Fibrosis of the liver: causes, symptoms, diagnosis, treatment

Fibrosis of the liver is the accumulation of connective tissue in the liver in response to hepatocellular damage of any etiology. Fibrosis is a consequence of excessive formation or pathological destruction of the extracellular matrix. Fibrosis itself does not show any signs, but can lead to portal hypertension or cirrhosis of the liver. Diagnosis is based on liver biopsy. Treatment includes the elimination, if possible, of the underlying cause. Therapy is aimed at the reverse development of fibrosis and is currently at the research stage.

Activation of stellate perivascular liver cells (Ito cells, cells that deposit fat) causes fibrosis. These and adjacent cells proliferate, turning into contractile cells called myofibroblasts. Such cells cause degradation of the normal matrix and, in part, due to changes in metalloproteinase enzymes that regulate the matrix metabolism of collagen, stimulate excessive formation of the defective matrix. Kupffer cells (permanent macrophages),

Diseases and drugs that cause liver fibrosis

Diseases with direct liver damage

• Some hereditary diseases and congenital disorders of metabolism
• Deficiency of a1-antitrypsin
• Wilson's disease (excessive accumulation of copper)
• Fructoseemia
• Galactosemia
• Diseases of accumulation of glycogen (especially types III, IV, VI, IX and X)
• Syndromes of iron accumulation (hemochromatosis)
• Disorders of lipid metabolism (eg, Gaucher's disease)
• Peroxisomal diseases (Zellweger's syndrome) Tyrosinosus
• Congenital fibrosis of the liver
• Infections Bacterial (eg, brucellosis)
• Parasitic (eg, echinococcosis)
• Viral (eg, chronic hepatitis B or C)

Infringements affecting hepatic blood flow

• Badda-Chiari Syndrome
• Heart failure
• Occlusion diseases of the liver of the liver
• Thrombosis of the portal vein

Drugs and chemicals

• Alcohol
• Amiodarone
• Chlorpromazine
• Isoniazid
• Methotrexate
• Methyldopa
• Oxyphenazate
• Tolbutamide
• Toxins (for example, salts of iron, copper)

Damaged hepatocytes, platelets and aggregated leukocytes emit various O ₂ reactive forms and inflammatory mediators (eg, platelet growth factor, transformed growth factors and connective tissue growth factor) that accelerate fibrosis.

Myofibroblasts, stimulated by endothelin-1, also contribute to increasing the resistance of the portal vein, which increases the density of the altered matrix. Fiber strands are divided at the fusion points bringing branches of the portal vein and vessels draining off the hepatic veins, bypassing the hepatocytes and limiting their blood supply. Consequently, fibrosis contributes to ischemia of hepatocytes (and hepatocellular dysfunction), as well as to the development of portal hypertension. The significance of each process depends on the nature of the liver damage. For example, congenital liver fibrosis involves the branches of the portal vein, largely protecting the parenchyma. As a result, portal hypertension develops with a preserved hepatocellular function.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Symptoms of liver fibrosis

The liver fibrosis itself is not manifested by symptoms. Symptoms may occur with the development of secondary changes or portal hypertension. However, portal hypertension is often asymptomatic until cirrhosis develops.

A liver biopsy is the only method for diagnosing and verifying liver fibrosis. Quite often, the diagnosis is established after a liver biopsy performed according to other indications. A special color (for example, aniline blue, trichrome, silver color) can initially reveal fibrous tissue.

Treatment of hepatic fibrosis

Since fibrosis is a sign of liver damage, treatment is usually directed to the underlying cause. Methods of treatment aimed at the reverse development of fibrosis itself are at the research stage and are aimed at studying the following areas:

1. reduction of inflammation (eg, ursodeoxycholic acid, glucocorticoids),
2. inhibition of activation of hepatic stellate cells (eg, a-interferon, vitamin E as an antioxidant, activated proliferator-peroxisome receptor ligand [PPAR], eg, thiazolidinedione),
3. inhibition of the synthesis or metabolism of collagen (eg, penicillamine, colchicines, glucocorticoids),
4. Suppression of contraction of stellate cells (eg, endothelin antagonists or nitrogen oxide donators) and
5. increased extracellular matrix degradation (for example, the use of various experimental drugs that cause degradation of the extracellular matrix through action on the transforming growth factor p or matrix metalloproteinases).

Unfortunately, many drugs are very harmful for dpitelnoe application (eg, glucocorticoids, penicillamine) or do not have proven efficacy (eg colchicine). Complex antisclerosis therapy can be the most effective.