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Liver Knowledge Base: Liver fibrosis

Liver fibrosis and its end-stage disease cirrhosis are major world health problems arising from chronic injury of the liver by a variety of factors including viruses, the metabolic syndrome, autoimmune disease, alcohol and drug abuse, and inherited (genetic) disorders of metabolism. Cirrhosis is the final common pathway through which nearly all chronic diseases of the liver produce morbidity and mortality.

What is liver fibrosis?

Fibrosis is a scarring process of body organs and hepatic fibrosis is scarring of the liver. Fibrosis is the excessive accumulation of extracellular matrix proteins including collagen proteins in abnormal ratio. In other words liver fibrosis is associated with major alterations in both the quantity and composition of extracellular matrix proteins. In advanced stages, the liver contains approximately 6 times more extracellular matrix proteins than normal.

  • Fibrosis process occurs in most types of chronic liver diseases.
  • It is the consequence of chronic liver injury of any etiology.
  • Hepatic fibrosis is the result of the wound-healing response of the liver to repeated injury.

The liver has an incredible ability to heal itself, but it can only heal itself if nothing is damaging it time and again. After an acute liver injury (e.g., acute viral hepatitis), liver cells regenerate and replace the damaged and dead cells. This process is associated with an inflammatory response and a limited deposition of extracellular matrix proteins. If the hepatic injury persists, then eventually the liver regeneration response becomes wrong, pathologically activated hepatic stellate cells become t he main source of scar-like matrix composed of cross-linked collagen. As fibrotic liver diseases advance, disease progression from collagen bands to bridging fibrosis and frank cirrhosis occurs.

Activated hepatic stellate cells (cells that encircle the sinusoids and in healthy condition are quiescent and store vitamin A) are primarily responsible for hepatic fibrosis and subsequent progression to cirrhosis. In response to liver injury stellate cells undergo a phenotypic transformation into myofibroblast-like cells that is termed activation, and characterized by proliferation, fibrogenesis, and reorganization of normal extracellular matrix proteins. Under conditions of persistent injury the behavioral responses of these stellate cells act in concert to put about fibrosis of the liver.

The onset of liver fibrosis is usually insidious and inconspicuous, and most of the related morbidity and mortality occur after the development of advanced liver fibrosis, i.e. cirrhosis. In the majority of patients, progression to cirrhosis occurs after an interval of 10-15-20 years. Major clinical complications of cirrhosis include ascites, renal failure, hepatic encephalopathy, and variceal bleeding. Patients with cirrhosis can remain free of major complications for several years (compensated cirrhosis stage) but decompensated cirrhosis is associated with short survival. Cirrhosis is also a risk factor for developing hepatocellular carcinoma (primary liver cancer). Liver fibrosis evolves rapidly to cirrhosis in some clinical conditions, including repeated episodes of subfulminant hepatitis, and fibrosing cholestasis in patients with HCV reinfection after liver transplantation.

Historically, treatments for hepatic fibrosis have been directed against specific causes of chronic liver injury, and include for example corticosteroids for autoimmune hepatitis, interferon for hepatitis B and C, and iron depletion for haemochromatosis. Once treatments become ineffective, a liver transplant has been considered until the present.

However the underlying disease factor of deterioration of liver functions is progressive liver fibrosis; it is the driving gear of all chronic degenerative liver diseases which result ultimately in morbidity and mortality. And the most efficacious treatment according to our practice is transplantation of cultured liver cells. In most circumstances, liver cell infusion along with a proper adjuvant therapy (according to individual characteristics of patient's clinical course) reduces and reverse the harmful affects of advanced liver fibrosis and cirrhosis, and can prevent the need for a liver transplant. Transplanted cells stop activated hepatic stellate cells, stop their injurious fibrotic activity and reverse them into quiescent stage.

 

Synonyms and related keywords: end-stage liver disease, ESLD, end stage liver disease, end-stage liver failure, end stage liver failure, ESLF, chronic degenerative liver disease, degenerative liver disease, degenerative liver disease, cirrhotic, cirrhotic liver, cirrhosis, chronic liver disease, chronic liver failure, CLF, fulminant hepatic failure, subfulminant hepatic failure, alcoholic liver disease, hepatitis, hepatitis C virus, hepatitis B virus, viral hepatitis, hepatic fibrosis, liver fibrosis, portal hypertension, ascites, progressive liver fibrosis, hepatocellular carcinoma, HCC, liver transplant, liver transplantation, hepatitis B, autoimmune hepatitis, primary biliary cirrhosis, secondary biliary cirrhosis, drug-induced liver disease, veno-occlusive disease, nonalcoholic fatty liver disease, non-alcoholic fatty liver disease, NAFLD, necroinflammation, steatohepatitis, hepatosteatosis

 

 

 

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