For instance, given that the use of statins is associated with increased liver enzymes (in a quite small subset of individuals),[68] physicians might nevertheless be more prone to prescribe these drugs to individuals with less elevated liver enzymes, such as, for instance, alcoholic cirrhosis and carriers of HBV with a lower viral load, both populations

being per se typically less prone to develop HCC.[69, 70] Not surprisingly, the inclusion of the etiology of HCC into the statistical model attenuated the observed inverse association between the use of statins and HCC.[62] Moreover, AP24534 cost pharmacy records of statins prescriptions used in some studies provides evidence for dispensing rather than true statins usage and strict adherence to medical prescription of these drugs.[62] In addition, selleck screening library cohort studies tend to discriminate poorly among the various subtypes of statins,[62] despite the recognized major chemical and biological differences that may occur among the various statins[55, 68] Finally, studies have provided inconsistent results concerning the dose-response relationship protection of HCC exerted by statins.[62, 63] Not surprisingly, given the number of methodological limitations of the studies discussed above,

the results from a recent robust meta-analysis conflict with previous cohort studies reported above and fully agree with a previous population-based Danish study with prospectively registered and virtually selleck complete data on drug prescription and cancer diagnosis.[60] The Cholesterol Treatment Trialists’ Collaboration study, collecting data from over 10 000 cases of cancer and over 3500 deaths from cancer among

175 000 randomized patients,[71] aimed at ruling out that statin treatment might be associated with increased risk of cancer, has failed to show any decrease in incidence and mortality for liver cancer.[71] The strength of this study results from it being based on individual patient data, so providing a reliable gauge of the potential association between statins and the development of various cancer types, including HCC, to a significantly larger extent than that offered by previous studies.[71] In conclusion, on the basis of current evidence, the use of statins in the chemoprevention and treatment of HCC in humans cannot be recommended for clinical practice. However, given that preliminary studies are conflicting, further studies are needed. Portal hypertension commonly occurs in patients with HCC in whom it may precede the development of clinically detectable disease. Gastrointestinal bleeding occurs as the initial manifestation of HCC in 4% of cases and accounts for 15% of mortality in untreated HCC.[72] A recent prospective study has reported portal hypertension to be an independent predictor of HCC development, hepatic venous pressure gradient (HVPG) > 10 mmHg at baseline being associated with a sixfold increase of HCC risk during a 4-year follow-up.