NON INVASIVE EVALUATION OF LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS B AND C

Abstract

Chronic viral hepatitis is an important cause of morbidity and mortality in the present day world [Goldstein et al, 2005; Baldo et al, 2008] 1,2 . The situation is particularly precarious in the developing countries [Jafri et al, 2006] 3 . It is estimated that by the year 2020-5, there will be three fold rise in cirrhosis, and hepatocellular carcinoma from HBV and HCV [Nguyen et al, 2008; Law et al, 2003] 4,5 . In chronic viral hepatitis the prognosis and management are highly dependent on the extent of liver fibrosis [Sebastiani et al, 2006] 6 . Though classically considered the “gold standard”; the liver biopsy is far from perfect, and has significant limitations [Poynard et al, 2004] 7 . This has led researchers to look for other methods to assess the stage of liver fibrosis [Afdhal et al, 2004] 8 .The noninvasive markers are the most widely used alternative to liver biopsy [ Manning et al, 2008; Castera et al, 2007; Morra et al, 2007] 9,10,11 . In the study presented, the association between serum markers, platelet parameters and liver fibrosis was investigated taking liver biopsy as the reference standard. A set of 5 serum markers, Fibroscore, consisting of: bilirubin, gamma glutamyl transferase (GGT), hyaluronic acid (HA), alpha 2 macroglobulin (A2M), and platelets; has shown very high diagnostic accuracy for the near absence of fibrosis, and cirrhosis. The area under the ROC for F2 (stage 2) fibrosis was 0.808, for F3 the ROC was 0.938, and for F4 the ROC was 0.959. A central cut off point of > 0.5, in the model, predicted clinically significant fibrosis, (F2, F3 and F4) with a sensitivity of 82%, specificity of 92%, and overall diagnostic accuracy of 89%. By increasing the cut off to 0.65, for stages F2-F4, the PPV was 95%. Lowering the cut off to < 0.08 for the exclusion of stages F2-F4 provided 98% NPV, thus almost certainly ruling out stages F2-F4. The PDW index consists of platelet distribution width (PDW), mean platelet volume (MPV), and platelet count. The area under the ROC for advanced fibrosis (F3-F4) for PDW index was 0.840, compares with the well known AST to Platelet Ratio Index (APRI) with area under ROC of 0.888. It is concluded that, Fibroscore has a high diagnostic accuracy for stages F2-F4, and PDW Index reliably predicts advanced fibrosis. The noninvasive markers will be helpful in the screening and management of fibrotic liver disease [Morra et al, 2007] 11 , and will replace liver biopsy in most patients with chronic liver disease from viral related causes [Castera et al, 2007; Morra et al, 2007] 10,11 .