LAUSR

Wijarnpreecha et al. [1] demonstrated an association between Helicobacter pylori infection (Hp-I) and risk of hepatic encephalopathy (HE); focus only on Hp-related augmented ammonia level possibly associated with the frequent HE exacerbation, the authors concluded that its eradication to decrease urease activity could be one of the potential HE treatments [1]. In this regard, portal hypertension (PH) leads to devastating complications including HE from portosystemic shunting formation and bacterial translocation (BT) playing an important role in PH pathogenesis [2]. HE is a potentially reversible though not fully reversible condition, the mechanism behind the lack of reversibility of the neurocognitive status despite the resolution of mental status changes is unclear [3], and cognitive dysfunction (CD) associated with minimal or covert HE, also mentioned by the authors [1], is a factor associated with falls and traffic accidents (automobile crashes) in cirrhotic patients [4]. Hp-I appears to be a frequent denominator connected with CD-related falls and fractures and liver cirrhosis [5]. In this respect, we reported an association between Hp-I and neurodegenerative disorders including mild CD and Alzheimer’s disease (AD) and Hp eradication could positively influence AD manifestations at 2and 5-year clinical endpoints, thereby suggesting a role for this common infection in the pathobiology of the disease [6]. Other epidemiologic studies also reported that AD patients infected by Hp are more cognitively impaired [6]; Hp-I is strongly associated with viral-related cirrhosis in Europe [4]; recent meta-analysis supports the high Hp-I prevalence in patients with cirrhosis [7]; and Hp-I is common in cirrhotic patients with HE [3]. Apart from Hp-induced hyperammonemia, mentioned by the authors [1], Hp-I may be further involved in HE and post-HE persistent CD pathophysiology by promoting the release of proinflammatory and vasoactive substances involved, through blood–brain barrier (BBB) disruption, in brain pathologies [6]; promoting platelet–leukocyte aggregation proposed to play pathophysiologic roles in dementia and complications of cirrhosis [6]; producing reactive oxygen metabolites involved in the pathophysiology of AD and complications of cirrhosis [6]; or influencing the apoptotic process, an important form of cell death in AD and liver disease [6]. Moreover, Hp might access brain via the oral–nasal–olfactory pathway or by circulating monocytes (infected with Hp due to defective autophagy) through disrupted BBB, leading to neurodegeneration [6]. Likewise, human defensins might contribute to Hp-related brain pathophysiology by modulating innate and adaptive immune system responses [8]. Specifically, human β-defensin (hBD)-1 is upregulated and may serve as a biomarker of BT in cirrhotic patients [9]; BT observed in liver cirrhosis appears to play an important role in the pathogenesis of its complications such as infections and HE; and Hp-I induces hBD-1 mRNA expression [10], thereby possibly contributing to Hp-related defensinBT-HE sequence. Hp might be further involved in the BBB breakdown, by releasing defensins, particularly those that display unique distribution at BBB sites [8]. Hp can activate granulocytes and induce defensin release from granulocytes; consequently, defensins penetrate the BBB, gain access brain, thereby possibly contributing to neurodegeneration [8]; HBD-1 might be of importance early in the neurodegenerative process [10]. * Jannis Kountouras [email protected]