A 52-year-old man with type 2 diabetes and hypertension presents with total cholesterol 285 mg/dL, LDL 180 mg/dL, HDL 35 mg/dL, and triglycerides 320 mg/dL. He is started on a statin. Before initiating therapy, which investigation is most important to establish baseline status and monitor for drug-induced hepatotoxicity?

Explanation

## Baseline Investigation Before Statin Therapy **Key Point:** Liver function tests (LFTs) must be obtained before initiating statins and monitored during therapy because statins are hepatically metabolized and can cause dose-dependent hepatotoxicity. ### Why LFTs Are Essential 1. **Baseline Assessment**: Establishes pre-treatment hepatic function to detect any pre-existing liver disease that might contraindicate statin use or require dose adjustment. 2. **Drug Monitoring**: Statins undergo hepatic metabolism via CYP3A4 and other pathways; elevated transaminases (AST/ALT >3× ULN) warrant discontinuation. 3. **Guideline Recommendation**: ACC/AHA and ESC guidelines mandate baseline LFTs before statin initiation and periodic monitoring (annually or as clinically indicated). ### Statin-Induced Liver Injury Pattern - **Incidence**: ~3% develop mild transaminitis; <1% develop clinically significant hepatotoxicity. - **Mechanism**: Mitochondrial dysfunction and oxidative stress in hepatocytes. - **Management**: Discontinue if ALT/AST >3× ULN; rechallenge with lower dose or alternative statin if clinically necessary. **Clinical Pearl:** Muscle symptoms (myalgia, myositis, rhabdomyolysis) are more common than hepatotoxicity with statins, but LFTs remain the standard baseline investigation per guidelines. **High-Yield:** Baseline LFTs are mandatory before statin initiation; repeat testing is recommended at 4–12 weeks and then periodically. No need for routine monitoring if baseline is normal and patient asymptomatic.