Skip to main content

Integrated fibrosis scoring by ultrasonography predicts the occurrence of hepatocellular carcinoma in patients with chronic hepatitis C virus infection

Abstract

Purpose

This study was performed to elucidate whether evaluating the liver surface, edge, and texture by high-resolution ultrasonography is useful for predicting the occurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-associated chronic liver diseases (CLDs)

Methods

The integrated fibrosis stage (a comprehensive value of scores for liver edge, surface, and texture) of 337 patients with HCV-associated CLDs was evaluated, at entry, by ultrasonography (US), as a US score. The patients were followed up prospectively (mean observation period was 16.4 months; range 2.8–36.2 months) for the occurrence of HCC by US or helical CT at 3-month intervals. A total of 140 patients received interferon therapy, and the occurrence of HCC was compared between those with and without interferon therapy

Results

The annual incidence of HCC was 1.1, 5.5, and 10.2% in low, middle, and high US score groups, respectively. Univariate analysis showed that age, serum levels of total bilirubin, alpha-fetoprotein (AFP), platelet count, albumin, total cholesterol, and the US score were associated with HCC occurrence in the patients. A multivariate proportional hazard model revealed that only the middle and high US scores (p = 0.0922, hazard ratio 4.006, 95% CI 0.796–20.153 and p = 0.008, hazard ratio 7.991, 95% CI 1.721–37.10, respectively) and elevated AFP (p = 0.031, hazard ratio 2.774, CI 1.097–7.014) were independently associated with HCC occurrence. Our US scoring based on evaluation of the liver surface, edge, and texture was clearly and strongly associated with the occurrence of HCC in patients with HCV-associated CLDs, and with the higher occurrence rate of HCC in patients with higher US scores

Conclusion

Thus, US is a good tool for evaluating the fibrosis stage of the liver, and may therefore be useful in designing an optimum follow-up interval for each patient with HCV-associated CLD.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Ikeda K, Saitoh S, Suzuki Y, et al. Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis—a prospective observation of 2215 patients. J Hepatol. 1998;28:930–8.

    CAS  Article  PubMed  Google Scholar 

  2. Tsukuma H, Hiyama T, Tanaka S, et al. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993;328:1797–801.

    CAS  Article  PubMed  Google Scholar 

  3. Ikeda K, Saitoh S, Koida I, et al. A multivariate analysis of risk factor for hepatocellular carcinogenesis—a prospective observation of 795 cases with viral and alcoholic cirrhosis. Hepatology. 1993;18:47–53.

    CAS  Article  PubMed  Google Scholar 

  4. Simonetti RG, Camma C, Fiorello F, et al. Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case–control study. Ann Intern Med. 1992;116:97–102.

    CAS  PubMed  Google Scholar 

  5. Yoshida H, Shiratori Y, Moriyama M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. IHIT Study Group. Inhibition of Hepatocarcinogenesis by Interferon Therapy. Ann Intern Med. 1999;131(3):174–81.

    CAS  PubMed  Google Scholar 

  6. Hung C-H, Lu SN, Wang JH, et al. Correlation between ultrasonographic and pathologic diagnoses of hepatitis B and C virus-related cirrhosis. J Gastroenterol. 2003;38:153–7.

    Article  PubMed  Google Scholar 

  7. Khan KN, Yamasaki M, Yamasaki K, et al. Proposed abdominal sonographic staging to predict severity of liver diseases: analysis with peritoneoscopy and histology. Dig Dis Sci. 2000;45:554–64.

    CAS  Article  PubMed  Google Scholar 

  8. Gaiani S, Gramantieri L, Venturoli N, et al. What is the criterion for differentiating chronic hepatitis from compensated cirrhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy. J Hepatol. 1997;27:979–85.

    CAS  Article  PubMed  Google Scholar 

  9. Simonovsky V. The diagnosis of cirrhosis by high resolution ultrasound of the liver surface. Br J Radiol. 1999;72:29–34.

    CAS  PubMed  Google Scholar 

  10. Ferral H, Male R, Cardiel M, et al. Cirrhosis: diagnosis by liver surface analysis with high-frequency ultrasound. Gastrointest Radiol. 1992;17:74–8.

    CAS  Article  PubMed  Google Scholar 

  11. Nishiura T, Watanabe H, Ishibashi H, et al. Ultrasound evaluation of the fibrosis stage in chronic liver disease by the simultaneous use of low and high frequency probes. Br J Radiol. 2005;78:189–97.

    CAS  Article  PubMed  Google Scholar 

  12. Moriya K, Fujie H, Shintani Y, et al. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med. 1998;4:1065–7.

    CAS  Article  PubMed  Google Scholar 

  13. Niederau C, Lange S, Heintges T, et al. Prognosis of chronic hepatitis C: results of a large, prospective cohort study. Hepatology. 1998;28:1687–95.

    CAS  Article  PubMed  Google Scholar 

  14. Nishiura T, Watanabe H, Ishibashi H, et al. Efficacy of the Liver US Score for the discrimination of early-stage cirrhosis (F4) from advanced-stage chronic hepatitis (F3). Jpn J Med Ultrasonics. 2006;33(6):655–63.

    Google Scholar 

  15. Degos F, Christidis C, Ganne-Carrie N, et al. Hepatitis C virus related cirrhosis: time to occurrence of hepatocellular carcinoma and death. Gut. 2000;47:131–6.

    CAS  Article  PubMed  Google Scholar 

  16. Tarao K, Rino Y, Ohkawa S, et al. Association between high serum alanine aminotransferase levels and more rapid development and higher rate of incidence of hepatocellular carcinoma in patients with hepatitis C virus-associated cirrhosis. Cancer. 1999;86:589–95.

    CAS  Article  PubMed  Google Scholar 

  17. Kasahara A, Hayashi N, Mochizuki K, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology. 1998;27(5):1394–402.

    CAS  Article  PubMed  Google Scholar 

  18. Castéra L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343–50.

    Article  PubMed  Google Scholar 

  19. Vizzutti F, Arena U, Marra F, et al. Elastography for the non-invasive assessment of liver disease: limitations and future developments. Gut. 2009;58:157–60.

    Article  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Tetsuya Nishiura.

About this article

Cite this article

Nishiura, T., Watanabe, H., Yano, K. et al. Integrated fibrosis scoring by ultrasonography predicts the occurrence of hepatocellular carcinoma in patients with chronic hepatitis C virus infection. J Med Ultrasonics 38, 13–19 (2011). https://doi.org/10.1007/s10396-010-0285-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10396-010-0285-4

Keywords

  • Hepatocellular carcinoma
  • Hepatitis C virus
  • Fibrosis
  • High and low-frequency probe
  • US score