Ashraf Jibran, Ali Khan M, Minhaj Syed, Khatti Shahzad, Aarij Khawaja M, Shehzad Muhammad, Khan Tariq M
Cardiology, National Institute of Cardiovascular Diseases, Karachi, PAK.
Gastroenterology, Jinnah Postgraduate Medical Centre, Karachi, PAK.
Cureus. 2020 Aug 30;12(8):e10145. doi: 10.7759/cureus.10145.
Background Statins or 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors are one of the most commonly prescribed medications in cardiac patients. Just like any other class of drugs, they have the potential to cause liver injury over time even with judicious use. This drug-induced liver injury (DILI) can be either direct (hepatocellular) or idiosyncratic. As with multiple other hepatic pathologies, DILI may be asymptomatic or clinically silent. Therefore, it is prudent to carry out liver function tests (LFTs) from time to time. LFTs are an inexpensive, noninvasive, and quick first-line investigation to monitor liver status. However, the pattern of liver injury with statin use is not specific and a correlation over time may not be apparent. Aims To evaluate derangement in LFTs over time with respect to statin use and determine if a correlation exists. Methods This was a retrospective observational cohort. All data were collected from the online database of the National Institute of Cardiovascular Diseases (NICVD), Karachi. Patients admitted to the NICVD from July 1, 2018, to December 31, 2018, were eligible for inclusion in the study. Only patients already taking a statin (in any dose) were considered for inclusion. LFTs were recorded from the database at inclusion, post-induction at six and 12 months. Extensive workup was done and great care taken to rule out other diseases that may have affected the LFTs. Results Two hundred and four patients were eventually inducted into the study after a meticulous exclusion process. The male to female ratio was 4:1. The mean duration of statin use before induction into the study was 19.92±14.34 months. Patients were predominantly using only one of two statins, i.e., rosuvastatin 20mg/day or atorvastatin 40 mg/day. Elevations of LFTs were seen with both drugs throughout the study period. These elevations were almost always <2x the upper limit of normal (ULN); greater elevations were seen with atorvastatin 40 mg/day. The derangement in LFTs persisted and improvement was not seen. Conclusions Statins cause dose-dependent borderline elevations of liver function tests over time. These elevations are clinically and statistically insignificant and should not deter physicians from prescribing or continuing statins.
背景 他汀类药物或3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂是心脏病患者中最常用的处方药之一。与其他任何一类药物一样，即使谨慎使用，随着时间的推移它们也有可能导致肝损伤。这种药物性肝损伤（DILI）可以是直接的（肝细胞性）或特异质性的。与多种其他肝脏疾病一样，DILI可能无症状或临床上不明显。因此，定期进行肝功能检查（LFTs）是明智的。LFTs是一种廉价、无创且快速的一线检查，用于监测肝脏状态。然而，他汀类药物使用导致的肝损伤模式并不特异，且随时间的相关性可能不明显。目的 评估随着时间推移，他汀类药物使用与LFTs紊乱之间的关系，并确定是否存在相关性。方法 这是一项回顾性观察队列研究。所有数据均从卡拉奇国家心血管疾病研究所（NICVD）的在线数据库中收集。2018年7月1日至2018年12月31日入住NICVD的患者符合纳入本研究的条件。仅纳入已服用他汀类药物（任何剂量）的患者。在纳入时、诱导后6个月和12个月从数据库中记录LFTs。进行了广泛的检查，并非常小心地排除了其他可能影响LFTs的疾病。结果 经过细致的排除过程，最终有204名患者纳入研究。男女比例为4:1。纳入研究前他汀类药物的平均使用时间为19.92±14.34个月。患者主要仅使用两种他汀类药物中的一种，即瑞舒伐他汀20mg/天或阿托伐他汀40mg/天。在整个研究期间，两种药物均出现LFTs升高。这些升高几乎总是<正常上限（ULN）的2倍；阿托伐他汀40mg/天出现的升高幅度更大。LFTs紊乱持续存在，未见改善。结论 随着时间的推移，他汀类药物会导致肝功能检查出现剂量依赖性的临界升高。这些升高在临床和统计学上无显著意义，不应阻止医生开具或继续使用他汀类药物。
