Liver fibrosis is the excess of extracellular matrix that accumulates after persistent inflammation and sustained liver damage that leads to an exaggerated tissue repair process. When hepatic fibrosis is very severe, cirrhosis develops. In the liver, the most frequent causes that produce fibrosis are chronic viral hepatitis B or C, autoimmune hepatitis, biliary diseases, alcoholic, and non-alcoholic steatohepatitis.
Is Fibrosis of the Liver Reversible?
From the clinical point of view, mild fibrosis is asymptomatic, however the progression to cirrhosis characterized by replacement of the functional parenchyma by scar tissue, distortion and change of the vascular architecture with nodule formation of regeneration, clinically may manifest itself with alterations in hepatic synthetic function with problems in coagulation, nitrogen management and detoxification systems, as well as portal hypertension data with formation of ascites and hemorrhage due to esophageal varices, increased susceptibility to infections and increased risk of hepatocellular carcinoma.
If these problems are detected initially before the development of liver cirrhosis, the antiviral treatment could be indicated in the case of viral hepatitis, treatment with diet and exercise for non-alcoholic steatohepatitis, the discontinuation of alcohol consumption in case of alcoholic steatohepatitis, thus as the treatment for the rest of the hepatitis, and to avoid that hepatic cirrhosis is reached. However, many patients go to the doctor with advanced fibrosis or cirrhosis and in this case the process is usually irreversible. For this reason, the development of an anti-fibrotic treatment to prevent the progression of advanced fibrosis to cirrhosis and to provide regression to avoid complications is very important.
Pathogenic Bases Of The Progression Of Hepatic Fibrosis And Reversibility
There are key mechanisms and different cells that determine the progression of fibrosis (fibrogenesis) and regression (fibrolysis). The extracellular matrix is formed due to growth factors, cytokines, chemokines and a series of events that include the processes of fibrogenesis and fibrolysis.
Hepatic fibrosis is a dynamic process that results in hepatic remodeling. The liver has a great capacity for regeneration. However, this function is lost when there is hepatic damage and results in inadequate regeneration with progressive scarring (cirrhosis) and an increased risk of hepatocellular carcinoma.
Currently there is no effective therapeutic method to limit and not even to reverse this process, but research in the area of cellular pathology and molecular biology have revealed very encouraging perspectives about the possibility of finding effective treatments for this condition.
The central pathogenic process of cirrhosis is progressive fibrosis. Since decades ago it was suspected that the deposit of connective tissue was an abnormal scar response to liver injury caused by chemical or infectious agents and that it was the consequence of the infiltration of fibroblasts in the liver parenchyma. Therefore, it has been considered an irreversible process as with any other scar. Currently there is a more accurate picture of the biomolecular complexity of the fibrogenesis process based on studies of the connective tissue of the normal liver as well as the cirrhotic liver. In the normal liver, interstitial collagen (type I and III) are found almost exclusively around the portal spaces and central veins, while type IV collagen forms very delicate fibers around the spaces of Disse. In contrast, in cirrhosis, collagen I and III are deposited in and through the hepatic lobules, progressively creating irregular septa that can become very thick and that cut and enclose portions of the hepatic lobule, forming what is known as regeneration nodules. This distortion of the architecture is the cause of the serious alteration of arterial and venous intrahepatic circulation. The deposit of collagen type IV in the space of Disse is accompanied by loss of fenestrations in the sinusoidal endothelial cells, which limits the exchange between the hepatocytes and the plasma.
Undoubtedly, cellular biology and molecular pathology have found very promising routes to prevent and reverse liver cirrhosis, at least in experimental models.
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