Risk of Liver Injury Associated with Intravenous Lipid Emulsions: A Prescription Sequence Symmetry Analysis

Abstract

Aims: To determine the risk of liver injury associated with the use of different intravenous lipid emulsions (LEs) in large populations in a real-world setting in China.Methods: A prescription sequence symmetry analysis was performed using data from 2015 Chinese Basic Health Insurance for Urban Employees. Patients newly prescribed both intravenous LEs and hepatic protectors within time windows of 7, 14, 28, 42, and 60 days of each other were included. The washout period was set to one month according to the waiting-time distribution. After adjusting prescribing time trends, we quantify the deviation from symmetry of patients initiating LEs first and those initiating hepatic protectors first, by calculating adjusted sequence ratios (ASRs) and relevant 95% confidence intervals. Analyses were further stratified by age, gender, and different generations of LEs developed.Results: In total, 416, 997, 1,697, 2,072, and 2,342 patients filled their first prescriptions with both drugs within 7, 14, 28, 42, and 60 days, respectively. Significantly increased risks of liver injury were found across all time windows, and the strongest effect was observed in the first 2 weeks [ASR 6.97 (5.77–8.42) ∼ 7.87 (6.04–10.61)] in overall patients. In subgroup analyses, female gender, age more than 60 years, and soybean oil-based and alternative-LEs showed higher ASRs in almost all time windows. Specially, a lower risk for liver injury was observed in the first 14 days following FO-LEs administration (ASR, 3.42; 95% CI, 0.81–14.47), but the risk started to rise in longer time windows.Conclusion: A strong association was found between LEs use and liver injury through prescription sequence symmetry analysis in a real-world setting, which aligns with trial evidence and clinical experience. Differences revealed in the risks of liver injury among various LEs need further evaluation.

Prescribing Cascades with Recommendations to Prevent or Reverse Them: A Systematic Review

“…More research is needed to assess whether using low dosages in patients at a high risk of developing an ADR, such as older people or women [ 75 , 86 , 116 ], can prevent prescribing cascades and is also sufficient to reverse existing ADRs. Furthermore, recommendations to switch a medication without specific advice are not helpful for HCPs.…”

Early Detection of Adverse Drug Reaction Signals by Association Rule Mining Using Large-Scale Administrative Claims Data

“…A proof-of-concept study on SSA was published in 1996, and since then the number of SSA-related articles published per year and the total number of articles are on the rise [ 38 , 39 ]. By using SSA, several ADRs associated with a wide array of organs have been identified [ 20 – 22 ]. Therefore, we considered SSA as a good baseline method for comparing the performance of ARM.…”

“…Sequence symmetry analysis (SSA) is a frequently used tool for ADR signal detection based on administrative claims data [ 18 , 19 ]. Several research works have been undertaken using SSA for administrative claim data to detect ADR signals [ 20 – 22 ], but most of these studies used long-term data (e.g., 17-year period) and examined specific hypotheses about the effects of a particular drug class and subsequent health outcomes. Recently, several studies have assessed a wide range of relationships between drugs and ADRs using prescription databases [ 23 – 26 ]; however, the detection of ADR signals was based on long-term data, and early detection of ADR signals was not examined.…”

Hepatic dysfunction in patients receiving intravenous lipid emulsions

“…In a 12-month study in adults on HPN, lower rates of ILE infusion (0.6–0.8 g/kg/day), using either SO, OO/SO or SMOF were administered, and there was little to no significant change in liver tests [13 ▪ ]. A recent retrospective study from China suggests that the threshold for liver injury from ILEs in adults is a dose >1 g/kg/day [14]. These observations indicate that ILEs can induce cholestasis, but the effect is, at least to some extent, dose-related.…”