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. 2001 Feb;48(2):251–259. doi: 10.1136/gut.48.2.251

Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis

L Bolondi 1, S Sofia 1, S Siringo 1, S Gaiani 1, A Casali 1, G Zironi 1, F Piscaglia 1, L Gramantieri 1, M Zanetti 1, M Sherman 1
PMCID: PMC1728189  PMID: 11156649

Abstract

BACKGROUND—Hepatocellular carcinoma (HCC) is a major cause of death in cirrhotic patients. This neoplasm is associated with liver cirrhosis (LC) in more than 90% of cases. Early diagnosis and treatment of HCC are expected to improve survival of patients.
AIMS—To assess the cost effectiveness of a surveillance programme of patients with LC for the early diagnosis and treatment of HCC.
PATIENTS—A cohort of 313 Italian patients with LC were enrolled in the surveillance programme between March 1989 and November 1991. In the same period, 104 consecutive patients with incidentally detected HCC were referred to our centre and served as a control group.
METHODS—Surveillance was based on ultrasonography (US) and α fetoprotein (AFP) determinations repeated at six month intervals. Risk factors for HCC were assessed by multivariate analysis (Cox model). Outcome measures analysed were: (1) number and size of tumours; (2) eligibility for treatment; and (3) survival of patients. Economic issues were: (1) overall cost of surveillance programme; (2) cost per treatable HCC; and (3) cost per year of life saved (if any). Costs were assessed according to charges for procedures at our university hospital.
RESULTS—Surveillance lasted a mean of 56 (31) months (range 6-100). During the follow up, 61 patients (19.5%) developed HCC (unifocal at US in 49 cases), with an incidence of 4.1% per year of follow up. AFP, Child-Pugh classes B and C, and male sex were detected as independent risk factors for developing HCC. Only 42 (68.9%) of 61 liver tumours were treated by surgical resection, orthotopic liver transplantation, or local therapy. The cumulative survival rate of the 61 patients with liver tumours detected in the surveillance programme was significantly longer than that of controls (p=0.02) and multivariate analysis showed an association between surveillance and survival. The overall cost of the surveillance programme was US$753 226, the cost per treatable HCC was US$17 934, and the cost for year of life saved was US$112 993.
CONCLUSION—Our surveillance policy of patients with LC requires a large number of resources and offers little benefit in terms of patient survival. The decision whether to adopt a surveillance policy towards HCC should rely on the prevalence of the disease in the population and on the resources of a particular country.


Keywords: hepatocellular carcinoma; surveillance programme; cost effectiveness

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Figure 1  .

Figure 1  

Cumulative rate of patients free of hepatocellular carcinoma (HCC) in the cohort of 313 patients with liver cirrhosis.

Figure 2  .

Figure 2  

Cumulative rates of patients free of hepatocellular carcinoma (HCC) according to Child-Pugh class and α fetoprotein (AFP) level at entry into the study. 1, Child-Pugh class B/C and AFP >20 ng/ml (n=26); 2,Child-Pugh class A and AFP <20 ng/ml (n=173); 3, Child-Pugh class A and AFP >20 ng/ml (n=27); 4, Child-Pugh class B/C and AFP <20 ng/ml (n=87).

Figure 3  .

Figure 3  

Cumulative survival rates of hepatocellular carcinoma (HCC) detected during follow up and HCC detected in unscreened patients. 1, HCC detected in surveilled patients (36 dead, 25 censored); 2, HCC detected in unsurveilled patients (95 dead, nine censored).

Figure 4  .

Figure 4  

Cumulative survival rates of patients with liver cirrhosis (LC) enrolled in the study and patients with incidental hepatocellular carcinoma (HCC) stratified according to Child-Pugh class. 1, LC and Child-Pugh A class; 2, LC and Child-Pugh B/C class; 3, HCC and Child-Pugh A class; 4, HCC and Child-Pugh B/C class.

Selected References

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

  1. Attali P., Prod'Homme S., Pelletier G., Papoz L., Ink O., Buffet C., Etienne J. P. Prognostic factors in patients with hepatocellular carcinoma. Attempts for the selection of patients with prolonged survival. Cancer. 1987 Jun 15;59(12):2108–2111. doi: 10.1002/1097-0142(19870615)59:12<2108::aid-cncr2820591225>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  2. Barbara L., Benzi G., Gaiani S., Fusconi F., Zironi G., Siringo S., Rigamonti A., Barbara C., Grigioni W., Mazziotti A. Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival. Hepatology. 1992 Jul;16(1):132–137. doi: 10.1002/hep.1840160122. [DOI] [PubMed] [Google Scholar]
  3. Black W. C., Welch H. G. Advances in diagnostic imaging and overestimations of disease prevalence and the benefits of therapy. N Engl J Med. 1993 Apr 29;328(17):1237–1243. doi: 10.1056/NEJM199304293281706. [DOI] [PubMed] [Google Scholar]
  4. Bolondi L., Gramantieri L., Chieco P., Melchiorri C., Treré D., Stecca B., Derenzini M., Barbara L. Enzymatic cytochemistry, DNA ploidy and AgNOR quantitation in hepatocellular nodules of uncertain malignant potential in liver cirrhosis. Dig Dis Sci. 1996 Apr;41(4):800–808. doi: 10.1007/BF02213139. [DOI] [PubMed] [Google Scholar]
  5. Borzio M., Bruno S., Roncalli M., Mels G. C., Ramella G., Borzio F., Leandro G., Servida E., Podda M. Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: a prospective study. Gastroenterology. 1995 Mar;108(3):812–817. doi: 10.1016/0016-5085(95)90455-7. [DOI] [PubMed] [Google Scholar]
  6. CUTLER S. J., EDERER F. Maximum utilization of the life table method in analyzing survival. J Chronic Dis. 1958 Dec;8(6):699–712. doi: 10.1016/0021-9681(58)90126-7. [DOI] [PubMed] [Google Scholar]
  7. Calvet X., Bruix J., Ginés P., Bru C., Solé M., Vilana R., Rodés J. Prognostic factors of hepatocellular carcinoma in the west: a multivariate analysis in 206 patients. Hepatology. 1990 Oct;12(4 Pt 1):753–760. doi: 10.1002/hep.1840120422. [DOI] [PubMed] [Google Scholar]
  8. Collier J., Sherman M. Screening for hepatocellular carcinoma. Hepatology. 1998 Jan;27(1):273–278. doi: 10.1002/hep.510270140. [DOI] [PubMed] [Google Scholar]
  9. Colombo M., de Franchis R., Del Ninno E., Sangiovanni A., De Fazio C., Tommasini M., Donato M. F., Piva A., Di Carlo V., Dioguardi N. Hepatocellular carcinoma in Italian patients with cirrhosis. N Engl J Med. 1991 Sep 5;325(10):675–680. doi: 10.1056/NEJM199109053251002. [DOI] [PubMed] [Google Scholar]
  10. Cottone M., Turri M., Caltagirone M., Maringhini A., Sciarrino E., Virdone R., Fusco G., Orlando A., Marino L., Pagliaro L. Early detection of hepatocellular carcinoma associated with cirrhosis by ultrasound and alfafetoprotein: a prospective study. Hepatogastroenterology. 1988 Jun;35(3):101–103. [PubMed] [Google Scholar]
  11. Cottone M., Turri M., Caltagirone M., Parisi P., Orlando A., Fiorentino G., Virdone R., Fusco G., Grasso R., Simonetti R. G. Screening for hepatocellular carcinoma in patients with Child's A cirrhosis: an 8-year prospective study by ultrasound and alphafetoprotein. J Hepatol. 1994 Dec;21(6):1029–1034. doi: 10.1016/s0168-8278(05)80613-0. [DOI] [PubMed] [Google Scholar]
  12. Detsky A. S., Naglie I. G. A clinician's guide to cost-effectiveness analysis. Ann Intern Med. 1990 Jul 15;113(2):147–154. doi: 10.7326/0003-4819-113-2-147. [DOI] [PubMed] [Google Scholar]
  13. Elixhauser A. Costs of breast cancer and the cost-effectiveness of breast cancer screening. Int J Technol Assess Health Care. 1991;7(4):604–615. doi: 10.1017/s0266462300007169. [DOI] [PubMed] [Google Scholar]
  14. Finkler S. A. The distinction between cost and charges. Ann Intern Med. 1982 Jan;96(1):102–109. doi: 10.7326/0003-4819-96-1-102. [DOI] [PubMed] [Google Scholar]
  15. Ikeda K., Saitoh S., Koida I., Arase Y., Tsubota A., Chayama K., Kumada H., Kawanishi M. A multivariate analysis of risk factors for hepatocellular carcinogenesis: a prospective observation of 795 patients with viral and alcoholic cirrhosis. Hepatology. 1993 Jul;18(1):47–53. [PubMed] [Google Scholar]
  16. Kobayashi K., Sugimoto T., Makino H., Kumagai M., Unoura M., Tanaka N., Kato Y., Hattori N. Screening methods for early detection of hepatocellular carcinoma. Hepatology. 1985 Nov-Dec;5(6):1100–1105. doi: 10.1002/hep.1840050607. [DOI] [PubMed] [Google Scholar]
  17. Liaw Y. F., Tai D. I., Chu C. M., Lin D. Y., Sheen I. S., Chen T. J., Pao C. C. Early detection of hepatocellular carcinoma in patients with chronic type B hepatitis. A prospective study. Gastroenterology. 1986 Feb;90(2):263–267. doi: 10.1016/0016-5085(86)90919-4. [DOI] [PubMed] [Google Scholar]
  18. Livraghi T., Bolondi L., Buscarini L., Cottone M., Mazziotti A., Morabito A., Torzilli G. No treatment, resection and ethanol injection in hepatocellular carcinoma: a retrospective analysis of survival in 391 patients with cirrhosis. Italian Cooperative HCC Study Group. J Hepatol. 1995 May;22(5):522–526. doi: 10.1016/0168-8278(95)80445-5. [DOI] [PubMed] [Google Scholar]
  19. Llovet J. M., Bustamante J., Castells A., Vilana R., Ayuso M. del C., Sala M., Brú C., Rodés J., Bruix J. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials. Hepatology. 1999 Jan;29(1):62–67. doi: 10.1002/hep.510290145. [DOI] [PubMed] [Google Scholar]
  20. Lok A. S., Lai C. L. alpha-Fetoprotein monitoring in Chinese patients with chronic hepatitis B virus infection: role in the early detection of hepatocellular carcinoma. Hepatology. 1989 Jan;9(1):110–115. doi: 10.1002/hep.1840090119. [DOI] [PubMed] [Google Scholar]
  21. Mima S., Sekiya C., Kanagawa H., Kohyama H., Gotoh K., Mizuo H., Ijiri M., Tanabe T., Maeda N., Okuda K. Mass screening for hepatocellular carcinoma: experience in Hokkaido, Japan. J Gastroenterol Hepatol. 1994 Jul-Aug;9(4):361–365. doi: 10.1111/j.1440-1746.1994.tb01256.x. [DOI] [PubMed] [Google Scholar]
  22. Oka H., Kurioka N., Kim K., Kanno T., Kuroki T., Mizoguchi Y., Kobayashi K. Prospective study of early detection of hepatocellular carcinoma in patients with cirrhosis. Hepatology. 1990 Oct;12(4 Pt 1):680–687. doi: 10.1002/hep.1840120411. [DOI] [PubMed] [Google Scholar]
  23. Okuda K., Ohtsuki T., Obata H., Tomimatsu M., Okazaki N., Hasegawa H., Nakajima Y., Ohnishi K. Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer. 1985 Aug 15;56(4):918–928. doi: 10.1002/1097-0142(19850815)56:4<918::aid-cncr2820560437>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  24. Pateron D., Ganne N., Trinchet J. C., Aurousseau M. H., Mal F., Meicler C., Coderc E., Reboullet P., Beaugrand M. Prospective study of screening for hepatocellular carcinoma in Caucasian patients with cirrhosis. J Hepatol. 1994 Jan;20(1):65–71. doi: 10.1016/s0168-8278(05)80468-4. [DOI] [PubMed] [Google Scholar]
  25. Peto R., Pike M. C., Armitage P., Breslow N. E., Cox D. R., Howard S. V., Mantel N., McPherson K., Peto J., Smith P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977 Jan;35(1):1–39. doi: 10.1038/bjc.1977.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pugh R. N., Murray-Lyon I. M., Dawson J. L., Pietroni M. C., Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646–649. doi: 10.1002/bjs.1800600817. [DOI] [PubMed] [Google Scholar]
  27. Sarasin F. P., Giostra E., Hadengue A. Cost-effectiveness of screening for detection of small hepatocellular carcinoma in western patients with Child-Pugh class A cirrhosis. Am J Med. 1996 Oct;101(4):422–434. doi: 10.1016/S0002-9343(96)00197-0. [DOI] [PubMed] [Google Scholar]
  28. Sheu J. C., Sung J. L., Chen D. S., Lai M. Y., Wang T. H., Yu J. Y., Yang P. M., Chuang C. N., Yang P. C., Lee C. S. Early detection of hepatocellular carcinoma by real-time ultrasonography. A prospective study. Cancer. 1985 Aug 1;56(3):660–666. doi: 10.1002/1097-0142(19850801)56:3<660::aid-cncr2820560338>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  29. Siegel J. E., Weinstein M. C., Russell L. B., Gold M. R. Recommendations for reporting cost-effectiveness analyses. Panel on Cost-Effectiveness in Health and Medicine. JAMA. 1996 Oct 23;276(16):1339–1341. doi: 10.1001/jama.276.16.1339. [DOI] [PubMed] [Google Scholar]
  30. Solmi L., Primerano A. M., Gandolfi L. Ultrasound follow-up of patients at risk for hepatocellular carcinoma: results of a prospective study on 360 cases. Am J Gastroenterol. 1996 Jun;91(6):1189–1194. [PubMed] [Google Scholar]
  31. Tanaka R., Itoshima T., Nagashima H. Follow-up study of 582 liver cirrhosis patients for 26 years in Japan. Liver. 1987 Dec;7(6):316–324. doi: 10.1111/j.1600-0676.1987.tb00362.x. [DOI] [PubMed] [Google Scholar]
  32. Tremolda F., Benevegnù L., Drago C., Casarin C., Cechetto A., Realdi G., Ruol A. Early detection of hepatocellular carcinoma in patients with cirrhosis by alphafetoprotein, ultrasound and fine-needle biopsy. Hepatogastroenterology. 1989 Dec;36(6):519–521. [PubMed] [Google Scholar]
  33. Tsukuma H., Hiyama T., Tanaka S., Nakao M., Yabuuchi T., Kitamura T., Nakanishi K., Fujimoto I., Inoue A., Yamazaki H. Risk factors for hepatocellular carcinoma among patients with chronic liver disease. N Engl J Med. 1993 Jun 24;328(25):1797–1801. doi: 10.1056/NEJM199306243282501. [DOI] [PubMed] [Google Scholar]
  34. Wright J. C., Weinstein M. C. Gains in life expectancy from medical interventions--standardizing data on outcomes. N Engl J Med. 1998 Aug 6;339(6):380–386. doi: 10.1056/NEJM199808063390606. [DOI] [PubMed] [Google Scholar]
  35. Yuen M. F., Cheng C. C., Lauder I. J., Lam S. K., Ooi C. G., Lai C. L. Early detection of hepatocellular carcinoma increases the chance of treatment: Hong Kong experience. Hepatology. 2000 Feb;31(2):330–335. doi: 10.1002/hep.510310211. [DOI] [PubMed] [Google Scholar]
  36. Zoli M., Magalotti D., Bianchi G., Gueli C., Marchesini G., Pisi E. Efficacy of a surveillance program for early detection of hepatocellular carcinoma. Cancer. 1996 Sep 1;78(5):977–985. doi: 10.1002/(SICI)1097-0142(19960901)78:5<977::AID-CNCR6>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]

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