Time-out

Before we consider the patient’s labs, let’s review the ABCs of cirrhosis. Hematologists are often asked to see these patients, and it is helpful to have some background information.

Definition

Cirrhosis of the liver is end-stage liver disease characterized by pathologic fibrosis and regenerative nodules with resultant liver dysfunction:

  • Compensated cirrhosis – cirrhosis without any symptoms
  • Decompensated cirrhosis – cirrhosis with complications such as:
    • Ascites
    • Variceal bleeding
    • Hepatic encephalopathy
    • Nonobstructive jaundice

Causes

The most common causes of cirrhosis worldwide are:

  • Alcohol-related liver disease:
    • Closely associated with drinking patterns.
    • Increases substantially with > three drinks per day.
  • Non-alcoholic fatty liver disease
  • Chronic viral hepatitis B and C

Diagnosis

  • Goals include:
    • Quantifying degree of hepatic fibrosis:
      • Liver biopsy is the gold standard, but no longer commonly carried out for this purpose.
      • Liver elastography (Fibroscan):
        • Stiffness of the liver
        • Correlates well with the degree of fibrosis in the fasted state
      • Standard liver biochemistry and ultrasound:
        • Low sensitivity
        • Not recommended for this purpose
    • Assessing presence of portal hypertension.
    • Determining the cause(s) of the disease.

Pathophysiology

Distortion of the hepatic angioarchitecture, which increases intrahepatic resistance to portal blood, leading to splanchnic arterial vasodilation. Splanchnic vasodilation results in:

  • Increase in portal blood flow that, together with an increase in intrahepatic vascular resistance, results in portal hypertension.
  • Decrease in effective arterial blood volume causing:
    • Systemic hypotension
    • Arterial underfilling
    • Activation of neurohumoral vasoconstrictive systems including:
      • Sympathetic nervous system
      • Renin–angiotensin–aldosterone system
      • Non-osmotic release of vasopressin)
  • With progression of cirrhosis, intense vasoconstriction (a response to the increased vasodilation) may result in vasoconstriction in the renal circulation, leading to hepatorenal syndrome, which is a type of acute kidney injury.

Portal hypertension results in:

  • Ascites
  • Gastro-esophageal varices
  • Splenomegaly

Portosystemic shunting, together with the deterioration in liver function, contributes to hepatic encephalopathy.

Clinical presentation

Physical findings (typically seen in patients with decompensated cirrhosis) include:

  • Palmar erythema
  • Terry’s nails
  • Clubbing of the fingernails
  • Parotid enlargement
  • Scleral icterus
  • Gynecomastia
  • Loss of secondary sexual characteristics
  • Spider angiomas (visible as a central arteriole with radiating vessels)
  • Caput medusae (abdominal veins distended by blood flow radiating from the umbilicus)
  • Enlarged left hepatic lobe (though liver shrinks with disease progression)
  • Splenomegaly
  • Ascites
  • Evidence of hepatic encephalopathy, including asterixis

Disease scores

Compensated cirrhosis (with a low risk of mortality) vs. decompensated cirrhosis (with a higher risk of mortality)

Child-Turcotte-Pugh score

  • Uses the following parameters:
    • Serum albumin
    • Serum bilirubin
    • Prothrombin time
    • Ascites
    • Hepatic encephalopathy
  • Classifies patients into classes:
    • Class A
    • Class B
    • Class C

The MELD score

  • Uses the following parameters:
    • Serum
    • International normalized ratio
    • Serum creatinine
  • Score ranges between 6 and 40.
  • The higher the MELD score, the greater is the risk of mortality.

The MELD-Na

  • Includes serum sodium, which is an independent predictor of mortality, as a variable.
  • Used in several parts of the world to prioritize allocation of organs for liver transplantation.

Treatment

It is not necessary to go into the details of treatment except to point out treatment principles in patients with cirrhosis:

  • Treatment of ascites:
    • Moderate salt restriction to reduce ascites.
    • Water restriction to prevent further reduction in serum sodium levels in patients with hypervolemic hyponatremia.
    • Diuretics, especially aldosterone antagonist such as spironolactone.
    • Transjugular intrahepatic portosystemic shunting (TIPS) for management of refractory ascites.
  • Treatment of esophageal varices:
    • Nonselective beta-blockers such as propranolol or nadolol for primary prophylaxis of first variceal bleed in patients with medium or large varices.
    • Combination of nonselective beta blockers and endoscopic variceal ligation (EVL) for secondary prophylaxis of variceal hemorrhage.
  • Hepatic encephalopathy:
    • Lactulose 
    • Rifaximin
  • Spontaneous bacterial peritonitis (SBP):
    • Antibiotics (especially those with upper gastrointestinal bleeding) for SBP prophylaxis.
    • Antibiotics to treat SBP.