Liver Transplantation. GENERAL PRINCIPLES Liver transplantation is treatment of choice for : Acute...

Liver Transplantation

GENERAL PRINCIPLES

Liver transplantation is treatment of choice for :Acute and chronic end-stage liver disease,

Hepatomas

Early cholangiocarcinoma

Some liver-based metabolic disorders

2dr .yekehfallah phd of nursing 201504/21/23

Depending on the patient's condition and organ availability, options include: whole-organ deceased donor

split-liver deceased donor

living donor transplantation.


Liver transplantation currently affords patients a survival

posttransplant of greater than 85% at 1 year and greater than

70% at 5 years.


Indications for Liver Transplantation in Adults:Etiologies of End-Stage Liver Disease

1. Fulminant Hepatic Failure

2. Alcoholic Liver Disease

3. Chronic Hepatitis C

4. Chronic Hepatitis B

5. Non-alcoholic steatohepatitis

6. Autoimmune Hepatitis

7. Primary Biliary Cirrhosis

8. Primary Sclerosing Cholangitis

9. Hepatic tumors

10. Metabolic and genetic disorders 5dr .yekehfallah phd of nursing 201504/21/23

Indications for Liver Transplantation in Adults

Presence of irreversible liver disease and a life expectancy of less than 12 months with no effective medical or surgical alternatives to transplantation Chronic liver disease that has progressed to the point of significant interference with the patient's ability to work or with his/her quality of life Progression of liver disease that will predictably result in mortality exceeding that of transplantation (85% one-year patient survival and 70% five-year survival)


Manifestations of End-Stage Liver Disease

Progressive jaundice Intractable ascites Spontaneous bacterial peritonitis Hepatorenal Syndrome Encephalopathy Variceal bleeding Intractable pruritus Chronic fatigue (such as resulting in loss of gainful employment) Bleeding diathesis or coagulopathy


Patient with liver failure


Contraindications

All RecipientsSepsis Recent extra-hepatic malignancyIrreversible cardiopulmonary diseaseActive substance abuse(HIV positive)Living donor recipients onlyRe-transplantAcute liver failure


CARE OF PATIENT DURING WAITING TIME

Required a regular follow-up

Every 2 to 4 weeks depending on severity of liver disease

Routine US doppler, surveillance of oesophagal varices,

management of ascites

This follow-up can be done:

• Directly by the transplant center

• By the referring general physician or specialist

• All therapeutic decisions should be made in accordance with the

transplant physicians


Expanding The Donor Pool

Age

Hepatitis B/C organs

High risk behavior

History of malignancy

Evaluate risk : benefit


Living Donor: Liver Transplantation

Driven by:

Expansion in number of patients requiring liver transplantation

Shortage of deceased donor organs

Increase in waiting list deaths


Living Donor Transplantation

Recipient Advantages• Elective surgery• Scheduled (less uncertainty)• Avoid long waiting time

Recipient Disadvantages• Increased technical complications

• Arterial stenosis / thrombosis• Biliary leak / stricture


Living Donor Transplantation

Donor Advantages• Emotional Gain

Donor Disadvantages• Psychological stress to donor and family• Inconvenience / risk of evaluation process• Operative mortality ( 1/150 liver)• Major postoperative complications (2-10%)• Minor post operative complications (50%)• Possible long term morbidity • Unrecognized covert liver disease


Living Liver Donor Evaluation

Donor Advocacy Team

• Age < 55yrs

• Compatible blood group

• History & physical

• Routine labs

• Ultrasound of liver

• Volumetric analysis by MRA• R. lobe wt. = 1% recipient total wt


Living Donor Evaluation

Decision to donate must be voluntary

Informed consent

Motivation to donate

Behavioral and psychological health

Donor recipient relationship

Diversity issues


Preoperative management of complications associated with hepatic failure & cirrhosis

Hepatic EncephalopathyCerebral EdemaAcute Renal FailureInfection & SepsisMetabolic DerangementsMalnutritionCoagulopathyPortal Hypertension


PRETRANSPLANT EVALUATION

The pretransplant evaluation has several purposes and should be systematic, covering all organ systems to ensure

that no major problems are overlooked.



A/Determine the etiology of liver disease and identify patients with decompensated liver cirrhosis:Spontaneous hepatic encephalopathyRefractory ascitesHepatorenal syndromeHepatopulmonary syndromeRecurrent or refractory variceal bleedingRecurrent infections such as cholangitis or spontaneous bacterial peritonitisIntractable pruritusSevere malnutrition



B/Identify underlying medical problems that should be dealt with to optimize the candidate's overall condition before transplant

C/Identify and address psychiatric, chemical dependency, and compliance issues and how they impact a potential candidate's appropriateness for, and timing of, transplant



D/Identify absolute contraindications:

Active extrahepatic sepsis

Extrahepatic malignancy

Acquired immune deficiency syndrome

Advanced cardiopulmonary disease

E/For patients with hepatic malignancy, order preoperative imaging to detect extrahepatic spread



F/For acute (fulminant) liver failure (ALF) patients (generally more ill than those with chronic failure), refer them early to a transplant center1/Poor prognostic indicators for spontaneous recovery from ALF:• Factor V level less than 30%• pH less than 7.3• International normalized ratio (INR) greater than 6.5• Stage 3 or 4 encephalopathy• Lack of response to medical therapy within 24 to 48 hours2/More severe hepatic parenchymal dysfunction, manifested by

coagulopathy, hypoglycemia, and lactic acidosis



3/More infectious complications4/Higher incidence of renal failure5/Higher incidence of cerebral edema and neurologic

complications a/Some centers use intracranial pressure monitoring to

monitor cerebral edema. b/Mannitol, hyperventilation, and thiopental have been

used to prevent elevated intracranial pressure (>15 mm Hg).

6/Multiple-organ dysfunction syndrome


Prasad, K R et al. BMJ 2001;322:845-847

Implantation of liver transplantation after hepatectomy


Removal of cirrhotic liver


Implanting the new liver


New liver


Vena Cava

Left lobe of liver

Right lobe of liver


Implantation in recipient


INTRAOPERATIVE CARE

A/ Venous and arterial monitoring catheters and large-volume infusion lines are placed in the operating room and can be a source of immediate morbidity (pneumothorax or hemothorax, pericardial tamponade, arterial pseudoaneurysm, air embolism) and hemorrhage in the coagulopathic patient.


INTRAOPERATIVE CARE B/The transplant operation is divided into three phases: 1/Pre-anhepatic (mobilizing the recipient's diseased liver in

preparation for its removal) 2/Anhepatic, characterized by coagulopathy and decreased

venous return to the heart because of occlusion of the inferior vena cava and portal vein• Many centers routinely use a venous bypass system during this

time.• After the native liver is removed, the donor liver is anastomosed to

the appropriate structures to place the new liver in an orthotopic or piggyback (using a side-to-side cavoplasty technique) position.

3/Post-anhepatic, beginning after reperfusion. Hemodynamic instability on reperfusion can result in hypotension and serious arrhythmias due to acidosis, electrolyte abnormalities, air embolus, and cardiac strain.


Early Post-operative Management

Extubate early

Remove lines as soon as possible

Immunosuppression

Replace ascitic losses with albumin

Avoid FFP unless• active bleeding

• Invasive intervention is required


POSTOPERATIVE CARE

The postoperative course can range from smooth to extremely complicated, depending mainly on the patient's preoperative status and the development of any complications. Initial posttransplant care should be in a critical care unit with continuous invasive hemodynamic monitoring and mechanical ventilation as needed.


POSTOPERATIVE CARE

A/Stabilization and recovery of major organ systems functions

B/Evaluation for continual improvement in graft function 1/Normalizing mental status 2/Normalizing coagulation profile 3/Resolution of hypoglycemia 4/Clearance of serum lactate 5/Serum transaminase levels usually rise during the first 24 to 48 hours

secondary to reperfusion and preservation injury and then fall rapidly over the next 48 to 72 hours. Serum bilirubin and alkaline phosphatase levels may take several days longer to normalize.


POSTOPERATIVE CARE C/Provision of adequate immunosuppression

D/Prevention along with vigilant monitoring for, and expeditious management of, complications in the immediate posttransplant period, to minimize morbidity and mortality

1/Avoid oversedation with benzodiazepines or morphine. 2/Avoid hypotension (systolic blood pressure below 100 mm Hg) to

avoid renal dysfunction and graft thrombosis. Provision of adequate preload is paramount.

3/Limit central venous pressure to 8 to 12 cm H2O to• optimize portocaval pressure gradient and graft perfusion• minimize liver graft congestion/edema and bleeding risk from caval

anastomoses53dr .yekehfallah phd of nursing 201504/21/23

POSTOPERATIVE COMPLICATIONS

A/Surgical complications 1/Hemorrhage. - Bleeding is common and can be compounded by deficits in coagulation factors, fibrinolysis, and platelet function. - Blood loss should be monitored by serial measurements of hemoglobin and detection of changes associated with acute hypovolemia (e.g., decreased central venous pressure and urine output). If bleeding persists despite correction of coagulation deficiencies, surgical exploration is indicated


POSTOPERATIVE COMPLICATIONS2/Vascular complications. The overall incidence of vascular

complications is reported to be 8% to 12%. Thrombosis is the most common early event; stenosis and pseudoaneurysm formation occur later.

Doppler ultrasound evaluation is the initial investigation of choice, with more than 90% sensitivity and specificity for thrombosis.

a/Hepatic artery thrombosis (HAT) has a reported incidence of approximately 2% in adults and 10% in children. If detected early, up to 70% of grafts can be salvaged with urgent exploration, thrombectomy, or revision of the anastomosis.

b/Thrombosis of the portal vein or hepatic veins is far less frequent. Liver dysfunction, tense ascites, and variceal bleeding can occur. If thrombosis is diagnosed early, operative thrombectomy and revision of the anastomosis may be successful. If thrombosis occurs late, liver function is frequently preserved because of the collateral veins; a retransplant is usually not necessary


POSTOPERATIVE COMPLICATIONS3/Biliary complications. Biliary complications occur

in 15% to 35% of cases. a/Leak (early)

• (1) Clinical symptoms: fever, abdominal pain, and peritoneal irritation.• (2) Diagnosis: Bilious output from surgical drains; ultrasound may demonstrate a

fluid collection; hepatobiliary scintigraphy (e.g., HIDA [hepatobiliary iminodiacetic acid] scan) may demonstrate extravasation of radioactive tracer; cholangiography] or ERCP [endoscopic retrograde cholangiopancreatography])

• (3) Management: Endoscopic stent placement and biloma drainage, or operative repair hepaticojejunostomy).

b/Stricture (later)most common at the anastomotic site, likely related to local ischemia• (1) Clinical symptoms: cholangitis or cholestasis, or both• (2) Diagnosis: Ultrasound, magnetic resonance cholangiopancreatography,

cholangiography• (3) Management: balloon dilatation or stent placement across the stricture, or both.



4/Wound complications a/Superficial wound infection, hematoma, and seroma

(early)• (1) Diagnosis: drainage, increasing pain, erythema, fluctuance• (2) Management: (Re)incision and drainage, allowing for healing

by secondary intention (serial open wound dressing changes) ,antibiotics

b/Incisional hernias (later), associated with malnutrition, attenuated fascia, and immunosuppression


POSTOPERATIVE COMPLICATIONS 5/Primary nonfunction a/Incidence: 3% to 5% b/Mortality rate is more than 80% without a retransplant c/Definition: poor or no hepatic function from the time of transplant d/Associated donor factors.

• (1) Donor age greater than 49 years• (2) Macrosteatosis greater than 30%• (3) Donor intensive care unit stay greater than 3 days• (4) Cold ischemia time greater than 18 hours• (5) Reduced-size grafts

e/Diagnosis: rule out HAT, severe preservation injury, accelerated acute rejection, and severe infection, because they can mimic primary nonfunction. The diagnosis is usually based on clinical parameters; graft biopsy may be helpful in some cases.

f/Treatment• (1) Intravenous prostaglandin E1• (2) Early relisting for retransplantation



B/Medical complications 1/Neurologic most commonly related to drugs or a poorly functioning graft

• a/Symptoms:• (1) Decreased level of consciousness• (2) Seizures• (3) Focal neurologic deficits

• b/Other neurologic complications:• (1) Hypoxic ischemic encephalopathy• (2) Central pontine myelinolysis• (3) Cerebral edema• (4) Intracranial hematomas



2/Pulmonary in up to 75% of recipients

a/Noninfectious complications (first postoperative week):• (1) Pulmonary edema• (2) Pleural effusions• (3) Atelectasis• (4) Acute respiratory distress syndrome (ARDS)

• (a) incidence less than 5%, but mortality greater than 80%• (b) most common when underlying bacterial infection is present, multiple transfusions,

hypertension, aspiration, and antilymphocyte therapy

b/Infectious complications (after the first week):• (1) Bacterial• (2) Fungal• (3) Viral



3/Renal affecting almost all liver recipients. Renal failure increases the mortality rate.

Causes of renal failure:a/Pretransplant• (1) Hepatorenal syndrome• (2) Acute tubular necrosis

b/Postoperative• (1) Hypovolemia• (2) Ischemic acute tubular necrosis• (3) Drug nephrotoxicity (calcineurin inhibitors)• (4) Preexisting subclinical or overt renal disease (e.g., diabetic

nephropathy, hepatitis ,membranoproliferative glomerulonephritis)



4/Immunosuppressive:

a/Posttransplant diabetes

b/Hyperlipidemia

c/Viral and fungal infections

d/Squamous and basal cell skin cancers and lymphoma


POSTOPERATIVE COMPLICATIONS5/Recurrence of primary liver disease may require treatment and can significantly impact graft and patient

survivala/Hepatitis B (Highly effective peritransplant and posttransplant long-term prophylaxis protocols that include lamivudine and/or hepatitis B immune globulin [HBIg] prevent hepatitis B recurrence.)b/Hepatitis C (~20% cirrhosis rate from recurrent hepatitis C at 5 years posttransplant; no evidence-based recommendations on posttransplant treatment and efficacy of prophylaxis with pegylated interferon and ribavirin available)c/Autoimmune liver diseases (Recurrence rates of clinically significant autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis are low and controversial; long-term posttransplant immunosuppression that includes steroids may offer theoretical [but not evidence-based] added benefits with regard to autoimmune disease recurrence prevention.)


Post-operative complications & management of liver transplant patients

Right pleural effusion• May affect ventilation, necessitating drainage.

Hepatic edema secondary to aggressive resuscitation & increased intravascular volume.• Goal CVP 6-10. Minimize increased hepatic vein pressures



Renal failure• Elevation of creatinine & BUN observed in

nearly all transplant patients secondary to ATN, hepatorenal syndrome. Usually self-limiting.

May necessitate therapy with loop diuretics, renal replacement therapy.



Electrolyte Derangements• Recovering graft increases demand for magnesium &

phosphorous.• Transfusion of citrate rich blood products results in

decreased serum magnesium & calcium.• Rapid correction of chronic hyponatremia with isotonic

solution can have severe neurological consequence.

Judicious use of hypotonic solutions with goal of serum Na 125-130 advised.



Thrombocytopenia• Preoperative portal hypertension results in

splenomegaly & platelet sequestration. Generally improves as graft recovers. May necessitate replacement if bleeding is encountered or invasive procedures are planned. Splenectomy is rarely indicated.

• Platelet dysfunction secondary to renal & hepatic failure may be improved acutely with DDAVP.



Biliary leak• RUQ pain, fever, persistent elevation of bilirubin, liver enzymes.

Biloma on CT.• Treated with endoscopic stent, percutaneous drainage. Possible

surgical revision if duct is ischemic.

Hepatic artery thrombosis• Persistent elevation or increasing liver enzymes, poor

graft function. Diagnosed with U/S, CT angiography, MRA.

• Treated with immediate revascularization.


Induction of Immunosuppression

Triple therapy Initiated immediately following transplantation.

• Calcineurin inhibitor (tacrolimus, cyclosporine)• anti-proliferative agent (mycophenolate)• corticosteroid taper.

Agents vary according to etiology of liver disease• Thymoglobulin & Hb Ig utilized in hepatitis patients along with

viral replication & to avoid coritocsteroid usage.


Allograft rejection

Hyperacute rejection• Secondary to preformed Ab to graft antigen.

• Extremely rare

• Necessitates retransplantation.

Acute Cellular Rejection• 70% of patients 5 to 14 days following transplant.

• Heralded by fever, jaundice, elevation of liver enzymes.

• Diagnosed by liver biopsy. Demonstrates endothelialitis & non-suppurative cholangitis.


Classification of Complications

Graft dysfuntion or non-function

Technical

Immunological

Infective

Extrahepatic

Drug effects

Medical

Recurrent Disease73dr .yekehfallah phd of nursing 201504/21/23

Technical Complications

Bleeding

Hepatic artery thrombosis / stenosis

Portal vein thrombosis / stenosis

Biliary complications• Leak

• Stricture

• Sludge


ImmunologicalAcute Rejection

5-10 days post transplant but may occur at any time

Clinical Elevated LFTS

Liver Biopsy Portal tract inflammatory infiltrate

Endothelialitis

Destruction of biliary epithelium

Treatment Steroids


Infective

Bacterial < 15 days• Commonly lines /chest /urine

Fungal > 15 days• Prolonged hospitalization• Broad spectrum antibiotics• Re transplant• Roux loop

Viral > 4 weeks• CMV – recipients of CMV + organs


Extra-hepaticCardiac failure / infarction

Pulmonary

Neurological

Renal

Endocrine• Diabetes (33%)

Drug effects

Recurrent disease


When to contact the transplant program:

Sooner rather than later

New medications

Fever

Abnormal liver functions tests

Vomiting / diarrhea


?


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