- Email: [email protected]
Methodologic issues with transfer of ultrasound-based transient elastography into clinical practice
Letters to the Editor / Journal of Hepatology 47 (2007) 295–302
in the pathogenesis of liver cirrhosis in patients with GSD III. Further work is needed to increase our understanding of factors contributing to HCC in the different GSDs, including altered fat acid oxidation as these can shed light on general health issues in the population. References [1] Herrema H, Smit GPA, Reijngoud DJ, Kuipers F. Does increased fatty acid oxidation enhance development of liver cirrhosis and progression to hepatocellular carcinoma in patients with glycogen storage disease type-III? J Hepatol 2007;47:298–300. [2] Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol 2006;290:G852–G858. [3] Raval J, Lyman S, Nitta T, Mohuczy D, Lemasters JJ, Kim JS, et al. Basal reactive oxygen species determine the susceptibility to apoptosis in cirrhotic hepatocytes. Free Radic Biol Med 2006;41: 1645–1654.
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[4] Demo E, Frush D, Gottfried M, Koepke J, Boney A, Bali D, et al. Glycogen storage disease type III-hepatocellular carcinoma a longterm complication? J Hepatol 2007;46:492–498. [5] Chen YT, Burchell A. Glycogen storage disease. In: Scriver C, Beaudet A, Sly W, Valle D, editors. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, Inc., Health Professions Division; 1995. p. 935–966. [6] de Moor RA, Schweizer JJ, van Hoek B, Wasser M, Vink R, Maaswinkel-Mooy PD. Hepatocellular carcinoma in glycogen storage disease type IV. Arch Dis Child 2000;82:479–480.
P.S. Kishnani Y.T. Chen Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 3528, Durham, NC 27710, USA E-mail address: [email protected] doi:10.1016/j.jhep.2007.05.008
Methodologic issues with transfer of ultrasound-based transient elastography into clinical practice To the Editor: The interest in developing clinical management strategies for ultrasound-based transient elastography (i.e. Fibroscan) in patients with chronic liver disease remains great. The article by Kettaneh and colleagues [1] with accompanying editorial by Afdhal and Curry [2] highlights the importance of translating findings of diagnostic accuracy from referral centers to clinical practice settings. In turn, there may be other aspects of diagnostic test research to consider with technology transfer into community-based settings. Test performance measured by sensitivity and specificity is usually linked to a diagnostic threshold (or cut-off value) for deciding when a target condition (such as fibrosis) is present or absent. By defining optimal test performance based on 95% sensitivity, 95% specificity, or a combination of both parameters which maximizes accuracy, there will be different threshold values observed for each of these approaches. In turn, these varying thresholds for detecting the same fibrosis stage could result in a pooled estimate from independent studies affected by heterogeneity related to diagnostic threshold bias [3]. This may raise questions about the consistency of a technique when applied in different populations. Consensus on which approach to use when determining threshold values for disease detection in future clinical practice trials should be pursued. The reproducibility of ultrasound-based transient elastography has been addressed in just a single published investigation to date [4]. Notably, an excellent
degree of reliability (0.98) was observed in this study measured by the intraclass coefficient (ICC) which accounts for the total variability among patients, measurement variability, and measurement error [5]. Notably, a reduction in ICC value was found in association with the presence of a body mass index > 28 kg/ m2, hepatic steatosis, and the presence of mild fibrosis (F0–1) in the study population. These characteristics are just the variables which are expected to be more prevalent in community populations in contrast to referral centers where the spectrum of disease severity is more narrow. Finally, there is a lack of normative data on liver stiffness measurement in patients without evidence or risk factors for chronic liver disease in the peer-reviewed literature. Available information in abstract form [6] suggests that 5.3 ± 1.5 kPa may represent the average liver stiffness value within general populations. Further confirmation of normative data would also be of importance prior to determining performance in clinical practice. References [1] Kettaneh A, Marcellin P, Douvin C, Poupon R, Ziol M, Beaugrand M, et al. Features associated with success rate and performance of fibroscan measurements for the diagnosis of cirrhosis in HCV patients: a prospective study of 935 patients. J Hepatol 2007;46:628–634. [2] Afdhal NH, Curry M. Technology evaluation: a critical step in the clinical utilization of novel diagnostic tests for liver fibrosis. J Hepatol 2007;46:543–545.
302
Letters to the Editor / Journal of Hepatology 47 (2007) 295–302
[3] Deeks JJ. Systematic reviews in health care: systematic reviews of evaluations of diagnostic and screening tests. BMJ 2001;323: 157–162. [4] Fraquelli M, Rigamonti C, Casazza G, Conte D, Donato MF, Ronchi G, et al. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut 2007;56:968–973. [5] Flemons WW, Littner MR. Measuring agreement between diagnostic devices. Chest 2003;124:1535–1542. [6] Roulot D, Costes J, Le Clesiau H, Grando V, Beaugrand M. Liver stiffness values in subjects without known risk factor for chronic liver diseases. Hepatology 2006;44:490A.
Jayant A. Talwalkar Advanced Liver Diseases Study Group, Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA E-mail address: [email protected]
doi:10.1016/j.jhep.2007.05.004
in the pathogenesis of liver cirrhosis in patients with GSD III. Further work is needed to increase our understanding of factors contributing to HCC in the different GSDs, including altered fat acid oxidation as these can shed light on general health issues in the population. References [1] Herrema H, Smit GPA, Reijngoud DJ, Kuipers F. Does increased fatty acid oxidation enhance development of liver cirrhosis and progression to hepatocellular carcinoma in patients with glycogen storage disease type-III? J Hepatol 2007;47:298–300. [2] Reddy JK, Rao MS. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol 2006;290:G852–G858. [3] Raval J, Lyman S, Nitta T, Mohuczy D, Lemasters JJ, Kim JS, et al. Basal reactive oxygen species determine the susceptibility to apoptosis in cirrhotic hepatocytes. Free Radic Biol Med 2006;41: 1645–1654.
301
[4] Demo E, Frush D, Gottfried M, Koepke J, Boney A, Bali D, et al. Glycogen storage disease type III-hepatocellular carcinoma a longterm complication? J Hepatol 2007;46:492–498. [5] Chen YT, Burchell A. Glycogen storage disease. In: Scriver C, Beaudet A, Sly W, Valle D, editors. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, Inc., Health Professions Division; 1995. p. 935–966. [6] de Moor RA, Schweizer JJ, van Hoek B, Wasser M, Vink R, Maaswinkel-Mooy PD. Hepatocellular carcinoma in glycogen storage disease type IV. Arch Dis Child 2000;82:479–480.
P.S. Kishnani Y.T. Chen Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 3528, Durham, NC 27710, USA E-mail address: [email protected] doi:10.1016/j.jhep.2007.05.008
Methodologic issues with transfer of ultrasound-based transient elastography into clinical practice To the Editor: The interest in developing clinical management strategies for ultrasound-based transient elastography (i.e. Fibroscan) in patients with chronic liver disease remains great. The article by Kettaneh and colleagues [1] with accompanying editorial by Afdhal and Curry [2] highlights the importance of translating findings of diagnostic accuracy from referral centers to clinical practice settings. In turn, there may be other aspects of diagnostic test research to consider with technology transfer into community-based settings. Test performance measured by sensitivity and specificity is usually linked to a diagnostic threshold (or cut-off value) for deciding when a target condition (such as fibrosis) is present or absent. By defining optimal test performance based on 95% sensitivity, 95% specificity, or a combination of both parameters which maximizes accuracy, there will be different threshold values observed for each of these approaches. In turn, these varying thresholds for detecting the same fibrosis stage could result in a pooled estimate from independent studies affected by heterogeneity related to diagnostic threshold bias [3]. This may raise questions about the consistency of a technique when applied in different populations. Consensus on which approach to use when determining threshold values for disease detection in future clinical practice trials should be pursued. The reproducibility of ultrasound-based transient elastography has been addressed in just a single published investigation to date [4]. Notably, an excellent
degree of reliability (0.98) was observed in this study measured by the intraclass coefficient (ICC) which accounts for the total variability among patients, measurement variability, and measurement error [5]. Notably, a reduction in ICC value was found in association with the presence of a body mass index > 28 kg/ m2, hepatic steatosis, and the presence of mild fibrosis (F0–1) in the study population. These characteristics are just the variables which are expected to be more prevalent in community populations in contrast to referral centers where the spectrum of disease severity is more narrow. Finally, there is a lack of normative data on liver stiffness measurement in patients without evidence or risk factors for chronic liver disease in the peer-reviewed literature. Available information in abstract form [6] suggests that 5.3 ± 1.5 kPa may represent the average liver stiffness value within general populations. Further confirmation of normative data would also be of importance prior to determining performance in clinical practice. References [1] Kettaneh A, Marcellin P, Douvin C, Poupon R, Ziol M, Beaugrand M, et al. Features associated with success rate and performance of fibroscan measurements for the diagnosis of cirrhosis in HCV patients: a prospective study of 935 patients. J Hepatol 2007;46:628–634. [2] Afdhal NH, Curry M. Technology evaluation: a critical step in the clinical utilization of novel diagnostic tests for liver fibrosis. J Hepatol 2007;46:543–545.
302
Letters to the Editor / Journal of Hepatology 47 (2007) 295–302
[3] Deeks JJ. Systematic reviews in health care: systematic reviews of evaluations of diagnostic and screening tests. BMJ 2001;323: 157–162. [4] Fraquelli M, Rigamonti C, Casazza G, Conte D, Donato MF, Ronchi G, et al. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut 2007;56:968–973. [5] Flemons WW, Littner MR. Measuring agreement between diagnostic devices. Chest 2003;124:1535–1542. [6] Roulot D, Costes J, Le Clesiau H, Grando V, Beaugrand M. Liver stiffness values in subjects without known risk factor for chronic liver diseases. Hepatology 2006;44:490A.
Jayant A. Talwalkar Advanced Liver Diseases Study Group, Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA E-mail address: [email protected]
doi:10.1016/j.jhep.2007.05.004