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

Abstract

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.

Meta‐analysis: Chemoprevention of hepatocellular carcinoma with statins, aspirin and metformin

“…Two additional articles were retrieved for fulltext review after screening references of included articles, and a total of 23 articles were included in the final analysis (Figure 1). In total, nine articles originated from Taiwan, 17,19,[33][34][35][36][37][38][39] five from Korea, 18,[40][41][42][43] three from Hong Kong, [44][45][46] three from the United States, 20,47,48 two from Sweden, 49,50 and one from the United Kingdom. 51 Five studies used IPTW and the remaining 18 studies conducted PSM to adjust for confounding baseline characteristics.…”

“…However, prior meta‐analyses on this topic had some limitations such as pooling odds ratios that are not time‐to‐event measurements, 11,13–16 or pooling data that had not been adequately adjusted for background differences in treated versus untreated patients. There have also been several recent relevant large studies that were not included in previous meta‐analyses 17–20 …”

“…There have also been several recent relevant large studies that were not included in previous meta-analyses. [17][18][19][20] In light of these considerations, we performed an updated metaanalysis to determine the association between the risk of HCC and the use of statins, aspirin or metformin. We included cohort studies that balanced patient baseline characteristics between groups by propensity score matching (PSM) or inverse probability of treatment weighting (IPTW) to provide robust estimates of the comparative risk of HCC between study groups.…”