Talk delivered at the B Informed Conference, Doylestown, PA, June 2002
Hosted by the Hep B Foundation ( www.hepb.org) and HB-L
Consultant Gastroenterologist & Hepatologist
New Delhi, India
Hepatitis B virus (HBV) infection has an estimated prevalence of 400 million people world wide. This is of particular concern in the East (Asia-Pacific region) where it poses an important public health problem by virtue of its morbidity and mortality. It is estimated that 15-40% of those with chronic HBV infection will eventually develop serious complications (cirrhosis, liver cancer) and die. The dynamics of chronic HBV infection differs considerably in the East (prevalence > 10%) from the West (prevalence < 1%). The evolution of chronic hepatitis B (CHB) depends upon the geographic location of the host (East or West), age and mode of acquisition of virus (early childhood and perinatal transmission in East ; adulthood and horizontal transmission in West ) and predominant type of virus (precore mutant in East and wild type in West ; genotype B to E in the East and genotype A and H in the West ). It is thus important to understand the epidemiology and natural history of HBV infection in order to evolve effective measures for its prevention and treatment. Studies in migrant population have shown that the profile of CHB in immigrants is similar to that seen in the country of their origin which makes an interaction of the knowledge of the East and West even more worthwhile.
The natural course of CHB differs in Asians and Caucasians. In Caucasians, infection is acquired in adulthood with the wild type HB virus transmitted horizontally (parenteral, sexual or by unknown means). Caucasians are usually E antigen positive with high ALT and elevated HBV-DNA reflecting active liver injury (immune clearance). About 20 % of these progress to have chronic liver disease and its complications. However a majority enter a non-replicative phase, become E antigen negative with normal ALT, undetectable or low HBV-DNA and remain asymptomatic. Only a minority will then have a late exacerbation of their disease ( reactivation phase).
In Asians infection is usually contracted either at birth or in early childhood. Nearly half have persistence of E antigen till adulthood , high HBV- DNA but normal ALT (immune tolerance) . A set of these people go on to the immune clearance phase and become asymptomatic. However another subset who clear the E antigen develops a precore mutant virus which gradually replaces the wild type. This type of E negative CHB eventually enters a phase of intermittent liver injury ( reactivation or replicative phase) progressing in jumps and starts to fibrosis and cirrhosis. This type of CHB constitutes 40 to 80% infection in Asia-Pacific region and is the most difficult to treat. The factors that lead to the emergence of pre-core mutant during the course of CHB will be reviewed and the possible virus and host mediated interactions which cause liver injury (CHB, cirrhosis, liver cancer) will be presented.
It is thus important to develop differential therapeutic strategies for both types of CHB (E negative or positive) as their overall outcome maybe different .Short term treatment with Interferon or Lamivudine ( the only drugs approved in the USA) is effective for E positive CHB in 35-40 % of cases. In E antigen negative CHB this treatment is not very successful and long term Lamivudine therapy is further complicated by the emergence of the resistant YMDD mutant virus.
Newer strategies for the treatment of CHB include a one year of combination or sequential therapy ( Pegylated Interferon and Lamivudine) and the use of newer drugs
( Adefovir, Entecavir).
It is now time for the concepts of the East and West to merge in evolving a global platform from where a frontal assault in eradicating can Hepatitis B be launched.
Here are the guidelines from American Association for study of Liver Disease for Chronic Hepatitis B, published in 2002
AASLD Guidelines for Chronic Hepatitis B 2002