Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2018; 10(1): 73-81
Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.73
Collagen proportionate area correlates to hepatic venous pressure gradient in non-abstinent cirrhotic patients with alcoholic liver disease
Sophie Restellini, Nicolas Goossens, Sophie Clément, Nicolas Lanthier, Francesco Negro, Laura Rubbia-Brandt, Laurent Spahr
Sophie Restellini, Nicolas Goossens, Francesco Negro, Laurent Spahr, Department of Medical Specialties, Division of Gastroenterology and Hepatology, Geneva University Hospitals and University of Geneva, Geneva 1205, Switzerland
Sophie Clément, Francesco Negro, Laura Rubbia-Brandt, Department of Genetic and Laboratory Medicine, Division of Clinical Pathology, Geneva University Hospitals and University of Geneva, Geneva 1205, Switzerland
Nicolas Lanthier, Laboratory of Gastroenterology and Hepatology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels 1200, Belgium
Author contributions: Restellini S and Goossens N contributed equally to this work; Restellini S, Goossens N, Lanthier N, and Spahr L contributed to acquisition of data; Restellini S, Goossens N, and Spahr L contributed to drafting of the article; all of the authors contributed to conception and design, analysis and interpretation of the data, critical revision of the article for important intellectual content, and final approval of the article.
Institutional review board statement: The study was reviewed and approved by the Geneva University Hospital Institutional Review Board.
Informed consent statement: Due to the retrospective, non-interventional nature of the study and in view of the irreversible anonymization of all clinical specimens and data, the requirement form informed consent was not required by the ethics committee of Geneva’s University Hospitals and University of Geneva as per local guidelines at time of the study submission.
Conflict-of-interest statement: The authors have no relevant conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Laurent Spahr, MD, Professor, Department of Medical Specialties, Division of Gastroenterology and Hepatology, Geneva University Hospitals and University of Geneva, 4, Rue Gabrielle Perret-Gentil, Geneva 1205, Switzerland. laurent.spahr@hcuge.ch
Telephone: +41-223-729340 Fax: +41-223-729366
Received: November 21, 2017
Peer-review started: November 22, 2017
First decision: December 7, 2017
Revised: December 15, 2017
Accepted: January 9, 2018
Article in press: January 9, 2018
Published online: January 27, 2018
Processing time: 65 Days and 9.9 Hours
ARTICLE HIGHLIGHTS
Research background

Fibrosis staging in a liver biopsy is based on a semi-quantitative evaluation by the pathologist however inter-observer concordance may be a limiting factor. The quantitative measurement of liver fibrosis by a computer-assisted digital image analysis of a liver tissue specimen collagen proportionate area (CPA) overcomes some limitations of semiquantitative scores.

Research motivation

Previous studies have shown a good correlation between CPA and hepatic venous pressure gradient (HVPG) and association of CPA with prognosis. However, these results have been mostly obtained in HCV-related liver disease, and very few data are available in alcoholic liver disease (ALD).

Research objectives

The objective of the study was to explore the relationships between fibrosis density in liver biopsy, HVPG and development of clinical manifestations of portal hypertension (PHT) in patients with chronic advanced alcoholic liver disease (cALD) addressed for liver investigations. We aimed to better understand the relative prognostic contribution of HVPG and CPA in subjects with advanced ALD.

Research methods

We conduced a retrospective study with chart review of patients with ALD adressed to our center between January 2012 and December 2013 for a transjugular liver biopsy (TJLB) and hepatic hemodynamic study. Patients were included if they met the following criteria: (1) Medical indication for a liver biopsy in the setting of ALD; (2) recent (< 15 days) clinical, radiological, endoscopic and biological data available; (3) estimated follow-up of at least 6 mo. Liver tissue from cirrhotic subjects obtained from transjugular liver biopsies was stained with PicroSirius red and computer-assisted digital image analysis to determine fibrosis density using CPA was performed.

Research results

We included 61 patients with alcoholic ALD, subdivided in 41 active alcohol drinkers and 20 durably abstinent patients. Nine healthy liver donors served as controls. Mean CPA in patients with ALD was 7.1%, with no difference between active drinkers and abstinent patients (P = 0.17). Using a fibrosis density cutoff of 5%, we observed a positive correlation between high fibrosis density and the hepatic venous pressure gradient (HVPG) only in active drinkers (P = 0.02). At 12-month of follow-up, in the group of active alcohol drinkers, patients reaching a composite outcome showed a higher HVPG value as compared to those who did not (18.5 mmHg vs 14.5 mmHg P < 0.04) whereas CPA values were similar (6.9% vs 11%, P = 0.23).

Research conclusions

This is the first study exploring the relationships between fibrosis density assessed by CPA in liver biopsy, HVPG and development of clinical manifestations of portal hypertension in patients with ALD addressed for liver investigations. The results of this study suggest a positive correlation between high fibrosis density (using a fibrosis density cutoff of 5%), and HVPG only in active drinkers. At 12-mo of follow-up, in the group of active alcohol drinkers, patients reaching a composite outcome showed a higher HVPG value as compared to those who did not. Therefore, HVPG, but not CPA, predicts clinical events in active alcohol drinkers pointing to the role of alcohol as a modulator of portal hypertension.

Research perspectives

The validation of CPA as a quantitative method of measuring fibrosis density in liver biopsy of ALD patients requires further investigations in order to determine a correlation with clinical events, in particular overall and liver-related mortality in various subgroup of patients with difference etiologies of liver disease.