease progression and the risk factor analysis for chronic hepatitis C.2008
Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: a retrospective cohort study of 738 patients.2000
Alpha-fetoprotein above normal levels as a risk factor for the development of hepatocellular carcinoma in patients infected with hepatitis C virus.2011
Association of sustained virologic response with reduced progression to liver cirrhosis in elderly patients with chronic hepatitis C.
Interferon therapy prolonged life expectancy among chronic hepatitis C patients.2002
Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy.1999
A sustained virological response to interferon or interferon/ribavirin reduces hepatocellular carcinoma and improves survival in chronic hepatitis C: a nationwide, multicentre study in Taiwan.2006
Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Adolescents With Chronic Hepatitis C Virus: Part 1 of the DORA Study.2020
Efficacy of Glecaprevir/Pibrentasvir for 8 or 12 Weeks in Patients With Hepatitis C Virus Genotype 2, 4, 5, or 6 Infection Without Cirrhosis.2018
Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis.2018
Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial.2016
Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection.2018
The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12-17 years old with hepatitis C virus genotype 1 infection.2017
Sofosbuvir and ribavirin in adolescents 12-17 years old with hepatitis C virus genotype 2 or 3 infection.2017
Dual Sofosbuvir/Daclatasvir Therapy in Adolescent Patients With Chronic Hepatitis C Infection.2018
Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir and With or Without Ribavirin for Adolescents With HCV Genotype 1 or 4.2018

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