Common Flaws in Pharmacoepidemiologic Study Design and Analysis

PTEN downregulation may contribute to liver disease progression in these patients, possibly increasing the risk of HCC. In HCV infection, a single study has shown a negative impact of PTEN downregulation in HCC tissue on patients' survival. 16 Regrettably, whether the downregulation of PTEN predicts also the occurrence of HCC in the same setting is unknown because of lack of properly conducted prospective studies. However, the fact that the risk of developing HCC is higher in hepatitis C patients infected with the HCV genotype 3 17,18 or who have steatosis 19,20 is indirect evidence supporting this hypothesis. Thus, it would be interesting to have more detailed information on the virological characteristics of the patients included in the study of Tsan et al. In addition, we regret that no information was provided concerning the viral load status of the patients included in the study; history of anti-HCV treatment cannot be used as a surrogate marker of viremia or lack thereof because patients with therapy-induced viral eradication would have been considered together with treatment failures.