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PMID: 24691105 Published · epublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Systematic Review

Early detection, curative treatment, and survival rates for hepatocellular carcinoma surveillance in patients with cirrhosis: a meta-analysis.

PLoS medicine ·Vol. 11 ·No. 4 ·2014-04-00 ·Pages e1001624

Singal AG, Pillai A, Tiro J

Abstract

Surveillance for hepatocellular carcinoma (HCC) has level I evidence among patients with hepatitis B but only level II evidence in patients with cirrhosis. This lack of randomized data has spurred questions regarding the utility of HCC surveillance in this patient population; however, lack of randomized data does not equate to a lack of data supporting the efficacy of surveillance. The aim of our study was to determine the effect of HCC surveillance on early stage tumor detection, receipt of curative therapy, and overall survival in patients with cirrhosis. We performed a systematic literature review using Medline from January 1990 through January 2014 and a search of national meeting abstracts from 2009-2012. Two investigators identified studies that reported rates of early stage tumor detection, curative treatment receipt, or survival, stratified by HCC surveillance status, among patients with cirrhosis. Both investigators independently extracted data on patient populations, study methods, and results using standardized forms. Pooled odds ratios, according to HCC surveillance status, were calculated for each outcome using the DerSimonian and Laird method for a random effects model. We identified 47 studies with 15,158 patients, of whom 6,284 (41.4%) had HCC detected by surveillance. HCC surveillance was associated with improved early stage detection (odds ratio [OR] 2.08, 95% CI 1.80-2.37) and curative treatment rates (OR 2.24, 95% CI 1.99-2.52). HCC surveillance was associated with significantly prolonged survival (OR 1.90, 95% CI 1.67-2.17), which remained significant in the subset of studies adjusting for lead-time bias. Limitations of current data included many studies having insufficient duration of follow-up to assess survival and the majority not adjusting for liver function or lead-time bias. HCC surveillance is associated with significant improvements in early tumor detection, receipt of curative therapy, and overall survival in patients with cirrhosis. Please see later in the article for the Editors' Summary.

MeSH Terms
Carcinoma, Hepatocellular/complications,diagnosis,mortality,therapy Early Detection of Cancer/statistics & numerical data Humans Liver Cirrhosis/complications,diagnosis,mortality,therapy Liver Neoplasms/complications,diagnosis,mortality,therapy Population Surveillance Survival Rate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Singal Amit G
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America; Department of Clinical Sciences, University of Texas Southwestern, Dallas, Texas, United States of America; Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
Pillai Anjana
Department of Internal Medicine, Emory University, Atlanta, Georgia, United States of America.
Tiro Jasmin
Department of Clinical Sciences, University of Texas Southwestern, Dallas, Texas, United States of America; Harold C. Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
References (74)
74 references, click to expand
  1. Quantifying heterogeneity in a meta-analysis.
    Stat Med. 2002 Jun 15;21(11):1539-58 PMID: 12111919
  2. Colorectal cancer prevention 2000: screening recommendations of the American College of Gastroenterology. American College of Gastroenterology.
    Am J Gastroenterol. 2000 Apr;95(4):868-77 PMID: 10763931
  3. Clinical benefits of hepatocellular carcinoma surveillance: a single-center, hospital-based study.
    Oncol Rep. 2005 Oct;14(4):999-1003 PMID: 16142364
  4. Hepatocellular carcinoma in cirrhosis: incidence and risk factors.
    Gastroenterology. 2004 Nov;127(5 Suppl 1):S35-50 PMID: 15508101
  5. Utilization of hepatocellular carcinoma surveillance among American patients: a systematic review.
    J Gen Intern Med. 2012 Jul;27(7):861-7 PMID: 22215266
  6. Association between nonalcoholic fatty liver disease and risk for hepatocellular cancer, based on systematic review.
    Clin Gastroenterol Hepatol. 2012 Dec;10(12):1342-1359.e2 PMID: 23041539
  7. Machine learning algorithms outperform conventional regression models in predicting development of hepatocellular carcinoma.
    Am J Gastroenterol. 2013 Nov;108(11):1723-30 PMID: 24169273
  8. A sensitivity analysis for publication bias in systematic reviews.
    Stat Methods Med Res. 2001 Aug;10(4):251-65 PMID: 11491412
  9. Randomized controlled trial of screening for hepatocellular carcinoma.
    J Cancer Res Clin Oncol. 2004 Jul;130(7):417-22 PMID: 15042359
  10. [Usefulness of ultrasonography in the early diagnosis of hepatocarcinoma in patients with liver cirrhosis].
    Rev Esp Enferm Dig. 1995 Nov;87(11):798-801 PMID: 8534535
  11. Effectiveness of AFP and ultrasound tests on hepatocellular carcinoma mortality in HCV-infected patients in the USA.
    Gut. 2011 Jul;60(7):992-7 PMID: 21257990
  12. Utilization of screening for hepatocellular carcinoma in the United States.
    J Clin Gastroenterol. 2007 Sep;41(8):777-82 PMID: 17700427
  13. Effectiveness of hepatocellular carcinoma surveillance in patients with cirrhosis.
    Cancer Epidemiol Biomarkers Prev. 2012 May;21(5):793-9 PMID: 22374994
  14. Does screening or surveillance for primary hepatocellular carcinoma with ultrasonography improve the prognosis of patients?
    Cancer J. 2004 Sep-Oct;10(5):317-25 PMID: 15530261
  15. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
    Ann Intern Med. 2009 Aug 18;151(4):264-9, W64 PMID: 19622511
  16. Semiannual and annual surveillance of cirrhotic patients for hepatocellular carcinoma: effects on cancer stage and patient survival (Italian experience).
    Am J Gastroenterol. 2002 Mar;97(3):734-44 PMID: 11922571
  17. Factors related to survival in hepatocellular carcinoma in the geographic area of Sabadell (Catalonia, Spain).
    Rev Esp Enferm Dig. 2012 May;104(5):242-7 PMID: 22662776
  18. Feasibility of conducting a randomized control trial for liver cancer screening: is a randomized controlled trial for liver cancer screening feasible or still needed?
    Hepatology. 2011 Dec;54(6):1998-2004 PMID: 21800340
  19. Which colon cancer screening test? A comparison of costs, effectiveness, and compliance.
    Am J Med. 2001 Dec 1;111(8):593-601 PMID: 11755501
  20. Surveillance programme of cirrhotic patients for early diagnosis and treatment of hepatocellular carcinoma: a cost effectiveness analysis.
    Gut. 2001 Feb;48(2):251-9 PMID: 11156649
  21. Improving screening for hepatocellular carcinoma by incorporating data on levels of α-fetoprotein, over time.
    Clin Gastroenterol Hepatol. 2013 Apr;11(4):437-40 PMID: 23247324
  22. Surveillance for hepatocellular carcinoma improves survival in Asian-American patients with hepatitis B: results from a community-based clinic.
    Dig Dis Sci. 2010 Mar;55(3):826-35 PMID: 19960258
  23. Detection of hepatocellular carcinoma at advanced stages among patients in the HALT-C trial: where did surveillance fail?
    Am J Gastroenterol. 2013 Mar;108(3):425-32 PMID: 23337478
  24. Are hepatocellular carcinoma surveillance programs effective at improving the therapeutic options.
    Rev Esp Enferm Dig. 2010 Jul;102(8):484-8 PMID: 20670069
  25. Epidemiology of viral hepatitis and hepatocellular carcinoma.
    Gastroenterology. 2012 May;142(6):1264-1273.e1 PMID: 22537432
  26. Risk for hepatocellular carcinoma in patients with alcoholic cirrhosis: a Danish nationwide cohort study.
    Ann Intern Med. 2012 Jun 19;156(12):841-7, W295 PMID: 22711076
  27. Meta-analysis: surveillance with ultrasound for early-stage hepatocellular carcinoma in patients with cirrhosis.
    Aliment Pharmacol Ther. 2009 Jul;30(1):37-47 PMID: 19392863
  28. Does surveillance for hepatocellular carcinoma in HCV cirrhotic patients improve treatment outcome mainly due to better clinical status at diagnosis?
    Hepatogastroenterology. 2000 Sep-Oct;47(35):1395-8 PMID: 11100360
  29. Clinical practice. Screening for colorectal cancer.
    N Engl J Med. 2009 Sep 17;361(12):1179-87 PMID: 19759380
  30. Impact of surveillance on survival of patients with initial hepatocellular carcinoma: a study from Japan.
    Clin Gastroenterol Hepatol. 2006 Sep;4(9):1170-6 PMID: 16890027
  31. Failure rates in the hepatocellular carcinoma surveillance process.
    Cancer Prev Res (Phila). 2012 Sep;5(9):1124-30 PMID: 22846843
  32. Surveillance of hepatocellular carcinoma in patients with hepatitis C virus infection may improve patient survival.
    Liver Int. 2006 Jun;26(5):543-51 PMID: 16761998
  33. Changing aetiological factors of hepatocellular carcinoma and their potential impact on the effectiveness of surveillance.
    Dig Liver Dis. 2011 Nov;43(11):875-80 PMID: 21684821
  34. Epidemiology of hepatocellular carcinoma in Finistère. Prospective study from June 2002 to May 2003.
    Gastroenterol Clin Biol. 2007 Mar;31(3):259-64 PMID: 17396082
  35. Screening for liver cancer: results of a randomised controlled trial in Qidong, China.
    J Med Screen. 2003;10(4):204-9 PMID: 14738659
  36. High-risk groups and screening strategies for early detection of hepatocellular carcinoma in patients with chronic liver disease.
    Hepatogastroenterology. 1993 Aug;40(4):305-10 PMID: 8406298
  37. Rates of surveillance and management of hepatocellular carcinoma in patients evaluated at a liver transplant center.
    Dig Dis Sci. 2010 Dec;55(12):3591-6 PMID: 20683659
  38. Surveillance for hepatocellular carcinoma in patients with primary biliary cirrhosis.
    Hepatology. 2008 Oct;48(4):1149-56 PMID: 18785621
  39. Surveillance program for early detection of hepatocellular carcinoma in Japan: results of specialized department of liver disease.
    J Clin Gastroenterol. 2006 Nov-Dec;40(10):942-8 PMID: 17063116
  40. Do young hepatocellular carcinoma patients with relatively good liver function have poorer outcomes than elderly patients?
    J Gastroenterol Hepatol. 2007 Aug;22(8):1226-31 PMID: 17498220
  41. [Clinical characteristics, staging and treatment of patients with hepatocellular carcinoma in clinical practice. Prospective study of 136 patients].
    Gastroenterol Hepatol. 2011 Oct;34(8):524-31 PMID: 21940068
  42. Hepatocellular carcinoma screening practices and impact on survival among hepatitis B-infected Asian Americans.
    J Viral Hepat. 2012 Aug;19(8):594-600 PMID: 22762144
  43. Clinical features, biochemical parameters, and virological profiles of patients with hepatocellular carcinoma in Hong Kong.
    Aliment Pharmacol Ther. 2006 Aug 15;24(4):573-83 PMID: 16907890
  44. Regular surveillance by imaging for early detection and better prognosis of hepatocellular carcinoma in patients infected with hepatitis C virus.
    J Gastroenterol. 2010;45(1):105-12 PMID: 19866332
  45. Surveillance programme for hepatocellular carcinoma improves the survival of patients with chronic viral hepatitis.
    Liver Int. 2008 Jan;28(1):79-87 PMID: 17900247
  46. Screening of hepatocellular carcinoma in French patients.
    Dig Dis Sci. 1995 Mar;40(3):706-7 PMID: 7895568
  47. Usefulness of surveillance programmes for early diagnosis of hepatocellular carcinoma in clinical practice.
    Liver Int. 2008 May;28(5):682-9 PMID: 18433394
  48. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.
    N Engl J Med. 1996 Mar 14;334(11):693-9 PMID: 8594428
  49. Survival in Asian Americans after treatments for hepatocellular carcinoma: a seven-year experience at UCLA.
    J Clin Gastroenterol. 2010 Mar;44(3):e63-70 PMID: 19745756
  50. Recent advances in the treatment of hepatocellular carcinoma.
    Curr Opin Gastroenterol. 2013 May;29(3):285-92 PMID: 23507917
  51. Hepatocellular carcinoma surveillance and appropriate treatment options improve survival for patients with liver cirrhosis.
    Eur J Cancer. 2010 Mar;46(4):744-51 PMID: 20060710
  52. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials.
    Hepatology. 1999 Jan;29(1):62-7 PMID: 9862851
  53. Effectiveness of periodic checkup by ultrasonography for the early diagnosis of hepatocellular carcinoma.
    Cancer. 1990 Nov 15;66(10):2210-4 PMID: 2171749
  54. Outcomes of 116 patients with hepatocellular carcinoma.
    Cancer Chemother Pharmacol. 1994;33 Suppl:S103-8 PMID: 8137466
  55. Changing paradigm in the management of hepatocellular carcinoma improves the survival benefit of early detection by screening.
    Ann Surg. 2008 Apr;247(4):666-73 PMID: 18362630
  56. Improving hepatocellular carcinoma screening: applying lessons from colorectal cancer screening.
    Clin Gastroenterol Hepatol. 2013 May;11(5):472-7 PMID: 23200983
  57. The global NAFLD epidemic.
    Nat Rev Gastroenterol Hepatol. 2013 Nov;10(11):686-90 PMID: 24042449
  58. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update.
    Ann Intern Med. 2003 Nov 18;139(10):817-23 PMID: 14623619
  59. Surveillance for hepatocellular carcinoma in patients with cirrhosis improves outcome.
    Am J Med. 2008 Feb;121(2):119-26 PMID: 18261500
  60. Factors that affect risk for hepatocellular carcinoma and effects of surveillance.
    Clin Gastroenterol Hepatol. 2011 Jul;9(7):617-23.e1 PMID: 21459158
  61. Screening for liver cancer: the rush to judgment.
    Ann Intern Med. 2012 Mar 6;156(5):387-9 PMID: 22393134
  62. [Value of ultrasonography in the early diagnosis of hepatocellular carcinoma].
    Rev Esp Enferm Dig. 1993 Nov;84(5):311-4 PMID: 8305257
  63. Use of surveillance for hepatocellular carcinoma among patients with cirrhosis in the United States.
    Hepatology. 2010 Jul;52(1):132-41 PMID: 20578139
  64. Improved survival trend of patients with hepatocellular carcinoma at an Australian tertiary hospital between 1995-2009.
    Intern Med J. 2013 Feb;43(2):197-203 PMID: 22372378
  65. Meta-analysis: underutilisation and disparities of treatment among patients with hepatocellular carcinoma in the United States.
    Aliment Pharmacol Ther. 2013 Oct;38(7):703-12 PMID: 23957569
  66. Patient involvement in healthcare is associated with higher rates of surveillance for hepatocellular carcinoma.
    J Clin Gastroenterol. 2011 Sep;45(8):727-32 PMID: 21602704
  67. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver.
    J Hepatol. 2001 Sep;35(3):421-30 PMID: 11592607
  68. Correcting for lead time and length bias in estimating the effect of screen detection on cancer survival.
    Am J Epidemiol. 2008 Jul 1;168(1):98-104 PMID: 18504245
  69. Factors that affect accuracy of α-fetoprotein test in detection of hepatocellular carcinoma in patients with cirrhosis.
    Clin Gastroenterol Hepatol. 2014 May;12(5):870-7 PMID: 24095974
  70. The HepCar registry: report on a one-year registration program of hepatocellular carcinoma (HCC) in Belgium. What is daily practice in HCC?
    Acta Gastroenterol Belg. 2005 Oct-Dec;68(4):403-11 PMID: 16432990
  71. Screening for hepatocellular carcinoma among veterans with hepatitis C on disease stage, treatment received, and survival.
    Clin Gastroenterol Hepatol. 2007 Apr;5(4):508-12 PMID: 17382601
  72. Hepatocellular carcinoma in Sydney South West: late symptomatic presentation and poor outcome for most.
    Intern Med J. 2007 Aug;37(8):516-22 PMID: 17543001
  73. Improved survival with screening for hepatocellular carcinoma.
    Liver Transpl. 2000 May;6(3):320-5 PMID: 10827233
  74. Measuring inconsistency in meta-analyses.
    BMJ. 2003 Sep 6;327(7414):557-60 PMID: 12958120
Article Info
Journal
PLoS medicine
Abbr.
PLoS Med
ISSN
1549-1676
DOI
10.1371/journal.pmed.1001624
Published
2014-04-00
Epub
2014-00-01
Pages
e1001624
Language
English
Region
United States
NLM ID
101231360
PMCID
PMC3972088
Subset
IM
Grants
NCATS NIH HHS · UL1 TR001105 · United States
NCATS NIH HHS · UL1 TR000451 · United States
NCATS NIH HHS · KL2 TR001103 · United States
NCATS NIH HHS · KL2 TR000453 · United States
NCATS NIH HHS · UL1-TR000451 · United States
Corrections
CommentIn
PMID: 25081827
External Links
PubMed source DOI: 10.1371/journal.pmed.1001624 PMC Full Text View journal details
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