Hepatitis D virus infection, cirrhosis and hepatocellular carcinoma in The Gambia

Parag Mahale, Peter Aka, Xiaohua Chen, Ruth M. Pfeiffer, Ping Liu, Sarah Groover, Maimuna Mendy, Ramou Njie, James J. Goedert, Gregory D. Kirk, Jeffrey S. Glenn, Thomas R. O'Brien

Research output: Contribution to journalArticle

Abstract

Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q-MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case-control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha-foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q-MAC, western blot and RNA assays. We evaluated separate cut-offs of the Q-MAC assay for predicting anti-HDV and RNA positivity. Q-MAC correctly identified 29/29 subjects who were western blot-positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA-positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA−; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV-HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti-HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74-11.98) and HBV-HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97-134.95). In this Gambian population, HDV Q-MAC had high sensitivity and specificity for both anti-HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia.

Original languageEnglish
Pages (from-to)738-749
Number of pages12
JournalJournal of Viral Hepatitis
Volume26
Issue number6
DOIs
StatePublished - Jun 2019

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Gambia
Hepatitis Delta Virus
Virus Diseases
Hepatocellular Carcinoma
Fibrosis
Hepatitis B virus
Hepatitis B Surface Antigens
Antibodies
Odds Ratio
Coinfection
Sensitivity and Specificity
Western Blotting
RNA
Confidence Intervals
Aflatoxin B1
alpha-Fetoproteins
Liver Neoplasms

Keywords

  • epidemiology
  • HDV RNA
  • hepatitis B virus
  • hepatitis D virus
  • hepatocellular carcinoma

Cite this

Mahale, P., Aka, P., Chen, X., Pfeiffer, R. M., Liu, P., Groover, S., ... O'Brien, T. R. (2019). Hepatitis D virus infection, cirrhosis and hepatocellular carcinoma in The Gambia. Journal of Viral Hepatitis, 26(6), 738-749. https://doi.org/10.1111/jvh.13065
Mahale, Parag ; Aka, Peter ; Chen, Xiaohua ; Pfeiffer, Ruth M. ; Liu, Ping ; Groover, Sarah ; Mendy, Maimuna ; Njie, Ramou ; Goedert, James J. ; Kirk, Gregory D. ; Glenn, Jeffrey S. ; O'Brien, Thomas R. / Hepatitis D virus infection, cirrhosis and hepatocellular carcinoma in The Gambia. In: Journal of Viral Hepatitis. 2019 ; Vol. 26, No. 6. pp. 738-749.
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Mahale, P, Aka, P, Chen, X, Pfeiffer, RM, Liu, P, Groover, S, Mendy, M, Njie, R, Goedert, JJ, Kirk, GD, Glenn, JS & O'Brien, TR 2019, 'Hepatitis D virus infection, cirrhosis and hepatocellular carcinoma in The Gambia', Journal of Viral Hepatitis, vol. 26, no. 6, pp. 738-749. https://doi.org/10.1111/jvh.13065

Hepatitis D virus infection, cirrhosis and hepatocellular carcinoma in The Gambia. / Mahale, Parag; Aka, Peter; Chen, Xiaohua; Pfeiffer, Ruth M.; Liu, Ping; Groover, Sarah; Mendy, Maimuna; Njie, Ramou; Goedert, James J.; Kirk, Gregory D.; Glenn, Jeffrey S.; O'Brien, Thomas R.

In: Journal of Viral Hepatitis, Vol. 26, No. 6, 06.2019, p. 738-749.

Research output: Contribution to journalArticle

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T1 - Hepatitis D virus infection, cirrhosis and hepatocellular carcinoma in The Gambia

AU - Mahale, Parag

AU - Aka, Peter

AU - Chen, Xiaohua

AU - Pfeiffer, Ruth M.

AU - Liu, Ping

AU - Groover, Sarah

AU - Mendy, Maimuna

AU - Njie, Ramou

AU - Goedert, James J.

AU - Kirk, Gregory D.

AU - Glenn, Jeffrey S.

AU - O'Brien, Thomas R.

PY - 2019/6

Y1 - 2019/6

N2 - Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q-MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case-control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha-foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q-MAC, western blot and RNA assays. We evaluated separate cut-offs of the Q-MAC assay for predicting anti-HDV and RNA positivity. Q-MAC correctly identified 29/29 subjects who were western blot-positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA-positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA−; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV-HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti-HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74-11.98) and HBV-HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97-134.95). In this Gambian population, HDV Q-MAC had high sensitivity and specificity for both anti-HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia.

AB - Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q-MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case-control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha-foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q-MAC, western blot and RNA assays. We evaluated separate cut-offs of the Q-MAC assay for predicting anti-HDV and RNA positivity. Q-MAC correctly identified 29/29 subjects who were western blot-positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA-positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA−; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV-HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti-HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74-11.98) and HBV-HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97-134.95). In this Gambian population, HDV Q-MAC had high sensitivity and specificity for both anti-HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia.

KW - epidemiology

KW - HDV RNA

KW - hepatitis B virus

KW - hepatitis D virus

KW - hepatocellular carcinoma

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