Preoperative Ketogenic Diet for Reduction of Hepatic Steatosis

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

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.

Study Overview

• Status: Recruiting
• Conditions: NAFLD; Liver Metastasis Colon Cancer; Liver Steatoses
• Intervention / Treatment: Dietary supplement: Ketogenic Diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Crystal Engelage, PhD; Phone Number: 37517 519-685-8500; Email: Crystal.Engelage@lhsc.on.ca
• Study Contact Backup: Name: Anton Skaro, MD PhD; Phone Number: 32904 519-685-8500; Email: Anton.Skaro@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Recruiting
      • London Health Sciences Centre/Western University
      • Contact: Crystal Engelage, PhD; Phone Number: 37517 519-685-8500; Email: Crystal.Engelage@lhsc.on.ca
      • Principal Investigator: Anton Skaro, MD/PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketogenic Diet Arm; 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; 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
No Intervention: Control Arm; 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?

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

Collaborators and Investigators

• Sponsor: Anton Skaro
• Investigators: Principal Investigator: Anton Skaro, MD PhD, London Health Sciences Centre/Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 31, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: NAFLD; ketogenic diet; colorectal liver metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Therapeutics; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet Therapy; Nutrition Therapy; Diet; Diet, Carbohydrate-Restricted; Diet, Ketogenic
• Other Study ID Numbers: 122435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No