Liver malfunction after liver transplantation

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					Liver malfunction after
       liver transplantation

       by Intern 洪儷中
    Predict the severity of early graft
   Criteria obtained within the 72 postoperative hours
                 Parameter                 Assigned value
                            < 1000               1
     Serum ALT            1000-2500              2
                            > 2500               3
                             > 100               1
     Bile output            40-100               2
                             < 40                3
                      > 60(spontaneous)          1
       PT3 (%)         > 60 (with FFP)           2
                      < 60 (despite FFP)         3
 Patientswith a total score
 (1) good outcome: up to 6
 (2) poor graft function: a score of 7-9
Donor related factors
 Steatosis   > 50%
 Age  > 60
 High plasma Na
 Nutritional status
 Use of vasopressor drugs and
  hemodynamic instability
 Hypotension during harvesting
Cold preservation injury
      stored in the preservation solution
 Graft
 (UW) more than 12 hours is
 accompanied with injury of the vascular
 system with detachment of sinusoidal
 endothelial cells via specific angiogenic
Re-warming injury
 Intervalbetween removal of organ from
  cold storage and resumption of
  perfusion of organ with recipient blood,
  which correspond to the time to perform
  vascular anastomoses
 Long (> 120 min) period of rewarming
  ischemia is a risk factor for primary non
  function/ initial poor function due to
  hepatocellular damage
Reperfusing injury
 Reperfusion injury, begins at the time of
 reoxygenation, namely, the end of
 vascular sutures and unclamping of
 afferent vessels to the transplanted
Operative complexities

 1. Operative bleeding
 2. Thrombosis of the portal vein
 3. Hepatic arterial reconstruction
 4. Hyper acute rejection on ABO
     incompatible grafts
Post-transplant management
 Common   complications
 Immunologic consenquences
 Recurrent of disease
<1> Common complications
 1. Primary nonfunction
 2. Intra-abdominal bleeding
 3. Vascular thrombosis
 4. Biliary leak
 5. Infections
    1. Primary non-function
 2 to 5% of liver grafts
 May relate to donor variables, inadequate
  preservation, prolonged cold ischemia, or the
  humoral immune response.
 surgical emergency that can be successfully
  treated by early re-transplantation. (within 7 days)
 Delayed nonfunction:
     failure of all liver functions
     persistent coagulopathy, progressive hyperbilirubinemia.
     vital organs fail or get infections
2. Intra-abdominal bleeding
   High risks for postoperative bleeding
    (1) persistence of coagulopathy, fibrinolysis,
    (2) multiple vascular anastomoses

   Coagulopathy spontaneously corrects itself.

   A persistent drop in Hb and the need for
    transfusion of more than 6 units of PRBC are
    usually indications for reexploration and
    evacuation of the hematoma.
3. Vascular thrombosis
 More common in the pediatric population
 Directly related to the small size of the
  vessels used for reconstruction.
 The most frequent: hepatic artery thrombosis.

 Early recognition and successful
  thrombectomy may salvage the graft.
 Deteriorating liver function and bile duct
  necrosis indicate the need for immediate
4. Biliary leak
   Reconstruction:
    duct-to-duct anastomosis or choledochojejunostomy
 secondary to technical error or ischemia of
  the donor duct.
 Early diagnosed bile in the drains
 Confirmed T-tube cholangiogram, or a
  hepato-iminodiacetic acid (HIDA) scan.
 Surgical exploration and revision of the
 Ischemic bile duct injury secondary to early
  hepatic artery thrombosis is an indication for
   Direct correlation
    (1) preoperative status of the recipient,
             patients who await a transplant in ICU.
    (2) the incidence of bacterial and fungal infections.
             high-dose immunosuppression after TX
   Resistant G(+) bacteria > G(-).

   Broad-spectrum antibiotics in the
    immunosuppressed patient contributes in part to the
    development of systemic fungal infection ( Candida,
   Begin antibiotics for common bacteria as soon as
    clinical status suggests the presence of infection.
     modified if cultures and sensitivities available.
<2> Immunologic consequences
 Good  long-term outcome may due to
 (1) low immunogenicity
 (2) regeneration ability
 (3) ABO compatible
         (HLA matching may not to be necessary)
 Long-term  immunosuppression
   is necessary.
 Acute rejection  high dose steroids
 Chronic rejection retransplantation
<3> Recurrent of disease
 Recurrence of viral hepatitis is likely within a
  short time after transplantation in infected
 Control of active HBV infection is possible
  using lamivudine.
 In contrast, interferon alfa or ribavirin are
  ineffective in HCV infection.
 Reinfection of the liver graft may be mild and,
  in many cases, will not result in liver failure.
Long-term results
Higher mortality
 Poor preoperative status
 Immediate function of the liver allograft
 Older age
 Ventilator dependency
 The need for dialysis
 Re-transplantation
Back to the patient
 Pathology   report– liver biopsy
  marked centrilobular congestion with
  atrophy of hepatocyte and cholestasis.
  Focally, necrosis of centrilobular
  hepatocytes is seen.No evidence of
  cellular rejection is seen.
 Bedside echo:
  no evidence of vascular thrombosis is
 Pathology
  centrilobular congestion
         vein problem
 Echo
  No evidence of hepatic vein problem.

 Whathappened?
 smaller vein?
  VOD (venous-occlusive disease)
 1. Diagnosis: histologically
     fibrous obliteration of hepatic veins
     and centrilobular hemorrhagic
     necrosis on liver biopsy.
 2. Clinical diagnosis
     hyperbilirubinemia (bil > 2mg/dl)
       weight gain >2-5% of admission weight
 Cause:   (1) chemotherapeutic agents
          (2) irradiation.
          (3) azathioprine
 Incidence of VOD after liver Tx : 1.9%
 Occurred from 5-133 days after TX.
 Outcome was poor:
     63% of the patients died.
 89% of the patients with VOD had an
  episode of acute rejection before or at
  the time of VOD.
           Transplantation. 72(7):1237-1240, October 15, 2001.
Case report–
life threatening VOD after LRLT
   48 y/o male, s/p liver transplantation secondary to
    Caroli’s disease related cirrhosis.
   Left lobe graft from his elder sister.
   Immunosuppressive: FK-506, steroids
   POD12, ALT and AST increased, so did Bilirubin.
   POD20, liver biopsy acute rejection
   POD26, Bil 25.6mg/dl, coagulopathy, ascites
   POD45, ascites- Pseudomonas
             sputum- MRSA
   POD57, sepsis
   POD63, died of multiple organ failure.
                     Transplantation. 75(5):727-730, March 15, 2003.
 VOD with fatal outcome occurred in a LRLT
  recipient who had never been exposed to any
  agents that have the potential to induce VOD.
 Histologically :
  most small hepatic veins less than 300 m in
  diameter were affected, exhibiting concentric
  intimal thickening with sparse inflammatory
  cells. accompanied by severe congestion
  and centrilobular necrosis.
 Despite intensified immunosuppression, the
  observed fibrous obliterative changes were
  irreversible.  immunohistochemical studies
  for collagens I highlighted a proliferation of
  mature collagen in the subintimal zone of the
  hepatic veins.
 Although the cause of VOD in this patient is
  tentative, the damage to the endothelium,
  associated with acute rejection, is likely to be
 VOD deserves recognition as one of the
  causes for liver dysfunction and persistent
  ascites after liver transplantation.
Defibrotide for the treatment of VOD
                after liver transplantation
 The  use of antithrombotic and
  thrombolytic agents is limited by their
  toxicity (fatal hemorrhage).
 Defibrotide is a polydeoxyribonucleotide
  with thrombolytic and antithrombotic
  properties and no systemic
  anticoagulant effect.
  Transplantation. 72(7):1237-1240, October 15, 2001.
                       P1          P2
Age                    66          49
Disease               HCV         HBV
VOD develops        6 weeks     4 months
after Tx
Bilirubin             5.4          21.7
Cogulopathy            -            +
Azathioprine           -            +
VOD resolution         +        - (improved
6 months after Tx    alive    Died of sepsis
 Resolution  of VOD:
  42%, 55% in stem-cell transplant patient
 Defibrotide is a promising drug for the
  treatment of VOD after liver
 Needs to be evaluated in large,
  prospective studies.
Thank you for attention!
   Machanism
    (1) Increase levels of prostacyclin, PGE2
         and thrombomodulin.
    (2) Up-regulates tissue-factor pathway
        inhibitor and t-PA.
    (3) Decreases thrombin generation and
        levels of circulating plasminogen
        activator inhibitor
    (4) Inhibits fibrin deposition and modulate
        fibropectin release .

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