The Gambia Hepatitis Intervention Study

Lead Research Organisation: MRC Unit, The Gambia

Abstract

Hepatocellular carcinoma (HCC) is the most frequent form of liver cancer and is a major cause of death in sub-Saharan Africa. The main cause of this cancer in Africa is infection with hepatitis B virus (HBV). HBV infection and Aflatoxin exposure has a multiplicative effect on the risk of developing HCC which is the commonest cancer in The Gambia.||The main objective of the study is to evaluate the effectiveness of HBV vaccination in childhood in the prevention of chronic liver disease, particularly, HCC and cirrhosis later in adult life. The efficacy of HBV vaccine against infection and chronic carriage has been estimated in phase III (initiated in 1998) of the study, consisting of long-term follow-up through cancer registration, using HCC as the primary endpoint.||20 yrs after the introduction of GHIS, data from studies developed to examine the validity of certain assumptions made at the beginning of the study showed that (a) HBV vaccine coverage was 15% more than originally assumed, (b) protection against HBV infection was not dependent on the number of vaccine doses received, (c) HBV infection from mother to child was of negligible importance, and (d) the HBV risk of HCC at age <50 was 70% to 80%, lower than initially assumed. Based on these data, the final outcome of the GHIS should be measurable from 2017, sooner than originally assumed.||The design of GHIS takes into account the specific patterns of HBV infection and natural history of HCC in Africa, and by its public health impact, advocating the generalization of HBV vaccination in sub-Saharan Africa. The final success of this unique long-term endeavour will depend upon the continuing development of a sustainable infrastructure for cancer detection, diagnosis, and registration, for monitoring viral infections, and for doing record linkage. This infrastructure is contributing to capacity building in the Gambian health system. The strategy adopted for the development of GHIS provides a model for the evaluation of the introduction of new vaccines in the national infant vaccination Programmes of sub-Saharan African countries.||Studies on risk factors and aetiology of HCC were conducted in case control study design in the Gambia Liver Cancer Study (GLCS). Recruitment started in 1997 and ended in 2001. The data from GLCS study confirmed HBV infection as an important risk factor for HCC but also identified high HBV DNA concentration, HBV variants, dietary exposure to aflatoxin (a food contaminant) and the resultant ser249 mutation as significant risk factor for advanced liver diseases (HCC and cirrhosis).

Technical Summary

Hepatocellular carcinoma (HCC) is the most frequent form of primary liver cancer and is a major cause of death in sub-Saharan Africa and eastern Asia. The main etiologic factor in these regions is chronic infection with hepatitis B virus (HBV). The latter has a multiplicative effect in conjunction with HBV infection on the risk of developing HCC. Primary hepatocellular carcinoma is the commonest cancer in The Gambia.||The Gambian Hepatitis Intervention Study (GHIS) is a collaborative undertaking by the IARC, The Government of the Republic of The Gambia, and the Medical Research Council. This program was launched in 1986 with the objective of evaluating the effectiveness of hepatitis B vaccination in childhood in the prevention of chronic liver disease, particularly, HCC and cirrhosis later in adult life.||The implementation of GHIS involves three overlapping phases. During phase I (1986-1990), hepatitis B vaccine, approved by the WHO, was phased into the Gambian Expanded Programme of Immunization over a 4-year period from July 1986 to February 1990. Two groups of children were recruited, one of about 60,000 children who received all Expanded Programme of Immunization vaccines and the other of a similar number of children who received all vaccines plus hepatitis B. Since February 1990, hepatitis B vaccination has been offered to all newborns as part of the Expanded Programme of Immunization in The Gambia. During Phase II (1991-1997), the efficacy of hepatitis B vaccine against infection and chronic carriage has been estimated through longitudinal and cross-sectional surveys in selected groups of hepatitis B vaccinated and unvaccinated children. Phase III (initiated in 1998) consists of long-term follow-up through cancer registration, using HCC as the primary endpoint.||Twenty years following the introduction of GHIS, data from observational and epidemiologic studies developed to examine the validity of these assumptions made at the beginning of the study showed that (a) hepatitis B vaccine coverage was 15% more than originally assumed, (b) protection against hepatitis B virus (HBV) infection was not dependent on the number of vaccine doses received, (c) perinatal infection with HBV was of negligible importance, and (d) the HBV attributable risk of HCC at age <50 was 70% to 80%, lower than initially assumed. Based on these data, the final outcome of the GHIS should be measurable from 2017, sooner than originally assumed.||Studies on risk factors and aetiology of HCC were conducted in case control study design in the Gambia Liver Cancer Study (GLCS). Recruitment started in 1997 and ended in 2001. The data from GLCS study confirmed HBV infection as an important risk factor for HCC but also identified high HBV DNA concentration, HBV variant (mutation in HBV basal core region), dietary exposure to aflatoxin and resultant ser249 mutation as significant risk factor for advanced liver diseases (HCC and cirrhosis).

Publications

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Description Introduction of national HBV vaccination program
Geographic Reach Africa 
Policy Influence Type Gave evidence to a government review
 
Title Access programe for capturing of HBV serology data 
Description An access data base was developed to capture data from ELISA plate readers of HBV serology results. This then removed the data entry step and thus remove transcription error. 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2007 
Provided To Others? Yes  
Impact Data entry is faster and the time between laboratory tests are performed to when they are acvailable for analysis is shortened significantly.