368: Liver Transplantation Flashcards
The preferred and technically most advanced approach in liver transplantation : native organ is removed and donor organ is inserted in the same anatomic location
Orthotopic transplantation
Replacement of native, diseased liver by a normal organ (allograft)
Liver transplantation
Who are the potential candidates for liver transplantation?
Children and adults who, in the absence of contraindication, suffer from severe irreversible liver disease for which alternative medical or surgical treatments have been exhausted or are unavailable.
See Table 368-1 for list of all indications.
Most common indication of liver transplantation in children
Biliary atresia
T or F:
Liver transplantation is indicated for end-stage cirrhosis of all causes
True
Most common indications for liver transplantation in adults
Chronic hepatitis C
Alcoholic liver disease
ABSOLUTE contraindications for transplantation
- Life threatening systemic diseases
- Uncontrolled extrahepatic bacterial or fungal infections
- Preexisting advanced cardiovascular or pulmonary disease
- Multiple uncorrectable life-threatening congenital anomalies
- Metastatic malignancy
- Active drug or alcohol abuse
See Table 368-2 for all absolute and relative contraindications
Criteria for organs of brain-dead donors up to age 60 are acceptable
- Hemodynamic instability
- Adequate oxygenation
- Absence of bacterial or fungal infection
- Absence of abdominal trauma
- Absence of hepatic dysfunction
- Serologic exclusion of Hepatitis B and C, and HIV
T or F:
For transplantation to proceed, donor and recipient should be compatible in ABO blood group and organ size.
False.
It can be performed in emergencies or marked donor scarcity.
A reasonable limit for cold ischemic time, wherein donor liver is removed and packed in ice before transplantation
12 hours
Using University of Wisconsin (UW) solution, time can extend up to 20 hours
5 variables in Child-Turcotte-Pugh (CTP) score
- Encephalopathy stage
- Ascites
- Bilirubin
- Albumin
- Prothrombin time
Replaced by MELD score
What is the best predictor of pretransplantation mortality in liver transplant?
MELD score
MELD scores <15 has higher posttransplantation mortality
Policy: allocate donor organs to candidates with MELD scores >15
Variables of MELD score
- Bilirubin
- Creatinine
- Prothombin time expressed as INR
T or F:
Serum potassium is another important predictor of survival in liver transplantation candidates.
False
Serum SODIUM
Status 1 or highest priority set by United Network for Organ Sharing (UNOS) Liver Transplantation Waiting List Criteria
Fulminant hepatic failure (including primary graft nonfunction and hepatic artery thrombosis within 7 days after transplantation as well as acute decompensated Wilson’s diease)
For children <18, status 1 includes acute or chronic liver failure + hospitalization in an ICU or inborn errors of metabolism;
Validated predictor of survival in patients with liver disease
Creatinine
For children <18, Pediatric End-stage Liver Disease (PELD) scale is used. What are its variables?
- Albumin
- Bilirubin
- INR
- Growth failure
- Age
T or F:
One cadaver organ can be split between 2 recipients (1 adult and 1 child)
True
Alternative liver donor aside from cadaver donors.
Healthy adult donor
Right lobe or left lobe can be donated
Risks of healthy liver donor
- Mean of 10 weeks of medical instability
- Biliary complication in 5%
- Postop complications: wound infection, small-bowel obstruction, incisional hernias, death)
Risks in liver recipients using healthy liver donors
Increased frequency of biliary and vascular complications
T or F: Potential donors must participate voluntarily without coercion.
True
Criteria for living donors
- 18-60 years old
- Compatible blood type with recipient
- No chronic medical problems or history of major abdominal surgery
- Related genetically or emotionally(??) to the recipient
- Pass an exhaustive series of clinical, biochemical and serologic evaluations to unearth disqualifying medical disorders
During the anhepatic phase (native liver is removed) what conditions can be encountered on the patient?
- Coagulopathy
- Hypoglycemia
- Hypocalcemia
- Hypothermia
Must be managed by anedthesiology team
Sequence of anastomoses in orthotopic liver transplantation
- Suprahepatic and infrahepatic vena cava
- Portal vein
- Hepatic artery
- Common bile duct-to-duct anastomosis
Duration of transplant operation
8hours (6-18hours)
Type of transplantation wherein donor liver is inserted without removal of native liver
Heterotopic liver transplantation
has very limited success and acceptance
Recipients of left and right lobes of the liver
Left lobe: Children or small adults
Right lobe : Adults
Calcineurin inhibitor used as immunosuppresive agent that blocks early activation of T cells and is specific for T cell functions that result from the interaction of the T cell with its receptor and that involve the calcium-dependent signal transduction pathway
Cyclosporine (IV)
Most common and important side effect of cyclosporine therapy
Nephrotoxicity (Reversible)
Dose-dependent renal tubular injury
Direct renal artery vasospasm
Adverse effects of cyclosporine therapy
Hypertension Hyperkalemia Tremor Hirsutism Glucose intolerance Gingival hyperplasia
A macrolide lactone antibiotic isolated from a Japanese soil fungus, Streptomyces tsukubaensis, that has same mechanism of action as cyclosporine as immunosuppresive agent but is 10-100 times more potent
Tacrolimus (oral)
Advantages of Tacrolimus
- Minimizing episodes of rejection
- Reducing the need for additional glucocorticoid doses
- Reducing the likelihood of bacterial and cytomegalovirus (CMV) infection
- Oral absorption more predictable
- Does not cause hirsutism and gingival hyperplasia
Side effects of Tacrolimus
- Nephrotoxic
2. Neurotoxic (tremor, seizures, hallucinations, psychoses, coma)
This drug inhibits cytochrome P450 however is used occasionally to help boost Tacrolimus levels
Itraconazole
Cyclosporine and Tacrolimus are both associated with this risk
Lymphoproliferative malignancies
Preferred regimens: Combine with Prednisone and an antimetabolite (azathioprine or mycophenolic acid)
A nonnucleoside purine metabolism inhibitor derived as a fermentation product from several Penicillium species, used as immunosuppresive drug for post liver transplants
Mycophenolic acid
Most common adverse effects of Mycophenolate
Bone marrow suppression
GI complaints
In patients with pretransplantation renal dysfunction or renal deterioration, tacrolimus and cyclosporine may not be practical. What can be used?
Antithymocyte globulin (ATG, thymoglobulin) Monoclonal antibodies to T cells, OKT3
These drugs has been demonstrated to be effective in preventing rejection with improvement in renal function however due to increased hepatic artery thrombosis, these are not recommended as immunosuppresants.
Sirolimus
Everolimus
T or F: In general, given sufficient immunosuppresion, acute liver allograft rejection is nearly always reversible.
True
T or F: Prophylactic antibiotic therapy are administered routinely in immediate postoperative period
True
Antiviral prophylaxis for CMV post liver transplant
Ganciclovir
Antibiotic prophylaxis for Pneumocystis carinii pneumonia post liver transplant
Co-trimoxazole
Other leading cause of late mortality after liver transplantation
Renal failure
Cardiovascular disease
Hepatic complications post liver transplant
- Primary graft failure
- Vascular compromise secondary to thrombosis or stenosis of portal vein
- Failure or stricture of the biliary anastomoses
- Rejection
When does transplant rejection begins?
1-2 weeks after surgery
Clinical signs suggesting rejection
Fever
RUQ pain
Reduced bile pigment and volume
Leukocytosis
Most reliable indicators:
Increase in serum bilirubin and aminotransferase levels
Treatment of transplant rejection
IV Methylprenisolone in repeated boluses
Thymoglobulin
OKT3
Chronic rejection
Relatively rare
Progressive cholestasis
Focal parenchymal necrosis, mononuclear infiltration, vascular lesions
