We are delighted that Halfon et al. provided external validation for FibroIndex. They proposed a problem in gamma globulin for the discrepancy between our study and their data. The importance of serum gamma globulin in chronic hepatitis C has already been reported by several investigators.1–3 Imbert-Bismut et al.1 reported that serum gamma globulin was higher in patients with F2 or F3 than in those with F0 or F1. Our other study series3 also revealed that serum gamma globulin values were quantitatively correlated with staging scores. Therefore, it leaves no doubt that serum gamma globulin reflects the hepatic fibrosis in chronic hepatitis C.

Next, they point out that the measurement method of gamma globulin is not always reliable. We also emphasized the importance of the accuracy control of each parameter in the index comprising laboratory tests. In fact, we have described in the text that each parameter is under strict quality control. In our study, gamma globulin was measured using a single and dedicated analyzer with minimal interlaboratory variability (coefficient of variation at least <6%) as well as aspartate aminotransferase (AST) and platelet count. Although Halfon et al. do not show their quality control of gamma globulin measurement, this discrepancy may indicate the importance of the standardization and the strict quality control of each parameter. Indeed, AUROCs of APRI and Forns index conducted by AST and platelet in our study are higher than those in Halfon's study.


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  • 1
    Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T; MULTIVIRC Group. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 2001; 357: 10691075.
  • 2
    Ikeda K, Saitoh S, Kobayashi M, Suzuki Y, Tsubota A, Suzuki F, et al. Distinction between chronic hepatitis and liver cirrhosis in patients with hepatitis C virus infection. Practical discriminant function using common laboratory data. Hepatol Res 2000; 18: 252266.
  • 3
    Maruyama S, Hirayama C, Horie Y, Yorozu K, Maeda K, Inoue M, et al. Serum immunoglobulins in patients with chronic hepatitis C: A surrogate marker of disease severity and treatment outcome. Hepatogastroenterology 2007; 54: 493498.

Masahiko Koda*, Yoshikazu Murawaki*, * Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.