Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Mar 1;90(5):1848–1851. doi: 10.1073/pnas.90.5.1848

Hepatitis C virus RNA in southern African blacks with hepatocellular carcinoma.

J Bukh 1, R H Miller 1, M C Kew 1, R H Purcell 1
PMCID: PMC45977  PMID: 8383330

Abstract

We used a sensitive and specific cDNA polymerase chain reaction assay to detect hepatitis C virus (HCV) RNA in serum samples from 128 unselected southern African Blacks with hepatocellular carcinoma (HCC) and found HCV RNA in 26 (20.3%) of these patients. Antibodies to HCV (anti-HCV) were detected in 59 patients (46.1%) with a first-generation ELISA test, and only 19 of these patients were HCV RNA-positive. Anti-HCV was detected in 25 patients (19.5%) with a second-generation ELISA test, and 17 of these patients were HCV RNA-positive. Among the second-generation ELISA- and HCV RNA-positive patients, 14 were anti-HCV positive, 2 were indeterminate, and 1 was anti-HCV negative in a second-generation recombinant immunoblot assay, whereas all patients who were second-generation ELISA positive, but HCV RNA negative, were anti-HCV negative in this immunoblot assay. A total of 5 patients were negative in both ELISA tests but were HCV RNA positive. Seventy-one patients (55.5%) had evidence of a current HBV infection, 50 (39.1%) had evidence of a previous infection, and 7 (5.5%) had no evidence of a current or previous HBV infection. The prevalence of current HBV infection was significantly lower in patients who were positive for HCV RNA than in those who were negative (P = 0.001). This difference was not dependent on sex, age, or geographical location of the patients. The mean age of HCC patients positive for HCV RNA (52.3 years) was significantly higher (P < 0.001) than that of negative patients (40.3 years), and the difference was not dependent on HBV status or geographical location. Patients positive for HCV RNA were more likely to be urban than were negative patients. Thus, a significant number of southern African Blacks with HCC had a current HCV infection but not a current HBV infection, further suggesting that infection with HCV plays a role, albeit minor, in the development of HCC in this population.

Full text

PDF
1848

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. 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]
  2. Bukh J., Purcell R. H., Miller R. H. Importance of primer selection for the detection of hepatitis C virus RNA with the polymerase chain reaction assay. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):187–191. doi: 10.1073/pnas.89.1.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bukh J., Purcell R. H., Miller R. H. Sequence analysis of the 5' noncoding region of hepatitis C virus. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4942–4946. doi: 10.1073/pnas.89.11.4942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Chou W. H., Yoneyama T., Takeuchi K., Harada H., Saito I., Miyamura T. Discrimination of hepatitis C virus in liver tissues from different patients with hepatocellular carcinomas by direct nucleotide sequencing of amplified cDNA of the viral genome. J Clin Microbiol. 1991 Dec;29(12):2860–2864. doi: 10.1128/jcm.29.12.2860-2864.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Cohen E. B., Gang D. L., Zeldis J. B. Primary hepatocellular carcinoma following nonspecific non-B hepatitis with tumor DNA negative for HBV DNA. Dig Dis Sci. 1987 Dec;32(12):1428–1430. doi: 10.1007/BF01296671. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Coursaget P., Bourdil C., Kastally R., Yvonnet B., Rampanarivo Z., Chiron J. P., Bao O., Diop-Mar I., Perrin J., Ntarème F. Prevalence of hepatitis C virus infection in Africa: anti-HCV antibodies in the general population and in patients suffering from cirrhosis or primary liver cancer. Res Virol. 1990 Jul-Aug;141(4):449–454. doi: 10.1016/0923-2516(90)90045-k. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Dienstag J. L., Alter H. J. Non-A, non-B hepatitis: evolving epidemiologic and clinical perspective. Semin Liver Dis. 1986 Feb;6(1):67–81. doi: 10.1055/s-2008-1040795. [DOI] [PubMed] [Google Scholar]
  13. Garson J. A., Tedder R. S., Briggs M., Tuke P., Glazebrook J. A., Trute A., Parker D., Barbara J. A., Contreras M., Aloysius S. Detection of hepatitis C viral sequences in blood donations by "nested" polymerase chain reaction and prediction of infectivity. Lancet. 1990 Jun 16;335(8703):1419–1422. doi: 10.1016/0140-6736(90)91446-h. [DOI] [PubMed] [Google Scholar]
  14. Gilliam J. H., 3rd, Geisinger K. R., Richter J. E. Primary hepatocellular carcinoma after chronic non-A, non-B post-transfusion hepatitis. Ann Intern Med. 1984 Dec;101(6):794–795. doi: 10.7326/0003-4819-101-6-794. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Jeng J. E., Tsai J. F. Hepatitis C virus antibody in hepatocellular carcinoma in Taiwan. J Med Virol. 1991 May;34(1):74–77. doi: 10.1002/jmv.1890340113. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Kew M. C., Houghton M., Choo Q. L., Kuo G. Hepatitis C virus antibodies in southern African blacks with hepatocellular carcinoma. Lancet. 1990 Apr 14;335(8694):873–874. doi: 10.1016/0140-6736(90)90474-j. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Kiyosawa K., Tanaka E., Sodeyama T., Furuta K., Usuda S., Yousuf M., Furuta S. Transition of antibody to hepatitis C virus from chronic hepatitis to hepatocellular carcinoma. Jpn J Cancer Res. 1990 Nov;81(11):1089–1091. doi: 10.1111/j.1349-7006.1990.tb02517.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Levrero M., Tagger A., Balsano C., De Marzio E., Avantaggiati M. L., Natoli G., Diop D., Villa E., Diodati G., Alberti A. Antibodies to hepatitis C virus in patients with hepatocellular carcinoma. J Hepatol. 1991 Jan;12(1):60–63. doi: 10.1016/0168-8278(91)90910-4. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Muchmore E., Popper H., Peterson D. A., Miller M. F., Lieberman H. M. Non-A, non-B hepatitis-related hepatocellular carcinoma in a chimpanzee. J Med Primatol. 1988;17(5):235–246. [PubMed] [Google Scholar]
  26. Nalpas B., Driss F., Pol S., Hamelin B., Housset C., Brechot C., Berthelot P. Association between HCV and HBV infection in hepatocellular carcinoma and alcoholic liver disease. J Hepatol. 1991 Jan;12(1):70–74. doi: 10.1016/0168-8278(91)90912-u. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Ohkoshi S., Kojima H., Tawaraya H., Miyajima T., Kamimura T., Asakura H., Satoh A., Hirose S., Hijikata M., Kato N. Prevalence of antibody against non-A, non-B hepatitis virus in Japanese patients with hepatocellular carcinoma. Jpn J Cancer Res. 1990 Jun-Jul;81(6-7):550–553. doi: 10.1111/j.1349-7006.1990.tb02605.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Okamoto H., Okada S., Sugiyama Y., Tanaka T., Sugai Y., Akahane Y., Machida A., Mishiro S., Yoshizawa H., Miyakawa Y. Detection of hepatitis C virus RNA by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5'-noncoding region. Jpn J Exp Med. 1990 Aug;60(4):215–222. [PubMed] [Google Scholar]
  30. Resnick R. H., Stone K., Antonioli D. Primary hepatocellular carcinoma following non-A, non-B posttransfusion hepatitis. Dig Dis Sci. 1983 Oct;28(10):908–911. doi: 10.1007/BF01317042. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Saito I., Miyamura T., Ohbayashi A., Harada H., Katayama T., Kikuchi S., Watanabe Y., Koi S., Onji M., Ohta Y. Hepatitis C virus infection is associated with the development of hepatocellular carcinoma. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6547–6549. doi: 10.1073/pnas.87.17.6547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sbolli G., Zanetti A. R., Tanzi E., Cavanna L., Civardi G., Fornari F., Di Stasi M., Buscarini L. Serum antibodies to hepatitis C virus in Italian patients with hepatocellular carcinoma. J Med Virol. 1990 Mar;30(3):230–232. doi: 10.1002/jmv.1890300316. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. 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]
  36. Thomas D. G. Exact and asymptotic methods for the combination of 2 times 2 tables. Comput Biomed Res. 1975 Oct;8(5):423–446. doi: 10.1016/0010-4809(75)90048-8. [DOI] [PubMed] [Google Scholar]
  37. Watanabe Y., Harada S., Saito I., Miyamura T. Prevalence of antibody against the core protein of hepatitis C virus in patients with hepatocellular carcinoma. Int J Cancer. 1991 May 30;48(3):340–343. doi: 10.1002/ijc.2910480305. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Yoneyama T., Takeuchi K., Watanabe Y., Harada H., Ohbayashi A., Tanaka Y., Yuasa T., Saito I., Miyamura T. Detection of hepatitis C virus cDNA sequence by the polymerase chain reaction in hepatocellular carcinoma tissues. Jpn J Med Sci Biol. 1990 Jun;43(3):89–94. doi: 10.7883/yoken1952.43.89. [DOI] [PubMed] [Google Scholar]
  40. 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]
  41. Yu M. W., You S. L., Chang A. S., Lu S. N., Liaw Y. F., Chen C. J. Association between hepatitis C virus antibodies and hepatocellular carcinoma in Taiwan. Cancer Res. 1991 Oct 15;51(20):5621–5625. [PubMed] [Google Scholar]
  42. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES