الفهرس 
Anatomy and morphology of the liverOnly 14 pages are availabe for public view
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Abstract
Hepatic fibrosis refers to the accumulation of interstitial or ’scar’ extracellular matrix after either acute or chronic liver injury. Cirrhosis, the end-stage of progressive fibrosis, is characterized by septum formation and rings of scar that surround nodules of hepatocytes .
Typically fibrosis requires years or decades to become clinically apparent, but notable exceptions in which cirrhosis develops over months may include pediatric liver disease (e.g. biliary atresia), drug-induced liver disease, and viral hepatitis associated with immunosuppression after liver transplantation.
The composition of extracellular matrix molecules in the fibrotic liver is similar to those of other fibrosing parenchyma, including lung and kidney, and is also similar among different etiologies of liver diseas
Determinants of fibrosis progression include both environmental and genetic factors, with ongoing efforts to define specific polymorphisms correlating with fibrosis progression rates. Human studies now indicate that fibrosis and even cirrhosis could be reversible, especially if the underlying disease is eradicated. A key challenge is to establish noninvasive means of assessing fibrosis stage and progression using either serum tests and/or imaging. In addition, endpoints of antifibrotic clinical trials need to be established so that reliable evidence of benefit can be identified
Rapid progress in understanding the mechanisms of hepatic fibrosis exemplifies how basic research has begun to yield meaningful prospects for translation into new diagnostics and treatments for patients with liver disease. These advances include the isolation and characterization of fibrogenic cell types in liver, the clarification of general and disease-specific pathogenic mechanisms, and the broader appreciation of the natural history and reversibility of hepatic fibrosis.
The foremost challenge is to find the optimal method of diagnosing fibrosis. Although liver biopsy combined with connective tissue stains has been a mainstay of diagnosis, it is prone to sampling error and inter-observer variability. There has been significant progress in the development of noninvasive markers, which will be essential to obtain early biomarkers of efficacy for clinical trials and to guide clinical usage. Third are imaging methods (CT, MRI, PET, elastography, radionuclide receptor scanning), which can assess either intrahepatic blood flow patterns, organ texture, or the mass of activated stellate cells using cell-specific reagents to bind membrane receptors.
The ideal noninvasive fibrosis marker must be reproducible and linear, reflecting fibrosis in all types of chronic liver disease, and correlating with matrixcontent and clinical outcome] It must also be sensitive enough in individual patients to discriminate between different stages of fibrosis, and reflect the response to antifibrotic therapy over time. There are several approaches currently being developed. First is the serum measurement of one or more circulating matrix proteins and/or serum biochemistries in combination. Second are serum proteomics or glycomics, which assess patterns of protein peaks or glycoprotein branching, respectively. A recent study combined glycomics with a serum marker panel.[53] It achieved a high level of discrimination in diagnosing compensated and decompensated cirrhosis, however, these patients are also readily diagnosed by standard clinical means.
The liver offers a unique targeting advantage because orally administrated agents will be metabolized first in liver and need not reach extrahepatic tissues, possibly allowing for lower, safer dosages. it is important to realize that for an antifibrotic drug to be successful, it need not eradicate hepatic fibrosis entirely, because the liver has an enormous functional reserve and most patients with fibrosis have normal liver function. Instead, any drug that sufficiently attenuates fibrosis progression to prevent the development of cirrhosis and/or hepatocellular carcinoma will be viewed as a success, and will fuel what is already a dynamic and rapidly advancing field. Hepatic fibrosis, or scarring of the liver, is emerging as a treatable complication of advanced liver disease, following significant progress in understanding its underlying mechanisms.