Graft Inflow Modulation for Portal Hyper-perfusion in Live Donor Liver Transplantation
Condition: Cirrhosis, Liver
MeSH terms: Liver Cirrhosis
Study type: Interventional

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.
    

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.
    

Intervention name(s): Splenic artery ligation; No intervention
Intervention type(s): Procedure; Other
Intervention description(s): Splenic artery will be ligated just after takeoff from coeliac trunk at the level of body of pancreas; Splenic artery is not ligated despite the presence of portal hyperperfusion
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment