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Structured Early detection of Asymptomatic Liver Cirrhosis: Results of the population-based liver screening program SEAL

Published:April 22, 2022DOI:https://doi.org/10.1016/j.jhep.2022.04.009

      Highlights

      • The detection of patients with early cirrhosis is important to improve prognosis.
      • The SEAL algorithm evaluates the utility of population-based screening to detect cirrhosis as early as possible.
      • Excluding patients with decompensated cirrhosis at initial diagnosis, SEAL was associated with a 60% higher chance of early cirrhosis detection.
      • Only 50% of the patients identified by SEAL in primary care utilized specialist assessment.

      Background & Aims

      Detection of patients with early cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. The SEAL program aimed at evaluating the usefulness of a structured screening procedure to detect cirrhosis as early as possible.

      Methods

      SEAL was a prospective cohort study with a control cohort from routine care data. Individuals participating in the general German health check-up after the age of 35 (“Check-up 35”) at their primary care physicians were offered a questionnaire, liver function tests (aspartate and alanine aminotransferase [AST and ALT]), and follow-up. If AST/ALT levels were elevated, the AST-to-platelet ratio index (APRI) score was calculated, and patients with a score >0.5 were referred to a liver expert in secondary and/or tertiary care.

      Results

      A total of 11,859 participants were enrolled and available for final analysis. The control group comprised 349,570 participants of the regular Check-up 35. SEAL detected 488 individuals with elevated APRI scores (4.12%) and 45 incident cases of advanced fibrosis/cirrhosis. The standardized incidence of advanced fibrosis/cirrhosis in the screening program was slightly higher than in controls (3.83‰ vs. 3.36‰). The comparison of the chance of fibrosis/cirrhosis diagnosis in SEAL vs. in standard care was inconclusive (marginal odds ratio 1.141, one-sided 95% CI 0.801, +Inf). Of note, when patients with decompensated cirrhosis at initial diagnosis were excluded from both cohorts in a post hoc analysis, SEAL was associated with a 59% higher chance of early cirrhosis detection on average than routine care (marginal odds ratio 1.590, one-sided 95% CI 1.080, +Inf; SEAL 3.51‰, controls: 2.21‰).

      Conclusions

      The implementation of a structured screening program may increase the early detection rate of cirrhosis in the general population. In this context, the SEAL pathway represents a feasible and potentially cost-effective screening program.

      Registration

      DRKS00013460

      Lay summary

      Detection of patients with early liver cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. This study demonstrates that the implementation of a structured screening program using easily obtainable measures of liver function may increase the early detection rate of cirrhosis in the general population. In this context, the ‘SEAL’ pathway represents a feasible and potentially cost-effective screening program.

      Graphical abstract

      Keywords

      Linked Article

      • SEAL: Why was this approach not effective?
        Journal of HepatologyVol. 78Issue 1
        • Preview
          We read with great interest the study recently published by Labenz et al. in Journal of Hepatology.1 We congratulate the authors for undertaking such an initiative. However, we were astonished with the marginal advantage of the SEAL approach compared to the standard of care in the control group in the detection of compensated advanced chronic liver disease (cACLD). Several aspects could explain these results. One reason that the authors propose is that this study was performed in the general population and not focused on patients with high risk, such as patients with metabolic risk factors or with non-alcoholic fatty liver disease (NAFLD), where similar studies have shown a greater benefit in the detection of cACLD.
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      • An individualized cirrhosis screening strategy might be more cost-effective in the general population
        Journal of HepatologyVol. 77Issue 6
        • Preview
          We read with great interest the article by Labenz, Arslanow et al.1 recently published in Journal of Hepatology. This article showed that the structured early detection of asymptomatic liver cirrhosis (SEAL) approach, involving assessment of elevated liver enzymes and calculation of the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), has the potential to increase the detection of advanced liver fibrosis and cirrhosis in the general population. This prospective study is important and timely for guiding the detection of early cirrhosis in clinical practice.
        • Full-Text
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      • Reply to: “SEAL: Why was this approach not effective?”
        Journal of HepatologyVol. 78Issue 1
        • Preview
          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.1,2 Ripoll et al. raise some important points and potential limitations of SEAL that we would like to take the opportunity to reply to.
        • Full-Text
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      • Reply to: “An individualized cirrhosis screening strategy might be more cost-effective in the general population”
        Journal of HepatologyVol. 77Issue 6
        • Preview
          We thank Dr. Zhao, Dr. Liao and Dr. Fan for their commentary on our SEAL study funded by the Federal Joint Committee, the highest decision-making body of the self-government of physicians, hospitals and health insurance funds in Germany, and published in the Journal of Hepatology.1,2 In SEAL (Structured Early detection of Asymptomatic Liver cirrhosis), we were able to demonstrate that screening for cirrhosis and advanced fibrosis in the general population is feasible and that our approach has the potential to increase the early detection rate of these patients.
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      • Signed, SEALed, detected I’m your patient with advanced fibrosis or cirrhosis!
        Journal of HepatologyVol. 77Issue 3
        • Preview
          Today, many patients with chronic liver disease are not diagnosed until they present with complications of cirrhosis, such as ascites or hepatocellular carcinoma (HCC). A key challenge in the hepatology community, as articulated by the EASL-Lancet Commission and endorsed by others,1 is to identify patients with advanced fibrosis or cirrhosis earlier, so that preventive treatments and screening for HCC can be considered. This month’s issue of the Journal of Hepatology presents the results of a German liver screening programme - “Structured Early detection of Asymptomatic Liver cirrhosis” (SEAL) - which highlights the potential benefits, but also the barriers that need to be overcome.
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