Liver Angiogenesis As a Risk Factor for Hepatocellular Carcinoma Development in Hepatitis C Virus Cirrhotic Patients

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2007 Sep 15

PMID 17854145

Citations 4

Authors

Roberto Mazzanti

Luca Messerini

Camilla E Comin

Lorenzo Fedeli

Nathalie Ganne-Carrie

Michel Beaugrand

Affiliations

Soon will be listed here.

Abstract

Aim: To evaluate the predictive value of hepatocyte proliferation and hepatic angiogenesis for the occurrence of Hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients.

Methods: One hundred-five patients (69 males, 36 females; age range, 51-90 year; median 66 year) with biopsy proven HCV cirrhosis were prospectively monitored for HCC occurrence for a median time of 64 mo. Angiogenesis was assessed by using microvessel density (MVD), hepatocyte turnover by MIB1 and PCNA indexes at inclusion in liver biopsies.

Results: Forty six patients (43.8%) developed HCC after a median time of 55 (6-120) mo while 59 (56.2%) did not. Patients were divided into two groups according to the median value of each index. The difference between patients with low (median MVD = 3; range 0-20) and high (median MVD = 7; range 1-24) MVD was statistically significant (chi(2) = 22.06; P < 0.0001) which was not the case for MIB1 or PCNA (MIB-1: chi(2) = 1.41; P = 0.2351; PCNA: chi(2) = 1.27; P = 0.2589). The median MVD was higher in patients who developed HCC than in those who did not. HCC-free interval was significantly longer in patients with the MVD < or = 4 (P = 0.0006). No relationship was found between MIB1 or PCNA and MVD (MIB-1 r(2) = 0.00007116, P = 0.9281; PCNA: r(2) = 0.001950; P = 0.6692). MVD only was able to predict the occurrence of HCC in these patients. Among other known risk factors for HCC, only male sex was statistically associated with an increased risk.

Conclusion: Liver angiogenesis has a role for in HCV-related liver carcinogenesis and for defining patients at higher risk.

Citing Articles

DNMT1-induced miR-378a-3p silencing promotes angiogenesis via the NF-κB signaling pathway by targeting TRAF1 in hepatocellular carcinoma.

Zhu B, Chen J, Feng Y, Yang J, Huang H, Chung W J Exp Clin Cancer Res. 2021; 40(1):352.

PMID: 34749775 PMC: 8576931. DOI: 10.1186/s13046-021-02110-6.

Hepatocellular carcinoma: Where are we?.

Mazzanti R, Arena U, Tassi R World J Exp Med. 2016; 6(1):21-36.

PMID: 26929917 PMC: 4759352. DOI: 10.5493/wjem.v6.i1.21.

Angiogenesis and liver fibrosis.

Elpek G World J Hepatol. 2015; 7(3):377-91.

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Resection of a transplantable single-nodule hepatocellular carcinoma in Child-Pugh class A cirrhosis: factors affecting survival and recurrence.

Muscari F, Foppa B, Carrere N, Kamar N, Peron J, Suc B World J Surg. 2011; 35(5):1055-62.

PMID: 21360309 DOI: 10.1007/s00268-011-1000-3.

References

Ishikawa H, Nakao K, Matsumoto K, Ichikawa T, Hamasaki K, Nakata K . Antiangiogenic gene therapy for hepatocellular carcinoma using angiostatin gene. Hepatology. 2003; 37(3):696-704. DOI: 10.1053/jhep.2003.50077. View

Romeo R, Colombo M . The natural history of hepatocellular carcinoma. Toxicology. 2002; 181-182:39-42. DOI: 10.1016/s0300-483x(02)00252-4. View

Hino O, Kajino K, Umeda T, Arakawa Y . Understanding the hypercarcinogenic state in chronic hepatitis: a clue to the prevention of human hepatocellular carcinoma. J Gastroenterol. 2002; 37(11):883-7. DOI: 10.1007/s005350200149. View

Hlatky L, Hahnfeldt P, Folkman J . Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn't tell us. J Natl Cancer Inst. 2002; 94(12):883-93. DOI: 10.1093/jnci/94.12.883. View

Seeff L, Hoofnagle J . Appendix: The National Institutes of Health Consensus Development Conference Management of Hepatitis C 2002. Clin Liver Dis. 2003; 7(1):261-87. DOI: 10.1016/s1089-3261(02)00078-8. View

Anzola M . Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis. J Viral Hepat. 2004; 11(5):383-93. DOI: 10.1111/j.1365-2893.2004.00521.x. View

Block T, Mehta A, Fimmel C, Jordan R . Molecular viral oncology of hepatocellular carcinoma. Oncogene. 2003; 22(33):5093-107. DOI: 10.1038/sj.onc.1206557. View

Rahman M, Kohno H, Nagasue N . COX-2 - a target for preventing hepatic carcinoma?. Expert Opin Ther Targets. 2002; 6(4):483-90. DOI: 10.1517/14728222.6.4.483. View

Yamanoi A, Soda Y, Yamaguchi M, Igarashi M, Yamamoto A, Nabika T . Clinical significance of microvessel density and vascular endothelial growth factor expression in hepatocellular carcinoma and surrounding liver: possible involvement of vascular endothelial growth factor in the angiogenesis of cirrhotic liver. Hepatology. 1998; 27(6):1554-62. DOI: 10.1002/hep.510270613. View

10.

Poon R, Ng I, Lau C, Yu W, Yang Z, Fan S . Tumor microvessel density as a predictor of recurrence after resection of hepatocellular carcinoma: a prospective study. J Clin Oncol. 2002; 20(7):1775-85. DOI: 10.1200/JCO.2002.07.089. View

11.

Vermeulen P, Gasparini G, Fox S, Colpaert C, Marson L, Gion M . Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer. 2002; 38(12):1564-79. DOI: 10.1016/s0959-8049(02)00094-1. View

12.

Park Y, Kim Y, Yang K, Park C . Increased expression of vascular endothelial growth factor and angiogenesis in the early stage of multistep hepatocarcinogenesis. Arch Pathol Lab Med. 2000; 124(7):1061-5. DOI: 10.5858/2000-124-1061-IEOVEG. View

13.

McDonald D, Choyke P . Imaging of angiogenesis: from microscope to clinic. Nat Med. 2003; 9(6):713-25. DOI: 10.1038/nm0603-713. View

14.

Persico M, Palmentieri B, Coppola L, Di Giacomo Russo G, De Marino F, de Sio I . Occurrence of HCC in asymptomatic HCV-related chronic hepatitis. Dig Dis Sci. 2002; 47(11):2407-10. DOI: 10.1023/a:1020527118782. View

15.

Schulze Zur Wiesch J, Schmitz H, Borowski E, Borowski P . The proteins of the Hepatitis C virus: their features and interactions with intracellular protein phosphorylation. Arch Virol. 2003; 148(7):1247-67. DOI: 10.1007/s00705-003-0115-8. View

16.

Bruno S, Battezzati P, Bellati G, Manzin A, Maggioni M, Crosignani A . Long-term beneficial effects in sustained responders to interferon-alfa therapy for chronic hepatitis C. J Hepatol. 2001; 34(5):748-55. DOI: 10.1016/s0168-8278(01)00062-9. View

17.

Knodell R, Ishak K, Black W, Chen T, Craig R, Kaplowitz N . Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981; 1(5):431-5. DOI: 10.1002/hep.1840010511. View

18.

Hasan J, Byers R, Jayson G . Intra-tumoural microvessel density in human solid tumours. Br J Cancer. 2002; 86(10):1566-77. PMC: 2746601. DOI: 10.1038/sj.bjc.6600315. View

19.

Hayashi J, Aoki H, Arakawa Y, Hino O . Hepatitis C virus and hepatocarcinogenesis. Intervirology. 1999; 42(2-3):205-10. DOI: 10.1159/000024962. View

20.

Oon C, Chen W . Lymphoblastoid alpha-interferon in the prevention of hepatocellular carcinoma (HCC) in high-risk HbsAg-positive resected cirrhotic HCC cases: a 14-year follow-up. Cancer Invest. 2003; 21(3):394-9. DOI: 10.1081/cnv-120018231. View