Non-alcoholic steatohepatitis induces... : Liver International (original) (raw)

Sven Francque
Sam Wamutu
Shyama Chatterjee
Eric Van Marck
Arnold Herman
Albert Ramon
Alexander Jung
Wim Vermeulen
Benedicte De Winter
Paul Pelckmans
Peter Michielsen

Liver International

(

)

365

375

March 2010

| DOI: 10.1111/j.1478-3231.2009.02136.x

Abstract

Introduction:

Steatosis, without fibrosis, may lead to changes in liver blood flow, which are poorly understood, and to date have not been correlated to portal pressure and related haemodynamics.

Aims:

To study the temporal relation between progressive steatosis, portal pressure, systemic haemodynamics, vascular responsiveness, mesenteric and portal blood flow in methionine–choline-deficient diet (MCDD)-fed rats.

Methods:

Male Wistar rats fed the MCDD were examined at week (w) 0-1-2-3-4-5-6-7-8, respectively, including systemic haemodynamics and portal pressure. At w0-4-8, in vivo blood flow was measured in the portal vein and the superior mesenteric artery. Dose–response curves to phenylephrine (PE) were established in abdominal aortic rings.

Results:

Histology showed 100% steatosis from w3 on. Fibrosis was absent. Significant inflammation was nearly absent upon w4. Portal pressure slightly increased at w2, reached a maximum at w4 [9.4 ± 0.3 vs 2.9 ± 0.6 mmHg at w0 (_P_=0.003)] and remained stable upon w8. Mean arterial blood pressure (MABP) decreased from w2 on [98.7 ± 5.7 mmHg on w4 compared with 123.8 ± 1.8 on w0 (_P_=0.002)]. Portal flow increased from 1.85 ± 0.11 to 3.07 ± 0.44 ml/min/100 g on w0 and w8 respectively (_P_=0.039). Mesenteric artery flow increased from 3.40 ± 0.26 to 4.56 ± 0.30 ml/min/100 g on w0 and w8 respectively (_P_=0.043). Vascular responsiveness to PE gradually decreased from 138 ± 3% on w0 to 110 ± 5% on w4 (_P_=0.013).

Conclusion:

Steatohepatitis induces significant portal hypertension (PHT) in the absence of fibrosis, associated with an increase in mesenteric arterial and portal venous flow, arterial hyporesponsiveness to vasoconstrictors and a decrease in MABP, indicating the presence of splanchnic vasodilation and hyperdynamic circulation. These alterations resemble those seen in cirrhotic PHT.