Causes Of Liver Failure
Currently, approximately 85% of liver transplants in the UK are undertaken in adults, the remainder in children. Most (85%) are for chronic liver disease, with only a few for acute liver failure.
Chronic liver disease
Cirrhosis develops as a result of a (usually chronic) insult to the liver, which causes inflammation and liver cell damage, with resultant scarring and regeneration. The common causes of cirrhosis for which liver transplantation is performed are shown in Figure 33. Cirrhosis has four main consequences.
Hepatocellular failure manifests in three ways.
1. Impaired protein synthesis, best monitored by the prothombin time (or its ratio to an international normal value, the INR) and serum albumin. Progressive liver disease results in prolongation of the prothrombin time and a fall in serum albumin concentration. It also results in malnutrition, which may prejudice recovery from transplantation.
2. Impaired metabolism of toxins results in encephalopathy, char- acterised by confusion, somnolence, a ‘flapping’ hand tremor and coma.
3. Impaired in jaundice.
Portal hypertension is a consequence of the cirrhotic distortion of the liver’s architecture, which impedes the passage of portal venous blood, so raising the pressure in the portal circulation. As portal hypertension develops new collateral channels develop, draining blood from the portal to systemic venous system, along the peritoneal attachments of the liver, the ligamentum teres (the obliterated umbilical vein, which reopens in the presence of portal hypertension) and as varices alongside the gastrooesophageal junction. The collateral vessels around the liver, as well as the abnormal clotting cascade, account for much of the bleeding asso- ciated with transplantation of the liver.
Ascites is also consequence of portal hypertension and warrants transplantation if it is resistant to standard treatment with diuretics.
Hepatocellular carcinoma (hepatoma)
The chronic inflammatory processes of different aetiologies that lead to cirrhosis also can result in hepatoma formation, particularly when associated with viral infection such as hepatitis C. Because the liver is cirrhotic, insufficient functioning liver would remain if the liver lobe containing tumour was resected, so transplantation is the principle curative treatment. However, very large tumours, or multiple tumours, are less likely to be curable so access to transplantation is restricted to patients with solitary tumours under 5 cm in diameter or, if multiple, no more than three tumours each no greater than 3 cm in diameter – these criteria may vary from country to country.
Other liver tumours, such as cholangiocarcinoma, hepatoblastoma and metastatic neuroendocrine tumours, are associated with early recurrence and are not suitable indications for transplantation.
Clinical features of liver disease which warrant assessment for transplantation
Five clinical features suggest liver transplantation may be required.
1. Jaundice in the context of end-stage liver disease.
2. Intractable ascites (i.e. resistant to treatment).
3. Recurrent or refractory hepatic encephalopathy.
4. Breathlessness due to hepatopulmonary syndrome.
5. Intractable pruritis.
Who to list?
Since donor livers are in short supply it is usual not to offer a transplant to someone whose anticipated life expectancy after a liver transplant is short, and in the UK patients would be expected to have a 50% chance of surviving 5 years following liver transplantation.
When to list?
Assimilating biochemical data can indicate when a patient with chronic liver disease is at a point when transplantation is neces- sary, that is when their risk of death without a transplant is greater than that with a transplant; to this end a number of predictive equations based on serum bilirubin, INR and renal function have been developed, such as the Model for End-stage Liver Disease (MELD) and the equivalent UK model (UKELD) (see Figure 33). A MELD over 18, or UKELD ≥ 49 are taken as indications for transplantation, since at this point the survival following liver transplantation exceeds that without transplantation (9% mortal- ity at 1 year if UKELD = 49).
Acute liver failure
Liver transplantation is indicated as an emergency treatment for patients with unrecoverable acute liver failure. However, the low availability of donor livers means that one in three patients dies while waiting.
Assessing when to list a patient with acute liver failure can be difficult, and reliance is placed on factors that are known to predict poor outcome without transplantation. The Kings College criteria for predicting non-recovery in acute liver failure, and therefore indicating transplantation, are one such example. They are as follows.
· Arterial pH <7.3
· Grade III or IV encephalopathy and
· Prothrombin time >100 s (INR > 6.5) and
· Serum creatinine >300 µmol/L
Non-paracetamol acute liver failure
· Prothrombin time >100 s (INR > 6.5) or any three of
· Age <10 or >40 years
· Aetiology non-A, non-B; halothane hepatitis; idiosyncratic drug reaction
· Duration of jaundice before encephalopathy >7 days
· Prothrombin time >50 s (INR > 3.5)
· Serum bilirubin >300 µmol