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

Project Summary Title and Description

Title
Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults: A Systematic Review for the U.S. Preventive Services Task Force [Entered Retrospectively]
Description
Background: A 2014 review for the US Preventive Services Task Force (USPSTF) found antiviral therapy for hepatitis B virus (HBV) infection associated with improved intermediate outcomes, although evidence on clinical outcomes was limited. Purpose: To update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF. Data Sources: We utilized the 2014 review, searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020. Study Selection: Eligible studies included randomized controlled trials (RCTs) and cohort studies on the benefits and harms of screening versus no screening, and the yield of alternative screening strategies; RCTs on the effects of antiviral therapy versus placebo or no therapy and preferred versus nonpreferred therapies on intermediate outcomes, clinical outcomes, and harms; and cohort studies on clinical outcomes and on the association between intermediate outcomes following antiviral therapy and clinical outcomes. 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): Fifty total studies (30 trials and 20 cohort studies) with a total of 94,168 participants were included; of these, 22 were added for this update. No study directly evaluated the effects of screening for HBV infection versus no screening on clinical outcomes, such as mortality, hepatocellular carcinoma, or cirrhosis. Screening strategies that focused on risk factors such as ever having immigrated from high prevalence countries plus demographic and behavioral risk factors would identify nearly all HBV infection cases. In one study (N=21,008), only screening immigrants from high HBV prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (N=2,972), antiviral therapy was associated with greater likelihood than placebo or no treatment for achieving intermediate outcomes, such as virologic suppression and hepatitis B e antigen or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virological suppression to 17 for hepatitis B e antigen seroconversion. Based on 12 trials (N=4,127), preferred (first-line) antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (N=4,809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (N=3,893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes, but were heterogeneous (hazards ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events versus placebo or no antiviral therapy. Limitations: Only English-language articles were included, clinical outcome data for antiviral therapies were limited, observational studies were included on effects of antiviral therapy on long-term clinical outcomes and the association between intermediate and clinical outcomes, and some studies were conducted in countries where the prevalence and natural history of HBV infection are different from the United States. Conclusions: There was no direct evidence for the clinical benefits and harms of HBV screening versus no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes. Research is needed to clarify effects of screening and subsequent interventions on clinical outcomes and to identify optimal screening strategies.
Attribution
N/A
Authors of Report
N/A
Methodology description
Data Sources: We utilized the 2014 review, searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020. Study Selection: Eligible studies included randomized controlled trials (RCTs) and cohort studies on the benefits and harms of screening versus no screening, and the yield of alternative screening strategies; RCTs on the effects of antiviral therapy versus placebo or no therapy and preferred versus nonpreferred therapies on intermediate outcomes, clinical outcomes, and harms; and cohort studies on clinical outcomes and on the association between intermediate outcomes following antiviral therapy and clinical outcomes. 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
Latest version of Appendix B can be downloaded at: https://srdr.s3.amazonaws.com/uploads/12-04-2020/Appendix+B.docx The following tables have been uploaded: Appendix B. Data Abstraction and Quality Assessment Tables Appendix B Table 1. HBV Screening Strategies - Study Characteristics Appendix B Table 2. HBV Screening Strategies - Results Appendix B Table 3. HBV Screening Strategies - Quality Assessment Appendix B Table 4. Trials of HBV Antiviral Treatment Versus Placebo or No Treatment – Study Characteristics Appendix B Table 5. Trials of HBV Antiviral Treatment Versus Placebo or No Treatment - Results Appendix B Table 6. Trials of HBV Antiviral Treatment – Quality Assessment Appendix B Table 7. Trials of HBV Preferred Versus Non-preferred Treatments – Study Characteristics Appendix B Table 8. Trials of HBV Preferred Versus Non-preferred Treatments - Results Appendix B Table 9. Cohort Studies of HBV Treatment – Study Characteristics Appendix B Table 10. Cohort Studies of HBV Treatment - Results Appendix B Table 11. Cohort Studies of HBV Treatment – Quality Assessment Appendix B Table 12. Association Studies of HBV Intermediate and Health Outcomes - Study Characteristics Appendix B Table 13. Association Studies of HBV Intermediate and Health Outcomes - Results Appendix B Table 14. Association Studies of HBV Intermediate and Health Outcomes - Quality Assessment
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. HHSA290201500009-I, Task Order No. 14)

Key Questions

1. Key Question 1. What are the benefits of screening for hepatitis B virus (HBV) infection in asymptomatic, nonpregnant adolescents and adults on morbidity, mortality, and disease transmission?
2. Key Question 2. What are the harms of screening for HBV infection in asymptomatic, nonpregnant adolescents and adults (e.g., labeling or anxiety)?
3. Key Question 3. What is the yield (number of new diagnoses per tests performed) and sensitivity of alternative HBV screening strategies (e.g., universal vs. targeted screening or screening strategies based on alternative risk factors)?
4. Key Question 4. How effective is antiviral treatment in improving intermediate outcomes among nonpregnant adolescents and adults with chronic HBV infection, including virologic or histologic improvement, clearance of hepatitis B e-antigen (HBeAg) (as indicated by loss of HBeAg or acquisition of the antibody to HBeAg [anti-HBe]), or clearance of hepatitis B surface antigen (HBsAg) (as indicated by loss of HBsAg or acquisition of hepatitis B surface antibody [anti-HBs])?
5. Key Question 5. How effective is antiviral treatment in improving health outcomes among nonpregnant adolescents and adults with chronic HBV infection?
6. Key Question 6. What are the harms associated with antiviral treatment in nonpregnant adolescents and adults with chronic HBV infection?
7. Key Question 7. What is the association between improvements in intermediate outcomes as a result of antiviral treatment of chronic HBV infection and reduction in risk of HBV-related adverse health outcomes?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Current state of and needs for hepatitis B screening: results of a large screening study in a low-prevalent, metropolitan region.2014
Hepatitis B screening: who to target? A French sexually transmitted infection clinic experience.2013
Prevalence of elevated ALT values, HBsAg, and anti-HCV in the primary care setting and evaluation of guideline defined hepatitis risk scenarios.2015
Lamivudine treatment in HBeAg-negative chronic hepatitis B patients with low level viraemia.2005
Two-year lamivudine treatment for hepatitis B e antigen-negative chronic hepatitis B: a double-blind, placebo-controlled trial.2007
Results of up to 2 years of entecavir vs lamivudine therapy in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B.2009
A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B.
Lamivudine as initial treatment for chronic hepatitis B in the United States.1999
Entecavir therapy for up to 96 weeks in patients with HBeAg-positive chronic hepatitis B.2007
Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B.
Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients with normal to minimally elevated ALT and no cirrhosis.2016
Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection.2013
Tenofovir disoproxil fumarate vs adefovir dipivoxil in Chinese patients with chronic hepatitis B after 48 weeks: a randomized controlled trial.2015
A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group.1998
Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial.1997
Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B.2006
Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection.2002
A randomized, controlled trial of a 24-month course of interferon alfa 2b in patients with chronic hepatitis B who had hepatitis B virus DNA without hepatitis B e antigen in serum.1997
Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B.2005
Efficacy and safety of entecavir versus lamivudine over 5 years of treatment: A randomized controlled trial in Korean patients with hepatitis B e antigen-negative chronic hepatitis B.2017
Effect of Nucleos(t)ide Analogue Therapy on Risk of Intrahepatic Cholangiocarcinoma in Patients With Chronic Hepatitis B.2018
Beneficial effect of prednisolone withdrawal followed by human lymphoblastoid interferon on the treatment of chronic type B hepatitis in Asians: a randomized controlled trial.1994
Long-term beneficial effect of interferon therapy in patients with chronic hepatitis B virus infection.
Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B.2003
Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B.2008
Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: A multicenter retrospective study of 2795 patients.2005
Long-term results with interferon therapy in chronic type B hepatitis: a prospective randomized trial.1999
Treatment of chronic hepatitis B with interferon alfa-2b.
Problems in the management of chronic hepatitis B with interferon: experience in a randomized, multicentre study.1990
A one-year trial of entecavir treatment in patients with HBeAg-positive chronic hepatitis B.2007
Early viral kinetics of telbivudine and entecavir: results of a 12-week randomized exploratory study with patients with HBeAg-positive chronic hepatitis B.2010
Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group.1999
Comparative study of three doses of interferon-alpha 2a in chronic active hepatitis B. The International Hepatitis Trial Group.1994
Efficacy of entecavir in chronic hepatitis B patients with persistently normal alanine aminotransferase: randomized, double-blind, placebo-controlled study.2014
Nucleos(t)ide analogues associated with a reduced risk of hepatocellular carcinoma in hepatitis B patients: a population-based cohort study.2015
Antiviral therapy and the development of osteopenia/osteoporosis among Asians with chronic hepatitis B.2019
Effect of hepatitis B virus genotypes on the efficacy of adefovir dipivoxil antiviral therapy.2014
Association of nucleos(t)ide analogue therapy with reduced risk of hepatocellular carcinoma in patients with chronic hepatitis B: a nationwide cohort study.2014
A three-month course of lamivudine therapy in HBeAg-positive hepatitis B patients with normal aminotransferase levels.2004
Efficacy and safety of entecavir compared to lamivudine in nucleoside-naïve patients with chronic hepatitis B: a randomized double-blind trial in China.2007
A randomized double-blind placebo-controlled study of lamivudine in the treatment of patients with chronic hepatitis B virus infection.1999
Management of hepatitis B in China.2000
A 7-year study of lamivudine therapy for hepatitis B virus e antigen-positive chronic hepatitis B patients in China.2009
A 24-week, parallel-group, open-label, randomized clinical trial comparing the early antiviral efficacy of telbivudine and entecavir in the treatment of hepatitis B e antigen-positive chronic hepatitis B virus infection in adult Chinese patients.2010
Interferon-alpha therapy in HBeAg-negative chronic hepatitis B: a long-term prospective study from north-western Greece.2006
Antiviral therapy for chronic hepatitis B virus infection and development of hepatocellular carcinoma in a US population.2014
Changes in liver histology as a "surrogate" end point of antiviral therapy for chronic HBV can predict progression to liver complications.-- Not Found --
Long-term follow-up of patients with chronic hepatitis B treated with interferon alfa.1997
Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma.2007
Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B.1996
The long-term outcome of interferon-alpha treated and untreated patients with HBeAg-negative chronic hepatitis B.2001
Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study.2011

Downloadable Data Content

Files
  • XLSX Project Data