Orthotopic Liver Transplantation (OLT)
Discuss OLT?
The first human liver transplants were carried out by Starzl in 1963 but it was 4 years before there was a long term survivor. Operative techniques and anaesthetic care were optimised and the transplant numbers rose during 1980-90 achieving survival rates of 80-90% at 1 year in low risk patients. Survival rates now in all patients are 86% at 1 year and 76% at 3 years post OLT.
Discuss the indications for liver transplantation?
Liver transplantation is indicated for acute or chronic liver failure from any cause.
- Chronic Liver Disease (60%) – consider OLT when survival predicted < 2yrs
- Refractory ascites, hepatic encephalopathy, variceal bleeding
- Spontaneous bacterial peritonitis
- Poor quality of life in cholestatic liver disease (severe fatigue, pruritis)
- Child-Pugh, MELD (<9 = 4% 3 month mortality, >30 = 83% 3 month mortality) and UKELD scoring
- Malignancy (10%)- HCC-Optimal results are achieved in patients with a single lesion 2 cm or larger and less than 5 cm, or no more than three lesions, the largest of which is less than 3 cm, and no radiographic evidence of extrahepatic disease
- Acute Liver Failure (5-10%)
- In the UK the most common cause is Paracetamol OD
- Cholestasis (10-15%) PBC/PSC
Discuss how the need/timing for liver transplantation is determined?
- Transplantation should be considered when it offers better survival that the natural history of the patient’s disease. The clinical tools most widely used to determine prognosis in patients with chronic liver diseases include disease-specific indices for PBC/PSC, the Child-Turcotte-Pugh (CTP) classification, the prognostic model for end-stage liver disease (MELD), as well as the impact of specific complications of cirrhosis on patient survival.
- More than one third of patients with CTP scores of 10 or more (class C) who are waiting for transplantation can be expected to die within 1 year. In contrast, patients with CTP scores of 7 to 9 (class B) have an 80% chance of surviving 5 years without transplantation. Current survival rates 1, 3, and 5 years after liver transplantation in the United States are 88%, 80%, and 75%, respectively. As a result, patients with a MELD score of 15 or more and a CTP score of 7 or more can be expected to achieve improved survival with liver transplantation.
- Patients with cirrhosis should be referred for transplantation when they develop evidence of hepatic dysfunction (CTP > 7 and MELD > 10) or when they experience their first major complication (ascites, variceal bleeding, HRS, SBP or hepatic encephalopathy). Patients with type I hepatorenal syndrome and severe hepatopulmonary syndrome should have an expedited referral for liver transplantation.
- The 5-year survival rate of individuals in whom any of these complications develop is only 20% to 50% of patients with compensated cirrhosis. Less than half of those in whom spontaneous bacterial peritonitis develops can be expected to survive 1 year.
Discuss the pre transplant assessment?
The typical evaluation of potential transplant recipients performed at most transplant centers includes:
- Careful history and physical examination;
- Cardiopulmonary assessment, including cardiac echocardiography, pulmonary function tests, dobutamine stress testing, and cardiac catheterization in selected patients;
- Laboratory studies to confirm the aetiology and severity of liver disease;
- Creatinine clearance;
- Laboratory studies to determine the status of current or previous hepatitis B virus (HBV), hepatitis C virus (HCV), Epstein-Barr virus, cytomegalovirus, and human immunodeficiency virus (HIV) infections; and
- Abdominal imaging to determine hepatic artery and portal vein anatomy and the presence of hepatocellular carcinoma (HCC).
NB- Chronic smokers, patients over the age of 50, and those with a clinical or family history of heart disease or diabetes should undergo evaluation for coronary artery disease.
Dobutamine stress echocardiography is used as a screening test; however, positive test results should be confirmed with cardiac catheterization.
Discuss King’s College criteria for liver transplantation in acute liver failure?
Paracetamol
- Arterial pH < 7.3 after aggressive rehydration + NAC
OR
- All of the following
- PT > 100s
- Creat > 300µmol/l
- Grade III or IV encephalopathy
Non-paracetamol
- PT > 100s, INR > 6.7
OR
- Any 3 of the following
- Aetiology – halothane hepatitis, drug reaction, seronegative hepatitis
- Age < 10, > 40 years
- PT > 50, INR > 4.0
- Serum bilirubin > 300µmol/l
Discuss the contraindications for liver transplantation?
- Morbid obesity (BMI>40)
- Portal vein occlusion is associated with increased risk of perioperative mortality and graft loss. Thrombosis of the main portal vein can be successfully bypassed; however, if the entire portal venous system is occluded , attempts at transplantation are associated with a high risk of graft loss and perioperative mortality
- HIV is not a contraindication, however Liver transplantation in patients with HIV infection requires a well-coordinated, multidisciplinary team with expertise both in transplantation and HIV management
- Patients with severe pulmonary hypertension (systolic pulmonary artery pressure, >60 mmHg) should be considered for liver transplantation only if the condition can be effectively controlled with medical therapy. All patients undergoing evaluation for potential liver transplantation should undergo screening for pulmonary hypertension.9. Doppler echocardiography is an excellent screening test in this setting.
- Continued destructive behavior resulting from drug and alcohol addiction. Any form of addictive behavior also should be addressed and be well controlled before patients are accepted for transplantation.
- There is no specific age limitation to successful liver transplantation.
- Extra hepatic malignancy
- Advanced cardiopulmonary disease
Discuss the types of graft?
- Whole cadaveric graft – majority of patients
- Split-liver graft – commonly an adult gets the right lobe and a child gets the left lobe
- Auxillary liver – donor liver is implanted next to part or all of native liver in the hope that it will regenerate
- Live-related transplantation – liver lobe donation from a family member
Discuss the post-transplant complications?
- Rejection
- Hyperacute – antibody and complement-mediated reaction with massive hepatic necrosis < 10 days post OLT. Requires urgent retransplantation
- Acute – occurs in 30-70% of patients 7-9 days post OLT. Diagnosed on liver biopsy. Usually responds well to high dose immunosuppression
- Chronic – progressive bile duct loss with fibrosis and cholestasis. Usually results in graft failure. Associated with previous acute rejection, CMV and HCV recurrence
- Problems with the vessels
- Hepatic artery, portal vein or vena cava thrombosis
- Anastomotic leak and haemorrhage
- Biliary anastomotic leak + strictures
- Drug effects
- Tacrolimus commonly can cause confusion in toxicity and is nephrotoxic
- Infection
- Commonly bacterial or viral
- Viruses to beware of – CMV, Epstein-Barr, Herpes Simplex, Parvovirus, Adenovirus and Varicella Zoster
- Disease recurrence
- Reinfection with HCV is universal – can lead to accelerated cirrhosis & graft loss
- HBV reinfection can be limited/prevented by HBV treatment + using HBIg (Hepatitis B immunoglobulin)
- 20-30% patients transplanted for alcoholic liver disease return to drinking
- Autoimmune hepatitis, primary sclerosing cholangitis + primary biliary sclerosis may also return
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