Excerpt

Chronic hepatitis B describes a spectrum of disease usually characterised by the presence of detectable hepatitis B surface antigen (HBsAg) in the blood or serum for longer than 6 months. In some people, chronic hepatitis B is inactive and does not present significant health problems, but others may progress to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The progression of liver disease is associated with hepatitis B virus (HBV) DNA levels in the blood. Without antiviral treatment, the 5-year cumulative incidence of cirrhosis ranges from 8 to 20%. People with cirrhosis face a significant risk of decompensated liver disease if they remain untreated. Five-year survival rates among people with untreated decompensated cirrhosis can be as low as 15%. Chronic hepatitis B can be divided into e antigen- (HBeAg) positive or HBeAg-negative disease based on the presence or absence of e antigen. The presence of HBeAg is typically associated with higher rates of viral replication and therefore increased infectivity.

The goal of treatment for chronic hepatitis B is to prevent cirrhosis, HCC and liver failure. In clinical practice surrogate markers are used to monitor progression of disease and treatment response, and include normalisation of serum alanine aminotransferase (ALT) levels, decrease in inflammation scores with no worsening or improvement in fibrosis on liver biopsies, suppression of serum HBV DNA to undetectable levels, loss of HBeAg and seroconversion to HBe antibody (anti-HBe), and loss of HBsAg and seroconversion to HBs antibody (anti-HBs).

Antiviral therapy suppresses HBV replication and decreases hepatic inflammation and fibrosis, thereby reducing the likelihood of serious clinical disease. Since the introduction of effective treatment in the form of interferon alfa, several nucleoside and nucleotide analogues are now approved for use in adults with chronic hepatitis B, together with a pegylated form of interferon alfa. With multiple treatment options that are efficacious and safe, the key questions are which patients need immediate treatment and what sequence and combination of drug regimens should be used, and which patients can be monitored and delay treatment.

In this guideline we cover the following: information needs of people with chronic hepatitis B and their carers; where children, young people and adults with chronic hepatitis B should be assessed; assessment of liver disease, including the use of non-invasive tests and genotype testing; criteria for offering antiviral treatment; the efficacy, safety and cost effectiveness of currently available treatments; selection of first-line therapy; management of treatment failure or drug resistance; whether there is a role for combination therapy; when it is possible to stop treatment; managing the care of pregnant and breastfeeding women and prevention of vertical transmission; prophylactic treatment during immunosuppressive therapy; and monitoring for treatment response, severity of fibrosis and development of HCC.

Contents

• Guideline development group members
• NCGC Technical team members
• Acknowledgments
• 1. Introduction
• 2. Development of the guideline
  • 2.1. What is a NICE clinical guideline?
  • 2.2. Remit
  • 2.3. Who developed this guideline?
  • 2.4. What this guideline covers
  • 2.5. What this guideline does not cover
  • 2.6. Relationships between the guideline and other NICE guidance
• 3. Methods
  • 3.1. Developing the review questions and outcomes
  • 3.2. Searching for evidence
  • 3.3. Evidence of effectiveness
  • 3.4. Evidence of cost-effectiveness
  • 3.5. Developing recommendations
• 4. Guideline summary
  • 4.1. Key priorities for implementation
  • 4.2. Full list of recommendations
  • 4.3. Key research recommendations
  • 4.4. Algorithms
• 5. Patient information
  • 5.1. Introduction
  • 5.2. Review question: What information do patients with CHB and their carers need about the benefits and risks of treatment options?
  • 5.3. Clinical evidence
  • 5.4. Economic evidence
  • 5.5. Evidence statements
  • 5.6. Recommendations and Links to evidence
• 6. Assessment and referral
  • 6.1. Introduction
  • 6.2. Review question: What is the most appropriate healthcare setting to initiate relevant diagnostic tests (for example, Liver Function Tests, HBeAg, quantitative HBsAg, quantitative HBV DNA, anti HCV, anti HDV, anti HIV) in people who are HBsAg positive?
  • 6.3. Clinical evidence
  • 6.4. Economic evidence
  • 6.5. Evidence statements
  • 6.6. Recommendations and Link to evidence
• 7. Assessment of liver disease in secondary specialist care
  • 7.1. Introduction
  • 7.2. Review question: What is the diagnostic accuracy of non-invasive methods (e.g. transient elastography, serum fibrosis markers, aspartate aminotransferase/ platelet ratio index, magnetic resonance spectroscopy) to assess severity of necro-inflammatory activity and liver fibrosis?
  • 7.3. Clinical evidence
  • 7.4. Economic evidence
  • 7.5. Evidence statements
  • 7.6. Recommendations and links to evidence
• 8. Genotype testing
  • 8.1. Introduction
  • 8.2. Review question: What is the clinical and cost-effectiveness of genotypic testing in determining whether to offer antiviral treatment in people with CHB?
  • 8.3. Clinical evidence for the response of patients with CHB to antiviral treatment by genotype
  • 8.4. Economic evidence
  • 8.5. Evidence statements
  • 8.6. Recommendations and link to evidence
• 9. Thresholds for treatment
  • 9.1. Introduction
  • 9.2. Review question: What are the thresholds (e.g. HBV DNA, ALT levels) for starting treatment after initial diagnosis and pre-therapeutic tests of CHB?
  • 9.3. Clinical evidence
  • 9.4. Summary table of evidence
  • 9.5. Economic evidence
  • 9.6. Evidence statements
  • 9.7. Recommendations and links to evidence
• 10. Antiviral therapies
  • 10.1. Pharmacological therapies
  • 10.2. Liver decompensation
  • 10.3. Pregnancy
  • 10.4. Prophylactic treatment
• 11. Monitoring and surveillance
  • 11.1. Monitoring
  • 11.2. Surveillance testing for HCC
• 12. Acronyms and abbreviations
• 13. Glossary
• 14. Reference List
• Appendices
  • Appendix A. Scope
  • Appendix B. Declarations of interest
  • Appendix C. Review Protocols
  • Appendix D. Literature Search Strategies
  • Appendix E. Clinical evidence tables
  • Appendix F. Economic evidence tables
  • Appendix G. Forest plots
  • Appendix H. Cost-effectiveness analysis – Antiviral therapy for decompensated HBV cirrhosis
  • Appendix I. Cost-effectiveness analysis – Treatment of patients with HBeAg positive and HbeAg negative CHB
  • Appendix J. Network meta analysis (NMA) of interventions in the pharmacological treatment of chronic hepatitis B for adults
  • Appendix K. Research recommendations
  • Appendix L. Excluded clinical studies
  • Appendix M. Excluded economic studies
  • Appendix N. Quality Assessment Checklists
  • Appendix O. Diagnostics – 2×2 tables

Disclaimer: Healthcare professionals are expected to take NICE clinical guidelines fully into account when exercising their clinical judgement. However, the guidance does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of each patient, in consultation with the patient and/or their guardian or carer.