Genotype C Hepatitis B Virus Infection is Associated with an Increased Risk of Hepatocellular Carcinoma

Overview

Journal Gut

Specialty Gastroenterology

Date 2004 Sep 14

PMID 15361502

Citations 167

Authors

H L-Y Chan

A Y Hui

M L Wong

A M-L Tse

L C-T Hung

V W-S Wong

J J-Y Sung

Affiliations

Soon will be listed here.

Abstract

Background: Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients.

Patients And Methods: Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of alpha fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy.

Results: In total, 426 patients were followed up for 1664 person years; median 225 (range 12-295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14-236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39-23.89; p<0.001) and 2.84 (95% CI 1.05-7.72; p = 0.040), respectively. Patient age, sex, hepatitis B e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, and basal core promoter mutations did not predict HCC development. Patients infected with HBV genotype C tended to have persistently positive HBeAg or fluctuating HBeAg status and higher ALT levels during the follow up period.

Conclusion: Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.

Citing Articles

Hepatitis B virus as a risk factor for hepatocellular carcinoma: There is still much work to do.

Abdelhamed W, El-Kassas M Liver Res. 2025; 8(2):83-90.

PMID: 39959873 PMC: 11771266. DOI: 10.1016/j.livres.2024.05.004.

Long-Term Outcome of Chronic Hepatitis B-Histological Score and Viral Genotype Are Important Predictors of Hepatocellular Carcinoma.

Eilard A, Ringlander J, Andersson M, Nilsson S, Norkrans G, Lindh M J Viral Hepat. 2025; 32(3):e70008.

PMID: 39878776 PMC: 11777188. DOI: 10.1111/jvh.70008.

Identifying Childhood Risk Factors for Hepatitis B with a Focus on Vertical Transmission.

Forna L, Lupu A, Bozomitu L, Paduraru G, Cojocariu C, Anton C Diseases. 2024; 12(9).

PMID: 39329884 PMC: 11431014. DOI: 10.3390/diseases12090215.

Occult Hepatitis B Virus Infection in Hepatic Diseases and Its Significance for the WHO's Elimination Plan of Viral Hepatitis.

Bucio-Ortiz L, Enriquez-Navarro K, Maldonado-Rodriguez A, Torres-Flores J, Cevallos A, Salcedo M Pathogens. 2024; 13(8).

PMID: 39204261 PMC: 11357063. DOI: 10.3390/pathogens13080662.

Disease modifiers and novel markers in hepatitis B virus-related hepatocellular carcinoma.

Mak L J Liver Cancer. 2024; 24(2):145-154.

PMID: 39099070 PMC: 11449577. DOI: 10.17998/jlc.2024.08.03.

References

Gust I . Epidemiology of hepatitis B infection in the Western Pacific and South East Asia. Gut. 1996; 38 Suppl 2:S18-23. PMC: 1398038. DOI: 10.1136/gut.38.suppl_2.s18. View

Sherman M, Peltekian K, Lee C . Screening for hepatocellular carcinoma in chronic carriers of hepatitis B virus: incidence and prevalence of hepatocellular carcinoma in a North American urban population. Hepatology. 1995; 22(2):432-8. View

Lee W . Hepatitis B virus infection. N Engl J Med. 1997; 337(24):1733-45. DOI: 10.1056/NEJM199712113372406. View

Baptista M, Kramvis A, Kew M . High prevalence of 1762(T) 1764(A) mutations in the basic core promoter of hepatitis B virus isolated from black Africans with hepatocellular carcinoma compared with asymptomatic carriers. Hepatology. 1999; 29(3):946-53. DOI: 10.1002/hep.510290336. View

Chan H, Hussain M, Lok A . Different hepatitis B virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversion. Hepatology. 1999; 29(3):976-84. DOI: 10.1002/hep.510290352. View

Stuyver L, Gendt S, Van Geyt C, Zoulim F, Fried M, Schinazi R . A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. J Gen Virol. 2000; 81(Pt 1):67-74. DOI: 10.1099/0022-1317-81-1-67. View

Yuen M, Cheng C, Lauder I, Lam S, Ooi C, Lai C . Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience. Hepatology. 2000; 31(2):330-5. DOI: 10.1002/hep.510310211. View

Kao J, Chen P, Lai M, Chen D . Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology. 2000; 118(3):554-9. DOI: 10.1016/s0016-5085(00)70261-7. View

Chan H, Leung N, Hussain M, Wong M, Lok A . Hepatitis B e antigen-negative chronic hepatitis B in Hong Kong. Hepatology. 2000; 31(3):763-8. DOI: 10.1002/hep.510310330. View

10.

McMahon B, Bulkow L, Harpster A, Snowball M, Lanier A, Sacco F . Screening for hepatocellular carcinoma in Alaska natives infected with chronic hepatitis B: a 16-year population-based study. Hepatology. 2000; 32(4 Pt 1):842-6. DOI: 10.1053/jhep.2000.17914. View

11.

Fujie H, Moriya K, Shintani Y, Yotsuyanagi H, Iino S, Koike K . Hepatitis B virus genotypes and hepatocellular carcinoma in Japan. Gastroenterology. 2001; 120(6):1564-5. DOI: 10.1053/gast.2001.24501. View

12.

Orito E, Ichida T, Sakugawa H, Sata M, Horiike N, Hino K . Geographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan. Hepatology. 2001; 34(3):590-4. DOI: 10.1053/jhep.2001.27221. View

13.

McMahon B, Holck P, Bulkow L, Snowball M . Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus. Ann Intern Med. 2001; 135(9):759-68. DOI: 10.7326/0003-4819-135-9-200111060-00006. View

14.

Chan H, Tsang S, Tse C, Wong M, Ching J, Leung N . Viral genotype and hepatitis B virus DNA levels are correlated with histological liver damage in HBeAg-negative chronic hepatitis B virus infection. Am J Gastroenterol. 2002; 97(2):406-12. DOI: 10.1111/j.1572-0241.2002.05478.x. View

15.

Chien R, Yeh C, Sheen I, Chiou H, Chu C, Liaw Y . Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology. 2002; 35(6):1522-7. DOI: 10.1053/jhep.2002.33638. View

16.

Chu C, Hussain M, Lok A . Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology. 2002; 122(7):1756-62. DOI: 10.1053/gast.2002.33588. View

17.

Arauz-Ruiz P, Norder H, Robertson B, Magnius L . Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America. J Gen Virol. 2002; 83(Pt 8):2059-2073. DOI: 10.1099/0022-1317-83-8-2059. View

18.

Yang H, Lu S, Liaw Y, You S, Sun C, Wang L . Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002; 347(3):168-74. DOI: 10.1056/NEJMoa013215. View

19.

Ohkubo K, Kato Y, Ichikawa T, Kajiya Y, Takeda Y, Higashi S . Viral load is a significant prognostic factor for hepatitis B virus-associated hepatocellular carcinoma. Cancer. 2002; 94(10):2663-8. DOI: 10.1002/cncr.10557. View

20.

Chu C, Hussain M, Lok A . Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology. 2002; 36(6):1408-15. DOI: 10.1053/jhep.2002.36949. View