الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Portal hypertension is a key event in the evolution of chronic liver disorders when severe fibrosis or cirrhosis develops. Once portal pressure exceeds 10 mmHg (clinical significant portal hypertension – CSPH), patients are at risk of experiencing severe complications such as variceal bleeding or ascites.
In patients with chronic liver disease, histopathological examination of biopsy samples has traditionally been considered the gold standard for staging the severity of fibrosis and for diagnosing progression to cirrhosis. However, liver biopsy has important limitations (it is invasive and sampling error is very frequent),and in the last decade many studies have been devoted to the search of non-invasive methods to diagnose fibrosis and cirrhosis.
The ideal test for fibrosis and cirrhosis diagnosis should be safe, easy to perform, inexpensive, reproducible (within patients and between and within laboratories) and should provide an accurate assessment of the degree of liver fibrosis from pre-cirrhotic scarring, through very early and early compensated cirrhosis. The test should be predictive of long term outcomes such as portal hypertension, decompensation, need for transplantation, and death.
On the other hand, HVPG measurement is the gold standard technique to evaluate the presence and severity of portal hypertension. Also in this case some limitations exist, since HVPG measurements are not available in all centers, the technique is invasive and some patients are unwilling to be submitted to it. This is even more relevant when the repetition of the procedure is needed to monitor treatment response. These issues have raised interest to non-invasively determine when CSPH is present, so allowing defining a patient at risk of developing portal hypertension-related complications.
In conclusion, Serum markers of fibrosis have the advantage over liver biopsy of offering a sampling of the all liver, allowing frequent repetition, being far less invasive and having less dependence on professional expertise. Moreover, they may reflect the severity of liver fibrosis and predict clinically relevant outcomes.
Direct markers or true markers are biochemical parameters measurable in the peripheral blood that express liver matrix constituents or enzymes involved in their regulation, which allow a quantitative assessment of the total amount of hepatic extracellular matrix, and its deposition or removal.