In their prospective study, Verrijken et al. concluded that, in obesity, nonalcoholic fatty liver disease (NAFLD) severity independently contributes to plasminogen activator inhibitor-1 (PAI-1) increased levels, whereas other coagulation factors are unaltered; this finding might, in part, explain the possible role of NAFLD in cardiovascular disease (CVD) development. In this regard, a widespread environmental factor (i.e., Helicobacter pylori; Hp) might be a common denominator underlying the NAFLD-related risk of cardiovascular events by inducing PAI-1 and other prothrombotic and inflammatory agents.[2, 3]
Our data indicate that Hp infection (Hp-I), strongly associated with chronic liver disease in Europe, might represent one further hit contributing to NAFLD pathogenesis, though not to nonalcoholic steatohepatitis (NASH) progression. In a systematic review, we also reported an association between Hp-I and insulin resistance (IR); there is a causal link between hepatic IR and NAFLD development/progression and CVD. Furthermore, Hp stimulates the expression of PAI-1, a major player in cancer and CVD pathogenesis. Likewise, a large body of evidence has linked Hp-I to CVD.[2, 3] In this regard, our series demonstrated that increased fibrinogen levels (an independent risk factor for CVD), also mentioned by the researchers, are associated with Hp-I and can be reduced by Hp eradication. Other follow-up studies also reported that Hp eradication is associated with modification of certain CVD clinical and biochemical parameters; high-density lipoprotein-cholesterol increases, whereas C-reactive protein and fibrinogen levels diminish significantly. Apart from its effect on fibrinogen levels, Hp could influence the development of CVD through many other mechanisms.[2, 3] For instance, von Willebrand factor antigen, also mentioned by the researchers, is strongly associated with Hp-I, providing solid evidence that Hp-positive patients have increased CVD risk; Hp-I induces platelet activation/aggregation and an increase in triglycerides and various proatherogenic factors, including homocysteine, thereby contributing to Hp-related CVD risk; Hp-I is associated with increased tumor necrosis factor alpha (TNF-α), a circulating cytokine able to exert its effects at a distance. TNF-α and interleukin (IL)−6 (TNF-α is the main trigger for the production of IL-6 by a variety of cells) play important roles in the regulation of synthesis of other acute phase proteins, which are established risk factors for atherosclerosis, such as the mentioned fibrinogen and factor VIII; and circulating lipid peroxides, also associated with cardiovascular risk, are raised in Hp-positive patients.
Therefore, Hp eradication might display a positive effect on Hp-related NAFLD and CVD development/progression by inhibiting various prothrombotic and proinflammatory agents partly in some Hp-positive ethnic subpopulations. Because there is a lack of literature showing any demonstrable evidence to support the aforementioned hypothesis, large-scale studies are warranted to elucidate our hypothesis.
Jannis Kountouras, M.D., Ph.D.
Stergios A. Polyzos, M.D., Ph.D.
Christos Zavos, M.D., Ph.D.
Georgia Deretzi, M.D., Ph.D.
Constantinos Kountouras, Ph.D.
Elizabeth Vardaka, Ph.D.
Panagiotis Katsinelos, M.D., Ph.D.
Elena Tsiaousi, M.D.
Nikolaos Grigoriadis, M.D., Ph.D.
Iordanis Romiopoulos, M.D.
Dimitrios Tzilves, M.D., Ph.D.
Evangelia Giartza-Taxidou, M.D., Ph.D.
Department of Medicine
Second Medical Clinic
Aristotle University of Thessaloniki