Published online Jan 27, 2018. doi: 10.4254/wjh.v10.i1.73
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
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.
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).
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.
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.
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).
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.
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.