Liver International ISSN 1478-3223
Letter to the Editor DOI:10.1111/liv.12650 Liver Int. 2015: 35: 285
Interfering parameters in nonalcoholic fatty liver disease fibrosis score To the Editor: We have read with great interest the article by Petta et al. (1). In this study, the performance of combined noninvasive tools for identifying advanced fibrosis was assessed in two independent cohorts of Italian biopsyproven nonalcoholic fatty liver disease (NAFLD) patients. In conclusion, the combination of liver stiffness measurement (LSM) with NAFLD fibrosis score (NFS) was found to be able to accurately diagnose or exclude the presence of severe liver fibrosis, also reducing of about 50–60% the number of needed diagnostic liver biopsies. However, we would like to share our thoughts and contributions with Petta and colleagues. First, when the statistical analysis of the original study was evaluated, before comparing NAFLD patients from Sicily and northern Italy in terms of demographic, laboratory, metabolic and histological features, as shown in Table 1 of the original article, normality analysis should have been performed to assess whether data of the patient groups were normally distributed or not. Afterwards, P values should be calculated by using Student’s t-test or Mann–Whitney U-test, as appropriate. Second, it is obvious that presence of impaired fasting glucose (IFG)/Type 2 diabetes (DM) affects the NFS results significantly. Moreover, as demonstrated in Table 1 of the original article, the number (percentage) of patients with IFG and DM was significantly different between groups. When assessing the performance of NFS, to avoid the bias arising from this issue, assessment of the patients with or without IFG/ DM should separately be selected in patient cohort. Third, considering the indices evaluated in this study, there will most probably be correlations with
each other owing to including common parameters like AST, ALT and platelet in the formulations. In addition to the ROC analysis, multivariate logistic regression analysis should also be performed to avoid the effects of correlation between these parameters. Moreover, the strength of the combination of NFS and LSM should be evaluated by this analysis comparing the other evaluated parameters. In conclusion, NAFLD fibrosis score may be interfered by the selection of patient group especially consisting of the patients with IFG/DM. Acknowledgements
Conflict of Interests: The authors do not have any disclosures to report.
Erdim Sertoglu1 Huseyin Kayadibi2, Metin Uyanik3 1 Department of Medical Biochemistry, Ankara Mevki Military Hospital, Anittepe Dispensary, Ankara, Turkey 2 Department of Medical Biochemistry, Adana Military Hospital, Ankara,Turkey 3 Department of Medical Biochemistry, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey
References 1. Petta S, Vanni E, Bugianesi E, et al. The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease. Liver Int. 2014; doi: 10.1111/liv.12584. [Epub ahead of print].
DOI:10.1111/liv.12653 Liver Int. 2015: 35: 285–286
Response to Dr. Sertoglu and Colleagues We recently demonstrated that the combination of liver stiffness measurement with NAFLD fibrosis score
Liver International (2015) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
(NFS), two complementary, easy-to-perform, and widely available tools, is able to accurately diagnose or
285
Sertoglu et al.
Letter to the Editor
exclude the presence of severe liver fibrosis, in addition to reducing the number of needed diagnostic liver biopsies by about 50–60% (1). We thank Dr. Sertoglu and colleagues for their comments, which prompted us to further clarify the results of our analyses. First, they pointed out that data from Sicilian and northern Italian patients should be assessed for normal distribution before comparing these patients in terms of demographic, laboratory, metabolic, and histological variables. In response, we examined the data, and found that only some variables, such as ALT levels, did not have normal distribution. However, this does not alter the comparison between the two groups, or the significance of the results. Second, the authors suggested testing the performance of NFS by separately considering patients with impaired fasting glucose (IFG)/diabetes against their counterparts, because of the higher prevalence of IFG/ diabetes in the Sicilian cohort. Reviewing our data, we found that similar results were observed in both the Sicilian and northern Italian cohorts in subgroups with and without IFG/diabetes, as expected, because the NFS already takes into account the presence/absence of IFG/ diabetes. In the Sicilian population, false-positive and false-negative rates were 16.6% (1/6) and 18.8% (2/11) in the IFG/diabetes group, and 0% (0/1) and 8.9% (10/ 112) in those without IFG/diabetes respectively. Similarly, in the northern Italian cohort, false-positive and false-negative rates were 0% (0/2) and 26.6% (8/30) in the IFG/diabetes group, and 0% (0/0) and 6.3% (5/79) in those without IFG/diabetes respectively. Finally, Sertoglu and colleagues highlighted the concern that the non-invasive scores assessed in our study
included some common parameters, such as AST, ALT and platelets. However, one of the aims of our study was to assess the performance of these scores separately in the diagnosis of liver fibrosis. In conclusion, we think that NFS is a reliable noninvasive score for the diagnosis of severe fibrosis in NAFLD, as reported elsewhere in the literature (2), and that in combination with LSM could improve diagnostic accuracy. Acknowledgements
Conflict of Interest: The authors do not have any disclosures to report.
Salvatore Petta1, Ester Vanni2 and Antonio Craxı1 1 Sezione di Gastroenterologia, Di.Bi.M.I.S, Universita di Palermo, Palermo, Italia 2 Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy
References 1. Petta S, Vanni E, Bugianesi E, et al. The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease. Liver Int 2014. doi: 10.1111/liv.12584. 2. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007; 45: 846–54.
DOI:10.1111/liv.12654 Liver Int. 2015: 35: 286–287
Laboratory assessment may be dependent on the time of liver biopsy Dear Editor: We have read with great interest the recently published article by Goh et al. (1). In this study, authors aimed to evaluate association between the use of commonly used medications, particularly renin–angiotensin system (RAS) blocking agents, and severity of hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) patients with hypertension. In conclusion, hypertensive patients with NAFLD on baseline RAS blockers were found to be having less advanced hepatic fibrosis suggesting a beneficial effect of RAS blockers in NAFLD. However, we would like to share our thoughts and contributions with Goh and colleagues.
286
First, before performing the statistical analysis in the original study, normality analysis should have been performed to assess whether data of the patient groups were normally distributed or not. Afterwards, comparisons between groups should be done by using the Student’s t-test or Mann–Whitney U-test, as appropriate. Moreover, in the original study, it is noted that multivariate analysis using binary logistic regression was also performed to determine independent risk factors for advanced fibrosis. However, before performing the multivariate logistic regression analysis, univariate logistic regression analysis should be done and significant parameters derived therefrom should be evaluated
Liver International (2015) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Copyright of Liver International is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Letter to the Editor DOI:10.1111/liv.12650 Liver Int. 2015: 35: 285
Interfering parameters in nonalcoholic fatty liver disease fibrosis score To the Editor: We have read with great interest the article by Petta et al. (1). In this study, the performance of combined noninvasive tools for identifying advanced fibrosis was assessed in two independent cohorts of Italian biopsyproven nonalcoholic fatty liver disease (NAFLD) patients. In conclusion, the combination of liver stiffness measurement (LSM) with NAFLD fibrosis score (NFS) was found to be able to accurately diagnose or exclude the presence of severe liver fibrosis, also reducing of about 50–60% the number of needed diagnostic liver biopsies. However, we would like to share our thoughts and contributions with Petta and colleagues. First, when the statistical analysis of the original study was evaluated, before comparing NAFLD patients from Sicily and northern Italy in terms of demographic, laboratory, metabolic and histological features, as shown in Table 1 of the original article, normality analysis should have been performed to assess whether data of the patient groups were normally distributed or not. Afterwards, P values should be calculated by using Student’s t-test or Mann–Whitney U-test, as appropriate. Second, it is obvious that presence of impaired fasting glucose (IFG)/Type 2 diabetes (DM) affects the NFS results significantly. Moreover, as demonstrated in Table 1 of the original article, the number (percentage) of patients with IFG and DM was significantly different between groups. When assessing the performance of NFS, to avoid the bias arising from this issue, assessment of the patients with or without IFG/ DM should separately be selected in patient cohort. Third, considering the indices evaluated in this study, there will most probably be correlations with
each other owing to including common parameters like AST, ALT and platelet in the formulations. In addition to the ROC analysis, multivariate logistic regression analysis should also be performed to avoid the effects of correlation between these parameters. Moreover, the strength of the combination of NFS and LSM should be evaluated by this analysis comparing the other evaluated parameters. In conclusion, NAFLD fibrosis score may be interfered by the selection of patient group especially consisting of the patients with IFG/DM. Acknowledgements
Conflict of Interests: The authors do not have any disclosures to report.
Erdim Sertoglu1 Huseyin Kayadibi2, Metin Uyanik3 1 Department of Medical Biochemistry, Ankara Mevki Military Hospital, Anittepe Dispensary, Ankara, Turkey 2 Department of Medical Biochemistry, Adana Military Hospital, Ankara,Turkey 3 Department of Medical Biochemistry, Gulhane Military Medical Academy, School of Medicine, Ankara, Turkey
References 1. Petta S, Vanni E, Bugianesi E, et al. The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease. Liver Int. 2014; doi: 10.1111/liv.12584. [Epub ahead of print].
DOI:10.1111/liv.12653 Liver Int. 2015: 35: 285–286
Response to Dr. Sertoglu and Colleagues We recently demonstrated that the combination of liver stiffness measurement with NAFLD fibrosis score
Liver International (2015) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
(NFS), two complementary, easy-to-perform, and widely available tools, is able to accurately diagnose or
285
Sertoglu et al.
Letter to the Editor
exclude the presence of severe liver fibrosis, in addition to reducing the number of needed diagnostic liver biopsies by about 50–60% (1). We thank Dr. Sertoglu and colleagues for their comments, which prompted us to further clarify the results of our analyses. First, they pointed out that data from Sicilian and northern Italian patients should be assessed for normal distribution before comparing these patients in terms of demographic, laboratory, metabolic, and histological variables. In response, we examined the data, and found that only some variables, such as ALT levels, did not have normal distribution. However, this does not alter the comparison between the two groups, or the significance of the results. Second, the authors suggested testing the performance of NFS by separately considering patients with impaired fasting glucose (IFG)/diabetes against their counterparts, because of the higher prevalence of IFG/ diabetes in the Sicilian cohort. Reviewing our data, we found that similar results were observed in both the Sicilian and northern Italian cohorts in subgroups with and without IFG/diabetes, as expected, because the NFS already takes into account the presence/absence of IFG/ diabetes. In the Sicilian population, false-positive and false-negative rates were 16.6% (1/6) and 18.8% (2/11) in the IFG/diabetes group, and 0% (0/1) and 8.9% (10/ 112) in those without IFG/diabetes respectively. Similarly, in the northern Italian cohort, false-positive and false-negative rates were 0% (0/2) and 26.6% (8/30) in the IFG/diabetes group, and 0% (0/0) and 6.3% (5/79) in those without IFG/diabetes respectively. Finally, Sertoglu and colleagues highlighted the concern that the non-invasive scores assessed in our study
included some common parameters, such as AST, ALT and platelets. However, one of the aims of our study was to assess the performance of these scores separately in the diagnosis of liver fibrosis. In conclusion, we think that NFS is a reliable noninvasive score for the diagnosis of severe fibrosis in NAFLD, as reported elsewhere in the literature (2), and that in combination with LSM could improve diagnostic accuracy. Acknowledgements
Conflict of Interest: The authors do not have any disclosures to report.
Salvatore Petta1, Ester Vanni2 and Antonio Craxı1 1 Sezione di Gastroenterologia, Di.Bi.M.I.S, Universita di Palermo, Palermo, Italia 2 Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy
References 1. Petta S, Vanni E, Bugianesi E, et al. The combination of liver stiffness measurement and NAFLD fibrosis score improves the noninvasive diagnostic accuracy for severe liver fibrosis in patients with nonalcoholic fatty liver disease. Liver Int 2014. doi: 10.1111/liv.12584. 2. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007; 45: 846–54.
DOI:10.1111/liv.12654 Liver Int. 2015: 35: 286–287
Laboratory assessment may be dependent on the time of liver biopsy Dear Editor: We have read with great interest the recently published article by Goh et al. (1). In this study, authors aimed to evaluate association between the use of commonly used medications, particularly renin–angiotensin system (RAS) blocking agents, and severity of hepatic fibrosis in non-alcoholic fatty liver disease (NAFLD) patients with hypertension. In conclusion, hypertensive patients with NAFLD on baseline RAS blockers were found to be having less advanced hepatic fibrosis suggesting a beneficial effect of RAS blockers in NAFLD. However, we would like to share our thoughts and contributions with Goh and colleagues.
286
First, before performing the statistical analysis in the original study, normality analysis should have been performed to assess whether data of the patient groups were normally distributed or not. Afterwards, comparisons between groups should be done by using the Student’s t-test or Mann–Whitney U-test, as appropriate. Moreover, in the original study, it is noted that multivariate analysis using binary logistic regression was also performed to determine independent risk factors for advanced fibrosis. However, before performing the multivariate logistic regression analysis, univariate logistic regression analysis should be done and significant parameters derived therefrom should be evaluated
Liver International (2015) © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Copyright of Liver International is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
