Diabetes Mellitus, Metabolic Complication, Non-Alcoholic Fatty Liver Disease, Pancreatic Diabetes, Pancreaticoduodenectomy, Total Pancreatectomy
Conditions
Keywords
liver biopsy, Lipid metabolism, Glucose metabolism, Postoperative complications, Pancreatic surgery
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Rigshospitalet, Denmark
University of Copenhagen
Herlev and Gentofte Hospital
Steno Diabetes Center Copenhagen
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in hepatic lipid content (steatosis) after total pancreatektomy or pancreaticoduodenectomy | Baseline and after 12 months. | Evaluated by light microscopy of the liver biopsy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnosis and grade of steatohepatitis (steatosis, ballooning and lobular inflammation) | Baseline and after 12 months. | Evaluated by light microscopy of the liver biopsy |
| Fibrosis stage (Kleiner classification) | Baseline and after 12 months. | Evaluated by light microscopy of the liver biopsy |
| NAFLD activity score (NAS) | Baseline and after 12 months. | Evaluated by light microscopy of the liver biopsy |
| Liver steatosis | After 12 months. | Measured by controlled attenuation parametre (Fibroscan) in decibel per meter (dB/m) |
| Liver stiffness | After 12 months | Measured by transcient elastrography (Fibroscan) in kilopascals (kPa) |
| Pancreatic endocrine dysfunction | After 12 months | defined by HbA1c ≥ 6.5% and/or need for diabetes therapy |
| Alpha- and beta cell function | After 12 months | measured by arginine stimulation test |
| Hepatic lipid content | After 12 months | Evaluated by magnetic resonance spectroscopy |
| Blood markers of liver function | Baseline and after 12 months | including alanine transaminase (ALAT), aspartate aminotransferase (ASAT), gamma-glutamyltransferase (GGT), alkaline phosphatase, lactate dehydrogenase and bilirubin |
| Blood markers of glucose metabolism | Baseline and after 12 months | HbA1c |
| Blood markers of lipid metabolism | Baseline and after 12 months | including lipid profiling |
| Blood markers of protein metabolism | Baseline and after 12 months | including fractionated amino acids |
| Blood markers of nutritional status | Baseline and after 12 months | including vitamin E and D, trace elements, lymphocytes and albumin |
| Blood markers related to bile-acid metabolism | Baseline and after 12 months | including complement 4 (C4) and fibroblast growth factor 19 (FGF-19) |
| Changes in NAFLD/NASH biomarkers | Baseline and after 12 months | including FGF-21 |
| Pancreatic exocrine dysfunction | After 12 months | defined by f-elastase \< 100 μg/g |
Countries
Denmark
Outcome results
None listed