Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD. HIV-1 dynamics in vivo: ... Dandri M, Murray JM, Lutgehetmann M, Volz T, Lohse AW, Petersen J.
HEPATOLOGY, Vol. 49, No. 5, 2009
CORRESPONDENCE
3. Nowak MA, Bonhoeffer S, Hill AM, Boehme R, Thomas HC, McDade H. Viral dynamics in hepatitis B virus infection. Proc Natl Acad Sci U S A 1996;93:4398-4402. 4. Tsiang M, Rooney JF, Toole JJ, Gibbs CS. Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy. HEPATOLOGY 1999;29:1863-1869. 5. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD. HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 1996;271:1582-1586. 6. Dandri M, Murray JM, Lutgehetmann M, Volz T, Lohse AW, Petersen J. Virion half-life in chronic hepatitis B infection is strongly correlated with levels of viremia. HEPATOLOGY 2008;48:1079-1086. 7. Guidotti LG, Chisari FV. Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol 2006;1:23-61. 8. Murray JM, Purcell RH, Wieland SF. The half-life of hepatitis B virions. HEPATOLOGY 2006;44:1117-1121.
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9. Dahari H, Shudo E, Ribeiro RM, Perelson AS. Modeling complex decay profiles of hepatitis B virus during antiviral therapy. HEPATOLOGY 2009; 49:32-38. 10. Volz T, Lutgehetmann M, Wachtler P, Jacob A, Quaas A, Murray JM, et al. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. Gastroenterology 2007;133: 843-852. 11. Boni C, Fisicaro P, Valdatta C, Amadei B, Di Vincenzo P, Giuberti T, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol 2007;81:4215-4225. Copyright © 2009 by the American Association for the Study of Liver Diseases. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hep.22918 Potential conflict of interest: Nothing to report.
Hemochromatosis: Platelets and Aspartate Aminotransferase Are Useful High-Degree Fibrosis Markers To the Editor:
References
We read with great interest the article by Crawford et al.1 about the utility of hyaluronic acid with ferritin in the prediction of cirrhosis for C282Y hemochromatosis. It is a very important advance for noninvasive fibrosis prediction in hemochromatosis patients. We would like to add that in their study they included 56 hereditary hemochromatosis patients, and in a cohort of 48 for whom data on serum ferritin, platelet count, and aspartate aminotransferase (AST) values were available, they applied Beaton et al.’s predictive model2 and compared their findings with those from French and Canadian hereditary hemochromatosis populations. In this cohort, 26 patients had serum ferritin ⬎ 1000 g/L, and in 15 of the patients, the platelet count was ⬎200,000 ⫻ 103/mL. Two of the 15 patients had cirrhosis, and both had raised AST. It is stated that the combination of a platelet count ⬍ 200,000, ferritin ⬎ 1000, and raised AST failed to detect 30% (3/10) of the patients with cirrhosis (they did not have all the predicting factors), but it seems that none of the patients with cirrhosis had a platelet count ⬎ 200,000 and normal AST. We recently reported the utility of various noninvasive methods for fibrosis prediction in hemochromatosis, with 32 patients included and nine presenting stage F3 or F4 fibrosis (four patients had cirrhosis).3 In our study, the combination of raised AST and a platelet count ⬍ 200,000 revealed a negative predictive value of 100% for high-degree fibrosis. Platelets alone had a 94% negative predictive value for high-degree fibrosis; the four patients with cirrhosis had a platelet count ⬍ 200,000, and three of them had a serum ferritin value ⬍ 1000 (three were homozygous for C282Y, and one lacked the hemochromatosis gene study). We think that the combination of a platelet count ⬍ 200,000 and raised AST is a useful tool for cirrhosis prediction in hemochromatosis. Noninvasive markers for fibrosis prediction are a very interesting field of investigation in hemochromatosis, but perhaps results differ in different populations. AGUSTIN CASTIELLA1 EVA ZAPATA1 PEDRO OTAZUA2 1Hepatogastroenterology Mendaro Hospital Mendaro, Spain 2Hepatogastroenterology Mondragon Hospital Mondragon, Spain
1. Crawford DHG, Murphy TL, Ramm LE, Fletcher LM, Clouston AD, Anderson GJ, et al. Serum hyaluronic acid with serum ferritin accurately predicts cirrhosis and reduces the need for liver biopsy in C282Y hemochromatosis. HEPATOLOGY 2009;49:418-425. 2. Beaton MD, Guyader D, Deugnier Y, Moirand R, Chakrabarti S, Adams P. Noninvasive prediction of fibrosis in C282Y homozygous hemochromatosis. HEPATOLOGY 2002;36:673-678. 3. Castiella A, Zapata E, Otazua P, Fernandez J, Alustiza JM, Ugarte M, et al. Utility of various non-invasive methods for fibrosis prediction among Basque Country patients with phenotypic hemochromatosis. Rev Esp Enferm Dig (Madrid) 2008;100:611-614. Copyright © 2009 by the American Association for the Study of Liver Diseases. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hep.22925 Potential conflict of interest: Nothing to report.
Reply: Utility of Platelets and Aspartate Aminotransferase vs Serum Ferritin and Serum Hyaluronic Acid as Markers of Cirrhosis in Hemochromatosis We thank Dr. Castiella and his colleagues for their interest in our recent study of noninvasive markers of fibrosis in patients with C282Y hemochromatosis.1 We agree that studying the clinical role of noninvasive markers in this population is of great interest with significant potential implications for patient care. Dr. Castiella and his colleagues are correct to point out that none of the patients in our study with cirrhosis had a platelet count ⬎ 200 ⫻ 109/L and normal aspartate aminotransferase; this supports their own contention that these characteristics confer a high negative predictive value for cirrhosis. We agree that these variables should be taken into account when liver biopsy is considered in affected patients. However, in our study, only 10 of the 26 patients with serum ferritin ⬎ 1000 g/L had cirrhosis, and this indicates the need for better noninvasive markers of cirrhosis in this population. In our population, a serum hyaluronic acid concentration ⬎ 46.5 ng/mL was 100% sensitive and 100% specific in identifying the C282Y hemochromatosis patients with cirrhosis. Therefore, we concluded that a combination of serum hyaluronic acid and serum ferritin concentration is an accurate method for the diagnosis of cirrhosis and that this strategy is likely to be very cost-effective. We found their own report very interesting because they describe three of four patients with cirrhosis having a serum ferritin-
