Research ArticleStructured Early detection of Asymptomatic Liver Cirrhosis: Results of the population-based liver screening program SEAL
Graphical abstract
Introduction
Globally, cirrhosis as a common consequence of end-stage liver diseases accounts for more than 1.3 million deaths every year.1 The incidence of deaths caused by cirrhosis as a proportion of all deaths increased from 1.9% in 1990 to 2.4% in 2017.1 In general, cirrhosis can be stratified into compensated and decompensated cirrhosis. Decompensated cirrhosis is defined by the occurrence of ascites, hepatic encephalopathy, variceal bleeding or jaundice and is associated with a very poor prognosis.2 In contrast, compensated cirrhosis is more benign as life expectancy is comparable to healthy individuals if cirrhosis remains compensated.2 In routine care, it is challenging to differentiate between patients with advanced fibrosis and early cirrhosis. Additionally, patients with advanced fibrosis are also at risk of disease progression and may as well qualify for hepatocellular carcinoma surveillance.3 For this reason, the term compensated advanced chronic liver disease has been introduced as an umbrella term for those 2 disease stages.4
Whereas the treatment of patients with decompensated cirrhosis focuses on the management of complications and frequently results in the need for liver transplantation, patients with advanced fibrosis and asymptomatic cirrhosis can benefit from causal treatment of their underlying liver disease.5 In this context, recent studies indicated that causal treatment may not only result in fibrosis regression, but also in an amelioration of portal hypertension, which is one of the best predictors of future decompensation.[6], [7], [8] Unfortunately, the minority of patients with cirrhosis are diagnosed at an early stage, and about 3 out of 4 show decompensation at initial diagnosis.9 Therefore, the development of screening pathways for the detection of patients with advanced fibrosis and early cirrhosis appears of pivotal importance to improve prognosis, disease burden, and reduce healthcare expenditures. For this reason, the aim of the SEAL (Structured Early Detection of Asymptomatic Liver Cirrhosis) program was to evaluate the feasibility and usefulness of a systematic screening program to detect patients with cirrhosis at early stage in the general population.
Section snippets
SEAL cohort and algorithm
SEAL was a prospective cohort study conducted in 2 federal states in Germany, Rhineland-Palatinate and Saarland, between 01/2018 and 02/2021. Fig. 1 outlines the SEAL algorithm for the detection of patients with advanced fibrosis and cirrhosis. In total, 201 practices of general practitioners in Rhineland-Palatinate (n = 141) and Saarland (n = 60) joined the study by signing a special contract (§ 140a SGB V Besondere Versorgung) with the major social health insurance AOK Rhineland-Palatinate
Implementation of the SEAL pathway
In total, 12,093 patients were registered and screened in the SEAL program. Of these, 234 (1.94%) patients did not fully meet the inclusion criteria and were excluded, resulting in the analysis cohort of 11,859 patients with available data (Fig. 2). Most patients were recruited in 2019 during the pre-COVID-19 era (Fig. S1). Of 11,859 patients included into SEAL, 488 patients (4.12%) met the criteria of elevated aminotransferase activities and APRI >0.5. The number of patients with elevated AST
Discussion
In this study, we report the results of the SEAL project – a prospective study to evaluate the usefulness of structured screening to detect cirrhosis in the general population. To the best of our knowledge, this study represents the largest reported trial using a predefined pathway primarily designed for the early detection of cirrhosis. SEAL not only provides a robust overview of the incidence of chronic liver diseases in patients with suspected advanced liver disease in 2 German territorial
Financial support
This project was funded by the Innovationsausschuss beim Gemeinsamen Bundesausschuss from 2016 to 2021 (G-BA 01NVF16026).
Authors’ contributions
Performed research: C.L., A.A., M.N.T., M.N., E.G., D.S., J.O., F.L., P.R.G. Contributed to acquisition of data: C.L., A.A., M.N.T., M.N., M.A.W., M.R., F.J.H., D.M., G.Z., B.R., F.L., P.R.G. Designed the experiments and analyzed the data: C.L., A.A., M.N.T., M.N., M.A.W., H.B., E.F.G., U.F., E.G., D.S., R.V.E., J.U., L.V., F.L., P.R.G. Wrote the manuscript: C.L., P.R.G. Critical revision of the manuscript: all authors. Statistical analysis: H.B., D.S., E.G., E.F.G, U.F. All authors approved
Data availability statement
The datasets generated and analyzed during the current study are not publicly available due to ethical restrictions but are available from the corresponding author on reasonable request.
Conflict of interest
The authors disclose no potential financial or non-financial conflict of interests regarding this study.
Please refer to the accompanying ICMJE disclosure forms for further details.
Acknowledgments
We are grateful for continuous support of this project from the AOK RLP Health insurance, in particular to Martin Giesen, Jutta Bartmann, Alexandra Schanzenbach and Inge Bearzatto, Felix Strobel, Jörg Eppers, and Monika Behrendts.
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2023, Journal of HepatologyCitation Excerpt :A study in Germany suggests a structured population screening programme, using simple blood tests such as aspartate aminotransferase/alanine aminotransferase, could be feasible. The detection of advanced fibrosis/cirrhosis in the screening programme was slightly higher than in controls (3.83% vs. 3.36%).27 The effectiveness may be improved by refining the initial “screening “population and diagnostic tools.
Reply to: “SEAL: Why was this approach not effective?”
2023, Journal of HepatologySEAL: Why was this approach not effective?
2023, Journal of Hepatology
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Both authors share first authorship.
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Both authors share senior-authorship.