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Before we can find an evidence base for HCC surveillance, we need to define our target demographic

  • Charmaine Matthews
    Correspondence
    Corresponding authors. Addresses: The Royal Liverpool University Hospitals NHS foundation Trust, Prescot Street Liverpool, UK, L7 8XP, 0151 706 2313
    Affiliations
    The Royal Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
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  • Timothy J.S. Cross
    Correspondence
    Department of molecular and clinical cancer medicine, University of Liverpool, Liverpool, UK, L69 3GE, 0151 706 2313.
    Affiliations
    Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
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      Linked Article

      • We need stronger evidence for (or against) hepatocellular carcinoma surveillance
        Journal of HepatologyVol. 74Issue 5
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          Current guidelines from EASL recommend that most patients with cirrhosis are offered surveillance for hepatocellular carcinoma (HCC), but fewer patients than expected actually receive it. The recommendation is based on observational studies and simulations, not randomised trials. In this opinion piece we argue that a randomised trial of HCC surveillance vs. no surveillance is necessary and feasible, and we believe that clinician and patient participation in HCC surveillance would be better if it were based on trial results demonstrating its value.
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      To the Editor:
      We read with interest the expert opinion on surveillance for hepatocellular carcinoma by Jepsen and West.
      • Jepsen P.
      • West J.
      We need stronger evidence for (or against) hepatocellular carcinoma surveillance.
      The authors propose that a randomized control trial of HCC surveillance vs. no surveillance is necessary and feasible; they postulate that clinician and patient involvement would be improved if trial results proved its benefit.
      As alluded to, there is a gap in the support for HCC surveillance among many international liver societies, that runs contrary to the dearth of strong contempory evidence to advocate its use in heterogeneous aetiological and geographical populations. Within the United Kingdom, Public Health England recommend screening programmes, if there is “evidence from high quality randomised controlled trials” that the screening programme is effective in reducing mortality or morbidity. The evidence base on which our practice is based is thin.
      The main question posed to clinicians looking after patients at high risk of HCC should be what is the objective of surveillance?
      Wilson and Junger developed criteria for appraising the viability, effectiveness and appropriateness of a screening programme in 1968, but their principles are still valid.
      • Wilson J.M.G.
      • Jungner G.
      Principles and practice of screening for disease.
      There are fundamental issues raised by these criteria. Some of these principles include; a knowledge of the disease, a suitable test and the availability of potentially curative treatments.
      With regards to knowledge of the disease, it is well recognised that HCC is a major health problem worldwide that is associated with high mortality.
      • El-Serag H.B.
      Hepatocellular carcinoma.
      The risk factors for the development of HCC are known, but as Jepsen and West state, it is important to identify patients with a risk of HCC as opposed to merely observing the rate of HCC across all cirrhotic/higher risk patients. What we need to know is which group of patients have the highest chance of developing HCC and then dying from HCC, as compared to their chance of death from end-stage liver disease or other comorbidities. EASL suggest taking life expectancy and ability to tolerate potentially curative treatment into account before enrolment in HCC surveillance programmes, but the validated tools to accurately identify these patients, do not currently exist.
      • Galle Peter R.
      • Forner Alejandro
      • Llovet Josep M.
      • Mazzaferro Vincenzo
      • Piscaglia Fabio
      • Raoul Jean-Luc
      • et al.
      EASL clinical practice guidelines: management of hepatocellular carcinoma.
      There should be a suitable test or examination. It is recognized that liver ultrasound is not an ideal screening tool as it is time and resource heavy, and operator dependent. Furthermore, with increasing rates of obesity, there is a risk the test may be increasingly sub-optimal.
      • Paul S.B.
      • Gulati M.S.
      • Sreenivas V.
      • Madan K.
      • Gupta A.K.
      • Mukhopadhyay S.
      • et al.
      Evaluating patients with cirrhosis for hepatocellular carcinoma: value of clinical symptomatology, imaging and alpha-fetoprotein.
      Moreover the yield of alpha-fetoprotein is insufficiently sensitive to support its ongoing use.
      • Wolf E.
      • Rich N.E.
      • Marrero J.A.
      • Parikh N.D.
      • Singal A.G.
      Use of hepatocellular carcinoma surveillance in patients with cirrhosis: a systematic review and meta-analysis.
      The test should be acceptable to the population. The test needs to be cheap, accurate and convenient. Ultrasound is, in population terms, none of the above. Easier, more practical tests that do not mandate a visit to a health institution would be ideal. It is known that fewer than predicted cirrhotic patients actually receive surveillance.
      • Tzartzeva Kristina
      • Obi Joseph
      • Rich Nicole E.
      • Parikh Neehar D.
      • Marrero Jorge A.
      • Yopp Adam
      • et al.
      Surveillance imaging and alpha fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis.
      In the UK, funding for HCC surveillance and the infra-structure to run it appropriately has not been present in comparison to other screening programmes.
      Finally, there should be an agreed policy on whom to treat. This is perhaps the most contentious issue. The community has never reached agreement on not only who should be treated, but perhaps more importantly, who should not be treated, and de facto not placed into screening. Is the aim to identify HCC, or to identify HCC in patients in whom potentially curative treatments are a realistic option, and in whom treatment would confer tangible survival benefits? These benefits and what would constitute a successful intervention are, at present, undefined.
      The study by Zhang et al., on which much of our current practice is based, only had liver resection as a curative option.
      • Zhang B.H.
      • Yang B.H.
      • Tang Z.Y.
      Randomized controlled trial of screening for hepatocellular carcinoma.
      The array of potentially curative treatments has broadened to include liver transplantation, ablation techniques and continues to possibly expand with radiation-based therapies. This may make a broader coalition of patients eligible for potentially curative treatments.
      The liver community need to decide what their objectives are for surveillance, and how to better identify patients who fulfil those aims. Screening is inconsequential if the patient will die of something other than HCC or if the patient would never be suitable for potentially curative treatments. The focus has been wrong for too long, it is the patient and not the test that is the key to successful surveillance. Once we have identified the right patients, only then can we be in a position to design and deliver a randomized controlled trial.

      Financial support

      The authors received no financial support to produce this manuscript.

      Authors’ contributions

      Both authors were involved in drafting and final revision of the manuscript.

      Conflict of interest

      The authors declare no conflicts of interest that pertain to this work.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following is the supplementary data to this article:

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