| Baseline liver health |
• Pre‑existing liver disease (cirrhosis, chronic hepatitis B/C, non‑alcoholic fatty liver disease, cholestatic liver disease)
• Baseline transaminases > 2× upper limit of normal (ULN)
• History of hepatic failure or decompensation |
Tigecycline is metabolized by the liver; impaired function leads to higher systemic exposure and a higher likelihood of hepatocellular injury. |
| Alcohol use |
• Chronic alcohol consumption or recent heavy drinking |
Alcohol itself stresses hepatocytes and can synergize with drug‑induced liver injury. |
| Metabolic syndrome / obesity |
• Obesity, type 2 diabetes, or metabolic‑associated fatty liver disease (MAFLD) |
These conditions predispose to non‑alcoholic fatty liver disease, which can be exacerbated by additional hepatic insults. |
| Age |
• Elderly (≥ 65 years) |
Age‑related decline in hepatic blood flow and regenerative capacity increases vulnerability to drug‑related liver injury. |
| Concomitant medications |
• Other hepatotoxic drugs (e.g., acetaminophen, valproate, statins, certain antifungals, antivirals)
• Medications that compete for hepatic transporters or metabolic enzymes |
Combined hepatotoxic effects or impaired clearance of tigecycline. |
| Duration and dosing |
• Prolonged therapy (> 7 days) or high‑dose regimens |
Longer exposure increases cumulative hepatic stress; higher doses raise peak serum levels. |
| Underlying critical illness |
• Sepsis, septic shock, multi‑organ failure |
Systemic inflammation and hypotension can impair hepatic perfusion, compounding drug‑induced liver stress. |
| Other comorbidities |
• Renal failure (CKD stage ≥ 3) |
While tigecycline is not renally cleared, reduced renal function often co‑exists with hepatic dysfunction and may necessitate dose adjustments that inadvertently alter hepatic exposure. |