Novel [alpha]-2-macroglobulin cleaved fragments as biomarkers of early liver fibrosis in patients with chronic hepatitis C

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From: Future Virology(Vol. 10, Issue 1)
Publisher: Future Medicine Ltd.
Document Type: Report
Length: 7,063 words
Lexile Measure: 1740L

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Author(s): Isabelle Batxelli-Molina [*] aff1 , Sophie Calvayrac-Pawlowski aff1 , Véronique Moulin aff1 , Martine Lapalus aff2 , Sonia Hem aff3 , Daniel Laune aff1 , Tarik Asselah aff2 , Bénédicte Jardin-Watelet aff1


40 kDa isoforms; [alpha]-2 macroglobulin; chronic hepatitis C; early diagnosis; liver fibrosis; serum

Hepatitis C virus (HCV) is a major cause of chronic liver disease and consequently a significant cause of morbidity and mortality [1 ]. About 180 million people are infected worldwide and up to 70% of HCV-positive patients develop chronic infection with severe risk of progression to hepatic fibrosis and cirrhosis. Liver fibrosis is mediated by necro-inflammation and activation of liver stellate cells and is characterized by accumulation of extracellular matrix proteins, including collagen [2 ]. Fibrosis progression in chronic hepatitis C (CHC) determines the final prognosis and the need of treatment. Currently, liver biopsy is considered the gold standard for hepatic fibrosis staging, but this invasive procedure is now progressively replaced by noninvasive methods, such as blood testing or hepatic elasticity measurement [3 ].

The standard of care for chronic HCV infection has been, for many years, peg-IFN/RBV combination, which eradicates the virus in approximately 50% of treated patients [4 ]. The recent development and availability of new molecules named direct antiviral agents are increasing HCV therapeutic options [5,6 ]. Many new antiviral drugs for HCV therapy are in preclinical or early clinical development, but these new regimens present novel challenges including complicated treatment algorithms based on virological response, numerous drug interactions and additional side effects especially in patients with advanced fibrosis [7 ]. Furthermore, new HCV infections still occur, especially in some of the poorest and low economic regions of the world with health burden. Challenges and opportunities will characterize the story of HCV infection also in the new era. Despite the great therapeutic advances, improvements in HCV surveillance, epidemiological mapping, prevention, testing and therapy are needed. Early diagnosis of hepatitis C and initiation of treatment before the development of serious liver damage - prior to reaching F3 fibrosis or cirrhosis - has the potential to save large sums of money and to make it affordable to treat a much larger number of people [8 ]. Currently, noninvasive tests cannot differentiate between adjacent stages of fibrosis, which limits assessment of disease progression and regression during therapy. However, in long-term perspectives, the importance of precise staging will diminish as therapy for HCV improves.

The monitoring of early stages of fibrosis (mild and moderate) is mandatory for the prognosis and the decision to treat in patients with CHC. Noninvasive methods (biomarkers and liver stiffness measurement) are available; however, their efficacy to identify patients with mild (F1) and moderate (F2) fibrosis remains limited. Clinical care for patients with HCV-related liver disease has advanced considerably during the last two decades, particularly during the last 5 years. Currently, dual therapy (peg-IFN and ribavirin) remains the standard of care for patients with genotype non-1, and for some patients with genotype 1 infection [7 ], and the treatment is mainly initiate at the F2 stage. New triple therapies are...

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Gale Document Number: GALE|A407934430