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Development and Validation of a Model to Predict Regression of Large Size Hepatocellular Adenoma

Klompenhouwer, Anne Julia MD1; Alblas, Maaike MSc2; Vivica van Rosmalen, Belle BSc3; Haring, Martinus Petrus Daniel BSc4; Venema, Esmee MD2; Doukas, Michail MD, PhD5; Thomeer, Maarten Guillaume Josephus MD, PhD6; Takkenberg, Robert Bart MD, PhD7; Verheij, Joanne MD, PhD8; de Meijer, Vincent Erwin MD, PhD4; van Gulik, Thomas Matthijs MD, PhD3; Lingsma, Hester Floor MPH, PhD2; de Man, Robert Auke MD, PhD9; Ijzermans, Jan Nicolaas Maria MD, PhD1

doi: 10.14309/ajg.0000000000000182
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INTRODUCTION: Surgery is advocated in hepatocellular adenomas (HCA) >5 cm that do not regress to <5 cm after 6–12 months. The aim of this study was to develop a model for these patients, estimating the probability of HCA regression to <5 cm at 1 and 2 years follow-up.

METHODS: Data were derived from a multicenter retrospective cohort of female patients diagnosed with HCA >5 cm at first follow-up. Potential predictors included age, body mass index, and HCA diameter at diagnosis (T0), HCA-subtype (hepatocyte nuclear factor 1α inactivated HCA, inflammatory-HCA, unclassified HCA) and “T0-T1 regression-over-time” (percentage of regression between T0 and first follow-up (T1) divided by weeks between T0 and T1). Cox proportional hazards regression was used to develop a multivariable model with time to regression of HCA < 5 cm as outcome. Probabilities at 1 and 2 years follow-up were calculated.

RESULTS: In total, 180 female patients were included. Median HCA diameter at T0 was 82.0 mm and at T1 65.0 mm. Eighty-one patients (45%) reached the clinical endpoint of regression to <5 cm after a median of 34 months. No complications occurred during follow-up. In multivariable analysis, the strongest predictors for regression to <5 cm were HCA diameter at T0 (logtransformed, hazard ratio (HR) 0.05), T0-T1 regression-over-time (HR 2.15) and HCA subtype inflammatory-HCA (HR 2.93) and unclassified HCA (HR 2.40), compared to hepatocyte nuclear factor 1α inactivated HCA (reference). The model yielded an internally validated c-index of 0.79.

CONCLUSIONS: In patients diagnosed with HCA > 5 cm that still exceed 5 cm at first follow-up, regression to <5 cm can be predicted at 1 and 2 years follow-up using this model. Although external validation in an independent population is required, this model may aid in decision-making and potentially avoid unnecessary surgery.

1Department of Surgery, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands;

2Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands;

3Department of Surgery, Amsterdam University Medical Centers, University of Amsterdam (Location Academic Medical Center), Amsterdam, the Netherlands;

4Division of Hepatopancreatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands;

5Department of Pathology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands;

6Department of Radiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands;

7Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, University of Amsterdam (Location Academic Medical Center), Amsterdam, the Netherlands;

8Department of Pathology, Amsterdam University Medical Centers, University of Amsterdam (Location Academic Medical Center), Amsterdam, the Netherlands;

9Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Correspondence: Jan Nicolaas Maria Ijzermans. E-mail: j.ijzermans@erasmusmc.nl.

The first two authors shared first authorship.

SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/A80

Data from this paper will be presented as a poster of distinction at The Liver Meeting 2018 of the American Association of the Liver, San Francisco, November 9–13, 2018.

Received November 19, 2018

Accepted January 25, 2019

© The American College of Gastroenterology 2019. All Rights Reserved.
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