Oesophageal varices predict complications in compensated advanced non-alcoholic fatty liver disease

Grazia Pennisi; Marco Enea; Mauro Viganò; Filippo Schepis; Victor de Ledinghen; Annalisa Berzigotti; Vincent Wai-Sun Wong; Anna Ludovica Fracanzani; Giada Sebastiani; Carmen Lara-Romero; Elisabetta Bugianesi; Gianluca Svegliati-Baroni; Fabio Marra; Alessio Aghemo; Luca Valenti; Vincenza Calvaruso; Antonio Colecchia; Gabriele Di Maria; Claudia La Mantia; Huapeng Lin; Yuly P Mendoza; Nicola Pugliese; Federico Ravaioli; Manuel Romero-Gomez; Dario Saltini; Antonio Craxì; Vito Di Marco; Calogero Cammà; Salvatore Petta

doi:10.1016/j.jhepr.2023.100809

Oesophageal varices predict complications in compensated advanced non-alcoholic fatty liver disease

JHEP Rep. 2023 Jun 7;5(9):100809. doi: 10.1016/j.jhepr.2023.100809. eCollection 2023 Sep.

Authors

Grazia Pennisi¹, Marco Enea¹, Mauro Viganò², Filippo Schepis³, Victor de Ledinghen⁴, Annalisa Berzigotti⁵, Vincent Wai-Sun Wong⁶, Anna Ludovica Fracanzani⁷, Giada Sebastiani⁸, Carmen Lara-Romero⁹, Elisabetta Bugianesi¹⁰, Gianluca Svegliati-Baroni¹¹, Fabio Marra^{12

13}, Alessio Aghemo^{14

15}, Luca Valenti^{16

17}, Vincenza Calvaruso¹, Antonio Colecchia³, Gabriele Di Maria¹, Claudia La Mantia¹, Huapeng Lin⁶, Yuly P Mendoza⁵, Nicola Pugliese¹⁵, Federico Ravaioli^{3

18}, Manuel Romero-Gomez⁹, Dario Saltini³, Antonio Craxì¹, Vito Di Marco¹, Calogero Cammà¹, Salvatore Petta¹

Affiliations

¹ Sezione di Gastroenterologia e Epatologia, PROMISE, Università di Palermo, Palermo, Italy.
² Hepatology Unit, Ospedale San Giuseppe, University of Milan, Milan, Italy.
³ Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy.
⁴ Centre d'Investigation de la Fibrose Hépatique, INSERM U1053, Hôpital Haut-Lévêque, Bordeaux University Hospital, Pessac, France.
⁵ Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁶ Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
⁷ Department of Pathophysiology and Transplantation, Ca' Granda IRCCS Foundation, Policlinico Hospital, University of Milan, Milan, Italy.
⁸ Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada.
⁹ UCM Digestive Diseases, Virgen del Rocio University Hospital, Institute of Biomedicine of Seville (HUVR/CSIC/US), CIBEREHD, University of Seville, Ciberehd, Seville, Spain.
¹⁰ Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy.
¹¹ Liver Injury and Transplant Unit, Università Politecnica delle Marche, Ancona, Italy.
¹² Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy.
¹³ Research Center DENOTHE, University of Florence, Florence, Italy.
¹⁴ Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
¹⁵ Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy.
¹⁶ Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy.
¹⁷ Precision Medicine and Biological Resource Center, Department of Transfusion Medicine, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico IRCCS, Milan, Italy.
¹⁸ IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

Abstract

Background & aims: We aimed to evaluate the impact of oesophageal varices (OV) and their evolution on the risk of complications of compensated advanced chronic liver disease (cACLD) caused by non-alcoholic fatty liver disease (NAFLD). We also assessed the accuracy of non-invasive scores for predicting the development of complications and for identifying patients at low risk of high-risk OV.

Methods: We performed a retrospective assessment of 629 patients with NAFLD-related cACLD who had baseline and follow-up oesophagogastroduodenoscopy and clinical follow-up to record decompensation, portal vein thrombosis (PVT), and hepatocellular carcinoma.

Results: Small and large OV were observed at baseline in 30 and 15.9% of patients, respectively. The 4-year incidence of OV from absence at baseline, and that of progression from small to large OV were 16.3 and 22.4%, respectively. Diabetes and a ≥5% increase in BMI were associated with OV progression. Multivariate Cox regression revealed that small (hazard ratio [HR] 2.24, 95% CI 1.47-3.41) and large (HR 3.86, 95% CI 2.34-6.39) OV were independently associated with decompensation. When considering OV status and trajectories, small (HR 2.65, 95% CI 1.39-5.05) and large (HR 4.90, 95% CI 2.49-9.63) OV at baseline and/or follow-up were independently associated with decompensation compared with the absence of OV at baseline and/or follow-up. The presence of either small (HR 2.8, 95% CI 1.16-6.74) or large (HR 5.29, 95% CI 1.96-14.2) OV was also independently associated with incident PVT.

Conclusion: In NAFLD-related cACLD, the presence, severity, and evolution of OV stratify the risk of developing decompensation and PVT.

Impact and implications: Portal hypertension is the main driver of liver decompensation in chronic liver diseases, and its non-invasive markers can help risk prediction. The presence, severity, and progression of oesophageal varices stratify the risk of complications of non-alcoholic fatty liver disease. Easily obtainable laboratory values and liver stiffness measurement can identify patients at low risk for whom endoscopy may be withheld, and can also stratify the risk of liver-related complications.

Keywords: NAFLD; Portal Vein Thrombosis; baveno; cACLD; liver decompensation; liver stiffness; varices.