Effect of Novel Donor Lifestyle Optimisation Protocol on Liver Regeneration in Live Liver Donors
Condition: Liver Regeneration
Study type: Interventional

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.
    

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.
    

Intervention name(s): Novel donor lifestyle optimisation protocol
Intervention type(s): Behavioral
Intervention description(s): Diet based on calorie requirement as calculated by indirect calorimetry. Daily exercise.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention