Cirrhosis results from the necrosis of liver cells followed by fibrosis and nodule formation. The liver architecture is diffusely abnormal and this interferes with liver blood flow and function. This derangement produces the clinical features of portal hypertension and impaired liver cell function.
The causes of cirrhosis are shown . Alcohol is now the commonest cause in the Western World but HBV infection is the commonest cause worldwide and HCV is increasingly being diagnosed. With the identification of new hepatic viruses, idiopathic or cryptogenic cirrhosis is less commonly diagnosed. Young patients with cirrhosis must be carefully investigated as the cause may be treatable, e.g. Wilson’s disease.
Two types have been described which give clues to the underlying cause:
1 Micronodular cirrhosis, in which regenerating nodules are usually less than 3 mm in size and are surrounded by fibrous septa and the condition uniformly involves the liver. This type is often caused by ongoing alcohol damage or biliary tract disease.
2 Macronodular cirrhosis, in which the nodules are of variable size and normal acini may be seen within the larger nodules. This type is often seen following previous hepatic illness, e.g. HBV infection. A mixed picture with small and large nodules is sometimes seen and an aetiological cause cannot necessarily be inferred from the pathological picture. Symptoms and signs are described.
These are performed to assess the severity and type of liver disease.
LIVER BIOCHEMISTRY. This can be normal depending on the severity of cirrhosis. In most cases there is at least a slight elevation in the serum AP and serum aminotransferases.
In decompensated cirrhosis all biochemistry is deranged. The serum albumin is the best indicator of liver function.
SERUM ELECTROLYTES. A low sodium indicates severe liver disease because of dilution secondary to free water clearance or to excess diuretic therapy.
HAEMATOLOGY The PT is prolonged commensurate to the severity of the liver disease. SERUM (l’-FETOPROTEIN is a useful screening test for a hepatocellular carcinoma.
This can be determined by the following:
MISCELLANEOUS: serum copper and serum ai-antitrypsin should always be measured in young cirrhotics. Serum iron, total iron binding capacity (TIBC) and ferritin should be measured to exclude haemochromatosis.
ULTRASOUND EXAMINATION. This can demonstrate changes in size and shape of the liver. Fatty change and fibrosis produce a diffuse increased echogenicity. The patency of the portal and hepatic veins can be evaluated. It is useful to detect hepatocellular carcinoma. CT is rarely necessary but can detect a fatty liver as well
as excess iron deposition.
BARIUM SWALLOW can detect varices.
SCINTISCANNING is only helpful in advanced cirrhosis when clotting abnormalities preclude a biopsy.
ENDOSCOPY is performed for the detection and treatment of varices.
This is also necessary to confirm the severity and type of liver disease. The core of liver often fragments and sampling errors occur in macro nodular cirrhosis. Special stains may be required for iron and copper.
Management is that of the complications seen in decompensated cirrhosis and patients should be followed up in order to detect complications as early as possible. There is no treatment that will arrest or reverse the cirrhotic changes. Progression may be halted by correcting the underlying cause (see below). Patients with compensated cirrhosis should lead a normal life and no particular diet is helpful. Alcohol should be avoided, although if the cirrhosis is not due to alcohol, small amounts are not harmful.
This is extremely variable, depending on many factors, including the aetiology and the presence of complications. Poor prognostic indicators are given. Development of any complication usually worsens the prognosis. In general, the 5-year survival rate is approximately 50% but this also varies depending on the aetiology and the stage at which the diagnosis is made. There are a number of prognostic classifications based on modifications of Child’s grading (A, B and C). This is based on the presence of jaundice, ascites, encephalopathy and the level of serum albumin. Patients with good liver function- Child’s Grade A-do better than patients with poor liver function (albumin <30 g litre “, bilirubin >50 /-Lmollitre-‘ and ascites)-Child’s Grade C. Surgical procedures carry an operative mortality of 30% in non-bleeding cirrhotics (10% in Child’s Grade A to 76% in Grade C patients).
This is now an established treatment for a number of liver diseases and is becoming more widely available. Indications include:
ACUTE LIVER DISEASE-patients with fulminant hepatic failure of any cause including acute viral hepatitis.
CHRONIC LIVER DISEASE, the indications for transplantation vary and the timing of the transplant is often difficult. All patients with end-stage (Child’s Grade C) cirrhosis should be considered. PRIMARY BILIARY CIRRHOSIs-patients with this disease should be transplanted when their serum bilirubin rises above 100/-Lmollitre-‘.
CHRONIC HEPATITIS B-recurrence of the hepatitis occurs in some transplanted cases and thus longer term survival is reduced.
CHRONIC HEPATITIS C -in end-stage disease the prognosis .of the graft is good despite HCV RNA being found in the grafted liver, indicating re-infection.
ALCOHOLIC LIVER DISEASE -well-motivated patients who have stopped drinking can be offered a transplant. PRIMARY METABOLIC DISORDERS, e.g. Wilson’s disease. OTHER CONDITIONS, e.g. sclerosing cholangitis.
Absolute contraindications include active sepsis outside the hepatobiliary tree, metastatic malignancy, AIDS infection and if the patient is not psychologically committed. Relative contraindications are mainly anatomical considerations that would make surgery more difficult, e.g. portal vein thrombosis, previous portocaval shunts or complex surgery. With exceptions patients over 65 years are usually not transplanted. In hepatocellular carcinoma the recurrence rate is high and transplantation is not recommended.
Pretransplant workup includes the confirmation of the diagnosis, ultrasound and CT scanning, radiological demonstration of the hepatic arterial and biliary tree. Because of the ethical and financial implications of this operation psychiatric counselling and regular psychosocial support are vital.
The donor should be ABO, but not necessarily HLA, compatible, be preferably less than 50 years of age and have no evidence of sepsis, malignancy, HIV or HBV infection. The recipient operation takes approximately 8- hours and requires a large blood transfusion. Various immunosuppressive agents are used and include cyclosporin, methylprednisolone, azathioprine and FK506, a macrolide antibiotic which is more powerful than cyclosporin in inhibiting interleukin-2. The operative mortality is low. Most postoperative deaths occur in the first 3 months. Sepsis, haemorrhage, metabolic acidosis and hyperkalaemia occur.
infections are still a problem due to immunosuppression.
Rejection can be early (reversible) or late (irreversible).
Acute or cellular rejection is usually seen 5-10 days post transplant; the patient feels ill with a pyrexia and tender hepatomegaly. Histologically there is portal inflammation, bile duct damage and endothelialitis of the liver. This type of rejection responds to immunosuppressive therapy. Irreversible chronic ductopenic rejection is seen 6 weeks to 9 months post-transplant with disappearing bile ducts (vanishing bile duct syndrome, VBDS) and an arteriopathy with narrowing and occlusion of the arteries.
Ductopenic rejection is not reversed by immunosuppression and requires retransplantation. Graft-versus-host disease is extremely rare.
Elective liver transplantation in low-risk patients now has a 90% 1-year survival; 5-year survivals are as high as 70- 85% largely due to the introduction of cyclosporin and FK 506. Patients require lifelong immunosuppression.