Cirrhosis: Definition, Causes, Symptoms, Evolution, Diagnosis and Treatment

It is the last stage of chronic liver disease; its origin is viral, pharmacological, or alcoholic.

Clinically, it is a very advanced and often irreversible fibrous scar that disrupts the functioning of the liver.

Cirrhosis is a diffuse  and irreversible liver disease, whose definition is anatomical, with the association of three types of lesions:

  • Liver cells cannot regenerate.
  • Fibrous connective tissue excess.
  • Regeneration nodules where liver cells try to function but are unsuccessful because the architectural design of the new cells does not fulfill their functions.

Depending on the size of the nodules, there is micronodular and macronodular cirrhosis.

It is characterized by chronic inflammation that produces a set of diffuse lesions.

These lesions, mainly the destruction of liver cells (hepatocytes), induce an anarchic regeneration of these cells associated with scarring (fibrosis).

This reorganization of liver cells alters the structure of the liver and forms abnormal nodules (cell clusters).

 

Cirrhosis is the result of a slow transformation of the liver by fibrosis.

In alcoholics and obese patients, cirrhosis is often preceded by a fatty liver, which corresponds to an accumulation and infiltration of fat in the liver (an event also associated with metabolic syndrome).

These changes make the liver more complex. The formation of nodules leads to an obstruction of blood circulation in the liver, which leads to the loss of its functions (metabolic and regulatory functions) and leads to multiple complications.

Cirrhosis, therefore, changes the function and structure of the liver, which has several consequences:

  • The liver’s primary functions, such as filtering the blood and secreting bile, are no longer fulfilled.
  • Portal hypertension (increased pressure within the venous system that carries blood from the digestive system to the liver) develops, promoting the formation of varicose veins (enlarged veins) in the esophagus that can bleed.
  • Over time, cirrhosis can progress to liver cancer within 15 to 20 years of onset.

Causes of cirrhosis

The causes of liver cirrhosis are multiple, but alcohol abuse is the leading cause.

The second cause of liver cirrhosis is chronic viral hepatitis, but cirrhosis can also be induced due to a rare disease.

Cirrhosis, therefore, develops in several situations:

Chronic alcoholism: excessive and prolonged consumption of alcohol causes 50 to 75% of cases of cirrhosis. An excess of alcohol, around three glasses a day for a man and two for a woman, is toxic to the liver and can cause cirrhosis.

Chronic viral hepatitis types B, C, and D (liver disease due to viral infection): In 15 to 25% of cases, hepatitis C is involved, compared to 5% of hepatitis B.

Autoimmune hepatitis, a form of destruction of the liver, is a chronic inflammatory liver disease of unknown cause associated in most cases with immunity abnormalities.

Metabolic syndrome (responsible for fat accumulation in the liver): Nonalcoholic steatosis, also known as fatty liver disease, is another cause of cirrhosis.

Furthermore, liver specialists today are alarmed by the damage caused by overweight to the liver at the origin of nonalcoholic fatty liver disease. Nonalcoholic steatohepatitis is a build-up of fatty acids in the form of triglycerides in the liver.

This abnormality is mainly found in people with diabetes, overweight, obese, or with a metabolic syndrome.

Diabetes and Obesity: Metabolic syndrome (associated with being overweight or obese) is the least known risk factor for cirrhosis.

However, it causes a significant increase in the incidence of cirrhosis in developing countries, countries where obesity is progressing and reaching an alarming rate.

Cirrhosis follows the formation of inflammatory lesions and an overproduction of collagen fibers that accumulate between the hepatocytes and suffocate.

The “active” cells of the liver die and are replaced by fibrous scar tissue that has no functional role. For these nonalcoholic people without viral hepatitis, the risk of developing cirrhosis or liver cancer is significant.

Hemochromatosis (iron overload of the tissues): Primary hemochromatosis is a genetic condition caused by a lack of regulation of the intestinal absorption of iron.

Iron accumulates in tissues, especially in the liver, causing fibrosis and cirrhosis.

The disease is ten times more common in men than in women (due to iron loss during menstruation) and is recognized around 40 to 60 years. Its treatment consists of repeated bleeding, which reduces iron deposits in the tissues.

Wilson’s disease is a genetic disease related to the accumulation of copper in different organs; the liver, the cornea, and the central nervous system.

The enzymatic mechanism is poorly understood (lack of ceruloplasmin synthesis). The disease is generally recognized in children or adolescents.

Liver involvement is characterized by fibrosis and cirrhosis.

Corneal involvement is manifested by a greenish-brown ring located on the cornea’s periphery (Kayser-Fleischer ring).

An extrapyramidal syndrome manifests central nervous system involvement. Treatment consists of the administration of a copper chelating drug (penicillamine).

Primary biliary cirrhosis is a condition that appears to be related to an obstruction of the intrahepatic bile ducts whose precise cause is unknown, but it is probably autoimmune.

The disease begins with itching that precedes the appearance of jaundice by several months.

The liver and spleen become enlarged, and signs of cholestasis appear.

The diagnosis is based on the detection of antimitochondrial antibodies in the serum. The prognosis is variable.

Biliary cirrhosis of the liver is caused by a localized obstruction in the bile ducts, such as lithiasis or pancreatitis. It can also be primary biliary cirrhosis, a chronic inflammatory disease of the liver that mainly affects women between 40 and 50.

Sometimes other causes of cirrhosis are found: cardiac cirrhosis, schistosomiasis, galactosemia, etc.

Symptoms of cirrhosis

Cirrhosis of the liver is a disease that does not cause symptoms or pain; it is the stage of compensated cirrhosis.

The diagnosis is often made while the patient is consulting for another reason.

Symptoms of cirrhosis include fatigue, weight loss, jaundice (yellowing), an enlargement of the liver accompanied by the presence of fluid inside the abdominal cavity, an abnormality called ascites, a digestive hemorrhage, or encephalopathy (altered consciousness, disorders of the mood, confusion, sleep disturbances).

The manifestations of cirrhosis when decompensation occurs are:

  • Jaundice (yellowing of the skin).
  • Presence of edema of the ankles.
  • The presence of water in the abdomen is called ascites.
  • Scanty urine
  • Digestive bleeding
  • Repetitive infections.
  • Neurological disorders can lead to coma.

The search for cirrhosis is also part of the follow-up of patients with nonalcoholic fatty liver disease or chronic viral hepatitis B or C.

Evolution of cirrhosis

The possible complications are numerous:

  • Ascites are the most common complication. It can be established quickly or gradually. It is a fluid effusion in the peritoneal cavity that occurs when it is essential due to the dull distention of the abdomen.
  • Jaundice is also a common complication. There is an increase in free and conjugated bilirubin in the blood. It is mixed jaundice.
  • Infections are prevalent and can be explained by decreased antibacterial defense systems. There is often a mild fever in cirrhosis whose origin is unknown.
  • Gastrointestinal bleeding (hematemesis, melena) are frequent and severe complication. They present under three leading causes: ruptured esophageal varices, peptic ulcer, and hemorrhagic gastritis.
  • Primary liver cancer (hepatoma) is a severe complication of cirrhosis. Different symptoms allow to suspect the appearance of cancer: fever, pain in the right upper quadrant (right side), very dark jaundice, gastrointestinal bleeding, increased alkaline phosphatase, increased alpha-2 globulins, and alpha-fetoprotein.
  • Hepatic encephalopathy can be spontaneous or caused by a specific cause (infection, gastrointestinal bleeding, sedatives, diuretics, etc.).

Diagnosis of cirrhosis

The treating physician questions his patient, investigates risk factors for chronic viral hepatitis and evaluates his use of alcohol, drugs, or substances toxic to the liver.

In the exam, the doctor calculates your body mass index and measures your waistline to look for overweight or malnutrition, present in cases of advanced cirrhosis.

The clinical signs suggestive of cirrhosis are:

  • The liver is palpable under the ribs, with a smooth and hard lower border, without pain.
  • The spleen may be swollen, and it is palpable.
  • The palms of the hands are red.
  • Small red vascular stars are visible on the skin (stellate angiomas).

Tests confirm the diagnosis of cirrhosis:

  • A blood test looks at liver function and looks for possible hepatitis C or chronic hepatitis B.
  • An abdominal ultrasound with a liver Doppler. These tests allow you to specify the appearance of the liver and look for signs of portal hypertension.
  • Upper digestive endoscopy to observe possible esophageal varices.
  • A liver biopsy right away or sometimes second-line for chronic hepatitis C. It makes it possible to diagnose cirrhosis and, in some cases, to identify its cause.

In the case of chronic hepatitis C, a blood test with the calculation of fibrosis or a measurement of the elasticity and fibrosis of the liver using an ultrasound device.

This initial evaluation of cirrhosis serves to:

  • Assess the severity of cirrhosis.
  • Identify its cause.
  • Look for possible complications (other tests are needed, such as a CT scan or an MRI).
  • Diagnose other diseases that can complicate management.
  • Long-term follow-up plan.

Treatment

The treatment of cirrhosis goes first through that of its cause if the cirrhosis is 75% of alcoholic origin.

They can also be caused by hemochromatosis, viral hepatitis B or C, or an autoimmune disease (primary biliary cirrhosis, sclerosing cholangitis, among others).

Eat balanced, in sufficient quantity, and avoid fat overloads.

Cessation of alcohol consumption remains essential in the treatment of cirrhosis.

Be careful when taking medications. The liver metabolizes many drugs.

Aspirin and non-steroidal anti-inflammatory drugs are of considerate use due to the risk of bleeding and kidney failure.

The same goes for antibiotics (aminoglycosides) due to the risk of kidney failure.

Some medications can reduce the effects of cirrhosis.

Diuretic drugs help to remove excess fluid and prevent the appearance of ascites.

Beta-blocker medications can reduce portal hypertension and the risk of bleeding.

Preventive treatment for ruptured varicose veins is taking a beta-blocker medication that reduces portal pressure.

Specific treatments are offered for bleeding varicose veins. Excess fluid in the abdomen can be removed during a puncture.

A liver transplant may be considered in some people with severe liver failure.

Liver transplantation is a surgical procedure that can replace a diseased liver with a healthy liver.

Liver transplantation is the primary treatment for liver cancer in specific cases.

It can only be proposed for small tumors. The results are very satisfactory: the recurrence rate at five years is 15%.

The main indications for this surgical procedure are:

  • In childhood, bile duct atresias.
  • Adults with primary biliary cirrhosis, primary sclerosing cholangitis, some chronic hepatitis B or C cases, cirrhosis with severe liver failure, some primary liver tumors, and rare metabolic diseases.
  • After transplantation, immunosuppressive therapy (corticosteroids, cyclosporine, azathioprine) is required.