Liver Transplantation. GENERAL PRINCIPLES Liver transplantation is treatment of choice for : Acute...
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Transcript of 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
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Depending on the patient's condition and organ availability, options include: whole-organ deceased donor
split-liver deceased donor
living donor transplantation.
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Liver transplantation currently affords patients a survival
posttransplant of greater than 85% at 1 year and greater than
70% at 5 years.
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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)
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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
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Patient with liver failure
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Contraindications
All RecipientsSepsis Recent extra-hepatic malignancyIrreversible cardiopulmonary diseaseActive substance abuse(HIV positive)Living donor recipients onlyRe-transplantAcute liver failure
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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
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Expanding The Donor Pool
Age
Hepatitis B/C organs
High risk behavior
History of malignancy
Evaluate risk : benefit
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Living Donor: Liver Transplantation
Driven by:
Expansion in number of patients requiring liver transplantation
Shortage of deceased donor organs
Increase in waiting list deaths
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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
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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
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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
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Living Donor Evaluation
Decision to donate must be voluntary
Informed consent
Motivation to donate
Behavioral and psychological health
Donor recipient relationship
Diversity issues
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Preoperative management of complications associated with hepatic failure & cirrhosis
Hepatic EncephalopathyCerebral EdemaAcute Renal FailureInfection & SepsisMetabolic DerangementsMalnutritionCoagulopathyPortal Hypertension
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PRETRANSPLANT EVALUATION
The pretransplant evaluation has several purposes and should be systematic, covering all organ systems to ensure
that no major problems are overlooked.
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PRETRANSPLANT EVALUATION
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
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PRETRANSPLANT EVALUATION
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
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PRETRANSPLANT EVALUATION
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
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PRETRANSPLANT EVALUATION
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
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PRETRANSPLANT EVALUATION
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
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Prasad, K R et al. BMJ 2001;322:845-847
Implantation of liver transplantation after hepatectomy
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Removal of cirrhotic liver
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Implanting the new liver
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New liver
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Vena Cava
Left lobe of liver
Right lobe of liver
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Implantation in recipient
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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.
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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.
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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
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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.
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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.
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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
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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
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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.
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POSTOPERATIVE COMPLICATIONS
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
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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
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POSTOPERATIVE COMPLICATIONS
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
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POSTOPERATIVE COMPLICATIONS
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
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POSTOPERATIVE COMPLICATIONS
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)
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POSTOPERATIVE COMPLICATIONS
4/Immunosuppressive:
a/Posttransplant diabetes
b/Hyperlipidemia
c/Viral and fungal infections
d/Squamous and basal cell skin cancers and lymphoma
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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.)
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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
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Post-operative complications & management of liver transplant patients
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.
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Post-operative complications & management of liver transplant patients
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.
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Post-operative complications & management of liver transplant patients
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.
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Post-operative complications & management of liver transplant patients
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.
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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.
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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.
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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
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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
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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
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Extra-hepaticCardiac failure / infarction
Pulmonary
Neurological
Renal
Endocrine• Diabetes (33%)
Drug effects
Recurrent disease
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When to contact the transplant program:
Sooner rather than later
New medications
Fever
Abnormal liver functions tests
Vomiting / diarrhea
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?
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