Preoperative assessment of hepatic function

4 Preoperative assessment of hepatic function LEO STRUNIN

Anaesthesia and surgery in patients with overt, or more particularly, unrecognized liver disease may lead to tragic consequences postoperatively. These result partly from the capacity of the liver to undergo extensive damage before a patient manifests any clinical signs or there are significant changes in the liver function tests, and also, even when liver damage is overt, the difficulty in estimating hepatic reserve. The liver is at the centre of most body processes, by virtue of its metabolism of carbohydrates, lipids, proteins, hormones and vitamins as well as its storage and excretory functions, and can respond to injury in a number of ways. The hepatic cells may be damaged chronically or acutely, there may be obstruction to blood or bile flow, or primary hepatoma (hepatocellular carcinoma) of the liver may occur. In addition the liver may be infected, most commonly with viruses, and may be the site of secondary deposits from malignancies elsewhere in the body. Congenital abnormalities of the vascular and biliary systems may be present at birth or manifest themselves in early childhood. Because of this variety many liver function tests and procedures have evolved. There is rarely one test alone that is diagnostic in any particular disease and in addition false positive and negative results occur. As a result, it is common to carry out batteries of tests as well as repeated estimations. For example, the combination of an increased plasma concentration of bilirubin, an elevated plasma concentration of aspartate aminotransferase (AST) or alanine aminotransferase (ALT), and an elevated plasma concentration of alkaline phosphatase (ALP) has a predictive accuracy for the presence of liver disease of over 90% (Henry et al, 1985). Another important point when comparing results from different institutions is to be aware of interlaboratory variations. All biochemistry laboratories publish their normal ranges and these should be taken into account when assessing results from different laboratories. Traditional liver function tests such as those outlined in Table 1 may be misleading in giving a sense of completeness. They are useful from a screening point of view as well as having some diagnostic and quantitative value, but they should be used in combination with a careful history, with specific questions concerning drug and alcohol intake, and exposure to the risk of viral and other infections, as well as clinical examination of the patient. In this respect it is important to remember that liver disease, depending on the cause, often involves other organs in the body. In Bailli~re's Clinical Anaesthesiology--

Vol. 6, No. 4, December 1992 ISBN 0-7020-1736-1

781 Copyright 9 1992, by Bailli6re Tindall All rights of reproduction in any form reserved

782

L. STRUNIN Table 1. Liver function tests.

Test

Normal range

If abnormal may indicate:

Aspartate aminotransferase Alanine aminotransferase Alkaline phosphatase ~/-Glutamyl transpeptidase Serum albumin Prothrombin time Serum bilirubin: Total

10--40 U/litre 10-37 U/litre 35-100 U/litre 11-64 U/litre 30-44 g/litre 1-1.3 INR

HepatoceUular damage/necrosis Hepatocellular damage/necrosis Cholestasis Alcohol- or drug-related damage Decreased synthetic function Decreased synthetic function

4-17 i~mol/litre

Unconjugated 5'-Nucleotidase Total serum bile acids Serum iron

< 0.3 ixmoFlitre 1-18 U/litre 0--6 i~mol/litre 8--31 i~mol/litre

Assessment of jaundice/primary biliary cirrhosis Gilbert's disease Cholestasis Cholestasis/portosystemic shunt Increased ferritin and transferritin suggests haemochromatosis

Transferritin saturation Ferritin Ceruloplasmin

<50% 10-250 I~g/litre 1.1-2.9 iLmol/litre

Serum copper Ctl-Antitrypsin a-Fetoprotein

11-24 i~mol/iitre 25--64 i~mol/litre < 0.29 nmol/lkre

J

.

Low with low copper suggests Wilson's disease Low in deficiency disease Increased in hepatoma

particular, renal function may be impaired, there may be primary myocardial damage as seen in alcoholic patients or secondary effects due to chronic right atrial back pressure in any patient with cirrhosis, pulmonary dysfunction is common, and encephalopathy accompanies the later stages of hepatic decompensation. Minor asymptomatic changes in liver function tests are not uncommon (Schemel, 1976; Hulcrantz et al, 1986). Many of these patients are obese, have increased alcohol consumption and diabetes mellitus is a common finding. A liver biopsy is the best method of determining the diagnosis and usually reveals a significant number of patients with either chronic active hepatitis or cirrhosis. In such patients, i.e. with compensated liver disease, the most likely outcome following anaesthesia and surgery is that there will be no major detrimental changes in hepatic function except for those related to the extent of the operation or any other extraneous factors such as blood transfusion, unplanned hypoxia or hypotension. From the anaesthetist's point of view, liver disease in relation to operations may be divided into three broad categories, although there is obvious overlap: firstly, the patient who presents for cholecystectomy with or without jaundice (cholestasis), secondly, those with chronic liver disease (cirrhosis) (see Chapter 7), and third, patients with an hepatic tumour either primary (hepatoma) or a secondary deposit and those with hepatic trauma (see Chapter 8). In all categories liver function tests and investigative procedures will help to arrive at a diagnosis. More important for the anaesthetist is the ability to assess whether the patient's condition can be improved, and thus the operation should be delayed, and to make some estimation of hepatic reserve. Until the advent of liver transplantation,

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783

acute liver failure was an obvious contraindication for anaesthesia except in an emergency. Experience with transplantation has shown that patients with acute liver failure can survive, although the result is obviously dependent on a good functioning transplant.

LIVER FUNCTION TESTS AND DIAGNOSTIC PROCEDURES Table 1 shows some common liver function tests and their usefulness in diagnosing various liver diseases. The plasma albumin concentration is related to the synthetic capacity of the liver. In chronic liver disease the albumin concentration is reduced and globulin concentration may increase. Globulins are produced in the reticuloendothelial system, including the liver, and their concentration increases in many forms of autoimmune liver disease. A reduced albumin concentration may enhance the action of drugs which are highly protein bound, allowing an increase in the unbound fraction of the drug. The prothrombin time--given in seconds as compared with a control, but now often expressed as an International Normalized Ratio (INR) i.e. 1 where there is no abnormality--is an important measurement in patients with both hepatic and biliary tract disease. In the latter, if there is biliary obstruction, the fat-soluble vitamin K cannot be absorbed from the normal diet via the gut because of a lack of bile salts and this results in deficiencies of plasma clotting factors II, VII, IX and X. Parenteral vitamin K should restore the INR and clotting factors to normal. However this may require some 12-24 h of repeated intramuscular injections to be effective. In the presence of hepatocellular disease it may be impossible to return the INR to normal by the administration of vitamin K because the clotting abnormalities are the result of failed synthesis. In this circumstance infusion of fresh frozen plasma will correct the abnormalities temporarily, e.g. for liver biopsy, although the risk of viral and other infections as well as sodium and fluid overload should be considered. When the bilirubin concentration exceeds 20 i~mol/litre jaundice will be evident on clinical examination of the patient. Since many causes of jaundice are not amenable to surgical treatment it is essential that a diagnosis be made before laparotomy is undertaken. In the presence of extrahepatic biliary obstruction, conventional intravenous cholangiography will not produce adequate images. Ultrasound is the major imaging technique used to determine the pathway for further diagnostic tests or therapeutic manoeuvres in the management of cholestasis. Further procedures include angiography, endoscopic retrograde cholangiopancreatography (ERCP) and papillotomy, percutaneous transhepatic cholangiography (PTC) computed tomography (CT) and magnetic resonance imaging (MRI). PTC, CT scanning and MRI in combination with ultrasound should determine the site and cause of biliary obstruction. Unnecessary diagnostic laparotomies should be a thing of the past, since the morbidity and mortality associated with such procedures, particularly in decompensated patients, is high

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L. STRUNIN

(Aranha et al, 1982; Powell-Jackson et al, 1982; Dobaneck et al, 1983; Aranha and Greenlee, 1986). Many enzymes (Table 1) are present within liver cells and take part in the normal metabolic processes. In liver disease these enzymes are released into the blood stream in increased amounts and measurement of them in plasma may be helpful in determining the cause of the hepatic dysfunction. The plasma concentrations of the aminotransferases AST and ALT are raised in the presence of hepatocellular damage and necrosis. However, these enzymes are present in all body cells and leak into the plasma when any cell is damaged. For example, after trauma, myocardial infarct or operations elevated aminotransferase concentrations will occur. However, these causes are usually easy to differentiate from liver damage and it is unusual to observe very high or prolonged elevations other than in liver disease. Many other enzymes have been studied to try and identify one that is specific to the liver and only increases when that organ is damaged. Recently attention has focused on plasma glutathione-S-transferase (Hussey et al, 1988; Murray and Trinick, 1992), which has been used to determine differences between the hepatocellular effects of volatile and intravenous anaesthetics. ALP is raised in the presence of biliary obstruction (cholestasis). ~/-Glutamyl transpeptidase (-r concentration increases in the presence of alcohol- or drug-related liver damage (Gluud et al, 1981). Although enzyme assays may be helpful for screening for liver damage or disease or for diagnostic purposes, they have little value in the estimation of hepatic reserve. Indeed in acute liver failure, although the initial concentration of aminotransferases may be high, a sudden fall in concentration may signal total liver cell failure rather than recovery. A number of other measurements may be helpful in determining the cause of liver dysfunction. For example, the serum a-fetoprotein concentration will be raised in 70-90% of patients with primary carcinoma of the liver (hepatoma). Measurement of et-fetoprotein concentration is also useful postoperatively after resection of hepatomas to determine the success of the surgery. Blood ammonia is raised in patients with acute liver failure but is not helpful in determining the cause. In patients with primary biliary cirrhosis 90% will have antimitochondrial antibodies present in their serum. In patients with Wilson's disease, an inherited disorder of copper metabolism, ceruloplasmin and copper concentrations will be low and there will be increased copper excretion. Increased ferritin and transferritin concentrations are suggestive of haemochromatosis. Finally, needle biopsy of the liver, either percutaneously or by laparoscopy, is a major diagnostic tool for determining various forms of cellular liver disease. Haemorrhage is the major risk of biopsy and this procedure should only be undertaken if the INR and platelet count are normal. Viral hepatitis is a common cause of liver disease and serological screening should be carried out routinely before operation, Patients in high risk groups should also be considered at risk for co-infection with acquired immune deficiency syndrome (AIDS). Legislation varies around the world concerning permission for serological screening for AIDS. However, even if screening for viral hepatitis and AIDS is performed, negative tests do not

PREOPERATIVE ASSESSMENT OF HEPATIC FUNCTION

785

rule out all potentially infectious patients. Therefore the World Health Organization recommendations that all patients be considered a risk for health care personnel should be observed, and appropriate precautions with regard to needle sticks and contact with body fluids should be followed. CHOLESTASIS Cholecystectomy to remove gall stones is one of the most commonly performed operations and in uncomplicated cases has a low mortality (< 1%). Assessment in such cases is straightforward. The gall stones are identified by imaging, and provided the INR is normal, the ALP is not elevated and no other disease states are identified such patients are very suitable for laparoscopic cholecystectomy. However, morbidity and mortality may increase dramatically if there is to be exploration of the common bile duct or if there is pre-existing sepsis, malignancy, diabetes, anaemia or jaundice (Pitt et al, 1981; Dixon et al, 1983; Pain et al, 1985). Jaundice is the clinical observation of a yellow colouring of the sclerae and skin which occurs when the bilirubin concentration in the plasma exceeds some 20 ~mol/litre. Jaundice results from cholestasis and may be classified according to mechanism: increased bile pigment production, defective uptake and transport within the hepatocyte, defective conjugation, or defective excretion. In practice it may be difficult to differentiate these mechanisms clearly. The liver's capacity to handle bile pigment may increase considerably. Even in chronic haemolytic diseases the serum bilirubin concentration rarely exceeds 50 p~mol/litre. In Gilbert's disease, the commonest variety of familial, unconjugated, non-haemolytic hyperbilirubinaemia, the bilirubin concentration also rarely exceeds 50 ixmol/litre. These causes of jaundice are not contraindications to anaesthesia and surgery but there may be a temporary rise in bilirubin concentration postoperatively in such patients. Defective conjugation by hepatic microsomes may result from two mechanisms: enzyme deficiency, such as is found in neonatal or 'physiological' jaundice and in the very rare, usually fatal, Crigler-Najjar hyperbilirubinaemia, or enzyme inhibition, when a factor in maternal serum, probably a pregestational steroid, may inhibit glucuronyltransferase and cause neonatal jaundice. Bilirubin is unconjugated in both situations and so does not appear in the urine. Defective excretion may occur either within the bile canaliculi and small ducts within the liver, i.e. intrahepatic cholestasis, or in the main bile ducts between the liver and the duodenum, i.e. extrahepatic obstruction. Intrahepatic cholestasis may occur as a result of widespread hepatocellular damage, such as in viral or alcoholic hepatitis or macronodular cirrhosis, and in these instances the serum bilirubin concentration may be dramatically reduced by steroid therapy. A cholestatic picture may be seen in patients with the Dubin-Johnson syndrome (familial conjugated hyperbilirubinaemia) which may be enhanced by ictogenic steroids (such as methyltestosterone or norethanandrolone). Cellular reactions around the ductules and intralobular ducts may occur as a result of drug sensitivity due,

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for example, to the phenothiazine group of drugs. Inflammatory reactions around the intralobular and septal bile ducts occur in primary biliary cirrhosis (PBC) and biliary atresia, and similar reactions around still larger ducts occur in ascending cholangitis. Extrahepatic obstruction in large bile ducts may result from gall stones, strictures, carcinomas of the bile duct and carcinoma of the head of the pancreas. Hyperbilirubinaemia in both the intra- and extrahepatic obstructive type is predominantly conjugated and is accompanied by bile in the urine. Unconjugated hyperbilirubinaemia may occur later, firstly because there is invariably a decrease in red cell survival in obstructive jaundice and secondly because conjugation becomes defective. From the anaesthetist's perspective, apart from cholecystectomy, the majority of adult patients (see Chapter 9 for discussion of paediatric patients) presenting with cholestasis will have extrahepatic obstructions amenable to operative relief. As indicated above, the site of obstruction must be elucidated before operation. Diagnostic laparotomy in patients with liver disease has a high complication rate (Powell-Jackson et al, 1982). An additional feature of long-standing biliary obstruction is infection of the biliary tree. Endotoxin may be found in the systemic circulation and be responsible for renal failure postoperatively (Bailey, 1976). When the serum bilirubin concentration is above 140 ixmol/lhre the following steps may be taken preoperatively to avoid postoperative renal failure (Pain et al, 1985). Percutaneous drainage of the biliary tree by a cannula inserted via the gall bladder or a biliary radicle will reduce the bilirubin concentration. This procedure may cause a hydropneumothorax so all patients should have a preoperative chest radiograph. Appropriate antibiotic therapy will reduce the endotoxin load on the liver. Fluid balance and nutrition are commonly disturbed in patients with long-standing cholestasis and should be corrected. In all jaundiced patients parenteral vitamin K should be given to correct the INR to normal. Anaemia is an additional risk factor and should be corrected preoperatively (Pain et al, 1985). CHRONIC LIVER DISEASE (CIRRHOSIS)

Cirrhosis is a pathological term indicating scarring of the liver and should be distinguished from hepatitis which indicates infection of the liver which is more consistent with an acute episode. Pathologists also describe chronic active and active chronic hepatitis; these are histological diagnoses related to autoimmune processes and viral infections. It should be noted that excess alcohol intake is the commonest cause of cirrhosis. Chronic liver disease often produces little alteration in liver function and may be clinically and biochemically undetectable. Only when some additional insult, often iatrogenic, produces further deterioration in liver function does the underlying liver disease become clinically obvious as jaundice, ascites or encephalopathy. Therefore the natural history of chronic liver disease is not necessarily one of progressive deterioration, and with careful management, avoiding the precipitation of complications, patients may be kept well for many years.

PREOPERATIVE ASSESSMENT OF HEPATIC FUNCTION

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Cirrhosis is not a single entity and the characteristic pathological changes of necrosis, fibrosis and regeneration nodules may result from many aetiological factors. In addition there may be histological features specific for certain diseases. The size of the liver is very variable, ranging from shrunken to very large, and may change during the course of the disease. However, there is always an increased resistance to the flow of blood in the portal venous system (portal hypertension), resulting eventually in congestive splenomegaly and collateral venous channels manifesting as oesophageal and gastric varices. A late complication of cirrhosis, particularly when due to viral hepatitis, is the development of primary liver cell carcinoma (hepatoma). Compensated chronic liver disease is compatible with a complete feeling of well-being and when symptoms do occur they are usually vague, such as malaise, dyspepsia, weight loss, loss of libido and menstrual disturbances. Physical signs are also often absent and many of the skin changes described in cirrhosis, such as white spots, paper money skin, white nails and palmar erythema, have little diagnostic value. Finger clubbing and cyanosis are occasionally seen, but are non-specific. Generalized pigmentation may indicate haemochromatosis or PBC. One of the most useful physical signs of cirrhosis is the presence of spider naevi on the skin of the face, arms and upper torso. They may occur transiently in pregnancy and viral hepatitis, but are particularly florid in alcoholic cirrhosis and chronic active hepatitis. Chronic liver disease characteristically produces evidence of a high output circulatory state, with flushed extremities, dilated veins, capillary pulsation and a collapsing pulse. Although arteriovenous fistulae in the lungs have been demonstrated in liver disease and may account for some of the changes, e.g. finger clubbing, the more likely explanation is that a vasodilator substance is either produced by, or not inactivated by, the damaged liver. In cirrhosis, the proportion of blood supply derived from the portal vein diminishes gradually and there is a relative increase from the hepatic artery. Thus the effects of portacaval anastomosis on the blood supply to the liver is less marked in the cirrhotic patient, but the effects of systemic hypotension and hypoxaemia are more marked. Since the regeneration nodules are mainly supplied by arterial blood, systemic hypoxaemia may result in severe liver necrosis. These regeneration nodules progressively distort the portal venous system with a consequent rise in portal venous pressure and the development of collateral channels bypassing the liver, splenomegaly and hypersplenism. A palpably enlarged liver is mainly associated with alcoholic cirrhosis or haemochromatosis, whereas a shrunken liver is more likely with cryptogenic cirrhosis. The cirrhotic liver is firm and it may be possible to detect irregularities on the surface in the macronodular type. Splenomegaly and venous collaterals on the abdominal wall are good indicators of portal hypertension. In the later stages of chronic liver disease there may be progressive water retention, hyponatraemia, azotaemia and oliguria due to reduced renal plasma flow, leading to the 'hepatorenal syndrome'. Signs which suggest that chronic liver disease has become decompensated include jaundice, oedema, ascites, a flapping tremor and other signs of impending hepatic

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coma. A change in size or shape of the liver may indicate a hepatoma. Patients with cirrhosis most commonly present for surgery unrelated to their liver disease. It has been estimated that of the 21 million anaesthetics administered per year in the United States, some 11 000 will be given to patients with alcoholic cirrhosis (Mezey, 1982). A few patients will require management of bleeding oesophageal varices and those in end-stage liver disease may be assessed for transplantation. Regardless of the cause of the cirrhosis, the most useful information for the anaesthetist is an estimation of hepatic reserve and thus by inference the risk associated with operation. Tables 2 and 3 outline the schemes developed by Child and Turcott (1964) and Pugh and his colleagues (1973) which allocate a score in relation to outcome. Although these scores may seem self-evident and not amenable to change, they may be helpful in making decisions about elective surgery (Alber et al, 1989). However, where an operation cannot be postponed, other investigations such as the aminopyrine breath test may be more helpful (Gill et al, 1983; Henry et al, 1985). It is by no means clear whether the many other assessments of liver function in patients with cirrhosis or cholestasis and after liver transplantation are helpful in predicting risk for anaesthesia anffsurgery (Garrison et al, 1984; McPherson et al, 1985; Cuervas-Mons et al, 1986; Stock et al, 1987; Schenker et al, 1990). The Child/Turcotte and Pugh classifications are easy to apply, do not require sophisticated laboratory facilities and are commonly used at present. In general only patients in Child/Turcotte group A should be recommended for elective operation. Those in group B may be acceptable but every effort should be made to correct abnormalities in nutrition to raise the plasma albumin and to correct anaemia and clotting abnormalities.

Table 2. Clinical and laboratory classification of patients with cirrhosis in terms of hepatic

functional reserve (Child and Turcotte, 1964). Group A

Group B

Group C

Serum bilirubin 0xmol/litre) Serum albumin (g/litre) Ascites Neurological disorder Nutrition

< 40 > 35 None None Excellent

40-50 30-35 Easily controlled Minimal Good

> 50 < 30 Poorly controlled Advanced coma Poor, wasting

Risk of operation

Good (5%)

Moderate (10%)

Poor (50%)

Table 3. Grading of severity of liver disease (Pugh et al, 1973).

Points scored for increasing abnormalities Clinical and biochemical measurement

1

2

3

Encephalopathy (grade) Bilirubin (~mol/litre) Albumin (g/litre) Prothrombin time (seconds prolonged)

None < 25 35 1--4

1 and 2 25-40 28-35 4--6

3 and 4 >40 < 28 >4

4--6 points = Child group A; 7-9 points = Child group B, 10-12 points = Child group C.

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789

Those in group C should only be considered for emergency operation, and sedation rather than general anaesthesia used for injection sclerotherapy if possible.

Portal hypertension It is assumed that patients with decompensated liver disease (Pugh 10-12 points--Table 3) will not be subjected to elective surgery. However, such patients may have to be anaesthetized for management of a complication of their cirrhotic process. Gastrointestinal haemorrhage in association with oesophageal varices, portal hypertension and chronic liver disease is often a dramatic event. Clearly if liver cell damage is extensive, haemorrhage may be a terminal event. Nevertheless, if bleeding can be controlled and the cause of the liver disease is reversible or can be arrested then the prognosis may not be hopeless. In patients who can be persuaded to abstain, where alcohol is the cause, the 5-year survival rates show an improvement over those who persist in drinking alcohol. In the past, portacaval anastomosis or other portosystemic shunts were carried out. There is no data to show clearly that any shunting procedures prolong the patient's life expectancy. Indeed, for many the operative and immediate postoperative mortality was extremely high. Patients in category B and C as described by Child and Turcotte (1964) are obviously at great risk, More recently injection sclerotherapy of oesophageal and gastric varices has been used to control haemorrhage. Initial treatment of oesophageal variceal haemorrhage includes fluid and blood transfusion, airway management, early endoscopy to establish the site of haemorrhage and sclerotherapy. Most centres still use short-term mechanical compression with the Sengstaken-Blakemore tube and some intravenous administration of vasopressin, which reduces portal vein pressure by splanchnic vasoconstriction but may be associated with coronary artery vasoconstriction; this may be offset by infusion of glyceryl trinitrate (Grossman et al, 1982; Lanza et al, 1982). Somatostatin infusion may be as effective as injection sclerotherapy in controlling acute variceal haemorrhage and also in preventing recurrent bleeding over a five-day period (Shields et al, 1992). Octreotide, a somatostatin analogue, is currently undergoing clinical trials and shows great promise (Jenkins and Baxter, 1993). The current results of oesophageal sclerotherapy are encouraging and in some series have shown a possible prolongation of life span. If the preoperative evaluation determines that vitamin K therapy or fresh frozen plasma are indicated, these should be given preoperatively. Patients who are on steroid therapy for the management of chronic liver disease may require additional steroids with their premedication. The use of 1-12antagonists is helpful in reducing the risk of gastrointestinal haemorrhage. The presence of oesophageal varices should be considered when passing nasogastric tubes. Clearly if there is compromised clotting ability then particular care should be taken with invasive monitoring and tracheal intubation. All patients with chronic liver disease should be considered as potential carriers of viral hepatitis.

790

L. STRUNIN

THE LIVER IN PREGNANCY

Liver function is not greatly altered during pregnancy. Although cardiac output during pregnancy may increase by 35%, liver blood flow remains constant. The majority of liver enzymes remain within normal limits during pregnancy; however, there may be an increase in ALP which reflects placental and fetal production. The serum albumin concentration falls mainly secondary to haemodilution. If biopsied, the liver has a normal appearance during pregnancy. Liver disease in pregnancy may be classified as that specific to pregnancy, liver disease aggravated by pregnancy, and liver disease concurrent with pregnancy. The liver diseases specific to pregnancy include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy. In toxaemic patients spontaneous hepatic rupture (Baska and Waxman, 1976; Herbert, 1986) may occur or there may be development of the HELLP syndrome---haemolysis (H), elevated liver enzymes (EL) and low platelets (LP) (Weinstein, 1982). Epidural anaesthesia is a recommended method for controlling hypertension in toxaemic patients. Apart from development of the HELLP syndrome, there may be a fall in platelet concentration alone. A low platelet count (< 100 000) is a contraindication for epidural anaesthesia. Hyperemesis has been associated with jaundice during pregnancy. Biopsy of the liver reveals normal histology in most patients, but some show fatty changes. It is important in these patients to rule out the presence of viral or drug-induced hepatitis. Cholestasis of pregnancy is a mild self-limited disease of unknown aetiology. Typically, the patient will present with pruritus, frequently the most severe symptom, and jaundice during the third trimester. Diagnosis is made by laboratory findings of elevated conjugated bilirubin and ALP concentrations with normal or slightly increased serum aminotransferase concentrations. Generally, these changes will regress rapidly after delivery. Where liver biopsies have been performed, a mild intrahepatic cholestasis has been found. Therapy consists of reassurance, cholestyramine for relief of the pruritus and intramuscular vitamin K if there is evidence of clotting abnormalities. Acute fatty liver of pregnancy is a rare but frequently fatal disease which usually presents in the third trimester of pregnancy. This disorder starts with mild constitutional symptoms of fatigue, nausea and vomiting; however, it is rapidly followed by development of jaundice and eventual hepatic failure. Frequently, there is associated renal failure and disseminated intravascular coagulation. On liver biopsy, a fine microvascular fatty infiltration is found. At present, there is no specific therapy, although caesarean section may be lifesaving for both mother and infant. Correction of coagulopathies is essential preoperatively. CARCINOID SYNDROME

In 25% of patients with carcinoid tumours, the carcinoid syndrome occurs with hepatic secondary metastases (Galland and Blumgart, 1986; Padfield,

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791

1987). This syndrome consists of a number of symptoms, which may include flushing attacks, diarrhoea, bronchospasm, hypertension and valvular heart lesions. Treatment consists of resection of the primary tumour, removal of hepatic metastases and cardiac valve replacement if necessary. Somatostatin, cyproheptadine and kentanserin (Houghton and Carter, 1986) have been used to control the hypertension and other symptoms during anaesthesia. HYDATID CYSTS The adult worm of the parasite Echinococcus granulosus resides in the intestinal lumen of dogs and related carnivores. Sheep and cattle become infected by the faeco--oral route and humans may end up as an intermediate host by eating contaminated meat. Ova from the parasite pass in the portal stream to the liver and form cysts for their larval colonies. These cysts are not toxic and do not injure the liver. However, they may grow to an extent where physically they interfere with the host. Diagnosis is made by examination of the abdomen, chest and abdominal radiographs, bidirectional radionuclide liver scan and ultrasound. The Casoni skin test which allegedly identifies allergy to hydatid fluid is of limited use. Calcified cysts do not usually require treatment as the calcification indicates death of the parasite. Surgical resection of the liver is not necessary; simple drainage is all that is required. Depending on the location of the cyst either laparotomy or thoracotomy is performed (Galland and Blumgart, 1986). Hydrocortisone should be given with the premedication to prevent an intraoperative anaphylactic reaction should any hydatid fluid be spilled accidentally. REYE'S SYNDROME

This syndrome (Reye et al, 1963; Mowat, 1983) of acute encephalitis and fatty infiltration of the viscera in children has been associated with all types of viral infections. In particular, influenza A or B and varicella when treated with salicylates (aspirin and paracetamol) seem to be precipitating causes; aflatoxin and insecticides have also been implicated. Liver biopsy shows vesicular fat and there is an increase in aminotransferases and blood ammonia. The latter, if combined with an increased INR, is a sign of a poor prognosis. The cause of death is cerebral oedema. There is no specific treatment. COMMENT Preoperative assessment of hepatic function is often neglected. This is partially due to the lack of easily defined criteria despite the plethora of tests and investigations available. In addition, many patients appear to do well despite the presence of considerable hepatic damage preoperatively. Nevertheless, if decompensation does occur in the postoperative period, morbidity

792

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and mortality are high. A good history and simple clinical examination along with sensible assessment of liver function tests can help to identify patients at risk. The classifications of Child/Turcotte and Pugh have stood the test of time and are easy to apply.

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