• Home
• Hepatitis B
  • Disease Background
  • Disease Management
  • Treatment
• Hepatitis C
• Glossary

Hepatitis B
Disease Background

• Epidemiology
• Aetiology
• HBeAg status

Disease Background

HBeAg status

Because of the distinct patterns in terms of markers of disease in geographic distribution, HBV genotype, risk of progression to liver disease and response rate to treatment, chronic HBV infection can be classified in two entities depending on HBeAg status:

• HBeAg-positive CHB (early phase of infection, harbouring wild type HBV) HBeAg-positive CHB, which represents the early phase in the disease process, is characterised by high levels of viraemia (107–1010 copies/mL) and persistently or intermittently increased ALT levels.¹ The majority of patients in this category, if untreated, maintain high HBV replication and active liver necroinflammation which is associated with the development of cirrhosis and an increased risk of HCC.²
• HBeAg-negative/anti-HBe-positive CHB (a later phase of infection with presence of mutant HBV) HBeAg-negative CHB, first described in 1989,³ is characterised by persistent HBV replication, lower viraemia (>105–106 copies/mL) and progressive necroinflammation and fibrosis of the liver. It represents a late phase in the natural history of chronic HBV infection, as demonstrated by the older age of patients and the higher rate of cirrhosis and HCC.⁴ HBeAg-negative HBV was thought to prevail in certain parts of the world (eg Mediterranean countries); however, recent data suggest that it is becoming more common worldwide.⁵ Some HBV genotypes (like genotype D) are more likely to mutate and to lead to the HBeAg-negative form of CHB. Spontaneous, sustained remissions are rare in HBeAg-negative CHB and this form of the disease is associated with a particularly negative clinical outcomes and low rates of response to therapy.⁶
  

The HBeAg-positive form of CHB can, but does not always, progress to the HBeAg-negative form of the disease. Between 15–40% of individuals chronically infected with HBV are expected to develop progressive liver disease, and it can take 15–25 years for the signs of liver damage from HBV to become apparent.⁷

The immune response to infected hepatocytes causes inflammation and necrosis within the liver and if necroinflammation persists, damaged cells are replaced with fibrous tissue. Fibrosis can eventually lead to compensated and possibly decompensated cirrhosis. Late in the course of the disease, patients classically present with jaundice, anorexia, fatigue, nausea and abdominal pain. In the end stages of the disease, patients may develop ascites, oesophageal varices and liver failure. Hepatocellular carcinoma is another serious consequence of chronic HBV infection and can occur indirectly through chronic liver injury, inflammation and regeneration. Additionally, HCC can also occur as a direct result of chronic HBV infection activating cellular oncogenes or inactivating tumour suppressor genes. Severe liver damage resulting in liver failure and HCC will eventually lead to death.

References:
1. Papatheodoridis GV, Hadziyannis SJ. Review article: current management of chronic hepatitis B. Aliment Pharmacol Ther 2004;19(1):25-37.
2. Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000 – summary of a workshop. Gastroenterology 2001;120(7):1828-53.
3. Carman WF, Jacyna MR, Hadziyannis S, et al. Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection. Lancet 1989;2(8663):588-91.
4. Fattovich G. Natural history and prognosis of hepatitis B. Semin Liver Dis 2003;23(1):47-58.
5. Funk ML, Rosenberg DM, Lok ASF. World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated pre-core and core promoter variants. J Viral Hepat 2002;9(1):52-61.
6. de Franchis R, Hadengue A, Lau G, et al. EASL International Consensus Conference on Hepatitis B. 13–14 September, 2002 Geneva, Switzerland. Consensus statement (long version). J Hepatol 2003;39 (Suppl 1) :S3-25.
7. Lok AS. Chronic hepatitis B. N Engl J Med 2002;346(22):1682-3.

Site Map | Print Version | Terms of Use

Developed in partnership with F.Hoffmann-la Roche by the EPG Online