Liver malfunction after liver transplantation

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Liver malfunction after liver
transplantation

• by Intern ???

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Overview
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Predict the severity of early graft dysfunction

• Criteria obtained within the 72 postoperative
  hours

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• Patients with a total score (1) good outcome up
  to 6(2) poor graft function a score of 7-9

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Donor related factors

• Steatosis gt 50
• Age gt 60
• High plasma Na
• Nutritional status
• Use of vasopressor drugs and hemodynamic
  instability
• Hypotension during harvesting

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Cold preservation injury

• Graft stored in the preservation solution (UW)
  more than 12 hours is accompanied with injury of
  the vascular system with detachment of sinusoidal
  endothelial cells via specific angiogenic
  mediators

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Re-warming injury

• Interval between 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 (gt 120 min) period of rewarming ischemia is
  a risk factor for primary non function/ initial
  poor function due to hepatocellular damage

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Reperfusing injury

• Reperfusion injury, begins at the time of
  reoxygenation, namely, the end of vascular
  sutures and unclamping of afferent vessels to the
  transplanted organ

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Operative complexities

• 1. Operative bleeding
• 2. Thrombosis of the portal vein
• 3. Hepatic arterial reconstruction
• 4. Hyper acute rejection on ABO incompatible
  grafts

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Post-transplant management

• Common complications
• Immunologic consenquences
• Recurrent of disease

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lt1gt Common complications

• 1. Primary nonfunction
• 2. Intra-abdominal bleeding
• 3. Vascular thrombosis
• 4. Biliary leak
• 5. Infections

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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

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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.

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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
  retransplantation.

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4. Biliary leak

• Reconstructionduct-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
  anastomosis
• Ischemic bile duct injury secondary to early
  hepatic artery thrombosis is an indication for
  retransplantation.

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5.Infections

• 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 gt G(-).
• Broad-spectrum antibiotics in the
  immunosuppressed patient contributes in part to
  the development of systemic fungal infection (
  Candida, Aspergillus).
• Begin antibiotics for common bacteria as soon as
  clinical status suggests the presence of
  infection. ? modified if cultures and
  sensitivities available.

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lt2gt 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

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lt3gt Recurrent of disease

• Recurrence of viral hepatitis is likely within a
  short time after transplantation in infected
  recipients.
• 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.

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Long-term results
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Higher mortality

• Poor preoperative status
• Immediate function of the liver allograft
• Older age
• Ventilator dependency
• The need for dialysis
• Re-transplantation

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Back to the patient

• Pathology report liver biopsymarked
  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 seen.

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• Pathology centrilobular congestion ?
  vein problem
• EchoNo evidence of hepatic vein problem.
• What happened?smaller vein? ? VOD
  (venous-occlusive disease)

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VOD

• 1. Diagnosis histologically fibrous
  obliteration of hepatic veins and
  centrilobular hemorrhagic necrosis on liver
  biopsy.
• 2. Clinical diagnosis hyperbilirubinemia (bil
  gt 2mg/dl) hepatomegaly weight gain gt2-5
  of admission weight

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• 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.

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Case report life threatening VOD after LRLT

• 48 y/o male, s/p liver transplantation secondary
  to Carolis 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.

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• 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.

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• 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
  attributable.
• VOD deserves recognition as one of the causes for
  liver dysfunction and persistent ascites after
  liver transplantation.

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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.

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• Resolution of VOD42, 55 in stem-cell
  transplant patient
• Defibrotide is a promising drug for the treatment
  of VOD after liver transplantation.
• Needs to be evaluated in large, prospective
  studies.

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Thank you for attention!
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Defibrotide

• 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 .