Hepatic Histology and Metabolism Following Total Pancreatectomy and Pancreaticoduodenectomy

Hepatic Histology and Metabolism Following Total Pancreatectomy and

The objective of the study is to investigate the development of NAFLD following total pancreatectomy and pancreaticoduodenectomy and to explore the histological and metabolic changes following the procedures.

After total pancreatectomy patients are treated with exogenous insulin and pancreatic enzyme supplementation in order to treat the endocrine and exocrine insufficiencies inherently occurring postoperatively. In addition to secondary diabetes and insufficient digestive capacity, totally pancreatectomised patients face a high risk of developing non-alcoholic hepatic steatosis. Under normal circumstances non-alcoholic fatty liver disease is regarded as the hepatic manifestation of metabolic syndrome and pathophysiologically related to excess energy intake and insulin resistance resulting in fat accumulation in adipose tissue as well as in the liver. Thus, the high incidence of hepatic steatosis following total pancreatectomy is surprising as patients typically are lean, peripherally insulin sensitive and properly insulinised.Interestingly, the pancreatic hormone glucagon has been implicated in lipid metabolism and recent human data from studies investigating the effect of glucagon receptor antagonism suggest that glucagon signalling may be essential for maintaining a fat-free liver. This makes the investigators speculate that the decreased glucagon levels following pancreatic surgery may play a hitherto unrecognised role in the development of hepatic steatosis after the operation.

The study will include 33 patients scheduled for pancreatectomy (total or pancreaticoduodenectomy). They will be followed for one year. A liver biopsy will be collected during the operation on all patients. After 12 months, participants will undergo magnetic resonance spectroscopy and those who have hepatic lipid content ≥2% will undergo an ultrasound-guided percutaneous liver biopsy. Furthermore, all participants will undergo a metabolic evaulation after one year.

Inclusion Criteria:

• Subject scheduled for total pancreatectomy or pancreaticoduodenectomy
• Informed consent signed prior to any study-related procedure

Exclusion Criteria:

• Known liver disease before total pancreatectomy or pancreaticoduodenectomy (excluding NAFLD)
• Severe co-morbid disease (besides from the indication for the pancreas surgery)
• Pregnancy
• Any condition that the investigator feels would interfere with the safety of the trial participation or the safety of the subject
• Metastatic disease

Percutaneous liver biopsy exclusion criteria (to be evaluated before last visit)

• MR spectroscopy demonstrating lipid content <2%
• Haemoglobin <6 mmol/L
• INR >1.5
• Trombocytes <40 × 109/L
• Skin infection in area where biopsy will be sampled