Question

A 53-year-old male with past medical history of obesity (BMI of 38 kg/m2) and borderline diabetes presents to you with abnormal liver enzymes (ALT/AST) discovered 6 months ago. His family history is significant for liver cirrhosis. On physical examination you notice mild hepatomegaly (enlarged liver).

A panel of lab tests revealed the following: aspartate aminotransferase (AST) 106 (normal range 10 – 40 U/L), alanine aminotransferase (ALT) 118 (normal range 7 – 56 U/L), with normal bilirubin (generated from the breakdown of hemoglobin). He had a liver ultrasonography that showed diffuse increase in echogenicity and vascular blurring consistent with fatty infiltration.

You suspect non-alcoholic fatty liver disease (NAFLD).

1. Under normal conditions, describe the metabolism and maturation of VLDL particles.

2. Describe how NAFLD could manifest and what potential processes could be impaired in order for this disease process to occur (consider both enzymatic and hormonal impairments).

Answer 1

A. Under normal conditions , the steps of metabolism and maturation of VLDL particles include :-

1- Liver secretes nascent TAG - rich VLDL particles

2- Apo C - ll and apo E are transferred from HDL to nascent VLDL .

3- Extracellular lipoprotein lipase ,activated by apo C -ll , degrades TAG in VLDL

4- Apo C- ll and apo E returned to HDL

5- LDL binds to specific receptors on extrahepatic tissuea and on the liver , where they are endocytosed .

B. Clinical manifestations of Non alcoholic fatty liver disease are :-

- enlarged liver

- fatigue

- pain in upper right abdomen

- ascites

- enlarged blood vessels

- enlarged breaths in men

- enlarged spleen

- red palms

- yellowish colouration of skin and eyes

# Potential factors leading to the disease process to occur are :-

- overweight or obesity

- insulin resistance ,in which the cells don't take sugar in response to the hormone insulin

- high blood sugar indicating prediabetes or type 2 diabetes mellitus

- high levels of fats , particularly triglycerides in the blood