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.
Study Type
OBSERVATIONAL
Enrollment
33
Steno Diabetes Center Copenhagen
Hellerup, Denmark
Change in hepatic lipid content (steatosis) after total pancreatektomy or pancreaticoduodenectomy
Evaluated by light microscopy of the liver biopsy
Time frame: Baseline and after 12 months.
Hepatic lipid content
Evaluated by magnetic resonance spectroscopy
Time frame: After 12 months
Diagnosis and grade of steatohepatitis (steatosis, ballooning and lobular inflammation)
Evaluated by light microscopy of the liver biopsy
Time frame: Baseline and after 12 months.
Fibrosis stage (Kleiner classification)
Evaluated by light microscopy of the liver biopsy
Time frame: Baseline and after 12 months.
NAFLD activity score (NAS)
Evaluated by light microscopy of the liver biopsy
Time frame: Baseline and after 12 months.
Liver steatosis
Measured by controlled attenuation parametre (Fibroscan) in decibel per meter (dB/m)
Time frame: After 12 months.
Liver stiffness
Measured by transcient elastrography (Fibroscan) in kilopascals (kPa)
Time frame: After 12 months
Pancreatic endocrine dysfunction
defined by HbA1c ≥ 6.5% and/or need for diabetes therapy
Time frame: After 12 months
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Alpha- and beta cell function
measured by arginine stimulation test
Time frame: After 12 months
Pancreatic exocrine dysfunction
defined by f-elastase \< 100 μg/g
Time frame: After 12 months
Blood markers of liver function
including alanine transaminase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyltransferase (GGT), alkaline phosphatase, lactate dehydrogenase and bilirubin
Time frame: Baseline and after 12 months
Blood markers of glucose metabolism
HbA1c
Time frame: Baseline and after 12 months
Blood markers of glucose metabolism
Insulin
Time frame: Baseline and after 12 months
Blood markers of glucose metabolism
C-peptide
Time frame: Baseline and after 12 months
Blood markers of glucose metabolism
Glucagon
Time frame: Baseline and after 12 months
Blood markers of lipid metabolism
including lipid profiling
Time frame: Baseline and after 12 months
Blood markers of protein metabolism
including fractionated amino acids
Time frame: Baseline and after 12 months
Blood markers of nutritional status
including vitamin E and D, trace elements, lymphocytes and albumin
Time frame: Baseline and after 12 months
Blood markers related to bile-acid metabolism
including complement 4 (C4) and fibroblast growth factor 19 (FGF-19)
Time frame: Baseline and after 12 months
Changes in NAFLD/NASH biomarkers
including FGF-21
Time frame: Baseline and after 12 months