ArticlesBiochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study
Introduction
Liver biopsy is thought mandatory for management of patients infected by hepatitis C virus (HCV), particularly to stage fibrosis.1, 2 However, after biopsy 30% of patients feel pain, 0·3% have severe complications, and 0·03% die.3, 4 Several markers have substantial predictive values for diagnosis of cirrhosis,4, 5, 6, 7, 8, 9, 10 but none are available for diagnosis of earlier stages—eg, with few septa (the start of bridging fibrosis). No prospective studies have been done in a large population infected only by HCV. We aimed to prospectively assess the predictive value of a combination of basic serum biochemical markers for the diagnosis of clinically significant fibrosis (ranging from a few septa to cirrhosis) and necroinflammatory activity (necrosis and inflammation). If markers with high positive or negative predictive values of important fibrosis can be obtained, fewer liver biopsies would need to be done and thus the cost and risk of liver biopsy would be lessened.3, 4
Section snippets
Patients
From August, 1997, to March, 2000, all liver-biopsy patients who gave informed consent and with detectable HCV by PCR were assessed for eligibility and had a blood sample taken on the day of biopsy. Patients belonged to a single centre cohort, Cohorte Hépatite C Pitié-Salpêtrière (DOSVIRC). This cohort included all patients with HCV infection (defined by a positive serological test by at least a second-generation ELISA) attending the liver and gastrointestinal unit of Pitié-Salpêtriére
Participants
We assessed 422 patients with chronic HCV infection for eligibility (figure 1). We excluded 45 because of: HIV coinfection (37), hepatitis B virus coinfection (seven), and transplantation (one). We could not stage fibrosis in 30 of the remaining 377 patients, and at least one of the 11 markers was missing in eight, which left 339 included patients. Patient characteristics and biochemical markers did not differ between first-year and second-year samples (table 1). The overall frequency of
Discussion
Our results show that a combination of five or six basic biochemical markers can have high positive or negative predictive value for diagnosis of clinically significant fibrosis, even at the early stage of a few septa. The most informative markers were, in decreasing rank: α2 macroglobulin, haptoglobin, GGT, γ globulin, total bilirubin, and apolipoprotein A1.
α2 globulin is mainly composed α2 macroglobulin nad haptoglobin. Fibrosis was associated with an increase of α2 macroglobulin and a
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