Statins Reduce Hepatocellular Carcinoma Risk in Patients with Chronic Kidney Disease and End-Stage Renal Disease: A 17-Year Longitudinal Study

Simple Summary Statins are medicines used to treat patients with high lipid levels (hyperlipidemia). Studies have reported that patients undergoing statin therapy are at reduced risk of developing liver cancer. In this study, we compared the risk of developing liver cancer among hyperlipidemic patients with and without statin therapy in three patient groups classified by renal function: normal renal function (NRF) group, chronic kidney disease (CKD) not requiring dialysis, and dialysis-dependent end stage of real disease (ESRD). Our results showed that the risk of developing liver cancer increased progressively from NRF group to CKD and ESRD groups, but was lower for patients receiving statins treatment than non-treated patients. We also found that the statin therapy effectiveness was better in patients taking hydrophilic statins than in those taking lipophilic statins, and in patients taking statin-ezetimibe combination than in those taking statin alone, particularly in the NRF group. Ezetimibe is also an effective option of treating hyperlipidemia. Hepatocellular carcinoma (HCC) is the most common cancer in end-stage renal disease (ESRD) patients in Taiwan. Whether statin therapy associated with the HCC risk in hyperlipidemic patients with chronic kidney disease (CKD) and ESRD is unclear. Using population-based insurance claim data from Taiwan, we identified from hyperlipidemic patients taking statins or not (677,364 versus 867,707) in 1999-2015. Among them, three pairs of propensity score matched statin and non-statin cohorts were established by renal function: 413,867 pairs with normal renal function (NRF), 46,851 pairs with CKD and 6372 pairs with ESRD. Incidence rates of HCC were compared, by the end of 2016, between statin and non-statin cohorts, between hydrophilic statins (HS) and lipophilic statins (LS) users, and between statin-ezetimibe combination therapy (SECT) and statin monotherapy (SM) users. The HCC incidence increased progressively from NRF to CKD and ESRD groups, was lower in the statin cohort than in the non-statin cohort, with the differences of incidence per 10,000 person-years increased from (7.77 vs. 21.4) in NRF group to (15.8 vs. 37.1) in CKD group to (19.1 vs. 47.8) in ESRD group. The incidence increased with age, but the Cox method estimated hazard ratios showed a greater statin effectiveness in older patients. Among statin users, the HCC incidence was lower in HS users than in LS users, and lower in SECT users than in SM users, but the difference was significant only in the NRF group. Hyperlipidemic patients with CKD and ESRD receiving statins are at reduced HCC risks; the treatment effectiveness is superior for HS users than for LS users, and for SECT users than for SM users, but not significant.

Automated summary

This study examined the association between statin therapy and the risk of liver cancer in hyperlipidemic patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). The results showed that patients receiving statin therapy had a reduced risk of liver cancer, especially those with normal renal function and those using hydrophilic statins or statin-ezetimibe combination therapy. The study also highlighted the effectiveness of ezetimibe as a treatment option for hyperlipidemia.