Liver Transplantation

Surgical Procedure

Initially auxiliary liver placed in recipient Þ add a liver in addition to the one you already have

Early 1960’s orthotopic transplantation

Orthotopic transplant advantages Þ take out old, put in new

Cures portal hypertension
Allows space for transplanted organ
Decreases toxins from sick liver
Eliminates risk of cancer in native liver

Early grafts were quickly rejected

Azothioprine, Prednisone era Þ drugs used in order to decrease rate of rejection

Cyclosporin introduced in 1978 (much better drug Þ increased success rate to 30 to 70%)

Recently Tacrolimus (FK-506) Þ drug of choice

Rejection episodes are treated with supplemental doses of steroids or with the monoclonal anti-T cell antibody OKT3

drawback to chronic immunosuppression Þ opportunistic infection (viral and fungal) and malignancy (skin carcinoma and lymphoma)

Candidate Selection

History

Prior to 1980 only patients with hopeless prognosis were selected

Cyclosporin era (1978): saves lives and improves quality of life

NIH consensus (1983) Þ no longer considered liver transplantation an experimental procedure

Improvement in survival has led to broadening selection criteria

Candidates with the following are accepted:

Advanced chronic liver disease (most common = cirrhosis); sometimes presents with severe portal hypertension

cirrhosis: due to biliary obstruction (primary or secondary biliary cirrhosis), chronic viral infection (HepB or C), alcoholism, autoimmune disease, or may be cryptogenic;
Acute fulminant hepatic failure (due to viral hipatitis, ingestion of liver toxins, or extensive trauma)
Inherited metabolic disease

Candidates who are considered controversial are ones who:

drink alcohol (must be sober for at least 6 months, undergo counseling, and vow to abstinence)
have cancer (must be confined to liver and unresectable)
have HepB

Candidates with the following are generally not accepted:

Metastatic cancer
Uncontrolled infection (ie sepsis)
Active drug and/or alcohol abuse (this population usually demonstrates poor compliance)
AIDs (HIV+ is a relative contraindication)
Advanced cardiopulmonary disease (may receive combined liver-kidney transplants)

80 to 85% of screened patients will comply

Primary indications for liver transplantation in children is biliary atresia with subsequent liver failure and inborn errors in metabolism such as alpha 1 anti-trypsin disease

Liver Transplant Waiting List

In 1994 Þ 4059 people listed; 1995 Þ 5700 listed; 1999 Þ >7000 expected to be listed

The list is growing exponentially
Problem: 2x as many people on the list than livers available

Getting on the waiting list

Patient is reviewed by UHC (selection committee)

If pass Þ patient is reviewed by OSOTC (selection committee)

If pass Þ listed with UNOS for local, regional and national organ availability

Organs come from organ stores (ie LifeBanc) Þ 61 nationwide Þ each one covers a specific region

UNOS matches donor and recipient via computer, based on your region
Sickest patients transplanted first, not first come first served

Requirements in order to be an organ donor

Must be brain dead!; once brain death is determined, the patient is considered dead at that time

causes of brain death Þ head trauma, subarachnoid or intracranial Hemorrhage, primary brain tumors, brain anoxia, drug overdose

Minimal Criteria if candidate passes above requirement

No malignancies; No sepsis; No life threatening conditions (ie AIDS)

After above requirements are met, must test liver to see if it is functioning normally

Must look at transaminases (AST, ALT, ALK PHOS); bilirubin, PT, platelet count, MEG-X

Procedure for extracting organs

Make one incision from neck to pubis Þ take organs in following order: heart Þ lungs Þ liver Þ kidneys

Preserve extracted organ:

Put organ in plastic bag with preservation solution (ie BioSpan) and place in a cooler

Recommended preservation time for liver Þ 18 hours max

Procedure of the Transplant

Take out old liver Þ anastomose vena cava Þ connect vessels of portal triad (bile duct, hepatic artery, portal vein)

Will need a veno-venous by-pass Þ blood from portal vein runs thru an external channel into the inferior vena cava

ensures adequate cardiac output when the portal vein and inferior vena cava are clamped

Always remove the gall bladder

Roux-Y limb Þ attach the bile duct to jejunum

Improvements to the transplant

Can segment the liver Þ get 2 for 1 Þ now able to transplant only half of the liver with success

Can treat two people with one liver or perform a live donor liver transplant

Live donor liver transplant: take half of a live donor’s liver and put it into the recipient Þ both segments will regenerate Þ best success rate using this procedure

Outcomes

Results of liver transplantation depends on age of recipient and their disease

1 year survival of 77% with a range of 64% (severely ill at time of transplant) to 86% (stable at time of transplant)

Children >10kg or 1yr of age have a 1yr survival rate of 85% whereas in very small infants is less successful

Graft Terminology

Autograft Þ transfer of an individual’s own tissue

Isograft (syngraft) Þ transfer of tissue between genetically identicle individuals (identical twins, inbred mice)

Allograft Þ transfer of tissue between genetically different members of the same species

Xenograft Þ transfer of tissue between members of a different species

Types of OLT allograft rejection

Hyperacute: preformed Ab specific for Ag expressed by allogeneic liver grafts; occurs within 24 hrs (rapid onset)

also occurs in rejection of vascularized xenografts
occurs with ABO incompatibility

Acute: rejection of liver allograft mediated by T cells; occurs within a few weeks to months

bile ductitis – main presentation of acute rejection
endothelialitis

Chronic (ductopenic): long-term solid organ graft rejection mediated by both humoral and cellular immunity

presents as portal inflammation; duct destruction especially lobular; portal tract fibrosis; cirrhosis is rare