Mechanisms of Malnutrition in Cirrhosis With Portosystemic Shunting

Mechanisms of Malnutrition in Cirrhosis With Portosystemic Shunting

Cirrhosis is characterized by loss of muscle as well as fat mass, which increases morbidity and mortality before, during, and after liver transplantation. A common mechanism for the reduced muscle and fat mass in cirrhosis is an increased expression of the TGF (transforming growth factor)beta superfamily member, myostatin, in the muscle and adipose tissue. The present study will examine the expression of myostatin, its receptor and intracellular signaling pathways in the skeletal muscle and mesenteric adipose tissue in cirrhotic patients undergoing liver transplantation as compared to healthy controls undergoing planned abdominal surgery. 16 cirrhotic patients will be identified from the transplant list, and 16 healthy controls from outpatient surgery lists. Nutritional assessment will be performed, including anthropometry (triceps skinfold thickness, mid arm circumference), dual energy x-ray absorptiometry (DEXA), and bioelectrical impedance analysis (BIA). Rectus abdominis muscle tissue and omental fat tissue will be harvested in the operating room, and the expression of signaling proteins involved in skeletal muscle protein synthesis will be quantified. The investigator will also quantify the expression of genes involved in lipolysis and lipid synthesis. The investigator anticipates that the expression of myostatin will be higher in the skeletal muscle and adipose tissue of cirrhotics as compared to controls. There will be a reduction in the expression of the signaling proteins that regulate skeletal muscle protein synthesis, as well as the expression of genes regulating lipogenesis. The increased expression of myostatin will also correlate with reduced anthropometric and DEXA measurements of lean body mass and fat mass.

Inclusion Criteria:

• Age 18-70 years
• Patients undergoing abdominal surgery (liver transplantation or other surgery)

Control

1. non liver transplant donor
2. Elective abdominal surgery (cholecystectomy, diverticulosis, acute gastrointestinal bleeding in the absence of exclusion criteria)

Exclusion Criteria:

• Exclusion criteria (all subjects)
• Average daily alcohol intake > 20 g in women and > 30 g in men
• Diabetes or a fasting serum glucose > 100 mg/dL
• Hyper- / hypo- thyroidism
• Renal disease with serum creatinine > 1.4 mg/dL
• Folate or vitamin B12 deficiency
• Active intravenous drug use
• History of bowel surgery or gastric bypass surgery
• Medications/supplements that affect fat mass or protein mass (creatine, glucocorticoids)
• Pregnancy
• Chronic diseases that result in cachexia (renal, cardiac, pulmonary, hematologic, cancer)
• Hepatocellular cancer

Exclusion criteria (controls)

• Evidence of malnutrition as quantified by triceps skinfold thickness, mid arm muscle area and creatinine height index)