Cirrhosis arises as a result of chronic liver disease. Cirrhosis is derived from Greek word meaning “orange” or “tawny”. In this process, liver undergoes fibrosis and forms abnormal nodules that result in end stage of liver disease. Various conditions that cause liver injury can lead to cirrhosis such as hepatitis, alcoholic liver disease, biliary problems, fatty liver, drugs, and toxins. Cirrhosis is a histologic diagnosis with some clinical manifestations, there is a development of portal hypertension, and liver failure that is usually irreversible. Fibrosis of the liver occurs due to the activation of hepatic stellate cells and leads to accumulation of collagen in the space of Disse and parenchyma. This leads to scar tissue formation that can obstruct portal blood flow. Portal hypertension has the most complications of cirrhosis associated to it.
Etiology & Risk Factors
There are many contributing risk factors for liver disease and patients can present with many of them. Risk factors for cirrhosis include the following:
- 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
- Alagille syndrome
- Drug-induced: amiodarone or methotrexate
Cirrhosis has many causes and one individual may have a combination of these problems. Firstly alcoholic liver disease is present in people who drink alcohol heavily for more than 10 years. This type of lifestyle can have serious consequences and lead to damage of the liver. Acetaldehyde forms from alcohol and accumulates in the liver leading to damage.
Chronic hepatitis B is an infection of the liver with chronic inflammation 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 inflammation of the liver, after several years of infection with fatty changes to the liver it can cause cirrhosis. 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 deposited and accumulates 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 occurs 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, Iron deposits 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.
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
- Coffee-ground vomit
The signs to look for on examination are as following:
- 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
- Hepatic fetor
- Peripheral oedema
- Muscle wasting
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. And coagulation studies will be deranged as well.
- 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) and reduction in blood neutrophil count, neutropenia.
- There can be a deficiency in platelet count, thrombocytopenia due to alcoholic marrow suppression, splenomegaly, reduced folate levels, or sepsis. This can result in bleeding and bruising of the skin.
It is essential to manage the underlying cause, as cirrhosis is the end-stage of chronic liver disease. Monitoring for complications such as diuretic therapy for ascites and sodium restriction is essential. And medically therapy where appropriate can be considered. 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. And alcohol cessation advice and support needs to be provided to heavy alcohol drinkers, as abstinence from alcohol is very important.
Medically patients can be treated with antibiotics to prevent infections. To decrease risk of constipation and prevent hepatic encephalopathy, laxatives, such as lactulose are given and aim for 3 to 4 loose stools per day. And medications such as Ursodeoxycholic acid is used to treat primary biliary cirrhosis and cholestyramine can help with pruritus. Chelation therapy such as penicillamine can treat Wilson’s disease. Autoimmune hepatitis can be treated with corticosteroids. For viral hepatitis medications such as interferon are first line.
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.
- Decompensation of cirrhosis can occur in patients who carry on drinking alcohol, those who become constipated, infections, medications, dehydration, bleeding from oesophageal varices. Patients with decompensated cirrhosis need to be admitted and treated as an inpatient. Patients with ascites need to be salt restricted, and prescribed diuretics for example Spironolactone an aldosterone antagonist or loop diuretic such as furosemide. 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 conscience levels and coma due to cirrhosis. Toxins accumulate in the blood that is normally cleared by the liver. Infection and constipation can lead to hepatic encephalopathy and should be treated with laxatives and antibiotics. Patients are at risk of obstructing the airways, and need to be intubated. Liver transplant can be an option to treat some patients.
- Spontaneous bacterial peritonitis occurs in patients with portal hypertension, ascites and cirrhosis. Diagnosis can be made with paracentesis and treated with antibiotics. Patients will need prophylactic antibiotics if they remain to have ascites.
- Hepatocellular carcinoma is a primary malignant tumour in the liver. Cirrhosis patients are screened with ultrasound scans. It can occur in patients with hepatitis B or C, hemochromatosis, non-alcoholic fatty liver disease, alpha 1 antitrypsin or alcoholic liver disease. Patients present with symptoms such as jaundice, weight loss, abdominal pain, nausea and vomiting. Management is by liver transplantation.