We read with much interest the recently published study on the association between carotid atherosclerosis and chronic hepatitis C by Salvatore Petta and colleagues.1 The authors demonstrate that severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in patients with genotype 1 chronic hepatitis C.1 We have also described in rats with long-term prehepatic portal hypertension (PH) the development of chronic inflammatory impairment of the abdominal aorta, which could be considered an atherosclerosis-like disease.2 Consequently, 22 months after PH, the rats developed aortic oxidative and nitrosative stress, with increased aortic mRNA expressions of nicotinamide adenine dinucleotide phosphate oxidase (NAD(P)H) p22phox, xanthine dehydrogenase (XDh), superoxide dismutase (SOD), and endothelial nitric oxide synthase (eNOS); higher aortic levels of proinflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β and IL-6 and remodeling markers such as collagen I, connective tissue growth factor (CTGF), and matrix metalloproteinase-9 (MMP-9); and higher collagen and extracellular matrix production. Very long-term PH in the rat, therefore, induces an aortic chronic inflammatory response that is associated with fibrosis (Fig. 1).2
Because the role of inflammation in the initiation and progression of vascular diseases is increasingly recognized,3 the cause of this morphofunctional aortic alteration in the prehepatic portal hypertensive rat could also be of an inflammatory nature. Additionally, the coexistence in this experimental model of liver steatosis and dyslipidemia4 suggests the involvement of an atherogenic pathogenic mechanism in the production of an aortic disease related to PH.2 Although animal studies require judicious interpretation and recognition of their limitations when extrapolating to human diseases,5 these results suggest that inflammation related to prehepatic PH could be an atherogenic risk during long-term follow-up in humans. Particularly, this pathogenic portal hypertension-aortic disease relationship must be researched in patients with hepatic fibrosis. PH per se seems to represent a systemic inflammatory risk factor for developing atherosclerosis. This is the reason why, in the patients described by Petta et al.1 in which they demonstrate that severe liver fibrosis related to chronic hepatitis C is associated with carotid atherosclerosis, portal hypertension could, therefore, stand out among the contributing factors.