To the Editors:
We would like to thank Professor Ripoll and colleagues for their interest and their commentary on our SEAL study published in the Journal of Hepatology.
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Ripoll et al. raise some important points and potential limitations of SEAL that we would like to take the opportunity to reply to.We agree with our colleagues who point out that people of lower socioeconomic status are less likely to participate in a preventive health care program such as the German Check-up 35 program, as targeted in SEAL. This is a non-negligible circumstance that leads to a potential selection bias and should be taken into account when interpreting the results of SEAL. However, it should be noted that all SEAL participants were members of AOK, the largest general medical insurance in Germany, excluding patients from alternative insurance companies and all with private insurance, who have in general higher socioeconomic status.
Notwithstanding this shortcoming, it is an important finding for the hepatology community that screening for compensated advanced chronic liver disease (cACLD) even in a population with a potentially higher degree of health awareness is feasible and provides benefit. On the other hand, SEAL suggests that future studies could specifically target populations at highest risk of chronic liver disease. Though, these populations may be more difficult to approach, since the awareness of liver health in these populations is lower than in Check-up 35 participants, and appointments with a liver specialist in SEAL were only attended by about 50% of cases. Therefore, we agree that awareness of liver health needs to be raised in all parts of our society.
Ripoll et al. proposed the recently published CLivD score to identify a high-risk population in the general population that deserves detailed screening for cACLD.
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We argue that a stepwise approach with defined strategies that help primary care physicians to identify patients at high risk for liver disease might indeed improve the care for patients with cACLD. Because this is another lesson that SEAL and other studies have taught us: Screening in the general population using traditional and simple non-invasive tests may not be sufficient and lacks positive predictive value.[1]
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However, it has to be acknowledged that scores such as the CLivD are frequently developed in retrospective cohorts. Therefore, studies testing the benefits of these algorithms as well as alternative methods (e.g., transient elastography) prospectively are needed before implementation. In this context, we believe that SEAL can serve as a blueprint for these studies by demonstrating not only what is possible in terms of patient recruitment and involvement of multiple levels of care, but also the future needs.In summary, we believe that we have only reached the tip of the iceberg in the early detection of cACLD and are eagerly awaiting the results of additional screening studies.
Financial support
This project was funded by the Innovationsausschuss beim Gemeinsamen Bundesausschuss from 2016 to 2021 (G-BA 01NVF16026).
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.
Authors' contributions
All authors contributed equally on conceptualization, drafting and writing of this reply.
Supplementary data
The following are the supplementary data to this article:
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References
- Structured early detection of asymptomatic liver cirrhosis: results of the population-based liver screening program SEAL.J Hepatol. 2022; 77: 695-701
- SEAL: why was this approach not effective?.J Hepatol. 2023; 78: e26-e27
- Development and validation of a model to predict incident chronic liver disease in the general population: the CLivD score.J Hepatol. 2022; 77: 302-311
- Low accuracy of FIB-4 and NAFLD fibrosis scores for screening for liver fibrosis in the population.Clin Gastroenterol Hepatol. 2021; 29 (S1542-3565(21)01358-6)
- Repeated FIB-4 measurements can help identify individuals at risk of severe liver disease.J Hepatol. 2020; 73: 1023-1029
Article info
Publication history
Published online: September 26, 2022
Accepted:
September 22,
2022
Received:
September 20,
2022
Footnotes
Author names in bold designate shared co-first authorship.
Identification
Copyright
© 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
