Graft Inflow Modulation for Portal Hyper-perfusion in Live Donor Liver Transplantation
Study Details
Study Description
Brief Summary
In this study, the investigators aim to prove that performing graft inflow modulation (GIM) in liver with portal hyper-perfusion is beneficial for early graft function postoperatively. Grafts at risk for portal hyper-perfusion will be identified by doing an intraoperative Doppler after reperfusion. In group A, the investigators will take 21 liver transplant recipients after reperfusion, randomly allocated, who will undergo intraoperative graft inflow modulation by splenic artery ligation. In group B, the investigators will be analyzing another randomly allocated 21 patients, who will not undergo any graft inflow modulation. The investigators will be analyzing trend of LFT's (liver function tests) after surgery, time for normalization of bilirubin, INR (international normalised ratio) and decrease in ascites, morbidity, mortality, ICU (intensive care unit) and total hospital stay.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
Due to shortage of deceased donor organs, LDLT (living donor living transplantation) is gaining importance all over world. Previous studies have showed poor outcomes with donor grafts having GRWR (graft to recipient weight ratio) < 0.8 due to development of SFSS (Small for Size Syndrome) where the graft is too small to meet the recipient's metabolic demands. SFSS is characterised by prolonged cholestasis, intractable ascites, prolonged INR and encephalopathy. However, it is not always possible to obtain larger graft from live donor owing to the risk's associated to donor. Various techniques have been developed in order to manage a smaller graft in recipient (ex: hemiportocaval shunts, splenic artery ligation, splenectomy). HPCS (hemiportocaval shunt) have been associated with risks of portal steal phenomenon and encephalopathy. Splenectomy is associated with increased risks of infections / sepsis and portal vein thrombosis postoperatively. Splenic artery ligation close to its origin is associated with least risks and is increasingly being used as the method of graft inflow modulation when required.
Recent studies have showed that Portal Flow Hemodynamics are more important than GRWR in predicting the occurrence of SFSS. Grafts whose GRWR is > 0.8 can also show features of SFSS after ruling out all other causes (5). Persistent portal hypertension leads to sinusoidal endothelial injury, haemorrhage, oedema and architectural distortion - these changes are more marked in SFS (small for size) grafts. Also, due to hepatic arterial buffer response, reduced flow in hepatic artery leads to further ischemic injury, cholestasis and ischemic cholangitis. A recipient portal venous flow of > 250 ml/min/100 grams of liver weight is defined as portal hyper perfusion.
H Y Ou et al retrospectively analysed data involving patients whose PVF > 250 ml/min/100 gr after reperfusion where 6 patients underwent inflow modulation (using splenic artery ligation) and other 2 didn't. They found that only 1 / 6 patients in those who underwent GIM developed SFSS where as both the patients who didn't undergo GIM developed SFSS (1 of them died). Also, none of the patients developed complications related to splenic artery ligation in their study.
Bhavin B et al in their retrospective study on 134 liver transplant recipients found that 19 patients met criteria for SFSS (as per Kyushu University). On analysis of the factors responsible for early graft dysfunction, only portal vein flow > 190 ml/min/100 gr of liver after reperfusion was found to be a significant predictor. GRWR was not significantly associated with graft dysfunction - 3 / 19 patients had GRWR < 0.8 while 16 patients in non-dysfunction group had GRWR < 0.8
Ogura et al retrospectively analysed data involving intentional portal pressure modulation when PVP (portal venous pressure) > 20 mm Hg. They found that the patients with a portal pressure < 15 mm Hg had better 2 year survival compared to those with > 15 mm Hg. Also, recovery from hyper bilirubinaemia and coagulopathy after transplantation was significantly better in those with PVP < 15 mm Hg.
Wang et al retrospectively analysed data involving 276 patients where they performed GIM by doing splenectomy (SPL) when PVP > 20 mm Hg. Group 1 had 134 patients who underwent SPL and Group 2 had 122 patients in whom GIM was not done. Graft compliance, Portal venous flow was significantly better in group 1 patients. Also, there was faster normalisation of bilirubin and ascites in group 1 when compared to group 2. Overall, 15.6 % patients had complications related to SPL - bleeding from splenic hilum, pancreatic leak, OPSS (overwhelming post spleenectomy sepsis) (1.9%).
Luca A et al in their study involving cirrhotic patients with portal hypertension, splenic artery occlusion causes a significant reduction in portal pressure gradient (PPG). This drop was indirectly related to liver volume and directly related to spleen volume. The spleen/liver volume ratio> 0.5 accurately predicts the drop in PPG and may be used to identify patients who can obtain a significant advantage from procedures decreasing splenic inflow.
Ayman et al had done a study wherethey aimed to keep final PVP < 20 mm Hg and analysed if PVP
15 is a better predictor than PVP > 20 mm Hg for SFSS. Peak bilirubin, INR, incidence of post-transplant HE and SFSS was significantly higher in those with PVP of 15 - 19 mm Hg (group B) vs in those with PVP < 15 mm Hg (group A). 90 day morbidity and mortality was also significantly higher in Group B when compared to group A. On comparing grafts with GRWR < 0.8 with > 0.8, no significant differences in postoperative outcomes were seen.
Troisi et al did a retrospective study where they used Splenic artery ligation as the method of GIM when Recipient Portal Venous Flow was three times that of Donor portal vein flow. Group 1 had 11 patients with no GIM and group 2 had 13 patients who underwent GIM. SFSS occurred in three patients in Group 1 where all three needed re-transplantation whereas none of the patients in Group 2 developed SFSS. Also, One-year overallsurvival was 62% and 93% respectively for Group 1 and Group 2.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Patients who undergo GIM If inclusion criteria are met, after randomisation, these group of patients will undergo splenic artery ligation (graft inflow modulation) |
Procedure: Splenic artery ligation
Splenic artery will be ligated just after takeoff from coeliac trunk at the level of body of pancreas
|
| Active Comparator: No splenic artery ligation If inclusion criteria are met, after randomisation, these group of patients will not undergo splenic artery ligation (graft inflow modulation) |
Other: No intervention
Splenic artery is not ligated despite the presence of portal hyperperfusion
|
Outcome Measures
Primary Outcome Measures
- Incidence of early graft dysfunction [first postoperative month]
Number of patients who develop early graft dysfunction in each group
- Time to normalisation of ascites output [first postoperative month]
time to normalisation of ascites output (in days)
- Time to normalisation of INR [first postoperative month]
time to normalisation of INR (in days)
- Time to normalisation of bilirubin [first postoperative month]
time to normalisation of bilirubin (in days)
Secondary Outcome Measures
- Morbidity [first postoperative month]
Morbidity as per Clavein Dindo classfification
- ICU stay [first operative month]
Duration of ICU stay (in days)
- Mortality [first postoperative month]
death
- Total hospital stay [till 3 months after surgery]
duration of total stay in hospital after liver transplatation (in days)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Portal Venous Pressure (PVP) > 15 mm Hg after reperfusion or
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Portal venous flow (PVF) > 250 ml/min/100 gr of liver after reperfusion
Exclusion Criteria:
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Significant peripancreatic collaterals preventing safe access to splenic artery
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Acute Liver Failure as an indication for transplant
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ABO incompatible transplants
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Pediatric transplants
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Refusal to participate in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institute of Liver and Biliary Sciences | New Delhi | India | 110074 |
Sponsors and Collaborators
- Institute of Liver and Biliary Sciences, India
Investigators
- Principal Investigator: Gattu Tharun, MS, Senior resident, Department of HPB surgery, ILBS, India
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- ILBS-Liver Transplant-02