**Core Concept**
Parenteral nutrition refers to the intravenous administration of nutrients to bypass the gastrointestinal tract. Long-term parenteral nutrition can lead to various complications due to the altered metabolic state and potential for nutrient imbalances.

**Why the Correct Answer is Right**
The most significant complication of long-term parenteral nutrition is **essential fatty acid deficiency (EFAD)**. This occurs because the standard parenteral nutrition solutions often lack adequate amounts of essential fatty acids, particularly linoleic and alpha-linolenic acid. EFAD can lead to impaired immune function, increased susceptibility to infections, and potentially, multi-organ failure.

**Why Each Wrong Option is Incorrect**
* **Option A:** **Liver dysfunction** is a potential complication of parenteral nutrition, but it is not the most significant one. Liver dysfunction is often related to the type of lipid emulsion used and the duration of parenteral nutrition.
* **Option B:** **Refeeding syndrome** is a potential complication of reinitiating enteral or parenteral nutrition in malnourished patients. However, it is not the most significant complication of long-term parenteral nutrition.
* **Option C:** **Infection** is a potential complication of parenteral nutrition, but it is not the most significant one. Infection can be caused by contaminated solutions, catheter-related infections, or the underlying condition of the patient.

**Clinical Pearl / High-Yield Fact**
To prevent essential fatty acid deficiency, parenteral nutrition solutions should contain a minimum of 5-10% of total calories as linoleic acid, and 0.5-1% as alpha-linolenic acid.

**Correct Answer:** D.