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LIVER TRANSPLANTATION
Dr Sudeep R Shah MS DNB FRCS (Edin)
Consultant GI & Hepatobiliary Pancreatic Surgeon
Email:
HYPERLINK "mailto:[email protected]"
[email protected]
Liver transplantation is, today, the only curative option for end-stage liver disease. Dr Thomas
Starzl in the USA and Sir Roy Calne in the UK who pioneered these surgeries in the 1960s
initially had success rates of 30%. However, paralleling advances in immunosuppression,
anesthesia, intensive care and refining of surgical techniques, survival of >80% have been
achieved.
INDICATIONS
These are summarized in Table 1. For end- stage liver disease, the timing is crucial and
transplantation should be offered when the patient is sick enough to need a transplant but well
enough to withstand this complex operation with good chance of success. This assessment is best
carried out by a team of transplant hepatologists, surgeons and anesthetists. Hepatitis C induced
cirrhosis is rapidly becoming the commonest indication worldwide. The MELD (Model for end
stage liver disease) score based on bilirubin, INR and serum creatinine is a useful prognostic
score and is used by the organ sharing networks in the USA. For patients with fulminant liver
failure fulfilling the Kings College criteria, with intact neurological function, timely
transplantation is lifesaving
CONTRAINDICATIONS
Systemic illnesses precluding anesthesia, untreated sepsis, AIDS and extrahepatic malignancy,
non neuroendocrine liver metastases, liver angiosarcoma and cholangiocarcinoma are
considered absolute contraindications. Patients with HCC beyond the Milan criteria (> 5 cm
tumour, >3 tumours each < 3cm) have post transplant survival reduced by tumour recurrence.
HCC with tumour thrombus in the portal vein inevitably recurs. HBV DNA positive patients
have high graft loss. Porto-pulmonary hypertension, if severe, is a contraindication. Noncompliers with treatment and active substance abusers are usually not considered.
DONOR SELECTION AND PROCEDURE
The donor may be a brain-stem dead cadaver from whom the whole liver may be retrieved, or a
relative who is fit, free of liver pathology and willing to donate part of the liver. An anatomical
lobe or sector may be removed amounting to 0.8 to 1% of recipient body weight. Living donor
risk to life is estimated at <0.5% , with a 10% risk of major morbidity. The donor liver
regenerates to near normal volume.
Brain stem dead cadavers may not provide a good quality liver if they have poor hemodynamic
stability, are on high pressor doses, have fatty change, long ICU stay or prolonged starvation.
Potential brain dead organ donors require careful maintainance in ICU. Cadaver livers may be
divided along anatomical planes to reduce size for children or alternately split to provide two
grafts- a smaller left lobe for children and right lobe for small adults, either in situ or on the
bench after retrieval.
The liver is perfused with University of Wisconsin (UW) solution or Histidine-tryptophanketoglutarate (HTK) solution. The liver may preserve for upto 24 hours in UW and 15 hours in
HTK solution.
THE RECIPIENT PROCEDURE
The native liver is removed, a step that is difficult because of portal hypertension collaterals and
coagulopathy, and replaced by the donor liver, joining the vena cava, portal vein, hepatic artery
and bile duct. T-tubes or stents are occasionally employed across the biliary anastomosis. In case
of bile duct disease such as biliary atresia, a Roux loop of jejunum is used. Veno-venous bypass
is no longer considered essential. The native vena cava is left in place in all living related
transplants and also in select cadaveric transplants.
IMMUNOSUPPRESSION AND REJECTION
Only blood group matching is required for liver transplantation. Though acute rejection may
occur in up to 50% of cases, chronic rejection leading to graft loss takes place in < 5% of
transplants. Diagnosis is suspected on altered LFT and established by biopsy.
Lifelong immunosuppression is required. Modern immunosuppression centers on the use of
calcineurin inhibitors- Tacrolimus (FK 506) or microemulsified Cyclosporine A levels are
closely monitored to limit toxicity. Steroids are started in high doses and rapidly tapered. In the
majority of cases these can be stopped by 3 months post operatively. Episodes of acute rejection
are treated by pulsed steroids for 3 days. In rare cases, severe rejection requires treatment with
antilymphocytic globulin or OKT3. Mycophenolate moefetil is used as an adjunct, especially to
reduce calcineurin inhibitor dose in case of renal dysfunction.. Recently induction agents such as
anti IL2 receptor antibodies- basiliximab and daclizumab and new drugs rapamycin and
sirolimus are also being used.
POST OPERATIVE COMPLICATIONS
Primary failure of graft function is most feared- occurring in 5% of cases. The causes include
poor donor liver quality- especially steatohepatitis., preservation injury and hepatic artery
thrombosis (HAT), which almost invariably requires retransplantation. HAT occurs in 5% of
adult and 15% of pediatric transplants. Portal vein thrombosis is rarer, occurring in 2%.
Biliary complications have been called the Achilles’ heel of liver transplantation and occur in 1230% of cases. HAT may be associated with this as the artery is the main supply to the bile duct.
Corrective surgery is often required.
Liver dysfunction due to a small graft is a particular problem of living related transplant in case
of small donor graft. Failure to establish adequate venous outflow especially from middle hepatic
vein branches of a right lobe graft may lead to graft congestion .
Infections owing to immunosuppression are the common cause of morbidity and mortality.
Besides nosocomial organisms, opportunistic infections of note are cytomegalovirus (CMV)
which occurs as fever, leucopenia and colitis, hepatitis, pneumonia or meningitis after the third
week. Prophylaxis is instituted especially if the donor has previous exposure and recipient does
not. Viral and fungal infections too are common. Live vaccines should be avoided post
transplant.
Drug toxicity is a major morbidity. Calcineurin inhibitors cause hypertension, hyperlipidemia
and diabetes. High levels are nephrotoxic and may lead to tremors, neuropsychiatric changes and
rarely, convusions. Cyclosporin leads to hirsuitism and gingival hypertrophy. Mycophenolate
causes leucopenia and diarrhoea. Rapamycin leads to retarded wound healing. Drug interactions
are common and complex, requiring physicians to be careful while adding new drugs. Post
transplant lymphoproliferative disorders and skin cancers occur in up to 7% of
immunosuppressed patients.
Disease recurrence is a major issue, especially in Hepatitis C, where accelerated cirrhosis may
occur in up to 25% cases. Autoimmune hepatitis, primary sclerosing cholangiitis and tumours
may recur. Recidivism causes graft loss in alcoholics.
PROGNOSIS
Modern transplant techniques offer a one year survival of 80-90% and 5 year survival of 70-80%
for appropriately selected patients with chronic liver disease undergoing timely transplants. The
survival for fulminant liver failure is marginally lesser. Living related and cadaver transplant
have similar survival rates.
Table: Indications for liver transplantation
Hepatitis C cirrhosis
Hepatitis B cirrhosis
Alcoholic liver disease
Cholestatic liver disease
Primary sclerosing cholangiitis
Biliary cirrhosis- primary and secondary
Autoimmune liver disease
Budd-Chiari syndrome
Metabolic disorders:
Wilsons disease
Haemochromatosis
Oxalosis
Alpha 1 antitrypsin deficiency
Erythropoetic porphyria
Hypercholesterolemia
Familial amyloid polyneuropathy
Liver space occupying lesions:
Polycystic disease
Multiple adenomatosis
Caroli’s disease
Fulminant liver failure
Viral hepatitits (B, A, E)
Drug toxicity
Paracetamol overdose
Halothane
Wilson’s disease
In children:
Biliary atresia
Progressive familial intrahepatic cholestasis
Metabolic disorders incl Criggler Najjar syndrome, Urea cycle disorders
Unresectable hepatoblastoma
RECOMMENDED READING
Humar A. Manual of liver transplant medical care. Minneapolis: Fairview Press 2002. 72 page
monograph on post operative management
Busuttil RW, Klintmalm GB (eds). Transplantation of the Liver. 2nd ed.: WB Saunders 2005.
Comprehensive book on all aspects of the subject.
HYPERLINK
"http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlu
s&list_uids=15062657&query_hl=13&itool=pubmed_docsum" Tanaka K, Kiuchi T, Kaihara S.
Living related liver donor transplantation: techniques and caution. Surg Clin North Am.
2004;84:481-93. A summary of the technique and pitfalls of living donor transplant by one of the
pioneers.
Rela M, Dhawan A. Liver transplantation in children. Indian J Pediatr 2002;69:175-83. Review
of indications, techniques and prognosis in children.
Sutcliffe R, Maguire D, Portmann B, Rela M, Heaton N. Selection of patients with hepatocellular
carcinoma for liver transplantation. Br J Surg 2006;93:11-8. Detailed review of transplantation
for hepatocellular cancer
HYPERLINK "http://www.eltr.org" www.eltr.org
Website of the European liver transplant
registry giving data on indications, survival and evolution of transplantation