Effect of Ursodeoxycholic Acid Supplementation on Liver Regeneration on Right Lobe Donor Hepatectomy

Study Overview
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Brief Summary
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The goal of this open label randomized trial is to understand the role of oral ursodeoxycholic acid(UDCA) supplementation in the liver regeneration (in terms of liver function and anatomical growth) following right lobe donor hepatectomy. The main question it aims to answer are: Does Ursodeoxycholic acid supplementation on patients undergoing donor hepatectomy improve anatomical liver regeneration after partial hepatectomy as compared to control group. Does ursodeoxycholic acid improve liver regeneration in terms of liver function tests and biomarkers of liver regeneration(HGF, IL6, TNF Alpha, AFP, TGF Beta) as compared to control group.

Detailed Description
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This open label randomized control study aims to analyze the effect of ursodeoxycholic acid supplementation on liver regeneration following a right donor hepatectomy. All eligible live donors who undergo right donor hepatectomy during the study period will be included in the study and randomized into two groups. One group will receive Tab. UDCA 450mg twice daily for 10 days and the other group will not receive Tab UDCA. Live donors who are not willing to participate in the study, have hypersensitivity to UDCA or have used Tab UDCA in the past 2 weeks, will be excluded from the study. All live donors will be screened in the pre-operative period in the outpatient department. Pre- operative, intra-operative and post-operative data will be collected from medical records, electronic hospital information system (HIS) and radiological images collected from the hospital Picture archiving and communication system(PACS). The enrolled subjects will be followed up till for a period of 14 days after the donor hepatectomy till Non contrast CT Abdomen is done and regenerated liver volumes are analyzed. The anatomic(volumetric), functional(liver function tests) and regenerative biomarkers( HGF, TNF-Alpha, IL6, AFP, TGF-Beta) will be compared between the two groups.

Official Title
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Effect of Ursodeoxycholic Acid Supplementation on Liver Regeneration on Right Lobe Donor Hepatectomy: An Open Label Randomised Trial

Conditions
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Liver Regeneration, Ursodeoxycholic Acid, Partial Liver Resection

Intervention / Treatment
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* Drug: Ursodeoxycholic acid
* Other: Standard Medical Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All live donors undergoing Right Donor Hepatectomy in ILBS from ethical board clearance to December 2024 in the Department of HPB Surgery and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi Exclusion Criteria: Negative consent Hypersensitivity to UDCA Past history of UDCA use in the last two weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Open label randomised controlled trial with 2 groups. One group receiving Tablet Ursodeoxycholic acid and the other group not receiving standard medical therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Arm<br>This group will recieve Tab Ursodeoxycholic acid 450mg twice daily from the day after donor hepatectomy till post operative day 10. | Drug: Ursodeoxycholic acid<br>* Tablet Ursodeoxycholic acid 450mg per orally twice daily from Post operative day 1 to post operative day 10.<br>|
| Active Comparator: Control Arm<br>This group will receive standard medical therapy following donor hepatectomy. | Other: Standard Medical Treatment<br>* Standard Medical Treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regenerated liver volume on Post-operative Day 7 between two groups. | This will be measured by a non contrast CT Abdomen and the size of the regenerated liver after hepatectomy will be measured in millilitres This value will be measured in both groups to identify a difference in the intervention group (getting UDCA) versus the control group ( standard medical therapy) | 7 days after operation | 
| Regenerated liver volume on Post-operative Day 14 between two groups. | This will be measured by a non contrast CT Abdomen and the size of the regenerated liver after hepatectomy will be measured in millilitres This value will be measured in both groups to identify a difference in the intervention group (getting UDCA) versus the control group ( standard medical therapy) | 14 days after operation | 
| Liver Regeneration index POD 7 | Ratio of regenerated liver volume to remnant liver volume(pre-operative) on Post operative day 7 | 7 days after operation | 
| Liver Regeneration index POD 14 | Ratio of regenerated liver volume to remnant liver volume(pre-operative) on Post operative day 14 | 14 days after operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total bilirubin | serum total bilirubin versus control group | Post-operative day 1-7, 10 and 14 | 
| Direct bilirubin | serum Direct bilirubin versus control group | Post-operative day 1-7, 10 and 14 | 
| Alanine Aminotransferase(ALT) | serum ALT versus control group | Post-operative day 1-7, 10 and 14 | 
| Aspartate Aminotransferase(AST) | serum AST versus control group | Post-operative day 1-7, 10 and 14 | 
| Serum Alkaline Phosphatase(SAP) | serum SAP versus control group | Post-operative day 1-7, 10 and 14 | 
| Serum Gamma Glutamyl Transferase(GGT) | serum SAP versus control group | Post-operative day 1-7, 10 and 14 | 
| Serum Albumin | serum Albumin versus control group | Post-operative day 1-7, 10 and 14 | 
| International normalized ratio(INR) | INR versus control group | Post-operative day 1-7, 10 and 14 | 
| Post hepatectomy liver failure(PHLF) | Grade of PHLF as per ISGLS criteria and 50/50 criteria | Post operative day 1-14 | 
| Abdominal Drain removal | Day of abdominal drain removal | Post operative day 1-14 | 
| Post-operative ascites | Volume of ascites | Post operative day 1-14 | 
| Post-operative complications | Grade of post-operative complications as per Clavien-Dindo classification | Post operative day 1-14 |