Which statement about CYP3A4 activity is true in obesity-related liver changes?

• A. Increased CYP3A4 activity
• B. No change in CYP3A4 activity
• C. Decreased CYP3A4 activity
• D. CYP2D6 activity increases

Answer: (C)

Obesity-related liver changes, especially fatty liver disease, can dampen the liver’s drug‑metabolizing capacity. CYP3A4 is a key enzyme responsible for metabolizing many medications, and its expression and activity can be lowered when the liver is inflamed, fatty, or damaged. Cytokines like IL‑6 and TNF‑α, oxidative stress, and reduced hepatocyte function all contribute to decreased CYP3A4 levels, so substrates that rely on this enzyme are cleared more slowly. That makes decreased CYP3A4 activity the best-supported statement in this context. Increased activity is not typically seen with fatty liver changes, and saying there’s no change ignores the impact of obesity-related liver pathology. Mentioning CYP2D6 shifts focus to a different enzyme and doesn’t address the CYP3A4-specific impact.