Cirrhosis

Etiology and risk factors

There are many contributing risk factors for liver disease:

• Excessive long-term alcoholism is a major risk factor
• Autoimmune disorders like vitiligo, diabetes, inflammatory bowel disease etc are also associated with autoimmune hepatitis
• Non-alcoholic fatty liver disease as a result of obesity or insulin resistance diabetes, dyslipidemia and hypertension
• Hepatitis B
• Hepatitis C
• Primary biliary cirrhosis due to primary sclerosing cholangitis
• Wilson's disease
• Alpha-1 antitrypsin deficiency
• Galactosemia
• Hemochromatosis
• Alagille syndrome
• Drug-induced: amiodarone or methotrexate

Let's have a quick overview of those risk factors and how they lead to liver cirrhosis.

Alcoholic liver disease is present in people who drink alcohol heavily for more than 10 years. Acetaldehyde is formed as a byproduc of alcohol metabolism, and accumulates to the liver leading to damage.

Chronic hepatitis B is an infection of the liver with chronic inflammation that may lead to cirrhosis. Hepatitis B virus is a circular double stranded DNA virus that can be transmitted by intravenous drug use, blood transfusion, and sexual intercourse.

Chronic hepatitis C is an inflammation of the liver. Hepatitis C virus is a single stranded RNA virus that can be transmitted by intravenous drug use, blood transfusions, non-sterile medical procedures, and sexual intercourse.

Non-alcoholic fatty liver disease occurs due to fat deposition in the liver; this is a progressive disease and can eventually result in cirrhosis. Metabolic risk factors like obesity, insulin resistance diabetes, dyslipidemia and hypertension are risk factors linked to non-alcohol fatty liver disease.

Autoimmune diseases like vitiligo, diabetes, thyroid disorders, pernicious anaemia, primary sclerosing cholangitis, primary biliary cirrhosis and inflammatory bowel disorder are associated with autoimmune hepatitis. Cholestasis can occur in those diseases which can lead to cirrhosis due to damage and destruction to the bile ducts and intrahepatic ductules.

Wilson's disease is an autosomal recessive disorder in which copper accumulates in tissues. This results in liver disease and neurological problems. Kayser-Fleischer rings are a sign of the disease where by dark rings encircle the iris of the eye due to copper deposition. It can cause hepatic encephalopathy, portal hypertension and chronic hepatitis leading to cirrhosis.

Alpha-1 antitrypsin deficiency is an inherited disorder that causes a defect in the production of alpha-1 antitrypsin by the liver. It leads to problems such as emphysema in a patient who may never have smoked cigarettes and damage to the liver leading to cirrhosis.

Galactosemia is an autosomal recessive disorder that causes problems in the metabolism of galactose. Lactose is metabolized into glucose and galactose. Then galactose cannot further be metabolized and leads to an accumulation of toxic levels, resulting in cirrhosis and other systemic problems. It is usually diagnosed at birth by the heel prick test. Treatment is by eliminating lactose from the diet.

Hemochromatosis is either hereditary disorder in which iron deposits into tissues or due to disease or condition that can cause iron overload. The iron accumulates mainly in liver, heart, joints, testes and skin. The deposition of iron in the liver can lead to cirrhosis.

Alagille syndrome is an autosomal dominant disorder that causes malformation of the bile ducts. This results in an accumulation of bile leading to liver scarring and cirrhosis.

Signs and symptoms

Cirrhosis can occur as compensated or decompensated cirrhosis. Compensated cirrhosis is usually diagnosed during a routine examination or incidentally. There are non-specific signs and symptoms like anorexia, fatigue, dyspepsia, weight loss and abdominal discomfort of upper right quadrant. Decompensated type is usually complicated with one or more following symptoms:

• Abdominal distension that is secondary to ascites in portal hypertension
• Jaundice
• Pruritus
• Coffee-ground vomit
• Melaena
• Confusion

The signs to look for on examination are as following:

• Hepatosplenomegaly
• Scleral jaundice
• Leukonychia – white spots on the nails
• Clubbing of the nails
• Palmar erythema – redness on the thenar and hypothenar eminences
• Spider naevi – swollen blood vessels under the skin radiating like a spiders web
• Telangiectasia – red thread-like lines on the skin due to widened venules
• Foetor hepaticus
• Ecchymosis
• Peripheral oedema
• Muscle wasting

Investigations

There are various investigations to do in order to distinguish an underlying cause of cirrhosis. Firstly blood tests checking in particular for full blood count, liver function tests, urea and electrolytes, albumin, INR, prothrombin time, hepatitis B and C serologic tests, iron studies that include total iron, ferritin, transferrin and Total iron binding capacity. Antibodies to test for are antinuclear antibody (for primary sclerosing cholangitis), anti-smooth muscle antibody (for autoimmune hepatitis), anti-mitochondrial antibody (for primary biliary cholangitis), serum ceruloplasmin (for Wilson’s disease), plasma alpha-1 antitrypsin and serum protein electrophoresis.

Imaging tests to consider, are an abdominal ultrasound, abdominal CT and abdominal MRI. If there is coffee ground vomit or signs of oesophageal varices an upper GI endoscopy should be done. Colonoscopy can be considered if patient has melaena. And if blood tests and imaging scans are abnormal a liver biopsy should be considered.

• Liver functions tests will demonstrate a moderately raised AST and ALT. Especially in alcoholic liver disease AST is more raised than ALT. ALP can be slightly raised by two to three times of the upper normal limit of the range and may indicate blockage of bile duct. GGT is typically higher in cirrhosis from alcoholic liver disease. Bilirubin can become raised as liver disease progresses. Albumin will decrease and this is a marker for reduced synthetic function of the liver.
  
• As the liver synthesizes clotting factors, this will be impaired in disease; prothrombin time will increase.
• Urea and electrolyte tests will show hyponatraemia due to increased levels of aldosterone and anti diuretic hormone.
• Splenomegaly can result is a reduction in white blood cell count (leukopenia).
• There can be a deficiency in platelet count (thrombocytopenia) due to alcoholic marrow suppression.

Management

It is essential to manage the underlying cause, as cirrhosis is the end-stage of chronic liver disease. Treatment of complications such as diuretic therapy for ascites and sodium restriction is essential. It is possible to delay or halt the progress of cirrhosis and decrease the chance of complications occurring by managing underlying conditions. In most cases liver disease is irreversible.

Lifestyle advice can be given to patients to eat a healthy diet. In addition, alcohol cessation advice and support need to be provided to heavy alcohol drinkers.

To decrease the risk of constipation and prevent hepatic encephalopathy, laxatives, such as lactulose are given and aim for 3 to 4 loose stools per day. Medications such as Ursodeoxycholic acid is used to treat primary biliary cirrhosis and cholestyramine can help with pruritus.

It is important to assess and monitor patients to prevent further liver damage. Close follow up is necessary and eventually liver transplantation is an option for some patients that have uncontrollable complications.

Complications

• Decompensation of cirrhosis can occur in patients who continue consuming alcohol. Patients with ascites need to be salt-restricted, and treatment with diuretics is necessary. Fluid can be drained of the ascites by paracentesis by inserting a tube into the peritoneal cavity and this rapidly reduces volume.
• Oesophageal varices bleeding can occur as a result of portal hypertension. Medication such as propranolol is prescribed to lower blood pressure. Transjugular intrahepatic portosystemic shunting (TIPS) is an option to reduce pressure on the portal vein.
• Hepatic encephalopathy results in altered consciousness levels and coma due to cirrhosis. Toxins accumulate in the blood that is normally cleared by the liver.
• Spontaneous bacterial peritonitis occurs in patients with portal hypertension, ascites and cirrhosis. Diagnosis can be made with paracentesis and treated with antibiotics.
• Hepatocellular carcinoma is a primary malignant tumour in the liver. Cirrhosis patients are screened with ultrasound scans.