368: Liver Transplantation

Question 1

The preferred and technically most advanced approach in liver transplantation : native organ is removed and donor organ is inserted in the same anatomic location

Answer 1

Orthotopic transplantation

Question 2

Replacement of native, diseased liver by a normal organ (allograft)

Answer 2

Liver transplantation

Question 3

Who are the potential candidates for liver transplantation?

Answer 3

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.

Question 4

Most common indication of liver transplantation in children

Answer 4

Biliary atresia

Question 5

T or F:

Liver transplantation is indicated for end-stage cirrhosis of all causes

Answer 5

True

Question 6

Most common indications for liver transplantation in adults

Answer 6

Chronic hepatitis C

Alcoholic liver disease

Question 7

ABSOLUTE contraindications for transplantation

Answer 7

1. Life threatening systemic diseases
2. Uncontrolled extrahepatic bacterial or fungal infections
3. Preexisting advanced cardiovascular or pulmonary disease
4. Multiple uncorrectable life-threatening congenital anomalies
5. Metastatic malignancy
6. Active drug or alcohol abuse

See Table 368-2 for all absolute and relative contraindications

Question 8

Criteria for organs of brain-dead donors up to age 60 are acceptable

Answer 8

1. Hemodynamic instability
2. Adequate oxygenation
3. Absence of bacterial or fungal infection
4. Absence of abdominal trauma
5. Absence of hepatic dysfunction
6. Serologic exclusion of Hepatitis B and C, and HIV

Question 9

T or F:

For transplantation to proceed, donor and recipient should be compatible in ABO blood group and organ size.

Answer 9

False.

It can be performed in emergencies or marked donor scarcity.

Question 10

A reasonable limit for cold ischemic time, wherein donor liver is removed and packed in ice before transplantation

Answer 10

12 hours

Using University of Wisconsin (UW) solution, time can extend up to 20 hours

Question 11

5 variables in Child-Turcotte-Pugh (CTP) score

Answer 11

1. Encephalopathy stage
2. Ascites
3. Bilirubin
4. Albumin
5. Prothrombin time

Replaced by MELD score

Question 12

What is the best predictor of pretransplantation mortality in liver transplant?

Answer 12

MELD score

MELD scores <15 has higher posttransplantation mortality

Policy: allocate donor organs to candidates with MELD scores >15

Question 13

Variables of MELD score

Answer 13

1. Bilirubin
2. Creatinine
3. Prothombin time expressed as INR

Question 14

T or F:

Serum potassium is another important predictor of survival in liver transplantation candidates.

Answer 14

False

Serum SODIUM

Question 15

Status 1 or highest priority set by United Network for Organ Sharing (UNOS) Liver Transplantation Waiting List Criteria

Answer 15

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;

Question 16

Validated predictor of survival in patients with liver disease

Answer 16

Creatinine

Question 17

For children <18, Pediatric End-stage Liver Disease (PELD) scale is used. What are its variables?

Answer 17

1. Albumin
2. Bilirubin
3. INR
4. Growth failure
5. Age

Question 18

T or F:

One cadaver organ can be split between 2 recipients (1 adult and 1 child)

Answer 18

True

Question 19

Alternative liver donor aside from cadaver donors.

Answer 19

Healthy adult donor

Right lobe or left lobe can be donated

Question 20

Risks of healthy liver donor

Answer 20

1. Mean of 10 weeks of medical instability
2. Biliary complication in 5%
3. Postop complications: wound infection, small-bowel obstruction, incisional hernias, death)

Question 21

Risks in liver recipients using healthy liver donors

Answer 21

Increased frequency of biliary and vascular complications

Question 22

T or F: Potential donors must participate voluntarily without coercion.

Answer 22

True

Question 23

Criteria for living donors

Answer 23

1. 18-60 years old
2. Compatible blood type with recipient
3. No chronic medical problems or history of major abdominal surgery
4. Related genetically or emotionally(??) to the recipient
5. Pass an exhaustive series of clinical, biochemical and serologic evaluations to unearth disqualifying medical disorders

Question 24

During the anhepatic phase (native liver is removed) what conditions can be encountered on the patient?

Answer 24

1. Coagulopathy
2. Hypoglycemia
3. Hypocalcemia
4. Hypothermia

Must be managed by anedthesiology team

Question 25

Sequence of anastomoses in orthotopic liver transplantation

Answer 25

1. Suprahepatic and infrahepatic vena cava 2. Portal vein 3. Hepatic artery 4. Common bile duct-to-duct anastomosis

Question 26

Duration of transplant operation

Answer 26

8hours (6-18hours)

Question 27

Type of transplantation wherein donor liver is inserted without removal of native liver

Answer 27

Heterotopic liver transplantation has very limited success and acceptance

Question 28

Recipients of left and right lobes of the liver

Answer 28

Left lobe: Children or small adults | Right lobe : Adults

Question 29

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

Answer 29

Cyclosporine (IV)

Question 30

Most common and important side effect of cyclosporine therapy

Answer 30

Nephrotoxicity (Reversible) Dose-dependent renal tubular injury Direct renal artery vasospasm

Question 31

Adverse effects of cyclosporine therapy

Answer 31

``` Hypertension Hyperkalemia Tremor Hirsutism Glucose intolerance Gingival hyperplasia ```

Question 32

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

Answer 32

Tacrolimus (oral)

Question 33

Advantages of Tacrolimus

Answer 33

1. Minimizing episodes of rejection 2. Reducing the need for additional glucocorticoid doses 3. Reducing the likelihood of bacterial and cytomegalovirus (CMV) infection 4. Oral absorption more predictable 5. Does not cause hirsutism and gingival hyperplasia

Question 34

Side effects of Tacrolimus

Answer 34

1. Nephrotoxic | 2. Neurotoxic (tremor, seizures, hallucinations, psychoses, coma)

Question 35

This drug inhibits cytochrome P450 however is used occasionally to help boost Tacrolimus levels

Answer 35

Itraconazole

Question 36

Cyclosporine and Tacrolimus are both associated with this risk

Answer 36

Lymphoproliferative malignancies Preferred regimens: Combine with Prednisone and an antimetabolite (azathioprine or mycophenolic acid)

Question 37

A nonnucleoside purine metabolism inhibitor derived as a fermentation product from several Penicillium species, used as immunosuppresive drug for post liver transplants

Answer 37

Mycophenolic acid

Question 38

Most common adverse effects of Mycophenolate

Answer 38

Bone marrow suppression | GI complaints

Question 39

In patients with pretransplantation renal dysfunction or renal deterioration, tacrolimus and cyclosporine may not be practical. What can be used?

Answer 39

``` Antithymocyte globulin (ATG, thymoglobulin) Monoclonal antibodies to T cells, OKT3 ```

Question 40

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.

Answer 40

Sirolimus | Everolimus

Question 41

T or F: In general, given sufficient immunosuppresion, acute liver allograft rejection is nearly always reversible.

Answer 41

True

Question 42

T or F: Prophylactic antibiotic therapy are administered routinely in immediate postoperative period

Answer 42

True

Question 43

Antiviral prophylaxis for CMV post liver transplant

Answer 43

Ganciclovir

Question 44

Antibiotic prophylaxis for Pneumocystis carinii pneumonia post liver transplant

Answer 44

Co-trimoxazole

Question 45

Other leading cause of late mortality after liver transplantation

Answer 45

Renal failure | Cardiovascular disease

Question 46

Hepatic complications post liver transplant

Answer 46

1. Primary graft failure 2. Vascular compromise secondary to thrombosis or stenosis of portal vein 3. Failure or stricture of the biliary anastomoses 4. Rejection

Question 47

When does transplant rejection begins?

Answer 47

1-2 weeks after surgery

Question 48

Clinical signs suggesting rejection

Answer 48

Fever RUQ pain Reduced bile pigment and volume Leukocytosis Most reliable indicators: Increase in serum bilirubin and aminotransferase levels

Question 49

Treatment of transplant rejection

Answer 49

IV Methylprenisolone in repeated boluses Thymoglobulin OKT3

Question 50

Chronic rejection

Answer 50

Relatively rare Progressive cholestasis Focal parenchymal necrosis, mononuclear infiltration, vascular lesions