Screening for Wilson disease in acute liver failure

A comparison of currently available diagnostic tests

Jessica D. Korman, Irene Volenberg, Jody Balko, Joe Webster, Frank V. Schiodt, Robert H. Squires, Robert J. Fontana, William M. Lee, Michael L. Schilsky, Julie Polson, Carla Pezzia, Ezmina Lalani, Linda S. Hynan, Joan S. Reisch, Anne M. Larson, Hao Do, Jeffrey S. Crippin, Laura Gerstle, Timothy J. Davern, Katherine Partovi & 41 others Sukru Emre, Timothy M. McCashland, Tamara Bernard, J. Eileen Hay, Cindy Groettum, Natalie Murray, Sonnya Coultrup, A. Obaid Shakil, Diane Morton, Andres T. Blei, Jeanne Gottstein, Atif Zaman, Jonathan Schwartz, Ken Ingram, Steven Han, Val Peacock, Robert J. Fontana, Suzanne Welch, Brendan McGuire, Linda Avant, Raymond Chung, Deborah Casson, Robert Jr Brown, Laren Senkbeil, M. Edwyn Harrison, Rebecca Rush, Adrian Reuben, Nancy Huntley, Santiago Munoz, Chandra Misra, Todd Stravitz, Jennifer Salvatori, Lorenzo Rossaro, Colette Prosser, Raj Satyanaryana, Wendy Taylor, Raj Reddy, Mical Campbell, Tarek Hassenein, Fatma Barakat, Alistair Smith

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD(ALF-WD), data and serum were collected from 140 ALF patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp<20 mg/dL by the oxidase method provided a diagnostic sensitivity of 21% and specificity of 84% while, by nephelometry, a sensitivity of 56% and specificity of 63%. Serum copper levels exceeded 200 μg/dL in all ALF-WD patients measured (13/16), but were also elevated in non-WD ALF. An alkaline phosphatase (AP) to total bilirubin (TB) ratio <4 yielded a sensitivity of 94%, specificity of 96%, and a likelihood ratio of 23 for diagnosing fulminant WD. In addition, an AST:ALT ratio>2.2 yielded a sensitivity of 94%, a specificity of 86%, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity and specificity of 100%. Conclusion: Conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum aminotransferases by contrast provides the most rapid and accurate method for diagnosis of ALF due to WD.

Original languageEnglish (US)
Pages (from-to)1167-1174
Number of pages8
JournalHepatology
Volume48
Issue number4
DOIs
StatePublished - Oct 2008

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Hepatolenticular Degeneration
Acute Liver Failure
Routine Diagnostic Tests
Serum
Ceruloplasmin
Copper
Chronic Disease
Nephelometry and Turbidimetry
Transaminases
Bilirubin
Liver Transplantation
Alkaline Phosphatase
Liver Diseases
Spectrum Analysis
Oxidoreductases
Emergencies
Transplants
Sensitivity and Specificity

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Korman, J. D., Volenberg, I., Balko, J., Webster, J., Schiodt, F. V., Squires, R. H., ... Smith, A. (2008). Screening for Wilson disease in acute liver failure: A comparison of currently available diagnostic tests. Hepatology, 48(4), 1167-1174. https://doi.org/10.1002/hep.22446

Screening for Wilson disease in acute liver failure : A comparison of currently available diagnostic tests. / Korman, Jessica D.; Volenberg, Irene; Balko, Jody; Webster, Joe; Schiodt, Frank V.; Squires, Robert H.; Fontana, Robert J.; Lee, William M.; Schilsky, Michael L.; Polson, Julie; Pezzia, Carla; Lalani, Ezmina; Hynan, Linda S.; Reisch, Joan S.; Larson, Anne M.; Do, Hao; Crippin, Jeffrey S.; Gerstle, Laura; Davern, Timothy J.; Partovi, Katherine; Emre, Sukru; McCashland, Timothy M.; Bernard, Tamara; Hay, J. Eileen; Groettum, Cindy; Murray, Natalie; Coultrup, Sonnya; Shakil, A. Obaid; Morton, Diane; Blei, Andres T.; Gottstein, Jeanne; Zaman, Atif; Schwartz, Jonathan; Ingram, Ken; Han, Steven; Peacock, Val; Fontana, Robert J.; Welch, Suzanne; McGuire, Brendan; Avant, Linda; Chung, Raymond; Casson, Deborah; Brown, Robert Jr; Senkbeil, Laren; Harrison, M. Edwyn; Rush, Rebecca; Reuben, Adrian; Huntley, Nancy; Munoz, Santiago; Misra, Chandra; Stravitz, Todd; Salvatori, Jennifer; Rossaro, Lorenzo; Prosser, Colette; Satyanaryana, Raj; Taylor, Wendy; Reddy, Raj; Campbell, Mical; Hassenein, Tarek; Barakat, Fatma; Smith, Alistair.

In: Hepatology, Vol. 48, No. 4, 10.2008, p. 1167-1174.

Research output: Contribution to journalArticle

Korman, JD, Volenberg, I, Balko, J, Webster, J, Schiodt, FV, Squires, RH, Fontana, RJ, Lee, WM, Schilsky, ML, Polson, J, Pezzia, C, Lalani, E, Hynan, LS, Reisch, JS, Larson, AM, Do, H, Crippin, JS, Gerstle, L, Davern, TJ, Partovi, K, Emre, S, McCashland, TM, Bernard, T, Hay, JE, Groettum, C, Murray, N, Coultrup, S, Shakil, AO, Morton, D, Blei, AT, Gottstein, J, Zaman, A, Schwartz, J, Ingram, K, Han, S, Peacock, V, Fontana, RJ, Welch, S, McGuire, B, Avant, L, Chung, R, Casson, D, Brown, RJ, Senkbeil, L, Harrison, ME, Rush, R, Reuben, A, Huntley, N, Munoz, S, Misra, C, Stravitz, T, Salvatori, J, Rossaro, L, Prosser, C, Satyanaryana, R, Taylor, W, Reddy, R, Campbell, M, Hassenein, T, Barakat, F & Smith, A 2008, 'Screening for Wilson disease in acute liver failure: A comparison of currently available diagnostic tests', Hepatology, vol. 48, no. 4, pp. 1167-1174. https://doi.org/10.1002/hep.22446
Korman JD, Volenberg I, Balko J, Webster J, Schiodt FV, Squires RH et al. Screening for Wilson disease in acute liver failure: A comparison of currently available diagnostic tests. Hepatology. 2008 Oct;48(4):1167-1174. https://doi.org/10.1002/hep.22446
Korman, Jessica D. ; Volenberg, Irene ; Balko, Jody ; Webster, Joe ; Schiodt, Frank V. ; Squires, Robert H. ; Fontana, Robert J. ; Lee, William M. ; Schilsky, Michael L. ; Polson, Julie ; Pezzia, Carla ; Lalani, Ezmina ; Hynan, Linda S. ; Reisch, Joan S. ; Larson, Anne M. ; Do, Hao ; Crippin, Jeffrey S. ; Gerstle, Laura ; Davern, Timothy J. ; Partovi, Katherine ; Emre, Sukru ; McCashland, Timothy M. ; Bernard, Tamara ; Hay, J. Eileen ; Groettum, Cindy ; Murray, Natalie ; Coultrup, Sonnya ; Shakil, A. Obaid ; Morton, Diane ; Blei, Andres T. ; Gottstein, Jeanne ; Zaman, Atif ; Schwartz, Jonathan ; Ingram, Ken ; Han, Steven ; Peacock, Val ; Fontana, Robert J. ; Welch, Suzanne ; McGuire, Brendan ; Avant, Linda ; Chung, Raymond ; Casson, Deborah ; Brown, Robert Jr ; Senkbeil, Laren ; Harrison, M. Edwyn ; Rush, Rebecca ; Reuben, Adrian ; Huntley, Nancy ; Munoz, Santiago ; Misra, Chandra ; Stravitz, Todd ; Salvatori, Jennifer ; Rossaro, Lorenzo ; Prosser, Colette ; Satyanaryana, Raj ; Taylor, Wendy ; Reddy, Raj ; Campbell, Mical ; Hassenein, Tarek ; Barakat, Fatma ; Smith, Alistair. / Screening for Wilson disease in acute liver failure : A comparison of currently available diagnostic tests. In: Hepatology. 2008 ; Vol. 48, No. 4. pp. 1167-1174.
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abstract = "Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD(ALF-WD), data and serum were collected from 140 ALF patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp<20 mg/dL by the oxidase method provided a diagnostic sensitivity of 21{\%} and specificity of 84{\%} while, by nephelometry, a sensitivity of 56{\%} and specificity of 63{\%}. Serum copper levels exceeded 200 μg/dL in all ALF-WD patients measured (13/16), but were also elevated in non-WD ALF. An alkaline phosphatase (AP) to total bilirubin (TB) ratio <4 yielded a sensitivity of 94{\%}, specificity of 96{\%}, and a likelihood ratio of 23 for diagnosing fulminant WD. In addition, an AST:ALT ratio>2.2 yielded a sensitivity of 94{\%}, a specificity of 86{\%}, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity and specificity of 100{\%}. Conclusion: Conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum aminotransferases by contrast provides the most rapid and accurate method for diagnosis of ALF due to WD.",
author = "Korman, {Jessica D.} and Irene Volenberg and Jody Balko and Joe Webster and Schiodt, {Frank V.} and Squires, {Robert H.} and Fontana, {Robert J.} and Lee, {William M.} and Schilsky, {Michael L.} and Julie Polson and Carla Pezzia and Ezmina Lalani and Hynan, {Linda S.} and Reisch, {Joan S.} and Larson, {Anne M.} and Hao Do and Crippin, {Jeffrey S.} and Laura Gerstle and Davern, {Timothy J.} and Katherine Partovi and Sukru Emre and McCashland, {Timothy M.} and Tamara Bernard and Hay, {J. Eileen} and Cindy Groettum and Natalie Murray and Sonnya Coultrup and Shakil, {A. Obaid} and Diane Morton and Blei, {Andres T.} and Jeanne Gottstein and Atif Zaman and Jonathan Schwartz and Ken Ingram and Steven Han and Val Peacock and Fontana, {Robert J.} and Suzanne Welch and Brendan McGuire and Linda Avant and Raymond Chung and Deborah Casson and Brown, {Robert Jr} and Laren Senkbeil and Harrison, {M. Edwyn} and Rebecca Rush and Adrian Reuben and Nancy Huntley and Santiago Munoz and Chandra Misra and Todd Stravitz and Jennifer Salvatori and Lorenzo Rossaro and Colette Prosser and Raj Satyanaryana and Wendy Taylor and Raj Reddy and Mical Campbell and Tarek Hassenein and Fatma Barakat and Alistair Smith",
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T1 - Screening for Wilson disease in acute liver failure

T2 - A comparison of currently available diagnostic tests

AU - Korman, Jessica D.

AU - Volenberg, Irene

AU - Balko, Jody

AU - Webster, Joe

AU - Schiodt, Frank V.

AU - Squires, Robert H.

AU - Fontana, Robert J.

AU - Lee, William M.

AU - Schilsky, Michael L.

AU - Polson, Julie

AU - Pezzia, Carla

AU - Lalani, Ezmina

AU - Hynan, Linda S.

AU - Reisch, Joan S.

AU - Larson, Anne M.

AU - Do, Hao

AU - Crippin, Jeffrey S.

AU - Gerstle, Laura

AU - Davern, Timothy J.

AU - Partovi, Katherine

AU - Emre, Sukru

AU - McCashland, Timothy M.

AU - Bernard, Tamara

AU - Hay, J. Eileen

AU - Groettum, Cindy

AU - Murray, Natalie

AU - Coultrup, Sonnya

AU - Shakil, A. Obaid

AU - Morton, Diane

AU - Blei, Andres T.

AU - Gottstein, Jeanne

AU - Zaman, Atif

AU - Schwartz, Jonathan

AU - Ingram, Ken

AU - Han, Steven

AU - Peacock, Val

AU - Fontana, Robert J.

AU - Welch, Suzanne

AU - McGuire, Brendan

AU - Avant, Linda

AU - Chung, Raymond

AU - Casson, Deborah

AU - Brown, Robert Jr

AU - Senkbeil, Laren

AU - Harrison, M. Edwyn

AU - Rush, Rebecca

AU - Reuben, Adrian

AU - Huntley, Nancy

AU - Munoz, Santiago

AU - Misra, Chandra

AU - Stravitz, Todd

AU - Salvatori, Jennifer

AU - Rossaro, Lorenzo

AU - Prosser, Colette

AU - Satyanaryana, Raj

AU - Taylor, Wendy

AU - Reddy, Raj

AU - Campbell, Mical

AU - Hassenein, Tarek

AU - Barakat, Fatma

AU - Smith, Alistair

PY - 2008/10

Y1 - 2008/10

N2 - Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD(ALF-WD), data and serum were collected from 140 ALF patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp<20 mg/dL by the oxidase method provided a diagnostic sensitivity of 21% and specificity of 84% while, by nephelometry, a sensitivity of 56% and specificity of 63%. Serum copper levels exceeded 200 μg/dL in all ALF-WD patients measured (13/16), but were also elevated in non-WD ALF. An alkaline phosphatase (AP) to total bilirubin (TB) ratio <4 yielded a sensitivity of 94%, specificity of 96%, and a likelihood ratio of 23 for diagnosing fulminant WD. In addition, an AST:ALT ratio>2.2 yielded a sensitivity of 94%, a specificity of 86%, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity and specificity of 100%. Conclusion: Conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum aminotransferases by contrast provides the most rapid and accurate method for diagnosis of ALF due to WD.

AB - Acute liver failure (ALF) due to Wilson disease (WD) is invariably fatal without emergency liver transplantation. Therefore, rapid diagnosis of WD should aid prompt transplant listing. To identify the best method for diagnosis of ALF due to WD(ALF-WD), data and serum were collected from 140 ALF patients (16 with WD), 29 with other chronic liver diseases and 17 with treated chronic WD. Ceruloplasmin (Cp) was measured by both oxidase activity and nephelometry and serum copper levels by atomic absorption spectroscopy. In patients with ALF, a serum Cp<20 mg/dL by the oxidase method provided a diagnostic sensitivity of 21% and specificity of 84% while, by nephelometry, a sensitivity of 56% and specificity of 63%. Serum copper levels exceeded 200 μg/dL in all ALF-WD patients measured (13/16), but were also elevated in non-WD ALF. An alkaline phosphatase (AP) to total bilirubin (TB) ratio <4 yielded a sensitivity of 94%, specificity of 96%, and a likelihood ratio of 23 for diagnosing fulminant WD. In addition, an AST:ALT ratio>2.2 yielded a sensitivity of 94%, a specificity of 86%, and a likelihood ratio of 7 for diagnosing fulminant WD. Combining the tests provided a diagnostic sensitivity and specificity of 100%. Conclusion: Conventional WD testing utilizing serum ceruloplasmin and/or serum copper levels are less sensitive and specific in identifying patients with ALF-WD than other available tests. More readily available laboratory tests including alkaline phosphatase, bilirubin and serum aminotransferases by contrast provides the most rapid and accurate method for diagnosis of ALF due to WD.

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