Abstract
In testing for antibodies to the hepatitis C virus (anti-HCV) in 112 patients with primary hepatocellular carcinoma, 10 of 33 white patients (30%) and 15 of 79 Asian patients (19%) had a positive response to the antibody. The antibody profile to individual hepatitis C viral antigens and the presence of circulating hepatitis C viral RNA were determined in the 25 patients. The anti-HCV antibodies most frequently detected were toward the antigens from the core (C22) and NS3 regions. Serum hepatitis C viral RNA was present in 17 of the 25 patients (68%), and these patients tended to have serum levels of alanine and aspartate aminotransferases higher than those patients without viremia (136 +/- 22 U per liter versus 64 +/- 11 U per liter and 161 +/- 26 U per liter versus 79 +/- 14 U per liter, respectively, both P < .05). Of the 15 Asian patients with hepatocellular carcinoma and anti-HCV, 4 (27%) had coexisting hepatitis B surface antigen (HBsAg) and 13 (87%) had antibodies to either hepatitis B core or surface antigen. Of the 10 white patients with anti-HCV, however, only 1 (10%) had hepatitis B virus antibodies (P < .01). Among 4 Asian patients with coexisting anti-HCV and HBsAg, 1 was found to have serum hepatitis B viral DNA and the other 3 had hepatitis C viral RNA. A history of blood transfusion was obtained from 12 of the 25 patients with anti-HCV (48%); 20 (80%) had coexisting cirrhosis. Our findings support the hypothesis that hepatitis C virus is an important etiologic agent in the development of primary hepatocellular carcinoma in both white and Asian patients in the United States.
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- Bruix J., Barrera J. M., Calvet X., Ercilla G., Costa J., Sanchez-Tapias J. M., Ventura M., Vall M., Bruguera M., Bru C. Prevalence of antibodies to hepatitis C virus in Spanish patients with hepatocellular carcinoma and hepatic cirrhosis. Lancet. 1989 Oct 28;2(8670):1004–1006. doi: 10.1016/s0140-6736(89)91015-5. [DOI] [PubMed] [Google Scholar]
- Bukh J., Miller R. H., Kew M. C., Purcell R. H. Hepatitis C virus RNA in southern African blacks with hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1848–1851. doi: 10.1073/pnas.90.5.1848. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caporaso N., Romano M., Marmo R., de Sio I., Morisco F., Minerva A., Coltorti M. Hepatitis C virus infection is an additive risk factor for development of hepatocellular carcinoma in patients with cirrhosis. J Hepatol. 1991 May;12(3):367–371. doi: 10.1016/0168-8278(91)90841-x. [DOI] [PubMed] [Google Scholar]
- Chen D. S., Kuo G. C., Sung J. L., Lai M. Y., Sheu J. C., Chen P. J., Yang P. M., Hsu H. M., Chang M. H., Chen C. J. Hepatitis C virus infection in an area hyperendemic for hepatitis B and chronic liver disease: the Taiwan experience. J Infect Dis. 1990 Oct;162(4):817–822. doi: 10.1093/infdis/162.4.817. [DOI] [PubMed] [Google Scholar]
- Cheyrou A., Guyomarc'h C., Jasserand P., Blouin P. Improved detection of HBV DNA by PCR after microwave treatment of serum. Nucleic Acids Res. 1991 Jul 25;19(14):4006–4006. doi: 10.1093/nar/19.14.4006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chien D. Y., Choo Q. L., Tabrizi A., Kuo C., McFarland J., Berger K., Lee C., Shuster J. R., Nguyen T., Moyer D. L. Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: reevaluation of the role of HCV in liver disease. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10011–10015. doi: 10.1073/pnas.89.21.10011. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Choo Q. L., Kuo G., Weiner A. J., Overby L. R., Bradley D. W., Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359–362. doi: 10.1126/science.2523562. [DOI] [PubMed] [Google Scholar]
- Chuang W. L., Chang W. Y., Lu S. N., Su W. P., Lin Z. Y., Chen S. C., Hsieh M. Y., Wang L. Y., You S. L., Chen C. J. The role of hepatitis B and C viruses in hepatocellular carcinoma in a hepatitis B endemic area. A case-control study. Cancer. 1992 Apr 15;69(8):2052–2054. doi: 10.1002/1097-0142(19920415)69:8<2052::aid-cncr2820690808>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
- Colombo M., Kuo G., Choo Q. L., Donato M. F., Del Ninno E., Tommasini M. A., Dioguardi N., Houghton M. Prevalence of antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. Lancet. 1989 Oct 28;2(8670):1006–1008. doi: 10.1016/s0140-6736(89)91016-7. [DOI] [PubMed] [Google Scholar]
- Crawford R. J., Frame W. D., Mitchell R. HCV confirmatory testing of blood donors. Lancet. 1992 Apr 11;339(8798):928–928. [PubMed] [Google Scholar]
- Di Bisceglie A. M., Order S. E., Klein J. L., Waggoner J. G., Sjogren M. H., Kuo G., Houghton M., Choo Q. L., Hoofnagle J. H. The role of chronic viral hepatitis in hepatocellular carcinoma in the United States. Am J Gastroenterol. 1991 Mar;86(3):335–338. [PubMed] [Google Scholar]
- Fattovich G., Tagger A., Brollo L., Giustina G., Pontisso P., Realdi G., Alberti A., Ruol A. Hepatitis C virus infection in chronic hepatitis B virus carriers. J Infect Dis. 1991 Feb;163(2):400–402. doi: 10.1093/infdis/163.2.400. [DOI] [PubMed] [Google Scholar]
- Fong T. L., Di Bisceglie A. M., Waggoner J. G., Banks S. M., Hoofnagle J. H. The significance of antibody to hepatitis C virus in patients with chronic hepatitis B. Hepatology. 1991 Jul;14(1):64–67. doi: 10.1002/hep.1840140111. [DOI] [PubMed] [Google Scholar]
- Han J. H., Shyamala V., Richman K. H., Brauer M. J., Irvine B., Urdea M. S., Tekamp-Olson P., Kuo G., Choo Q. L., Houghton M. Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1711–1715. doi: 10.1073/pnas.88.5.1711. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hasan F., Jeffers L. J., De Medina M., Reddy K. R., Parker T., Schiff E. R., Houghton M., Choo Q. L., Kuo G. Hepatitis C-associated hepatocellular carcinoma. Hepatology. 1990 Sep;12(3 Pt 1):589–591. doi: 10.1002/hep.1840120323. [DOI] [PubMed] [Google Scholar]
- Irving W. L., Day S., Eglin R. P., Bennett D. P., Jones D. A., Nuttall P., James V. HCV and PCR negativity. Lancet. 1992 Jun 6;339(8806):1425–1425. doi: 10.1016/0140-6736(92)91251-3. [DOI] [PubMed] [Google Scholar]
- Kaklamani E., Trichopoulos D., Tzonou A., Zavitsanos X., Koumantaki Y., Hatzakis A., Hsieh C. C., Hatziyannis S. Hepatitis B and C viruses and their interaction in the origin of hepatocellular carcinoma. JAMA. 1991 Apr 17;265(15):1974–1976. [PubMed] [Google Scholar]
- Kiyosawa K., Sodeyama T., Tanaka E., Gibo Y., Yoshizawa K., Nakano Y., Furuta S., Akahane Y., Nishioka K., Purcell R. H. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology. 1990 Oct;12(4 Pt 1):671–675. doi: 10.1002/hep.1840120409. [DOI] [PubMed] [Google Scholar]
- Kuo G., Choo Q. L., Alter H. J., Gitnick G. L., Redeker A. G., Purcell R. H., Miyamura T., Dienstag J. L., Alter M. J., Stevens C. E. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989 Apr 21;244(4902):362–364. doi: 10.1126/science.2496467. [DOI] [PubMed] [Google Scholar]
- Kwok S., Higuchi R. Avoiding false positives with PCR. Nature. 1989 May 18;339(6221):237–238. doi: 10.1038/339237a0. [DOI] [PubMed] [Google Scholar]
- Lee S. D., Lee F. Y., Wu J. C., Hwang S. J., Wang S. S., Lo K. J. The prevalence of anti-hepatitis C virus among Chinese patients with hepatocellular carcinoma. Cancer. 1992 Jan 15;69(2):342–345. doi: 10.1002/1097-0142(19920115)69:2<342::aid-cncr2820690211>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
- Liang T. J., Baruch Y., Ben-Porath E., Enat R., Bassan L., Brown N. V., Rimon N., Blum H. E., Wands J. R. Hepatitis B virus infection in patients with idiopathic liver disease. Hepatology. 1991 Jun;13(6):1044–1051. [PubMed] [Google Scholar]
- Lok A. S., Cheung R., Chan R., Liu V. Hepatitis C viremia in patients with hepatitis C virus infection. Hepatology. 1992 Jun;15(6):1007–1012. doi: 10.1002/hep.1840150606. [DOI] [PubMed] [Google Scholar]
- Mack D. H., Sninsky J. J. A sensitive method for the identification of uncharacterized viruses related to known virus groups: hepadnavirus model system. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6977–6981. doi: 10.1073/pnas.85.18.6977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Martin P., Muñoz S. J., Di Bisceglie A. M., Rubin R., Waggoner J. G., Armenti V. T., Moritz M. J., Jarrell B. E., Maddrey W. C. Recurrence of hepatitis C virus infection after orthotopic liver transplantation. Hepatology. 1991 Apr;13(4):719–721. [PubMed] [Google Scholar]
- Myers T. W., Gelfand D. H. Reverse transcription and DNA amplification by a Thermus thermophilus DNA polymerase. Biochemistry. 1991 Aug 6;30(31):7661–7666. doi: 10.1021/bi00245a001. [DOI] [PubMed] [Google Scholar]
- Nishioka K., Watanabe J., Furuta S., Tanaka E., Iino S., Suzuki H., Tsuji T., Yano M., Kuo G., Choo Q. L. A high prevalence of antibody to the hepatitis C virus in patients with hepatocellular carcinoma in Japan. Cancer. 1991 Jan 15;67(2):429–433. doi: 10.1002/1097-0142(19910115)67:2<429::aid-cncr2820670218>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
- Ohosone Y., Katayama K., Ando T., Arima K., Hanada T., Obana M., Matsuoka Y., Irimajiri S. The association of serum hepatitis C virus RNA with serum aminotransferase activities. Scand J Infect Dis. 1992;24(2):249–250. doi: 10.3109/00365549209052621. [DOI] [PubMed] [Google Scholar]
- Ruiz J., Sangro B., Cuende J. I., Beloqui O., Riezu-Boj J. I., Herrero J. I., Prieto J. Hepatitis B and C viral infections in patients with hepatocellular carcinoma. Hepatology. 1992 Sep;16(3):637–641. doi: 10.1002/hep.1840160305. [DOI] [PubMed] [Google Scholar]
- Seeff L. B., Buskell-Bales Z., Wright E. C., Durako S. J., Alter H. J., Iber F. L., Hollinger F. B., Gitnick G., Knodell R. G., Perrillo R. P. Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group. N Engl J Med. 1992 Dec 31;327(27):1906–1911. doi: 10.1056/NEJM199212313272703. [DOI] [PubMed] [Google Scholar]
- Sheu J. C., Huang G. T., Shih L. N., Lee W. C., Chou H. C., Wang J. T., Lee P. H., Lai M. Y., Wang C. Y., Yang P. M. Hepatitis C and B viruses in hepatitis B surface antigen-negative hepatocellular carcinoma. Gastroenterology. 1992 Oct;103(4):1322–1327. doi: 10.1016/0016-5085(92)91523-7. [DOI] [PubMed] [Google Scholar]
- Simonetti R. G., Cammà C., Fiorello F., Cottone M., Rapicetta M., Marino L., Fiorentino G., Craxì A., Ciccaglione A., Giuseppetti R. Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study. Ann Intern Med. 1992 Jan 15;116(2):97–102. doi: 10.7326/0003-4819-116-2-97. [DOI] [PubMed] [Google Scholar]
- Smith G. E., Ju G., Ericson B. L., Moschera J., Lahm H. W., Chizzonite R., Summers M. D. Modification and secretion of human interleukin 2 produced in insect cells by a baculovirus expression vector. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8404–8408. doi: 10.1073/pnas.82.24.8404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith G. E., Summers M. D., Fraser M. J. Production of human beta interferon in insect cells infected with a baculovirus expression vector. Mol Cell Biol. 1983 Dec;3(12):2156–2165. doi: 10.1128/mcb.3.12.2156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tanaka K., Hirohata T., Koga S., Sugimachi K., Kanematsu T., Ohryohji F., Nawata H., Ishibashi H., Maeda Y., Kiyokawa H. Hepatitis C and hepatitis B in the etiology of hepatocellular carcinoma in the Japanese population. Cancer Res. 1991 Jun 1;51(11):2842–2847. [PubMed] [Google Scholar]
- Thelu M. A., Zarski J. P., Dardelet D., Lunel F., Seigneurin J. M. Low prevalence of hepatitis C virus genome detected by PCR in serum of Caucasian patients with hepatocellular carcinoma. J Hepatol. 1992 Mar;14(2-3):415–416. doi: 10.1016/0168-8278(92)90202-z. [DOI] [PubMed] [Google Scholar]
- Tong M. J., Sun S. C., Schaeffer B. T., Chang N. K., Lo K. J., Peters R. L. Hepatitis-associated antigen and hepatocellular carcinoma in Taiwan. Ann Intern Med. 1971 Nov;75(5):687–691. doi: 10.7326/0003-4819-75-5-687. [DOI] [PubMed] [Google Scholar]
- Tremolada F., Casarin C., Alberti A., Drago C., Tagger A., Ribero M. L., Realdi G. Long-term follow-up of non-A, non-B (type C) post-transfusion hepatitis. J Hepatol. 1992 Nov;16(3):273–281. doi: 10.1016/s0168-8278(05)80657-9. [DOI] [PubMed] [Google Scholar]
- Weiner A. J., Brauer M. J., Rosenblatt J., Richman K. H., Tung J., Crawford K., Bonino F., Saracco G., Choo Q. L., Houghton M. Variable and hypervariable domains are found in the regions of HCV corresponding to the flavivirus envelope and NS1 proteins and the pestivirus envelope glycoproteins. Virology. 1991 Feb;180(2):842–848. doi: 10.1016/0042-6822(91)90104-j. [DOI] [PubMed] [Google Scholar]
- Weiner A. J., Kuo G., Bradley D. W., Bonino F., Saracco G., Lee C., Rosenblatt J., Choo Q. L., Houghton M. Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet. 1990 Jan 6;335(8680):1–3. doi: 10.1016/0140-6736(90)90134-q. [DOI] [PubMed] [Google Scholar]
- Yu M. C., Tong M. J., Coursaget P., Ross R. K., Govindarajan S., Henderson B. E. Prevalence of hepatitis B and C viral markers in black and white patients with hepatocellular carcinoma in the United States. J Natl Cancer Inst. 1990 Jun 20;82(12):1038–1041. doi: 10.1093/jnci/82.12.1038. [DOI] [PubMed] [Google Scholar]
- Yuki N., Hayashi N., Kasahara A., Hagiwara H., Katayama K., Fusamoto H., Kamada T. Hepatitis B virus markers and antibodies to hepatitis C virus in Japanese patients with hepatocellular carcinoma. Dig Dis Sci. 1992 Jan;37(1):65–72. doi: 10.1007/BF01308344. [DOI] [PubMed] [Google Scholar]
- Zaaijer H. L., Cuypers H. T., Reesink H. W., Winkel I. N., Gerken G., Lelie P. N. Reliability of polymerase chain reaction for detection of hepatitis C virus. Lancet. 1993 Mar 20;341(8847):722–724. doi: 10.1016/0140-6736(93)90488-3. [DOI] [PubMed] [Google Scholar]
- Zuckerman A. J. Viral superinfection. Hepatology. 1987 Jan-Feb;7(1):184–185. doi: 10.1002/hep.1840070134. [DOI] [PubMed] [Google Scholar]