However, for case ascertainment we considered only specific CKD codes and in presence of less specific codes, we considered these codes only if registered multiple times to ensure the disease was chronic. We cannot identify the exact date of onset of CKD as it was defined as the date of first registration of CKDrelated primary/secondary hospital discharge diagnosis, procedure or indication of use for drug prescription. Nonetheless, the frequency of use of nephrotoxic drugs after CKD diagnosis is very high and only slightly lower as compared to the year prior to the diagnosis, thus confirming poor awareness of prescribers about possible detrimental effects of these drugs in CKD patients. Some drugs are specifically contraindicated in patients with severe renal disease only. We could not identify the stage for most CKD patients due to lack of laboratory data and registration of CKD codes of unspecified stage. For this reason the rate of contraindicated nephrotoxic drug use may have been overestimated. However, CKD stage-specific codes were reported for 518 CKD patients and in a sensitivity analysis restricted to CKD stage IV and V patients, similar figures concerning contraindicated drug use were observed. We used outpatient prescription data and we had no information about actual filling of prescriptions and medication use. However, this study was primarily aimed at exploring the prescribing pattern of nephrotoxic drugs and it is unlikely that NSAIDs were not ultimately taken by the patient. Furthermore, the traceability of some nephrotoxic drug prescriptions was incomplete as being administered in the hospital or used as OTC drugs, as a consequence, the nephrotoxic drugs use could be underestimate. In addition, this study was carried out using outpatient data collected from a large general practice of Southern Italy. We therefore cannot exclude that these findings are not fully generalizable to the whole Italian general population. However, the applied methodology and the Arianna database have been shown to provide accurate and reliable information for pharmacoepidemiological research, as documented elsewhere. Hepatocellular carcinoma is a highly lethal cancer as its prognosis is typically poor in most patients. HCC is a lethal cancer, as it is the third leading cause of cancer ALK5 Inhibitor II company deaths in East Asia and sub-Saharan Africa. In China, it is far more lethal given the fact that it is the second leading cause of cancer deaths in Chinese men. In recent times, its incidence is also increasing steadily in the United States and Europe. HCC is generally with poor prognosis, given the fact thatthe 5-year survival rate is as low as 25–39% after surgery in patients. In most cases, HCC is diagnosedat an advanced stage. Chemotherapy and radiotherapy have limited efficacy in dealing with patients diagnosed with HCC at an advanced stage.