Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Perspective
  • Published:

Screening for liver fibrosis: lessons from colorectal and lung cancer screening

Nature Reviews Gastroenterology & Hepatology (2024)Cite this article

Subjects

Abstract

Many countries have incorporated population screening programmes for cancer, such as colorectal and lung cancer, into their health-care systems. Cirrhosis is more prevalent than colorectal cancer and has a comparable age-standardized mortality rate to lung cancer. Despite this fact, there are no screening programmes in place for early detection of liver fibrosis, the precursor of cirrhosis. In this Perspective, we use insights from colorectal and lung cancer screening to explore the benefits, challenges, implementation strategies and pathways for future liver fibrosis screening initiatives. Several non-invasive methods and referral pathways for early identification of liver fibrosis exist, but in addition to accurate detection, screening programmes must also be cost-effective and demonstrate benefit through a reduction in liver-related mortality. Randomized controlled trials are needed to confirm this. Future randomized screening trials should evaluate not only the screening tests, but also interventions used to halt disease progression in individuals identified through screening.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Flow chart of a potential targeted screening programme for liver fibrosis.
Fig. 2: Framework for a targeted liver fibrosis screening programme.

Similar content being viewed by others

References

  1. Kastrinos, F., Kupfer, S. S. & Gupta, S. Colorectal cancer risk assessment and precision approaches to screening: brave new world or worlds apart? Gastroenterology 164, 812–827 (2023).

    Article  PubMed  Google Scholar 

  2. Ten Haaf, K., van der Aalst, C. M., de Koning, H. J., Kaaks, R. & Tammemägi, M. C. Personalising lung cancer screening: an overview of risk-stratification opportunities and challenges. Int. J. Cancer 149, 250–263 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Pinsky, P. F. & Parnes, H. Screening for prostate cancer. N. Engl. J. Med. 388, 1405–1414 (2023).

    Article  PubMed  Google Scholar 

  4. Potnis, K. C., Ross, J. S., Aneja, S., Gross, C. P. & Richman, I. B. Artificial intelligence in breast cancer screening: evaluation of FDA device regulation and future recommendations. JAMA Intern. Med. 182, 1306–1312 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Asrani, S. K., Devarbhavi, H., Eaton, J. & Kamath, P. S. Burden of liver diseases in the world. J. Hepatol. 70, 151–171 (2019).

    Article  PubMed  Google Scholar 

  6. Huang, D. Q. et al. Global epidemiology of cirrhosis – aetiology, trends and predictions. Nat. Rev. Gastroenterol. Hepatol. 20, 388–398 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ginès, P. et al. Liver cirrhosis. Lancet 398, 1359–1376 (2021).

    Article  PubMed  Google Scholar 

  8. Pellicoro, A., Ramachandran, P., Iredale, J. P. & Fallowfield, J. A. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat. Rev. Immunol. 14, 181–194 (2014).

    Article  CAS  PubMed  Google Scholar 

  9. Berzigotti, A. et al. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis – 2021 update. J. Hepatol. 75, 659–689 (2021).

    Article  Google Scholar 

  10. Collaborators, G. C. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol. 5, 245–266 (2020).

    Article  Google Scholar 

  11. Vos, T. et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396, 1204–1222 (2020).

    Article  Google Scholar 

  12. Devarbhavi, H. et al. Global burden of liver disease: 2023 update. J. Hepatol. 79, 516–537 (2023).

    Article  PubMed  Google Scholar 

  13. Jepsen, P. & Younossi, Z. M. The global burden of cirrhosis: a review of disability-adjusted life-years lost and unmet needs. J. Hepatol. 75, S3–S13 (2021).

    Article  PubMed  Google Scholar 

  14. Ma, C. et al. Trends in the economic burden of chronic liver diseases and cirrhosis in the United States: 1996-2016. Am. J. Gastroenterol. 116, 2060–2067 (2021).

    Article  PubMed  Google Scholar 

  15. Rinella, M. E. et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. J. Hepatol. 78, 1966–1986 (2023).

    Article  Google Scholar 

  16. Riazi, K. et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol. Hepatol. 7, 851–861 (2022).

    Article  PubMed  Google Scholar 

  17. Allen, A. M. et al. Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design. J. Hepatol. 77, 1237–1245 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Karlsen, T. H. et al. The EASL Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality. Lancet 399, 61–116 (2022).

    Article  PubMed  Google Scholar 

  19. de Koning, H. J. et al. Reduced lung-cancer mortality with volume CT screening in a randomized trial. N. Engl. J. Med. 382, 503–513 (2020).

    Article  PubMed  Google Scholar 

  20. Bretthauer, M. et al. Effect of colonoscopy screening on risks of colorectal cancer and related death. N. Engl. J. Med. 387, 1547–1556 (2022).

    Article  PubMed  Google Scholar 

  21. World Health Organization. Screening programmes: a short guide. Increase effectiveness, maximize benefits and minimze harm. WHO https://www.who.int/europe/publications/i/item/9789289054782 (2020).

  22. Wilson, J. M. G. & Jungner, G. Principles and practice of screening for disease. Public Health Papers No. 34 (WHO, 1968).

  23. Shieh, Y. et al. Population-based screening for cancer: hope and hype. Nat. Rev. Clin. Oncol. 13, 550–565 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lindvig, K. P. et al. Diagnostic accuracy of routine liver function tests to identify patients with significant and advanced alcohol-related liver fibrosis. Scand. J. Gastroenterol. 56, 1088–1095 (2021).

    Article  CAS  PubMed  Google Scholar 

  25. Borzio, M. et al. Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: a prospective study. Gastroenterology 108, 812–817 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. D’Ambrosio, R. et al. Incidence of liver- and non-liver-related outcomes in patients with HCV-cirrhosis after SVR. J. Hepatol. 76, 302–310 (2022).

    Article  PubMed  Google Scholar 

  27. D’Amico, G. et al. Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment. Pharmacol. Ther. 39, 1180–1193 (2014).

    Article  PubMed  Google Scholar 

  28. Jepsen, P., Ott, P., Andersen, P. K., Sorensen, H. T. & Vilstrup, H. Clinical course of alcoholic liver cirrhosis: a Danish population-based cohort study. Hepatology 51, 1675–1682 (2010).

    Article  PubMed  Google Scholar 

  29. Carol, M. et al. Stigmatization is common in patients with non-alcoholic fatty liver disease and correlates with quality of life. PLoS ONE 17, e0265153 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Marchesini, G. et al. Factors associated with poor health-related quality of life of patients with cirrhosis. Gastroenterology 120, 170–178 (2001).

    Article  CAS  PubMed  Google Scholar 

  31. Askgaard, G. et al. Socioeconomic inequalities in the incidence of alcohol-related liver disease: a nationwide Danish study. Lancet Reg. Health Eur. 8, 100172 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  32. Ginès, P. et al. Population screening for liver fibrosis: towards early diagnosis and intervention for chronic liver diseases. Hepatology 75, 219–228 (2022).

    Article  PubMed  Google Scholar 

  33. Rasmussen, D. N. et al. Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease. J. Hepatol. 75, 1017–1025 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Boursier, J. et al. Non-invasive tests accurately stratify patients with NAFLD based on their risk of liver-related events. J. Hepatol. 76, 1013–1020 (2022).

    Article  CAS  PubMed  Google Scholar 

  35. Sanyal, A. J. et al. Prospective study of outcomes in adults with nonalcoholic fatty liver disease. N. Engl. J. Med. 385, 1559–1569 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Dobrow, M. J., Hagens, V., Chafe, R., Sullivan, T. & Rabeneck, L. Consolidated principles for screening based on a systematic review and consensus process. CMAJ 190, E422–E429 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Anstee, Q. M., Castera, L. & Loomba, R. Impact of non-invasive biomarkers on hepatology practice: past, present and future. J. Hepatol. 76, 1362–1378 (2022).

    Article  CAS  PubMed  Google Scholar 

  38. Sterling, R. K. et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43, 1317–1325 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Castéra, L. et al. Prospective comparison of transient elastography, Fibrotest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology 128, 343–350 (2005).

    Article  PubMed  Google Scholar 

  40. Angulo, P. et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 45, 846–854 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Labenz, C. et al. Structured early detection of asymptomatic liver cirrhosis: results of the population-based liver screening program SEAL. J. Hepatol. 77, 695–701 (2022).

    Article  PubMed  Google Scholar 

  42. Innes, H. et al. Performance of routine risk scores for predicting cirrhosis-related morbidity in the community. J. Hepatol. 77, 365–376 (2022).

    Article  PubMed  Google Scholar 

  43. Hagström, H., Talbäck, M., Andreasson, A., Walldius, G. & Hammar, N. Ability of noninvasive scoring systems to identify individuals in the population at risk for severe liver disease. Gastroenterology 158, 200–214 (2020).

    Article  PubMed  Google Scholar 

  44. Hagström, H., Talbäck, M., Andreasson, A., Walldius, G. & Hammar, N. Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease. J. Hepatol. 73, 1023–1029 (2020).

    Article  PubMed  Google Scholar 

  45. Kjaergaard, M. et al. Using the ELF test, FIB-4 and NAFLD fibrosis score to screen the population for liver disease. J. Hepatol. 79, 277–286 (2023).

    Article  CAS  PubMed  Google Scholar 

  46. Graupera, I. et al. Low accuracy of FIB-4 and NAFLD fibrosis scores for screening for liver fibrosis in the population. Clin. Gastroenterol. Hepatol. 20, 2567–2576 (2022).

    Article  CAS  PubMed  Google Scholar 

  47. Unalp-Arida, A. & Ruhl, C. E. Liver fibrosis scores predict liver disease mortality in the United States population. Hepatology 66, 84–95 (2017).

    Article  CAS  PubMed  Google Scholar 

  48. Caballería, L. et al. High prevalence of liver fibrosis among European adults with unknown liver disease: a population-based study. Clin. Gastroenterol. Hepatol. 16, 1138–1145 (2018).

    Article  PubMed  Google Scholar 

  49. Usher-Smith, J. A., Sharp, Stephen, J. & Griffin, S. J. The spectrum effect in tests for risk prediction, screening, and diagnosis. BMJ 353, i3139 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Serra-Burriel, M. et al. Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study. Lancet 402, 988–996 (2023).

    Article  PubMed  Google Scholar 

  51. Åberg, F. et al. Comparison of various strategies to define the optimal target population for liver fibrosis screening: a population-based cohort study. United Eur. Gastroenterol. J. 10, 1020–1028 (2022).

    Article  Google Scholar 

  52. Srivastava, A. et al. Prospective evaluation of a primary care referral pathway for patients with non-alcoholic fatty liver disease. J. Hepatol. 71, 371–378 (2019).

    Article  PubMed  Google Scholar 

  53. Thiele, M. et al. Accuracy of the Enhanced Liver Fibrosis test vs FibroTest, elastography and indirect markers in detection of advanced fibrosis in patients with alcoholic liver disease. Gastroenterology 154, 1369–1379 (2018).

    Article  PubMed  Google Scholar 

  54. Matthews, K., MacGilchrist, A., Coulter-Smith, M., Jones, J. & Cetnarskyj, R. A nurse-led FibroScan((R)) outreach clinic encourages socially deprived heavy drinkers to engage with liver services. J. Clin. Nurs. 28, 650–662 (2019).

    Article  PubMed  Google Scholar 

  55. Harris, R., Harman, D. J., Card, T. R., Aithal, G. P. & Guha, I. N. Prevalence of clinically significant liver disease within the general population, as defined by non-invasive markers of liver fibrosis: a systematic review. Lancet Gastroenterol. Hepatol. 2, 288–297 (2017).

    Article  PubMed  Google Scholar 

  56. Koehler, E. M. et al. Presence of diabetes mellitus and steatosis is associated with liver stiffness in a general population: the Rotterdam study. Hepatology 63, 138–147 (2016).

    Article  CAS  PubMed  Google Scholar 

  57. Vilar-Gomez, E. et al. Prevalence of high-risk nonalcoholic steatohepatitis (NASH) in the United States: results from NHANES 2017-2018. Clin. Gastroenterol. Hepatol. 21, 115–124.e7 (2021).

    Article  PubMed  Google Scholar 

  58. Kwok, R. et al. Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study. Gut 65, 1359–1368 (2016).

    Article  CAS  PubMed  Google Scholar 

  59. Petta, S. et al. Impact of obesity and alanine aminotransferase levels on the diagnostic accuracy for advanced liver fibrosis of noninvasive tools in patients with nonalcoholic fatty liver disease. Am. J. Gastroenterol. 114, 916–928 (2019).

    Article  PubMed  Google Scholar 

  60. Eslam, M. et al. The Asian Pacific Association for the Study of the Liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease. Hepatol. Int. 14, 889–919 (2020).

    Article  PubMed  Google Scholar 

  61. Arab, J. P. et al. Latin American Association for the Study of the Liver (ALEH) practice guidance for the diagnosis and treatment of non-alcoholic fatty liver disease. Ann. Hepatol. 19, 674–690 (2020).

    Article  CAS  PubMed  Google Scholar 

  62. Cusi, K. et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the diagnosis and management of nonalcoholic fatty liver disease in primary care and endocrinology clinical settings: co-sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr. Pract. 28, 528–562 (2022).

    Article  PubMed  Google Scholar 

  63. Rinella, M. E. et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology 77, 1797–1835 (2023).

    Article  PubMed  Google Scholar 

  64. Hardcastle, J. D. et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 348, 1472–1477 (1996).

    Article  CAS  PubMed  Google Scholar 

  65. Kronborg, O., Fenger, C., Olsen, J., Jorgensen, O. D. & Sondergaard, O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 348, 1467–1471 (1996).

    Article  CAS  PubMed  Google Scholar 

  66. Mandel, J. S. et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N. Engl. J. Med. 328, 1365–1371 (1993).

    Article  CAS  PubMed  Google Scholar 

  67. Brenner, H., Stock, C. & Hoffmeister, M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies. BMJ 348, g2467 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Young, G. P., Rabeneck, L. & Winawer, S. J. The global paradigm shift in screening for colorectal cancer. Gastroenterology 156, 843–851 (2019).

    Article  PubMed  Google Scholar 

  69. US Preventive Services Task Force Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. JAMA 325, 1965–1977 (2021).

    Article  Google Scholar 

  70. Castells, A. Choosing the optimal method in programmatic colorectal cancer screening: current evidence and controversies. Ther. Adv. Gastroenterol. 8, 221–233 (2015).

    Article  Google Scholar 

  71. Warren, J. L. et al. Adverse events after outpatient colonoscopy in the Medicare population. Ann. Intern. Med. 150, 849–857 (2009).

    Article  PubMed  Google Scholar 

  72. Quintero, E. et al. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N. Engl. J. Med. 366, 697–706 (2012).

    Article  CAS  PubMed  Google Scholar 

  73. Auge, J. M. et al. Risk stratification for advanced colorectal neoplasia according to fecal hemoglobin concentration in a colorectal cancer screening program. Gastroenterology 147, 628–636.e1 (2014).

    Article  CAS  PubMed  Google Scholar 

  74. Forsberg, A. et al. Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial. Lancet Gastroenterol. Hepatol. 7, 513–521 (2022).

    Article  PubMed  Google Scholar 

  75. Dominitz, J. A. et al. Colonoscopy vs. fecal immunochemical test in reducing mortality from colorectal cancer (CONFIRM): rationale for study design. Am. J. Gastroenterol. 112, 1736–1746 (2017).

    Article  PubMed  Google Scholar 

  76. Council of the European Union. Council Recommendation on strengthening prevention through early detection: A new EU approach on cancer screening replacing Council Recommendation 2003/878/EC. EUR-Lex eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32022H1213(01) (2022).

  77. The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N. Engl. J. Med. 365, 395–409 (2011).

    Article  PubMed Central  Google Scholar 

  78. Szatkowski, L., Lewis, S., McNeill, A. & Coleman, T. Is smoking status routinely recorded when patients register with a new GP? Fam. Pract. 27, 673–675 (2010).

    Article  PubMed  Google Scholar 

  79. Tammemägi, M. C. et al. USPSTF2013 versus PLCOm2012 lung cancer screening eligibility criteria (International Lung Screening Trial): interim analysis of a prospective cohort study. Lancet Oncol. 23, 138–148 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Pryke, R. & Guha, I. N. Time to focus on chronic liver diseases in the community: a review of primary care hepatology tools, pathways of care and reimbursement mechanisms. J. Hepatol. 78, 663–671 (2023).

    Article  PubMed  Google Scholar 

  81. Zhang, X. et al. Clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomised controlled trial. Gut 72, 2364–2371 (2023).

    Article  CAS  PubMed  Google Scholar 

  82. Chalmers, J. et al. The development and implementation of a commissioned pathway for the identification and stratification of liver disease in the community. Frontline Gastroenterol. 11, 86–92 (2020).

    Article  CAS  PubMed  Google Scholar 

  83. Tanajewski, L. et al. Economic evaluation of a community-based diagnostic pathway to stratify adults for non-alcoholic fatty liver disease: a Markov model informed by a feasibility study. BMJ Open. 7, e015659 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Fitzpatrick-Lewis, D. et al. Screening for colorectal cancer: a systematic review and meta-analysis. Clin. Colorectal Cancer 15, 298–313 (2016).

    Article  PubMed  Google Scholar 

  85. Ortner, J. et al. Costs of a structured early detection program for advanced liver fibrosis and cirrhosis: insights on the “plus” of Check-up 35. Z. Gastroenterol. 61, 1371–1381 (2023).

    Article  PubMed  Google Scholar 

  86. Long, M. T. et al. Hepatic fibrosis associates with multiple cardiometabolic disease risk factors: the Framingham Heart Study. Hepatology 73, 548–559 (2021).

    Article  CAS  PubMed  Google Scholar 

  87. Unalp-Arida, A. & Ruhl, C. E. Prepandemic prevalence estimates of fatty liver disease and fibrosis defined by liver elastography in the United States. Dig. Dis. Sci. 68, 1237–1252 (2023).

    Article  PubMed  Google Scholar 

  88. Jodal, H. C. et al. Colorectal cancer screening with faecal testing, sigmoidoscopy or colonoscopy: a systematic review and network meta-analysis. BMJ Open. 9, e032773 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Peterse, E. F. P. et al. Comparing the cost-effectiveness of innovative colorectal cancer screening tests. J. Natl Cancer Inst. 113, 154–161 (2021).

    Article  PubMed  Google Scholar 

  90. Criss, S. D. et al. Cost-effectiveness analysis of lung cancer screening in the United States: a comparative modeling study. Ann. Intern. Med. 171, 796–804 (2019).

    Article  PubMed  Google Scholar 

  91. Goffin, J. R. et al. Cost-effectiveness of lung cancer screening in Canada. JAMA Oncol. 1, 807–813 (2015).

    Article  PubMed  Google Scholar 

  92. Serra-Burriel, M. et al. Transient elastography for screening of liver fibrosis: cost-effectiveness analysis from six prospective cohorts in Europe and Asia. J. Hepatol. 71, 1141–1151 (2019).

    Article  PubMed  Google Scholar 

  93. Asphaug, L., Thiele, M., Krag, A. & Melberg, H. O. Cost-effectiveness of non-invasive screening for alcohol-related liver fibrosis using real-world data from primary and secondary care patients. Hepatology 71, 2093–2104 (2020).

    Article  PubMed  Google Scholar 

  94. O’Mahony, J. F. Risk stratification in cost-effectiveness analyses of cancer screening: intervention eligibility, strategy choice, and optimality. Med. Decis. Mak. 42, 513–523 (2022).

    Article  Google Scholar 

  95. Baldwin, D. R., Brain, K. & Quaife, S. Participation in lung cancer screening. Transl. Lung Cancer Res. 10, 1091–1098 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Theodoreson, M. D. et al. Extra-hepatic morbidity and mortality in alcohol-related liver disease: systematic review and meta-analysis. Liver Int. 43, 763–772 (2023).

    Article  PubMed  Google Scholar 

  97. Pennisi, G. et al. Liver-related and extrahepatic events in patients with non-alcoholic fatty liver disease: a retrospective competing risks analysis. Aliment. Pharmacol. Ther. 55, 604–615 (2022).

    Article  PubMed  Google Scholar 

  98. Schrag, D. et al. Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study. Lancet 402, 1251–1260 (2023).

    Article  PubMed  Google Scholar 

  99. van der Aalst, C. M. et al. Screening for cardiovascular disease risk using traditional risk factor assessment or coronary artery calcium scoring: the ROBINSCA trial. Eur. Heart J. Cardiovasc. Imaging 21, 1216–1224 (2020).

    Article  PubMed  Google Scholar 

  100. Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021).

    Article  PubMed  Google Scholar 

  101. Safiri, S. et al. The global, regional, and national burden of colorectal cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol. 4, 913–933 (2019).

    Article  Google Scholar 

  102. Lee, J. K., Liles, E. G., Bent, S., Levin, T. R. & Corley, D. A. Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis. Ann. Intern. Med. 160, 171–181 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Robertson, D. J. et al. Recommendations on fecal immunochemical testing to screen for colorectal neoplasia: a consensus statement by the US multi-society task force on colorectal cancer. Gastroenterology 152, 1217–1237.e3 (2017).

    Article  PubMed  Google Scholar 

  104. Eddowes, P. J. et al. Accuracy of fibroscan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology 156, 1717–1730 (2019).

    Article  PubMed  Google Scholar 

  105. Nguyen-Khac, E. et al. Non-invasive diagnosis of liver fibrosis in patients with alcohol-related liver disease by transient elastography: an individual patient data meta-analysis. Lancet Gastroenterol. Hepatol. 3, 614–625 (2018).

    Article  PubMed  Google Scholar 

  106. Spychalski, P. et al. Adenoma to colorectal cancer estimated transition rates stratified by BMI categories – a cross-sectional analysis of asymptomatic individuals from screening colonoscopy program. Cancers 14, 62 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Eyles, C. et al. Acceptability of screening for early detection of liver disease in hazardous/harmful drinkers in primary care. Br. J. Gen. Pract. 63, 516–522 (2013).

    Article  Google Scholar 

  108. Ran, T. et al. Cost-effectiveness of colorectal cancer screening strategies – a systematic review. Clin. Gastroenterol. Hepatol. 17, 1969–1981.e15 (2019).

    Article  PubMed  Google Scholar 

  109. Saquib, N., Saquib, J. & Ioannidis, J. P. Does screening for disease save lives in asymptomatic adults? Systematic review of meta-analyses and randomized trials. Int. J. Epidemiol. 44, 264–277 (2015).

    Article  PubMed  Google Scholar 

  110. Albillos, A. & Krag, A. Beta-blockers in the era of precision medicine in patients with cirrhosis. J. Hepatol. 78, 866–872 (2022).

    Article  PubMed  Google Scholar 

  111. Pinsky, P. F., Gierada, D. S., Nath, H., Kazerooni, E. A. & Amorosa, J. ROC curves for low-dose CT in the National Lung Screening Trial. J. Med. Screen. 20, 165–168 (2013).

    Article  PubMed  Google Scholar 

  112. Lancaster, H. L., Heuvelmans, M. A. & Oudkerk, M. Low-dose computed tomography lung cancer screening: clinical evidence and implementation research. J. Intern. Med. 292, 68–80 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. McPherson, S. et al. Age as a confounding factor for the accurate non-invasive diagnosis of advanced NAFLD fibrosis. Am. J. Gastroenterol. 112, 740–751 (2016).

    Article  PubMed  PubMed Central  ADS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the administrative support of B. Márquez in the preparation of the manuscript. The authors are funded by a grant from the European Union’s Horizon 2020 research and innovation programme to the LiverScreen project, grant number 847989. F.L. is funded by LiSyM (Federal Ministry of Education and Research (BMBF 031L0051 and 031L0257)). M.T. is funded by the Novo Nordisk Foundation (NNF20OC0059393).

Author information

Authors and Affiliations

  1. Centre for Liver Research, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark

    Maja Thiele

  2. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Maja Thiele

  3. Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA

    Patrick S. Kamath

  4. Liver Unit Hospital Clínic, Barcelona, Catalonia, Spain

    Isabel Graupera & Pere Ginès

  5. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain

    Isabel Graupera, Antoni Castells & Pere Ginès

  6. Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Catalonia, Spain

    Isabel Graupera, Antoni Castells & Pere Ginès

  7. Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Catalonia, Spain

    Isabel Graupera, Antoni Castells & Pere Ginès

  8. Department of Gastroenterology, Hospital Clínic, Barcelona, Catalonia, Spain

    Antoni Castells

  9. Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands

    Harry J. de Koning

  10. Epidemiology, Statistics, and Prevention Institute, University of Zurich, Zurich, Switzerland

    Miquel Serra-Burriel

  11. Department of Medicine II, Saarland University Medical Center, Homburg, Germany

    Frank Lammert

  12. Hannover Medical School (MHH), Hannover, Germany

    Frank Lammert

Authors
  1. Maja Thiele
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick S. Kamath
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isabel Graupera
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Antoni Castells
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Harry J. de Koning
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Miquel Serra-Burriel
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Frank Lammert
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Pere Ginès
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the manuscript.

Corresponding author

Correspondence to Pere Ginès.

Ethics declarations

Competing interests

M.T. reports speakers fees from Madrigal, Takeda, Siemens Healthcare, Echosens, Norgine and Tillotts Pharma, and advisory fees from AstraZeneca, Boehringer Ingelheim, GE Healthcare and GSK. M.T. is co-founder and board member of Evido, and a board member of Alcohol & Society (a non-governmental organization). P.G. has received research funding from Gilead & Grifols. P.G. has consulted or attended advisory boards for Gilead, RallyBio, SeaBeLife, Merck, Sharp and Dohme (MSD), Ocelot Bio, Behring, Roche Diagnostics International and Boehringer Ingelheim, and received speaking fees from Pfizer. A.C. has received funding from Fundación Científica de la Asociación Española contra el Cáncer and Universal Diagnostics, consulting fees from Goodgut, Amadix and iVascular, and speaker fees from Medial EarlySign and Abbvie. P.S.K., I.G., H.J.d.K., M.S.-B. and F.L. declare no competing interests.

Peer review

Peer review information

Nature Reviews Gastroenterology & Hepatology thanks Ann Zauber, Vincent Wong and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thiele, M., Kamath, P.S., Graupera, I. et al. Screening for liver fibrosis: lessons from colorectal and lung cancer screening. Nat Rev Gastroenterol Hepatol (2024). https://doi.org/10.1038/s41575-024-00907-2

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41575-024-00907-2

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing