Clinical trial NCT03864744: Hepatic Histology and Metabolism Following Total Pancreatectomy and Pancreaticoduodenectomy
Official title: Hepatic Histology and Metabolism Following Total Pancreatectomy and
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Total Pancreatectomy
Pancreaticoduodenectomy
Pancreatic Diabetes
Non-Alcoholic Fatty Liver Disease
Metabolic Complication
Diabetes Mellitus
Keywords: liver biopsy
Lipid metabolism
Glucose metabolism
Postoperative complications
Pancreatic surgery
Lead sponsor: Steno Diabetes Center Copenhagen
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: University of Copenhagen
name: Herlev and Gentofte Hospital
First posted: 2019-03-06
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects who undergo total pancreatectomy or pancreaticoduodenectomy at Rigshospitalet, Copenhagen.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in hepatic lipid content (steatosis) after total pancreatektomy or pancreaticoduodenectomy
timeFrame: Baseline and after 12 months.
Secondary outcomes:
measure: Hepatic lipid content
timeFrame: After 12 months
measure: Diagnosis and grade of steatohepatitis (steatosis, ballooning and lobular inflammation)
timeFrame: Baseline and after 12 months.
measure: Fibrosis stage (Kleiner classification)
timeFrame: Baseline and after 12 months.
measure: NAFLD activity score (NAS)
timeFrame: Baseline and after 12 months.
measure: Liver steatosis
timeFrame: After 12 months.
measure: Liver stiffness
timeFrame: After 12 months
measure: Pancreatic endocrine dysfunction
timeFrame: After 12 months
measure: Alpha- and beta cell function
timeFrame: After 12 months
measure: Pancreatic exocrine dysfunction
timeFrame: After 12 months
measure: Blood markers of liver function
timeFrame: Baseline and after 12 months
measure: Blood markers of glucose metabolism
timeFrame: Baseline and after 12 months
measure: Blood markers of glucose metabolism
timeFrame: Baseline and after 12 months
measure: Blood markers of glucose metabolism
timeFrame: Baseline and after 12 months
measure: Blood markers of glucose metabolism
timeFrame: Baseline and after 12 months
measure: Blood markers of lipid metabolism
timeFrame: Baseline and after 12 months
measure: Blood markers of protein metabolism
timeFrame: Baseline and after 12 months
measure: Blood markers of nutritional status
timeFrame: Baseline and after 12 months
measure: Blood markers related to bile-acid metabolism
timeFrame: Baseline and after 12 months
measure: Changes in NAFLD/NASH biomarkers
timeFrame: Baseline and after 12 months
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Steno Diabetes Center Copenhagen
Study officials:
affiliation: Steno Diabetes Center Copenhagen, Clinical metabolic physiology
name: Filip Krag Knop, Professor
role: STUDY_DIRECTOR
References: