Effect of Novel Donor Lifestyle Optimisation Protocol on Liver Regeneration in Live Liver Donors

• ClinicalTrials.gov Identifier: NCT04565535
• Recruitment Status: Recruiting
• First Posted: September 25, 2020
• Last Update Posted: November 1, 2021
• Sponsor: Institute of Liver and Biliary Sciences, India
• Information provided by (Responsible Party): Institute of Liver and Biliary Sciences, India

Study Description

Brief Summary:

Steatosis in case of live liver donors is on the rise and around 20- 40 % of prospective liver donors are estimated to have hepatic steatosis. Significant steatosis has been shown to be associated with inferior donor outcomes after liver transplant. Dietary and lifestyle modification has been shown to reduce steatosis and may help improve the donor outcomes after liver transplant. Donors will be randomized between two groups; one will be put under donor lifestyle optimization protocol and the other shall follow normal diet and lifestyle. Donors under optimization protocol would undergo diet modification in the form of healthy, low fat, high protein diet along with exercise for 2 weeks prior to the expected date of surgery. Investigations including liver volumetric assessment, LFT's , lipid profile , Fibroscan shall be done prior to initiation of the diet and then following completion of the 2 weeks of lifestyle modification before surgery. The intraoperative parameters including intraoperative blood loss shall be assessed and a liver biopsy will be taken intraoperatively to assess for steatosis and liver regeneration markers including CK7 and Ki 67 will be assessed. Following surgery, the liver regeneration in donor shall be assessed by doing a liver volumetry by Computed Tomography (CT) at POD7. Post surgery, the donor shall undergo daily LFT's, PT-INR and the time to its normalization and serum bilirubin shall be assessed. Markers of liver regeneration shall also be assessed initially a day before surgery and then at POD 1, 3 and 7.

Condition or disease	Intervention/treatment	Phase
Liver Regeneration	Behavioral: Novel donor lifestyle optimisation protocol	Not Applicable

Detailed Description:

All prospective donors provisionally planned for donor hepatectomy excluding those undergoing left lateral hepatectomy will be informed regarding the current study and informed written consent will be taken from donors willing to participate in the study. After step II evaluation of the donors, they will be randomized into two groups. First group will be put under donor lifestyle optimization protocol and the other shall follow normal diet and lifestyle. Donors under optimization protocol would undergo diet modification in the form of healthy, low fat, high protein diet along with exercise for 2 weeks prior to the expected date of surgery. If the expected date of surgery is delayed because of any cause, the proposed lifestyle optimization shall continue till the date of surgery. Step I of the evaluation including Blood group, coagulation profile, LFT, KFT, Viral serology, Liver attenuation index on Non contrast CT scan of abdomen and a Fibroscan shall be done. After step I investigations are found to be normal, patient would be subjected to step II evaluation consisting of CECT abdomen with liver volumetry including total liver volume, right lobe volume without MHV using ,expected remnant volume using software for analysis of CT volumes, MRCP for biliary anatomy, TFT and lipid profile. Body composition analysis, Fibroscan, lipid profile and LFT shall be done prior to initiation of the diet and then following completion of the 2 weeks of lifestyle modification. The intraoperative parameters including intraoperative blood loss shall be assessed. Intra operative liver biopsy will be taken from segment IV after completion of hepatectomy from all the donors undergoing donor hepatectomy using a core needle biopsy(B Braun® 18g). Precautions will be taken to take adequate tissue samples and avoid subcapsular sampling. Hemostasis of the needle tract will be obtained by use of electro thermal energy source. The core liver biopsy will be sent in formalin containing bottle to the histopathologist. Liver biopsy will be done independently by two expert histopathologists. Any abnormal histopathological finding will be noted, degree of steatosis assessed and regenerative markers from the tissue including CK7 and Ki67 will be assessed. Following surgery, the liver regeneration in donor shall be assessed by doing a liver volumetry at POD7 and POD 14. Following donor hepatectomy, routine parameters like LFT, PT-INR will be documented and the post operative day of normalisation of PT-INR and Serum Bilirubin will be noted. The volumetry of the regenerated liver will be done at day 7 and day 14 in all the donors. Seum level of liver regenerative markers shall(including HGF, IL6, TNF alpha, TGF beta, INF alpha) will be assessed on a day before surgery and then at Post operative day 1, 3 and 7. Liver function tests and PT-INR would be evaluated daily for one week. . In the post operative period , any surgical complication arising will be assessed till first month after surgery and the donor outcomes will be monitored. Complications shall be assessed based on Clavien Dindo Classification.

On follow ups liver function tests will be performed weekly for 1 month and then at monthly intervals till 3 months after surgery. At this time, any long term complication will be assessed.

Study population: Donors undergoing donor hepatectomy after giving informed written consent to be a part of the study.

Study Design: Randomised Control Pilot Study

Study Period: From time of ethical clearance to October 2021.

Sample Size: All the donors planned for donor hepatectomy meeting the inclusion criteria from time of clearance from ethical committee to october 2021 will be enrolled in this study following which randomization will be done on basis of computer generated numbers. Anticipated sample size would be 30 in each group after exclusion.

Inclusion Criteria

All donors planned for donor hepatectomy and found fit in step II evaluation.

Those who give consent to be a part of the study.

Exclusion criteria Patients refusing to consent for the study

Donor of ALF patients.

Donors undergoing left lateral hepatectomy.

Donors found unfit after step I/II evaluation.

Intervention: Diet and lifestyle modification group will receive customized two week diet plan which would consist of calorie restricted(based on basal requirement calculated by Harris Benedict Equation), high protein(25%), low fat(15%) diet along with regular exercise (brisk walk for 45 min/day). Assessment of compliance will be checked by calling each donor twice every week and during their regular weekly follow ups as well.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: "Effect of Novel Donor Lifestyle Optimisation Protocol on Liver Regeneration in Live Liver Donors: a Randomised Control Pilot Study"
• Actual Study Start Date: September 8, 2020
• Estimated Primary Completion Date: January 31, 2022
• Estimated Study Completion Date: January 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention arm; Liver donors undergoing lifestyle optimisation	Behavioral: Novel donor lifestyle optimisation protocol; Diet based on calorie requirement as calculated by indirect calorimetry. Daily exercise.
No Intervention: Control arm; Liver donors who continue normal lifestyle.

Outcome Measures

Primary Outcome Measures :

1. To study difference in Liver regeneration in Live Liver Donors on basis of: Post operative day of normalization of serum bilirubin and PT-INR between both the groups. [ Time Frame: post operative day 1 - day 14 ]
   Serum Bilirubin and PT-INR levels will be measured and their times of normalisation will be taken as markers for regeneration of liver.
2. Percentage growth of liver(on basis of CT Volumetry) [ Time Frame: post operative day 7 and post operative day 14 ]
   liver volumetry will be don eat POst operative day 7 and 14 to assess the percentage growth of liver by doing a CT volumetry.

Secondary Outcome Measures :

1. To study difference in Steatosis in both groups on basis of intra operative liver biopsy. [ Time Frame: Intra operative. ]
   Steatosis on basis of intra operative core needle liver biopsy will be seen by the pathologist by histopathological assessment of the core needle biopsy specimen.
2. To study difference in Serum level of markers of liver regeneration after liver transplant in both the groups. [ Time Frame: Pre op day 14 to post op day 7 ]
   Blood Markers of liver regeneration including Hepatocyte growth factor(HGF), Interleukin 6(IL6), TNF alpha, TGF beta, INF alpha will be assessed.
3. To study difference in Rates of early graft dysfunction in recipients in both the groups. [ Time Frame: Day 1-14 ]
   daily liver function tests and Pt-INR will be done in case of recipients and their levels seen to report the number of recipients having early graft dysfunction.
4. To study difference in Body composition analysis and fibroscan before and after lifestyle modification. [ Time Frame: at the time of enrollment to pre operative day( 2 weeks). ]
   Changes in body composition analysis using Bioelectrical impedance analysis and fibroscan will be done.
5. To study difference in Intraoperative blood loss, post op stay in the hospital and complication rates between both the groups [ Time Frame: post operative day 0 to post operative day 14 ]
   Difference in intra operative blood loss, post operative stay in the hospital and the complications(as per clavien dindo classification) will be noted.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• All donors planned for donor hepatectomy and found fit in step II evaluation.

Those who give consent to be a part of the study.

Exclusion Criteria:

• Patients refusing to consent for the study

Donor of ALF patients.

Donors undergoing left lateral hepatectomy.

Donors found unfit after step I/II evaluation.

Contacts and Locations

Contacts

Contact: Anish Gupta; 9796020957; Dranishgupta@yahoo.com

Locations

India

Institute of Liver & Biliary Sciences; Recruiting

New Delhi, Delhi, India, 110070

Contact: Dr Anish Gupta, MS 01146300000 dranishgupta@yahoo.com

Sponsors and Collaborators

Institute of Liver and Biliary Sciences, India

Investigators

• Study Director: Viniyendra Pamecha, FEBS; Institute of Liver & Biliary Sciences

More Information

Publications:

Barth RJ Jr, Mills JB, Suriawinata AA, Putra J, Tosteson TD, Axelrod D, Freeman R, Whalen GF, LaFemina J, Tarczewski SM, Kinlaw WB. Short-term Preoperative Diet Decreases Bleeding After Partial Hepatectomy: Results From a Multi-institutional Randomized Controlled Trial. Ann Surg. 2019 Jan;269(1):48-52. doi: 10.1097/SLA.0000000000002709.

Reeves JG, Suriawinata AA, Ng DP, Holubar SD, Mills JB, Barth RJ Jr. Short-term preoperative diet modification reduces steatosis and blood loss in patients undergoing liver resection. Surgery. 2013 Nov;154(5):1031-7. doi: 10.1016/j.surg.2013.04.012. Epub 2013 Jun 27.

Cho JY, Suh KS, Lee HW, Cho EH, Yang SH, Cho YB, Yi NJ, Kim MA, Jang JJ, Lee KU. Hepatic steatosis is associated with intrahepatic cholestasis and transient hyperbilirubinemia during regeneration after living donor liver transplantation. Transpl Int. 2006 Oct;19(10):807-13.

Nakamuta M, Morizono S, Soejima Y, Yoshizumi T, Aishima S, Takasugi S, Yoshimitsu K, Enjoji M, Kotoh K, Taketomi A, Uchiyama H, Shimada M, Nawata H, Maehara Y. Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation. Transplantation. 2005 Sep 15;80(5):608-12.

• Responsible Party: Institute of Liver and Biliary Sciences, India
• ClinicalTrials.gov Identifier: NCT04565535
• Other Study ID Numbers: ILBS-LIVEDONORS-02
• First Posted: September 25, 2020
• Last Update Posted: November 1, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No