Hepatology - Cirrhosis

Question 1

What is cirrhosis?

Answer 1

Cirrhosis results from necrosis of liver cells followed by fibrosis and nodule formation. The end result is impairment of liver cell function and gross distortion of the liver architecture, leading to portal hypertension.

Question 2

What causes cirrhosis?

Answer 2

Alcohol [MCC Western world]
Chronic hepatitis (B or C) [MCC worldwide]
NAFLD
Immune: PSC, autoimmune liver disease
Biliary: PBC, cystic fibrosis
Genetic: haemachromatosis, alpha 1 anti-trypsin deficiency, Wilson’s disease
Chronic venous outflow obstruction (veno-occlusive disease, Budd-Chiari)
Cryptogenic

Question 3

What are the clinical features of cirrhosis?

Answer 3

These are secondary to portal hypertension and liver cell failure. Cirrhosis with the complication of encephalopathy, ascites or variceal haemorrhage is designated decompensated cirrhosis. Cirrhosis without any of these complications is termed compensated cirrhosis.

Features include:

• xanthelasmas
• parotid enlargement
• spider naevi
• gynaecomastia
• liver (small = viral hepatitis, large = alcoholic liver disease)
• splenomegaly
• palmar erythema
• clubbing
• Dupuytren’s contracture
• Xanthomas
• jaundice (mostly due to failure to excrete bilirubin)
• fever
• loss of body hair

Question 4

Pathologically what are the two types of cirrhosis?

Answer 4

Histologically, two types are recognised:
1) Micronodular - uniform, small nodules up to 3mm in diameter. This type is often caused by ongoing alcohol damage or biliary tract disease

2) Macronodular - nodules of variable size and normal acini may be seen within large nodules. This type is often seen following chronic viral hepatitis

There is also a mixed picture with both small and large nodules.

Question 5

What investigations should be performed to assess severity in cirrhosis?

Answer 5

Investigations are performed to assess severity of liver disease, identify aetiology and screen for complications.

Severity:

• LFTs may be abnormal. In most cases there is at least a slight elevation in serum ALP and aminotransaminases
• FBC shows thrombocytopaenia in most patients, with leukopenia and anaemia developing later
• Liver function. Prothrombin time and serum albumin are the best indicators of liver function
• Serum electrolytes. A low sodium concentration indicates severe liver disease secondary to either impaired free water clearance or excess diuretic therapy. Elevated serum creatinine is associated with worse prognosis
• Serum alpha fetoprotein. This is usually undetectable after fetal life but raised levels may occur in chronic liver disease. A level greater than 200ng/mL is strongly suggestive of the presence of an HCC, developing as a complication of cirrhosis

Question 6

What investigations should be performed in cirrhosis to determine the aetiology?

Answer 6

Cirrhosis develops in response to chronic liver injury from any cause which is often apparent from the history combined with investigations. A liver biopsy is performed to confirm the severity and type of liver disease.

Question 7

What further investigations are required to investigate cirrhosis?

Answer 7

Oesophageal varices are sought with endoscopy and primary prophylaxis to reduce bleeding is offered to those with varices. An USS is helpful for detection of HCC, and to assess the patency of the portal and hepatic veins. A duel energy X-ray absorptiometry (DXA) scan is performed for osteoporosis.

Question 8

How should I manage cirrhosis?

Answer 8

Cirrhosis is irreversible and frequently progresses. Management is that of the complications seen in decompensated cirrhosis as they arise. Correcting the underlying cause, e.g. venesection for haemachromatosis, abstinence from alcoholic cirrhosis, may halt the progression of liver disease.

Screening for HCC (measurement of serum AFP and US every 6 months) is performed to identify tumours at an early stage. Liver transplantation should be considered in patients with end-stage cirrhosis. Patients should also be offered an influenza vaccination.

Question 9

What is the prognosis of cirrhosis?

Answer 9

This is variable and depends on the aetiology and presence of complications. The severity and prognosis of liver disease can be graded according to the modi ed Child–Pugh classification (dependent on ve variables: encephalopathy, ascites, prothrombin time, serum bilirubin and albumin) or the MELD score (modi cation of end-stage liver disease dependent on serum bilirubin and creatinine, and the international normalized ratio [INR]). Overall, the 5-year survival rate is approximately 50%.

Question 10

What is the Child-Pugh classification system?

Answer 10

This system grades the prognosis of cirrhosis depending on albumin, total bilirubin (distinguished based on PBC/SC and other causes of cirrhosis), prothrombin time, ascites severity and encephalopathy.

Interpretation:
<7 = Childs A = 1 yr survival 82%
7-9 = Childs B = 1 yr survival 62%
>9 = Childs C = 1 yr survival 42%

Question 11

What is the pathogenesis of cirrhosis?

Answer 11

Hepatocyte react to injury from any cause by forming regenerative nodules surrounded by collagen.
These lack the normal liver architecture (lack portal triads and sinusoids) and are surrounded by bands of fibrosis. They compress the remaining sinusoids and central venules. This leads to intrasinusoidal hypertension, a reduction in the number of normal sinusoids and an increase in hydrostatic pressure in the portal vein. Mason trichrome stain can be used to visualise the regenerative nodules and fibrotic tissue (appears blue).

Question 12

What are the complications of cirrhosis?

Answer 12

Portal hypertension and GI haemorrhage
Ascites
Portosystemic encephalopathy 
Acute kidney injury (heptorenal syndrome)
Hepatopulmonary syndrome 
HCC
Bacteraemias, infection
Malnutrition
Oesteoporosis