Clinical significance of hepatitis B virus-DNA in hepatocellular carcinoma negative for hepatitis B virus surface antigen

Tateiwa,Shinpei; Yano,Yoshihiko; Seo,Yasushi; Miki,Akira; Yuuki,Kawano; Azuma,Takeshi; Hayashi,Yoshitake

doi:10.3892/etm_00000053

Clinical significance of hepatitis B virus-DNA in hepatocellular carcinoma negative for hepatitis B virus surface antigen

Authors:
- Shinpei Tateiwa
- Yoshihiko Yano
- Yasushi Seo
- Akira Miki
- Kawano Yuuki
- Takeshi Azuma
- Yoshitake Hayashi
View Affiliations

Affiliations: Center for Infectious Disease, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Published online on: March 1, 2010 https://doi.org/10.3892/etm_00000053
Pages: 343-346

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

It is relatively rare for hepatocellular carcinoma (HCC) to develop in patients that are serologically negative for hepatitis B virus surface antigen (HBsAg) or anti-hepatitis C virus antibody (HCV-Ab). In addition, hepatitis B virus (HBV) is sometimes detected and associated with hepatocarcinogenesis in HCC cases without HBsAg and HCV-Ab (NBNC-HCC). In this study we focused on the characteristics of resected NBNC-HCC, and occult HBV infection in resected liver tissues was also examined in these cases. A total of 32 cases (26 males and 6 females, median age 65.7±13.9 years) that underwent liver resection were enrolled in this study. Clinical data from 19 cases with NBNC-HCC were compared with those from 13 cases of HCC related to hepatitis viruses (HV-HCC). Subsequently, occult HBV infection was assessed by the detection of HBV-DNA from extracted liver tissue in NBNC-HCC. Mutation and variation were also examined by the PCR-direct sequencing method in the occult HBV cases. The average diameter of NBNC-HCC was significantly larger than that of HV-HCC. In addition, the activity and fibrosis scores of the surrounding liver tissues were significantly higher in HV-HCC. Among 19 cases of NBNC-HCC, HBV-DNA was detected in 7. Four out of the 7 cases were detected in the Pre-S/S region. The insertion of four amino acids in the α-loop region was detected in 1 case. No significant difference between the occult HBV cases and the others was found in NBNC-HCC. All cases were classified into genotype C on phylogenetic analysis. HBV-DNA was frequently detected in the liver tissues of NBNC-HCC. Thus, our data revealed that HBV may be associated with hepatocarcinogenesis in cases of occult HBV infection.

View Figures

View References

1.	Lee WM: Hepatitis B virus infection. N Engl J Med. 337:1733–1743. 1997. View Article : Google Scholar : PubMed/NCBI
2.	Tang B, Kruger WD, Chen G, et al: Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic carriers. J Med Virol. 72:35–40. 2004. View Article : Google Scholar : PubMed/NCBI
3.	Harris RA, Chen G, Lin WY, Shen FM, London WT and Evans AA: Spontaneous clearance of high-titer serum HBV DNA and risk of hepatocellular carcinoma in a Chinese population. Cancer Causes Control. 14:995–1000. 2003. View Article : Google Scholar : PubMed/NCBI
4.	Shih LN, Sheu JC, Wang JT, et al: Serum hepatitis B virus DNA in healthy HBsAg-negative Chinese adults evaluated by polymerase chain reaction. J Med Virol. 32:257–260. 1990. View Article : Google Scholar : PubMed/NCBI
5.	Marusawa H, Uemoto S, Hijikata M, et al: Latent hepatitis B virus infection in healthy individuals with antibodies to hepatitis B core antigen. Hepatology. 31:488–495. 2000. View Article : Google Scholar : PubMed/NCBI
6.	Tuttleman JS, Pourcel C and Summers J: Formation of the pool of covalently closed circular viral DNA in hepadnavirus-infected cells. Cell. 47:451–460. 1986. View Article : Google Scholar : PubMed/NCBI
7.	Seeger C and Mason WS: Hepatitis B virus biology. Microbiol Mol Biol Rev. 64:51–68. 2000. View Article : Google Scholar
8.	Ichida F, Tsuji T, Omata M, et al: New Inuyama Classification; new criteria for histological assessment of chronic hepatitis. Int Hepatol Commun. 6:112–119. 1996. View Article : Google Scholar
9.	Sugauchi F, Mizokami M, Orito E, et al: A novel variant genotype C of hepatitis B virus identified in isolates from Australian Aborigines: complete genome sequence and phylogenetic relatedness. J Gen Virol. 82:883–892. 2001.
10.	Sugauchi F, Ohno T, Orito E, et al: Influence of hepatitis B virus genotypes on the development of preS deletions and advanced liver disease. J Med Virol. 70:537–544. 2003. View Article : Google Scholar : PubMed/NCBI
11.	Tamura K, Dudley J, Nei M and Kumar S: MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol. 24:1596–1599. 2007. View Article : Google Scholar : PubMed/NCBI
12.	Yeh CT, Shen CH, Tai DI, Chu CM and Liaw YF: Identification and characterization of a prevalent hepatitis B virus X protein mutant in Taiwanese patients with hepatocellular carcinoma. Oncogene. 19:5213–5220. 2000. View Article : Google Scholar : PubMed/NCBI
13.	Muroyama R, Kato N, Yoshida H, et al: Nucleotide change of codon 38 in the X gene of hepatitis B virus genotype C is associated with an increased risk of hepatocellular carcinoma. J Hepatol. 45:805–812. 2006. View Article : Google Scholar : PubMed/NCBI
14.	Sotiropoulos GC, Lang H, Frilling A, et al: Resectability of hepatocellular carcinoma: evaluation of 333 consecutive cases at a single hepatobiliary specialty center and systematic review of the literature. Hepatogastroenterology. 53:322–329. 2006.
15.	Hatanaka K, Kudo M, Fukunaga T, et al: Clinical characteristics of NonBNonC-HCC: comparison with HBV and HCV-related HCC. Intervirology. 50:24–31. 2007. View Article : Google Scholar : PubMed/NCBI
16.	Kao JH, Chen PJ, Lai MY and Chen DS: Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. J Clin Microbiol. 40:4068–4071. 2002. View Article : Google Scholar : PubMed/NCBI
17.	Mrani S, Chemin I, Menouar K, et al: Occult HBV infection may represent a major risk factor of non-response to antiviral therapy of chronic hepatitis C. J Med Virol. 79:1075–1081. 2007. View Article : Google Scholar : PubMed/NCBI
18.	Tamori A, Nishiguchi S, Kubo S, et al: Possible contribution to hepatocarcinogenesis of X transcript of hepatitis B virus in Japanese patients with hepatitis C virus. Hepatology. 29:1429–1434. 1999. View Article : Google Scholar : PubMed/NCBI
19.	Pollicino T, Squadrito G, Cerenzia G, et al: Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology. 126:102–110. 2004. View Article : Google Scholar : PubMed/NCBI
20.	Tamori A, Hayashi T, Shinzaki M, et al: Frequent detection of hepatitis B virus DNA in hepatocellular carcinoma of patients with sustained virologic response for hepatitis C virus. J Med Virol. 81:1009–1014. 2009. View Article : Google Scholar : PubMed/NCBI
21.	Kusakabe A, Tanaka Y, Orito E, et al: A weak association between occult HBV infection and non-B non-C hepatocellular carcinoma in Japan. J Gastroenterol. 42:298–305. 2007. View Article : Google Scholar : PubMed/NCBI
22.	Kim JK, Chang HY, Lee JM, et al: Specific mutations in the enhancer II/core promoter/precore regions of hepatitis B virus subgenotype C2 in Korean patients with hepatocellular carcinoma. J Med Virol. 81:1002–1008. 2009. View Article : Google Scholar : PubMed/NCBI
23.	Kao JH, Chen PJ, Lai MY and Chen DS: Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Gastroenterology. 124:327–334. 2003. View Article : Google Scholar : PubMed/NCBI
24.	Shinkai N, Tanaka Y, Ito K, et al: Influence of hepatitis B virus X and core promoter mutations on hepatocellular carcinoma among patients infected with subgenotype C2. J Clin Microbiol. 45:3191–3197. 2007. View Article : Google Scholar : PubMed/NCBI
25.	Tanaka Y, Mukaide M, Orito E, et al: Specific mutations in enhancer II/core promoter of hepatitis B virus subgenotypes C1/C2 increase the risk of hepatocellular carcinoma. J Hepatol. 45:646–653. 2006. View Article : Google Scholar : PubMed/NCBI
26.	Chen CH, Changchien CS, Lee CM, et al: A study on sequence variations in pre-S/surface, X and enhancer II/core promoter/precore regions of occult hepatitis B virus in non-B, non-C hepatocellular carcinoma patients in Taiwan. Int J Cancer. 125:621–629. 2009. View Article : Google Scholar : PubMed/NCBI
27.	Tabor E: Pathogenesis of hepatitis B virus-associated hepatocellular carcinoma. Hepatol Res. 37:110–114. 2007. View Article : Google Scholar : PubMed/NCBI
28.	Lupberger J and Hildt E: Hepatitis B virus-induced oncogenesis. World J Gastroenterol. 13:74–81. 2007. View Article : Google Scholar