Preoperative Ketogenic Diet for Reduction of Hepatic Steatosis

Study Overview
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Brief Summary
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Non-alcoholic fatty liver disease is becoming increasingly common in Canada and throughout the world. Fatty liver can increase the risks of perioperative complications for those who need liver surgery. A ketogenic diet is low in carbohydrates and can be very effective in reducing liver fat content. The purpose of this randomized control trial is to compare the effect of a short duration (4 week) preoperative ketogenic diet on operative and disease outcomes in patients undergoing liver surgery. One arm will be randomized to the ketogenic diet and the other will receive standard of care pre-operative dietary consultation.

Detailed Description
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The rise in obesity has contributed to increasing rates of non-alcoholic fatty liver disease (NAFLD) in Canada and globally. In the setting of liver surgery, fatty liver has been associated with higher rates of blood loss during surgery as well as higher rates of postoperative complications. A pre-operative ketogenic diet (KD) has been proposed as a strategy to decrease the risks of fatty liver in patients undergoing liver surgery and has shown promising results in reducing liver fat content, even with short-duration diets. The current literature contains a large variety of pre-operative diets aimed at reducing liver fat content and most studies are observational. Presently, there is no randomized control trial looking at the effects of a well-formulated and standardized KD prior to liver surgery and its effect on operative and disease outcomes. This study will randomize patients with NAFLD needing surgery to remove liver tumors to either the control group or intervention group. Patients in the control group will receive dietary consultation for a standard of care diet as recommended by Canada's Food Guide. Patients in the intervention group will consult with a dietician before starting a 4-week preoperative well-formulated very low carbohydrate KD. All participants will track daily nutritional intake and provide weekly summary reports via an app called Cronometer. The investigators will analyze differences in intraoperative blood loss and OR time, postoperative complications, disease recurrence and mortality rates between the two groups.

Official Title
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Implementation of a Preoperative Ketogenic Diet for Reduction of Hepatic Steatosis Prior to Hepatectomy: a Randomized Control Trial

Conditions
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Liver Steatoses, Liver Metastasis Colon Cancer, NAFLD

Intervention / Treatment
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* Dietary Supplement: Ketogenic Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age or older undergoing any type of liver resection (e.g. wedge, formal hepatectomy), either open or laparoscopic, for colorectal liver metastases (CRLM) Patients with evidence of hepatic steatosis on pre-operative imaging (CT or MR) or biopsy. Ability to use an app based nutritional program to track macronutrient uptake throughout the dietary intervention. Exclusion Criteria: Patients undergoing liver resection for any other indication Patients on sodium glucose co-transporter 2 (SGLT-2) inhibitors (these are contraindicated with a ketogenic diet). Patients without evidence of hepatic steatosis. Patients with evidence of liver fibrosis or cirrhosis on preoperative bloodwork or imaging. Patients with alcohol-related hepatic steatosis. Patients with a known bleeding disorder.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: preoperative ketogenic diet group vs control standard of care preoperative diet
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic Diet Arm<br>Participants in this group will be counselled by a registered dietician and then undergo a 4-week preoperative well formulated ketogenic diet. They will record all nutritional uptake during the diet using an app called Cronometer and provide weekly summary reports to the study team. | Dietary Supplement: Ketogenic Diet<br>* 4-week preoperative well-formulated very low carbohydrate isocaloric diet consisting of 50g net daily carbohydrates and 1.5g/kg protein with the remaining energy needs consisting of primarily mono- and polyunsaturated fats<br>|
| No Intervention: Control Arm<br>Participants in this group will be counselled by a registered dietician and then undergo a 4-week standard of care diet, as recommended by Canada's Food Guide. They will record all nutritional uptake during the diet using an app called Cronometer and provide weekly summary reports to the study team. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perioperative blood transfusion | receipt (binary) of packed red blood cell (pRBC) units intraoperatively and during the immediate postoperative time period (POD 0 - 7) | postoperative days 0-7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of perioperative blood transfusion | Number of pRBC units transfused | postoperative days 0-7 | 
| Intraoperative blood loss | Intraoperative blood loss: measured by net sponge weight and fluid suctioned minus irrigation fluid | Operative period | 
| Steatosis | Level of steatosis in liver resection specimen | Time of primary surgery | 
| Change in steatosis | Change in steatosis in liver pre-diet vs day of surgery |  6 weeks | 
| Operative time | time from surgery start to surgery stop | During primary surgery | 
| Postoperative complications | Postoperative complications (measured via the Clavien-Dindo Index) will be assessed within 30 days of the operation. | Postoperative days 0-30 | 
| Postoperative length of hospital stay | Postoperative length of hospital stay will be assessed. | Postoperative days 0-30 | 
| Postoperative hospital readmission | Hospital readmission will be assessed within 30 days of the operation | Postoperative days 0-30 | 
| Postoperative rates of reoperation | Reoperation rates will be assessed within 30 days of the initial surgery. | Postoperative days 0-30 | 
| Postoperative liver failure | Liver failure rates will be assessed within 30 days of the initial surgery. | Postoperative days 0-30 | 
| Postoperative mortality | Mortality rates will be assessed within 30 days of the initial surgery. | Postoperative days 0-30 | 
| Adherence to ketogenic diet | whether participants adhered to the diet assigned to them | 4 weeks | 
| Disease recurrence | Time to disease recurrence will be assessed up to 5 years postoperatively. | 0 - 5 years postoperatively | 
| Measurement of circulating cell-free tumor DNA | Circulating cell-free tumour DNA levels will be measured up to 5 years postoperatively. | 0 - 5 years postoperatively | 
| Cancer-related mortality | Cancer-related mortality rates will be assessed up to 5 years postoperatively. | 0 - 5 years postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketogenic diet, NAFLD, colorectal liver metastases