Liver and Small Bowel Transplantation


Liver Transplantation (OLT)

  1. Indications
    1. Cholestatic Liver Disease
      1. Primary Biliary Cirrhosis
        • autoimmune disorder that damages intralobular bile ducts
        • post-transplant results are excellent: 90% - 95% 1-year survival
        • disease recurrence (30%) is unlikely to require retransplant

      2. Primary Sclerosing Cholangitis
        • affects the large intrahepatic and extrahepatic bile ducts
        • majority of patients are males with ulcerative colitis
        • associated with cholangiocarcinoma

    2. Alcoholic Liver Disease
      • excellent 1-year results
      • incidence of recidivism is ~ 10%
      • most centers require a period of abstinence (6 months) prior to transplantation

    3. Chronic Hepatitis
      1. Hepatitis B
        • used to be a contraindication for transplant because of rapid reinfection of the graft
        • effective antiviral therapy and hyperimmune globulin has largely eradicated reinfection after transplantation

      2. Hepatitis C
        • most common indication in the West
        • associated with worse outcomes than other indications for transplantation
        • reinfection rate is 90% and may be unresponsive to alpha-interferon therapy
        • pretreatment with interferon and ribavirin is effective, but is often not tolerated in cirrhotic patients

    4. Malignancy
      • HCC patients are eligible for OLT if they cannot tolerate a resection because of advanced cirrhosis, and if they meet the Milan criteria
      • patients who meet the Milan criteria are given extra priority for transplantation

      1. Milan Criteria
        • single lesion ≤ 5 cm or up to 3 separate lesions all < 3 cm
        • no gross vascular invasion
        • no regional nodal or distant metastases

    5. Metabolic Diseases
      • many metabolic diseases and inborn errors of metabolism may be cured by OLT
      • examples include: Wilson’s disease, alpha1-antitrypsin disease, hemochromatosis

    6. Nonalcoholic Steatohepatitis
      • associated with obesity and metabolic syndrome
      • most common indication in some centers

    7. Biliary Atresia
      • most common indication in the pediatric population
      • majority of infants who undergo hepaticojejunostomy (Kasai procedure) will eventually require OLT

    8. Fulminant Hepatic Failure
      • often secondary to a hepatotoxin (acetaminophen) or fulminant viral infection
      • patients are given the highest priority on the transplant list (status 1)
      • it is difficult to predict who will recover with supportive therapy and who will benefit from an OLT

  2. Contraindications
    1. Insufficient Cardiopulmonary Reserve
      • patients should have a normal ejection fraction
      • patients with severe CAD may require revascularization pretransplant
      • oxygen-dependent COPD is a contraindication, as is refractory pulmonary hypertension

    2. Infections
      • uncontrolled bacterial and fungal infections are absolute contraindications
      • HIV infection is not a contraindication for most centers if the virus is controlled

    3. Malignancy
      • Metastatic HCC is an absolute contraindication
      • Patients with a prior treated malignancy (non-HCC) must be considered cured

    4. Psychosocial Issues
      • patients must have the financial and psychological capacity to care for the transplanted organ
      • continued drug or alcohol abuse is an absolute contraindication to OLT
      • lack of commitment to immunosuppressive drugs is an absolute contraindication

  3. Recipient Criteria for OLT
    1. Decompensated Cirrhosis
      • historic indication for OLT is decompensated cirrhosis manifested by hepatic encephalopathy, ascites, portal hypertensive bleeding, hepatorenal syndrome, or subacute bacterial peritonitis
      • has been replaced by the MELD score

    2. MELD Score
      • reflects the likelihood of dying from cirrhosis within 3 months
      • formula based on objective criteria that can be verified: creatine, bilirubin, INR, Na
      • allows livers to be directed towards the sickest patients
      • patients with a MELD score ≥ 15 are candidates for a liver transplant
      • the transplant evaluation should begin when the MELD score is > 10
      • multiple conditions exist that qualify for MELD exception points
      • patients with fulminant hepatic failure have the highest priority (status 1), which supersedes MELD score

  4. Operative Procedure
    1. Recipient Hepatectomy
      • formidable procedure in patients with extensive portal hypertension
      • requires simultaneous occlusion of both the IVC and portal veins
      • anhepatic phase of the surgery refers to the period of time in which the new liver is being sewn in, and is characterized by hemodynamic instability and increased variceal bleeding

      1. Venovenous Bypass
        • used in patients who cannot tolerate the anhepatic phase
        • improves venous return to the heart and minimizes mesenteric congestion
        • blood is removed via the femoral and portal veins, and returned via the subclavian vein

    2. Implantation
      • usually performed in the orthotopic position
      • suprahepatic caval anastomosis is performed first, followed by the infrahepatic caval anastomosis
      • portal vein anastomosis is performed next, followed by the hepatic artery anastomosis
      • methods of biliary reconstruction include choledochocholedochostomy and Roux-en-Y choledochojejunostomy

    3. Additional Techniques
      1. Piggyback Technique
        • recipient IVC is left intact and the liver is dissected off it
        • all hepatic vein branches to the IVC are ligated except the three major hepatic veins
        • orifices of the hepatic veins are then connected to form a common channel, which is then anastomosed to the donor suprahepatic IVC
        • advantages of this technique include avoidance of one vascular anastomosis and IVC blood flow can be restored after completion of the suprahepatic caval anastomosis
        • shortens the anhepatic phase and improves cardiovascular stability

        Liver Transplant Piggyback Technique
      2. Split-Liver Transplantation
        • left lateral segment (segments 2, 3) is used in a child; the remaining segments are used for an adult
        • donor vessels supplying the liver remain with the right lobe
        • pediatric graft is based on the left hepatic artery, left portal vein, and the left hepatic vein

        Liver Transplant Split Liver Technique
      3. Living-Related Transplantation
        • typically from a parent to a child
        • utilizes the donor’s left lateral segment
        • major risk is morbidity and possible mortality (0.2%) to the donor

  5. Postoperative Management
    1. Immunosuppression
      • maintenance therapy consists of a combination of a calcineurin inhibitor (tacrolimus), steroids, and antiproliferative agent (mycophenolate mofetil)
      • need for immunosuppression decreases over time
      • chronic rejection is uncommon

    2. Acute Rejection
      • occurs in 20% of patients, but rarely results in graft loss
      • suspected by an elevation of liver enzymes (GGT, alkaline phosphatase, bilirubin)
      • Doppler ultrasound is used to rule out hepatic artery thrombosis and bile duct obstruction
      • diagnosis is made histologically by percutaneous liver biopsy
      • usually responds to bolus steroid therapy or sirolimus

  6. Technical Complications
    1. Hepatic Artery Thrombosis
      • more common in the pediatric population
      • presents as a rapid rise in serum transaminase levels
      • diagnosed by Doppler ultrasound
      • treatment consists of revision of the anastomosis or retransplantation

    2. Portal Vein Thrombosis
      • clinical manifestations may include a rising serum ammonia level, ascites, or variceal bleeding
      • diagnosis is made by Doppler ultrasound
      • treatment is emergency thrombectomy and/or revision of the anastomosis

    3. Biliary Complications
      • leaks and strictures occur in 10% to 35% of patients, most likely due to vascular compromise
      • diagnosis is made by cholangiography
      • leaks usually require reoperation and surgical correction
      • strictures can usually be managed endoscopically or radiologically

Small Bowel Transplantation

  1. Indications
    • irreversible intestinal failure combined with TPN failure
    • small bowel transplants may also be combined with other organs, most commonly liver

    1. Intestinal Failure
      • great majority of patients have short-gut syndrome as a result of extensive small bowel resection
      • common indications in adults include: Crohn’s disease, mesenteric thrombosis, and trauma
      • common indications in children include: necrotizing enterocolitis, volvulus, intestinal atresia, and gastroschisis
      • intestinal failure is not defined based on a specific length of remaining bowel; but in practical terms, results when > 75% of the gut is resected or nonfunctional

    2. TPN Failure
      • TPN is associated with multiple potentially fatal complications
      • cholestasis can lead to liver failure, especially in the pediatric population
      • multiple central line infections or any fungal infection represents TPN failure
      • multiple central vein thromboses is another criteria for TPN failure

  2. Donor Criteria
    • must have a compatible blood type
    • since loss of abdominal domain is common in recipients who have had an extensive resection, the ideal donor would have a body weight 50% - 75% that of the recipient
    • cold ischemia time must be minimized because it can lead to loss of mucosal integrity with resulting increased bacterial translocation or intestinal perforation in the early post-op period

  3. Surgical Procedures
    1. Isolated Small Intestinal Transplant
      • includes the entire jejunum and ileum
      • arterial inflow is from the donor SMA to the recipient infrarenal aorta
      • venous outflow is from the donor SMV to the recipient portal vein (preferred) or IVC
      • donor arterial or venous conduits may be necessary to create the anastomoses
      • bowel continuity is established proximally through anastomosis of the donor jejunum to the recipient duodenum
      • distal bowel continuity is established from the donor terminal ileum to the recipient’s terminal ileum or colon
      • a distal ileostomy (end or loop) is created to allow monitoring of the graft

      Isolated Small Intestine Transplant
    2. Combined Small Bowel and Liver Transplants
      • several possible options
      • the grafts may come from the same donor, but are implanted separately
      • another option is when the liver, intestine, duodenum, and pancreas are procured and transplanted en bloc
      • the en bloc procedure eliminates biliary reconstruction, which almost totally avoids postoperative biliary complications

  4. Immunologic Considerations
    • the intestine is highly immunogenic because of its abundant lymphoid tissue
    • high levels of immunosuppression are required
    • rejection rate is highest among all the solid organ transplants

    1. Immunosuppression
      • induction is with a polyclonal T-cell antibody and high-dose steroids
      • tacrolimus is the primary maintenance drug, along with prednisone

    2. Diagnosis of Rejection
      • detected primarily by clinical symptoms, which mimic gastroenteritis, and graft histology
      • symptoms include fever, abdominal pain, ileus, increased stomal output, elevated white blood cell count
      • serum citrulline and stool calprotectin are useful markers for rejection
      • intestinal biopsies through the ileostomy may show cryptitis, shortening of villi, mononuclear infiltrates, or mucosal sloughing
      • liver transplants appear to have a protective effect for intestinal rejection

    3. Posttransplant Lymphoproliferative Disorder (PTLD)
      • incidence is high at 10% - 20% of transplant recipients
      • associated with Epstein-Barr virus infection, often from an EBV-positive donor to an EBV-negative recipient
      • initial treatment includes reduction of immunosuppression and antiviral medication
      • chemotherapy may be required for Burkitt or T-cell lymphoma
      • mortality rate is 25% - 60%

    4. Graft-versus-Host Disease
      • donor lymphoid cells attack recipient tissues
      • treatment involves increasing immunosuppression, which increases the infection risk
      • mortality rate is high in severe cases

  5. Surgical Complications
    • complication rate is ~ 50%
    • most common technical complications include anastomotic leaks, intestinal perforations, and intraabdominal abscesses
    • signs and symptoms are often masked by high levels of immunosuppression
    • graft thrombosis usually results in graft loss







References

  1. Sabiston, 20th ed., pgs 637 – 646, 666 – 674
  2. Schwartz, 10th ed. pgs 345 - 354
  3. UpToDate. Liver Transplantation in Adults: Patient Selection and Pretransplant Evaluation. Lorna M. Dove, MD, MPH, Robert S. Brown, Jr., MD, MPH. Mar 26, 2021. Pgs 1 – 26
  4. UpToDate. Overview of Intestinal and Multivisceral Transplantation. Farrukh A. Khan, MD, FACS, Gennaro Selvaggi, MD. Sep 16, 2020. Pgs 1 – 21