Abstract
The clinical course of cirrhosis has been typically described by a compensated and a decompensated state based on the absence or, respectively, the presence of any of bleeding, ascites, encephalopathy or jaundice. More recently, it has been recognized that increasing portal hypertension and several major clinical events are followed by a marked worsening in prognosis, and disease states have been proposed accordingly in a multistate model. The development of multistate models implies the assessment of the probabilities of more than one possible outcome from each disease state. This requires the use of competing risks analysis which investigates the risk of several competing outcomes. In such a situation, the Kaplan–Meier risk estimates and the Cox regression may be not appropriate. Clinical states of cirrhosis presently considered as suitable for a comprehensive multistate model include: in compensated cirrhosis, early (mild) portal hypertension with hepatic venous pressure gradient (HVPG) >5 and <10 mmHg, clinically significant portal hypertension (HVPG ≥ 10 mmHg) without gastro-esophageal varices (GEV), and GEV; in decompensated cirrhosis, a first variceal bleeding without other decompensating events, any first non-bleeding decompensation and any second decompensating event; and in a late decompensation state, refractory ascites, sepsis, renal failure, recurrent encephalopathy, profound jaundice, acute on chronic liver failure, all predicting a very short survival. In this review, we illustrate how competing risks analysis and multistate models may be applied to cirrhosis.
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P. Rebora was supported by the grant of the Italian Minister of Education, University and Research (MIUR) SIR 2014 (RBSI14LOVD).
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G. D’Amico, A. Morabito, M. D’Amico, L. Pasta, G. Malizia, P. Rebora, M. G. Valsecchi declare no conflict of interest.
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This article is a review article and does not contain any studies with human participants or animals performed by any of the authors.
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12072_2017_9808_MOESM1_ESM.tif
Supplementary material 1 A graphical example of the relationship between incidence rate and risk is shown. Among 100 subjects at risk, 10 experienced the event of interest during the first 12 months, 2 between month 13 and 24 and 6 between month 25 and 36. Incidence rate is calculated by dividing the total number of events by the total amount of observation time expressed as person-years and accounts for the occurrence of an event of interest or censoring for any reason (loss to the follow-up, retiring informed consent, others). The event risk is calculated by dividing the number of events by the total number of subjects at risk. In the example, the incidence rate and risk are calculated at 12, 24 and 36 months. While the risk increased along the whole observation period, the incidence rate decreased in the second and increased again during the third observation year (TIFF 4562 kb)
12072_2017_9808_MOESM2_ESM.tif
Supplementary material 2 the occurrence of ascites (A) is assessed in the context of a 2-state setting (left part of the figure: free of ascites or ascites) or in the context of a 3-state model by a competing risk approach (right part of the figure), where the 3 states are: free of events, ascites (A), bleeding (B). In the competing risks approach, any patient developing either bleeding or ascites is not anymore considered at risk (not free of events): in this situation, the unique relationship between rate and risk, typical of a 2-state model, is lost. Numbers close to A or B represent the number of patients developing ascites or bleeding during each observation period (TIFF 4557 kb)
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D’Amico, G., Morabito, A., D’Amico, M. et al. New concepts on the clinical course and stratification of compensated and decompensated cirrhosis. Hepatol Int 12 (Suppl 1), 34–43 (2018). https://doi.org/10.1007/s12072-017-9808-z
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DOI: https://doi.org/10.1007/s12072-017-9808-z