Introduction
Alcohol related liver disease, and particularly alcohol related hepatitis, is characterised by specific hepatic and systemic histo- and physiopathological changes (inflammation, ballooning, fibrosis, cholestasis, etc) [1]. On the other hand, increased HVPG was demonstrated to predict a worse outcome in AH [2]. In this study, we aimed to detect which specific AH changes are associated with an increased HVPG. Secondly, we analyzed the interrelation between canalicular cholestasis, systemic inflammation markers, and sepsis.
Aims & Methods
In this study, we aimed to detect which specific AH changes are associated with an increased HVPG. Secondly, we analyzed the interrelation between canalicular cholestasis, systemic inflammation markers, and sepsis.
We retrospectively re-evaluated the transjugular liver biopsy (TJLB) specimens of 90 patients with alcohol-related liver disease between 2016 and 2020 and rescored them using the SALVE scoring/grading system.
Serum from the biobank was used for ELISA tests for cytokeratin18 (CK18), heat shock protein 90 (Hsp90), toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNFα), and lipopolysaccharide (LPS).
We analyzed the correlation between HVPG, systemic inflammation, infection, and the SALVE grading/staging criteria.
Results
Of the 90 enrolled patients, 81 went through TJLB and HVPG measurement. The gender ratio was 24 (29.6%) female to 57 (70.4%) male. The age range was 28-73 (median of 45). Median MELD score and MaddreyDF scores were 22 (6.61 SD, 95% CI) and 82.5 (37.57 SD, 95% CI), respectively. Median HVPG was 20 mmHg (4.9 SD, 95%CI). The biopsy length had a median of 20 mm (range 8-80 mm).
In the univariate analysis, ductular cholestasis was correlated with the prognostic scores (MELD, Maddrey DF, Child-Pugh), which was confirmed at the multivariate analysis (p<0.05). The canalicular type of cholestasis was correlated in both univariate and multivariate analysis with the scores, but also with the number of leucocytes, neutrophils, platelets, the C-reactive protein (CRP), bilirubin level, and HVPG ( p<0.05).
HVPG was correlated with canalicular cholestasis, but not with the ductular type. There was a significant difference in the mean HVPG value between patients without canalicular cholestasis (M=19.14; SD=4.79) and those with canalicular cholestasis (M=21.61; SD=4.84); t(80)=2.31, p=0.023.
One-way ANOVA revealed a statistically significant difference in the HVPG value between the non-cirrhotic and the 3 cirrhotic stages, i.e., SALVE fibrosis stage (SFS) 4A, 4B, and 4C (F(3, 78)=3.99; p=0.01). HVPG did not show a correlation with other histological criteria, such as steatosis, ballooning, and neutrophils.
The systemic inflammation markers CK18, Hsp90, TLR4, TNFα, and LPS did not correlate with cholestasis in the univariate analysis.
Patients who had canalicular cholestasis on histology also had a higher probability of being infected (Pearson Chi square p=0.041) than those with the ductular type of cholestasis (p=0.611).
Overall survival was not influenced by the presence of cholestasis or the canalicular/ductular type (Chi square test p=0.476).
Conclusion
From the histological SALVE criteria, HVPG is correlated with cholestasis, particularly the canalicular type, and the SFS 4A-C.
Cholestasis was found to be an independent predictor of infection in these patients, although, in this vicious circle, infections and sepsis are usually the cause of cholestasis.
References
[1] Lackner C, Stauber RE, Davies S, Denk H, Dienes HP, Gnemmi V, Guido M, Miquel R, Paradis V, Schirmacher P, Terracciano L, Berghold A, Pregartner G, Binder L, Douschan P, Rainer F, Sygulla S, Jager M, Rautou PE, Bumbu A, Horhat A, Rusu I, Stefanescu H, Detlefsen S, Krag A, Thiele M, Cortez-Pinto H, Moreno C, Gouw ASH, Tiniakos DG. Development and prognostic relevance of a histologic grading and staging system for alcohol-related liver disease. J Hepatol. 2021 Oct;75(4):810-819. doi:10.1016/j.jhep.2021.05.029.
[2] Rincon D, Lo Iacono O, Ripoll C, Gomez-Camarero J, Salcedo M, Catalina MV, Hernando A, Clemente G, Matilla A, Nuñez O, Bañares R. Prognostic value of hepatic venous pressure gradient for in-hospital mortality of patients with severe acute alcoholic hepatitis. Aliment Pharmacol Ther. 2007 Apr 1;25(7):841-8. doi: 10.1111/j.1365-2036.2007.03258.x.
Disclosure
The authors have nothing to declare.
