Natural history of chronic HBV infection in West Africa: a longitudinal population-based study from The Gambia

Background The natural history of chronic HBV infection in sub-Saharan Africa is unknown. Data are required to inform WHO guidelines that are currently based on studies in Europe and Asia. Methods Between 1974 and 2008, serosurveys were repeated in two Gambian villages, and an open cohort of treatment-naive chronic HBV carriers was recruited. Participants were followed to estimate the rates of hepatitis B e (HBeAg) and surface antigen (HBsAg) clearance and incidence of hepatocellular carcinoma (HCC). In 2012–2013, a comprehensive liver assessment was conducted to estimate the prevalence of severe liver disease. Results 405 chronic carriers (95% genotype E), recruited at a median age of 10.8 years, were followed for a median length of 28.4 years. Annually, 7.4% (95% CI 6.3% to 8.8%) cleared HBeAg and 1.0% (0.8% to 1.2%) cleared HBsAg. The incidence of HCC was 55.5/100 000 carrier-years (95% CI 24.9 to 123.5). In the 2012–2013 survey (n=301), 5.5% (95% CI 3.4% to 9.0%) had significant liver fibrosis. HBV genotype A (versus E), chronic aflatoxin B1 exposure and an HBsAg-positive mother, a proxy for mother-to-infant transmission, were risk factors for liver fibrosis. A small proportion (16.0%) of chronic carriers were infected via mother-to-infant transmission; however, this population represented a large proportion (63.0%) of the cases requiring antiviral therapy. Conclusions The incidence of HCC among chronic HBV carriers in West Africa was higher than that in Europe but lower than rates in East Asia. High risk of severe liver disease among the few who are infected by their mothers underlines the importance of interrupting perinatal transmission in sub-Saharan Africa.

[1]  A. Hall,et al.  Birth order and risk of hepatocellular carcinoma in chronic carriers of hepatitis B virus: a case–control study in The Gambia , 2015, Liver international : official journal of the International Association for the Study of the Liver.

[2]  Maimuna Mendy,et al.  Validation of Rapid Point-of-Care (POC) Tests for Detection of Hepatitis B Surface Antigen in Field and Laboratory Settings in the Gambia, Western Africa , 2015, Journal of Clinical Microbiology.

[3]  S. Sodha,et al.  Global Routine Vaccination Coverage, 2013 , 2014, MMWR. Morbidity and mortality weekly report.

[4]  E. Gane,et al.  Serological and clinical outcomes of horizontally transmitted chronic hepatitis B infection in New Zealand Māori: results from a 28-year follow-up study , 2014, Gut.

[5]  M. Thursz,et al.  Prevention of materno‐foetal transmission of hepatitis B in sub‐Saharan Africa: the evidence, current practice and future challenges , 2014, Journal of viral hepatitis.

[6]  C. Bottomley,et al.  The association between maternal hepatitis B e antigen status, as a proxy for perinatal transmission, and the risk of hepatitis B e antigenaemia in Gambian children , 2014, BMC Public Health.

[7]  A. Hall,et al.  Population-Based Interventions to Reduce the Public Health Burden Related with Hepatitis B Virus Infection in The Gambia, West Africa , 2014, Tropical medicine and health.

[8]  H. Whittle,et al.  Efficacy and effectiveness of infant vaccination against chronic hepatitis B in the Gambia Hepatitis Intervention Study (1986–90) and in the nationwide immunisation program , 2014, BMC Infectious Diseases.

[9]  P. Hainaut,et al.  20-Years of Population-Based Cancer Registration in Hepatitis B and Liver Cancer Prevention in The Gambia, West Africa , 2013, PloS one.

[10]  A. Hall,et al.  Association of Early Age at Establishment of Chronic Hepatitis B Infection with Persistent Viral Replication, Liver Cirrhosis and Hepatocellular Carcinoma: A Systematic Review , 2013, PloS one.

[11]  H. Whittle,et al.  Observational Study of Vaccine Efficacy 24 Years after the Start of Hepatitis B Vaccination in Two Gambian Villages: No Need for a Booster Dose , 2013, PloS one.

[12]  A. Hall,et al.  Evaluation of data quality at the Gambia national cancer registry , 2013, International journal of cancer.

[13]  B. Cowie,et al.  The global burden of liver disease attributable to hepatitis B, hepatitis C, and alcohol: increasing mortality, differing causes , 2013 .

[14]  Chien-Jen Chen,et al.  Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. , 2011, Gastroenterology.

[15]  H. Whittle,et al.  Seasonal Variation in TP53 R249S-Mutated Serum DNA with Aflatoxin Exposure and Hepatitis B Virus Infection , 2011, Environmental health perspectives.

[16]  S. Hadziyannis Natural history of chronic hepatitis B in Euro-Mediterranean and African countries. , 2011, Journal of hepatology.

[17]  Penelope Vounatsou,et al.  Geostatistical Model-Based Estimates of Schistosomiasis Prevalence among Individuals Aged ≤20 Years in West Africa , 2011, PLoS neglected tropical diseases.

[18]  C. Chu,et al.  Age‐specific prognosis following spontaneous hepatitis B e antigen seroconversion in chronic hepatitis B , 2010, Hepatology.

[19]  Norman Gitlin,et al.  Chronic hepatitis B : an update , 2010 .

[20]  B. McMahon,et al.  Chronic hepatitis B: Update 2009 , 2009, Hepatology.

[21]  Mei‐Hwei Chang Natural history and clinical management of chronic hepatitis B virus infection in children , 2008, Hepatology international.

[22]  H. Whittle,et al.  Changes in viral load and HBsAg and HBeAg status with age in HBV chronic carriers in The Gambia , 2008, Virology Journal.

[23]  B. McMahon,et al.  Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. , 2007, Gastroenterology.

[24]  M. Kew,et al.  Epidemiology of hepatitis B virus in Africa, its genotypes and clinical associations of genotypes , 2007, Hepatology research : the official journal of the Japan Society of Hepatology.

[25]  C. Chu,et al.  Chronic hepatitis B virus infection acquired in childhood: special emphasis on prognostic and therapeutic implication of delayed HBeAg seroconversion , 2007, Journal of viral hepatitis.

[26]  P. Loehrer,et al.  Risk of Hepatocellular Carcinoma Across a Biological Gradient of Serum Hepatitis B Virus DNA Level , 2007 .

[27]  H. Whittle,et al.  Long-term protection against carriage of hepatitis B virus after infant vaccination. , 2006, The Journal of infectious diseases.

[28]  A. Gatta,et al.  Chronic hepatitis B in children after e antigen seroclearance: Final report of a 29‐year longitudinal study , 2006, Hepatology.

[29]  Guan-Tarn Huang,et al.  Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. , 2006, JAMA.

[30]  H. Whittle,et al.  Application of real-time PCR to quantify hepatitis B virus DNA in chronic carriers in The Gambia , 2006, Virology Journal.

[31]  A. Hall,et al.  Chronic hepatitis B virus infection in the Asia–Pacific region and Africa: Review of disease progression , 2005, Journal of gastroenterology and hepatology.

[32]  S. Akçalı,et al.  Serum hepatitis B DNA: stability in relation to multiple freeze-thaw procedures. , 2005, Journal of virological methods.

[33]  A. Hall,et al.  Mortality of hepatitis B surface antigen-positive blood donors in England and Wales. , 2003, International journal of epidemiology.

[34]  D. Shouval Hepatitis B vaccines. , 2003, Journal of hepatology.

[35]  H. Whittle,et al.  Observational study of vaccine efficacy 14 years after trial of hepatitis B vaccination in Gambian children , 2002, BMJ : British Medical Journal.

[36]  B. McMahon,et al.  Serologic and Clinical Outcomes of 1536 Alaska Natives Chronically Infected with Hepatitis B Virus , 2001, Annals of Internal Medicine.

[37]  W. Mason,et al.  Geographic variation in viral load among hepatitis B carriers with differing risks of hepatocellular carcinoma. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[38]  W. Edmunds,et al.  Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areasr , 1996, Epidemiology and Infection.

[39]  P. Bedossa,et al.  An algorithm for the grading of activity in chronic hepatitis C , 1996, Hepatology.

[40]  C. Kiire The epidemiology and prophylaxis of hepatitis B in sub-Saharan Africa: a view from tropical and subtropical Africa. , 1996, Gut.

[41]  H. Whittle,et al.  Long-term efficacy of continuing hepatitis B vaccination in infancy in two Gambian villages , 1995, The Lancet.

[42]  K. Hyams Risks of chronicity following acute hepatitis B virus infection: a review. , 1995, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[43]  H. Inskip,et al.  Vaccination aginst chronic viral carriage in The Gambia , 1991, The Lancet.

[44]  H. Inskip,et al.  Vaccination against hepatitis B and protection against chronic viral carriage in The Gambia. , 1991, Lancet.

[45]  H. Inskip,et al.  The pattern of childhood hepatitis B infection in two Gambian villages. , 1990, The Journal of infectious diseases.

[46]  H. Whittle,et al.  HEPATITIS B VIRUS INFECTION IN TWO GAMBIAN VILLAGES , 1983, The Lancet.

[47]  M. Kew,et al.  Hepatocellular Carcinoma in Rural Southern African Blacks , 1982, Medicine.

[48]  I. McGregor Health and communicable disease in a rural African environment , 1976 .

[49]  M. Dumont,et al.  European Association for the Study of the Liver , 1971 .

[50]  M. Graffar [Modern epidemiology]. , 1971, Bruxelles medical.

[51]  Hepatitis A vaccines WHO position paper , 2022 .