Letters to the Editor
DOI:10.1111/liv.12833 Liver Int. 2015: 35: 2062
Value of fetuin-A as a predictor of liver fibrosis in patients with nonalcoholic fatty liver disease. Author’s reply To the Editor: We thank Dr Sertoglu and the collaborators for their comments on our recently published article on the negative correlation between fetuin-A and organ fibrosis in NAFLD subjects (1). According to their comments, we calculated Forns index, FIB-4 score and AST-to-Platelet Ratio Index (APRI) in our original cohort (2–4). We found that there were also significant and negative correlations between serum fetuin-A levels and two scoring system results [Forns index (R = 0.112, P < 0.05) FIB-4 score (R = 0.131, P < 0.05)]. However, there was no significant correlation between serum fetuin-A and APRI score (R = 0.044, P = 0.46). The APRI score was developed in chronic hepatitis C subjects to predict advanced fibrosis, and the mean value of serum AST levels in the original paper were higher than our subjects [mean ± SEM; 2.20 ± 0.14 vs 0.83 ± 0.034 (/upper limit of normal)] (4). One of the reasons for this result would be caused by relatively low levels of serum AST values in our study subjects (within normal levels). Although our study subjects did not receive liver biopsy and did not have histological data, these findings (Forns index and FIB-4 score) would enhance the significance of serum fetuin-A levels in NAFLD patients receiving health check-ups. Previously, Sertoglu and the collaborators investigated serum fetuin-A levels in liver biopsy-proven NAFLD patients and could not find a significant correlation between fetuin-A and liver histology (5). We also investigated serum fetuin-A levels in 82 biopsy-proven NAFLD patients. Coincident with the Sertoglu report, our results also demonstrated no significant correlation between serum fetuin-A levels and the fibrosis stage [(F0/F1/F2/F3/F4; 219.7 ± 41.6/ 196.4 ± 41.4/240.0 ± 64.0/226.9 ± 69.9/240.1 ± 59.3 (lg/ml)]. Interestingly, the serum fetuin-A levels in stage F1 NAFLD patients tends to be low compared with F0 NAFLD patients (P = 0.067). These results indicate that the serum fetuin-A levels would also negatively correlate with the fibrosis progression in early stage NAFLD patients. Fetuin-A is abundantly produced from liver by various stimuli such as
2062
inflammation, steatosis and fibrosis. In clinical usage, liver biopsy for the NAFLD diagnosis is performed in subjects with prospective advanced disease (suspected to NASH). Therefore, fetuin-A production would enhance in biopsy-performed NAFLD patients, compared with the NAFLD patients without receiving liver biopsy. Collectively, decrease in serum fetuin-A levels in early stage NAFLD patients would have progressive effects in organ fibrosis including liver. Acknowledgement Conflict of interest: The authors do not have any disclo-
sures to report.
Yoshihiro Kamada and Eiji Miyoshi Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
References 1. Sato M, Kamada Y, Takeda Y, et al. Fetuin-A negatively correlates with liver and vascular fibrosis in nonalcoholic fatty liver disease subjects. Liver Int 2015; 35: 925–35. 2. Forns X, Ampurdanes S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology 2002; 36(4 Pt 1): 986–92. 3. Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7: 1104–12. 4. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003; 38: 518–26. 5. Dogru T, Genc H, Tapan S, et al. Plasma fetuin-A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease. Clin Endocrinol 2013; 78: 712–7.
Liver International (2015) © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
DOI:10.1111/liv.12833 Liver Int. 2015: 35: 2062
Value of fetuin-A as a predictor of liver fibrosis in patients with nonalcoholic fatty liver disease. Author’s reply To the Editor: We thank Dr Sertoglu and the collaborators for their comments on our recently published article on the negative correlation between fetuin-A and organ fibrosis in NAFLD subjects (1). According to their comments, we calculated Forns index, FIB-4 score and AST-to-Platelet Ratio Index (APRI) in our original cohort (2–4). We found that there were also significant and negative correlations between serum fetuin-A levels and two scoring system results [Forns index (R = 0.112, P < 0.05) FIB-4 score (R = 0.131, P < 0.05)]. However, there was no significant correlation between serum fetuin-A and APRI score (R = 0.044, P = 0.46). The APRI score was developed in chronic hepatitis C subjects to predict advanced fibrosis, and the mean value of serum AST levels in the original paper were higher than our subjects [mean ± SEM; 2.20 ± 0.14 vs 0.83 ± 0.034 (/upper limit of normal)] (4). One of the reasons for this result would be caused by relatively low levels of serum AST values in our study subjects (within normal levels). Although our study subjects did not receive liver biopsy and did not have histological data, these findings (Forns index and FIB-4 score) would enhance the significance of serum fetuin-A levels in NAFLD patients receiving health check-ups. Previously, Sertoglu and the collaborators investigated serum fetuin-A levels in liver biopsy-proven NAFLD patients and could not find a significant correlation between fetuin-A and liver histology (5). We also investigated serum fetuin-A levels in 82 biopsy-proven NAFLD patients. Coincident with the Sertoglu report, our results also demonstrated no significant correlation between serum fetuin-A levels and the fibrosis stage [(F0/F1/F2/F3/F4; 219.7 ± 41.6/ 196.4 ± 41.4/240.0 ± 64.0/226.9 ± 69.9/240.1 ± 59.3 (lg/ml)]. Interestingly, the serum fetuin-A levels in stage F1 NAFLD patients tends to be low compared with F0 NAFLD patients (P = 0.067). These results indicate that the serum fetuin-A levels would also negatively correlate with the fibrosis progression in early stage NAFLD patients. Fetuin-A is abundantly produced from liver by various stimuli such as
2062
inflammation, steatosis and fibrosis. In clinical usage, liver biopsy for the NAFLD diagnosis is performed in subjects with prospective advanced disease (suspected to NASH). Therefore, fetuin-A production would enhance in biopsy-performed NAFLD patients, compared with the NAFLD patients without receiving liver biopsy. Collectively, decrease in serum fetuin-A levels in early stage NAFLD patients would have progressive effects in organ fibrosis including liver. Acknowledgement Conflict of interest: The authors do not have any disclo-
sures to report.
Yoshihiro Kamada and Eiji Miyoshi Department of Molecular Biochemistry & Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
References 1. Sato M, Kamada Y, Takeda Y, et al. Fetuin-A negatively correlates with liver and vascular fibrosis in nonalcoholic fatty liver disease subjects. Liver Int 2015; 35: 925–35. 2. Forns X, Ampurdanes S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology 2002; 36(4 Pt 1): 986–92. 3. Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7: 1104–12. 4. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology 2003; 38: 518–26. 5. Dogru T, Genc H, Tapan S, et al. Plasma fetuin-A is associated with endothelial dysfunction and subclinical atherosclerosis in subjects with nonalcoholic fatty liver disease. Clin Endocrinol 2013; 78: 712–7.
Liver International (2015) © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
