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Wielders JPM, Porpiglia NM, Schellenberg F, Deenmamode J, Delanghe J, Anton RF, Bortolotti F, Siebelder C, Tagliaro F, Weykamp C, Helander A. Recommendations on the measurement and use of the alcohol consumption biomarker CDT. A position paper from the IFCC Working Group on CDT standardisation. Clin Chim Acta 2024; 555:117800. [PMID: 38309557 DOI: 10.1016/j.cca.2024.117800] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 01/10/2024] [Accepted: 01/22/2024] [Indexed: 02/05/2024]
Abstract
BACKGROUND Carbohydrate deficient transferrin (CDT) is a biomarker for excessive alcohol consumption utilized in clinical and forensic medicine and workplace testing. Previously, many different analytical methods for CDT were used and the measurand varied considerably, making direct comparison of test results difficult. To end this confusion, the IFCC established a working group on CDT standardisation (WG-CDT) which completed its tasks in 2017. METHODS This IFCC position paper by the WG-CDT summarizes state of the art information about the measurand and the analytical methods and gives concise recommendations for its utilization. RESULTS The results achieved by the CDT standardisation process led to accuracy improvements in national external quality assessment schemes over the years. A brief review of ROC based comparison studies with the traditional biomarkers (GGT, MCV, ALT and AST) discusses the bias resulting from inadequate study populations. In large groups of the general population the superior diagnostic performance of CDT is confirmed. CONCLUSION The relationship between alcohol intake versus resulting CDT is discussed as well as the cutoff and measurement uncertainty. Concerning the application in practice, potential pitfalls are considered and recommendations handling both analytical and preanalytical caveats are given. Finally, some examples of serious misunderstandings in publications about CDT are addressed.
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Affiliation(s)
- J P M Wielders
- Joseph Peter Marie Wielders, Amersfoort, the Netherlands.
| | - N M Porpiglia
- Nadia Maria Porpiglia, Department of Diagnostics and Public Health, Unit of Forensic Medicine, University of Verona, Verona, Italy.
| | | | | | - J Delanghe
- Joris Delanghe, Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - R F Anton
- Raymond Francis Anton, Medical University of South Carolina, Charleston, SC, USA
| | - F Bortolotti
- Federica Bortolotti, Department of Diagnostics and Public Health, Unit of Forensic Medicine, University of Verona, Verona, Italy
| | - C Siebelder
- Carla Siebelder, MCA Laboratory, Queen Beatrix Hospital, Winterswijk, the Netherlands
| | - F Tagliaro
- Franco Tagliaro, Department of Diagnostics and Public Health, Unit of Forensic Medicine, University of Verona, Verona, Italy
| | - C Weykamp
- Cas Weykamp, MCA Laboratory, Queen Beatrix Hospital, Winterswijk, the Netherlands
| | - A Helander
- Anders Helander, Karolinska Institutet, Karolinska University Laboratory, Stockholm, Sweden
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Caslavska J, Thormann W. Monitoring of transferrin isoforms in biological samples by capillary electrophoresis. J Sep Sci 2017; 41:303-322. [PMID: 28885776 DOI: 10.1002/jssc.201700914] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Revised: 09/04/2017] [Accepted: 09/04/2017] [Indexed: 11/10/2022]
Abstract
Work dealing with the monitoring of transferrin isoforms in human serum and other body fluids by capillary electrophoresis is reviewed. It comprises capillary zone electrophoresis and capillary isoelectric focusing efforts that led to the exploration and use of assays for the determination of carbohydrate-deficient transferrin as a marker for excessive alcohol intake, genetic variants of transferrin, congenital disorders of glycosylation and β-2-transferrin, which is a marker for cerebrospinal fluid leakage. This paper provides insight into the development, specifications, strengths, weaknesses, and routine use of the currently known capillary electrophoresis based assays suitable to detect transferrin isoforms in body fluids. The achievements reached so far indicate that capillary zone electrophoresis is an attractive technology to monitor the molecular forms of transferrin in biological specimens as the assays do not require an elaborate sample pretreatment and thus can be fully automated for high-throughput analyses on multicapillary instruments. Assays based on capillary isoelectric focusing are less attractive. They require immunoextraction of transferrin from the biological matrix and mobilization after focusing if instrumentation with a whole-column imaging detector is not available. Interactions of the carrier ampholytes with the iron of transferrin may prevent iron saturation and thus provide more complicated isoform patterns.
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Affiliation(s)
- Jitka Caslavska
- Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland
| | - Wolfgang Thormann
- Clinical Pharmacology Laboratory, Institute for Infectious Diseases, University of Bern, Bern, Switzerland
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Bertholet N, Winter MR, Cheng DM, Samet JH, Saitz R. How accurate are blood (or breath) tests for identifying self-reported heavy drinking among people with alcohol dependence? Alcohol Alcohol 2014; 49:423-9. [PMID: 24740846 DOI: 10.1093/alcalc/agu016] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
AIMS Managing patients with alcohol dependence includes assessment for heavy drinking, typically by asking patients. Some recommend biomarkers to detect heavy drinking but evidence of accuracy is limited. METHODS Among people with dependence, we assessed the performance of disialo-carbohydrate-deficient transferrin (%dCDT, ≥1.7%), gamma-glutamyltransferase (GGT, ≥66 U/l), either %dCDT or GGT positive, and breath alcohol (> 0) for identifying 3 self-reported heavy drinking levels: any heavy drinking (≥4 drinks/day or >7 drinks/week for women, ≥5 drinks/day or >14 drinks/week for men), recurrent (≥5 drinks/day on ≥5 days) and persistent heavy drinking (≥5 drinks/day on ≥7 consecutive days). Subjects (n = 402) with dependence and current heavy drinking were referred to primary care and assessed 6 months later with biomarkers and validated self-reported calendar method assessment of past 30-day alcohol use. RESULTS The self-reported prevalence of any, recurrent and persistent heavy drinking was 54, 34 and 17%. Sensitivity of %dCDT for detecting any, recurrent and persistent self-reported heavy drinking was 41, 53 and 66%. Specificity was 96, 90 and 84%, respectively. %dCDT had higher sensitivity than GGT and breath test for each alcohol use level but was not adequately sensitive to detect heavy drinking (missing 34-59% of the cases). Either %dCDT or GGT positive improved sensitivity but not to satisfactory levels, and specificity decreased. Neither a breath test nor GGT was sufficiently sensitive (both tests missed 70-80% of cases). CONCLUSIONS Although biomarkers may provide some useful information, their sensitivity is low the incremental value over self-report in clinical settings is questionable.
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Affiliation(s)
- Nicolas Bertholet
- Alcohol Treatment Center, Department of Community Medicine and Health, Lausanne University Hospital, Lausanne, Switzerland
| | - Michael R Winter
- Data Coordinating Center, Boston University School of Public Health, Boston, MA, USA
| | - Debbie M Cheng
- Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Boston University and Boston Medical Center, Boston, MA, USA Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
| | - Jeffrey H Samet
- Clinical Addiction Research and Education Unit, Section of General Internal Medicine, Boston University and Boston Medical Center, Boston, MA, USA Department of Community Health Sciences, Boston University School of Public Health, Boston, MA, USA
| | - Richard Saitz
- Data Coordinating Center, Boston University School of Public Health, Boston, MA, USA Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
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Affiliation(s)
- Jitka Caslavska
- Clinical Pharmacology Laboratory; Institute for Infectious Diseases; University of Bern; Bern; Switzerland
| | - Wolfgang Thormann
- Clinical Pharmacology Laboratory; Institute for Infectious Diseases; University of Bern; Bern; Switzerland
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Hagström H, Stål P, Stokkeland K, Bergquist A. Alcohol consumption in patients with primary sclerosing cholangitis. World J Gastroenterol 2012; 18:3105-11. [PMID: 22791946 PMCID: PMC3386324 DOI: 10.3748/wjg.v18.i24.3105] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2011] [Revised: 02/20/2012] [Accepted: 02/26/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the alcohol drinking patterns in a cohort of primary sclerosing cholangitis (PSC) patients and the possible influence on the development of fibrosis.
METHODS: Ninety-six patients with PSC were evaluated with a validated questionnaire about a patient’s lifetime drinking habits: the lifetime drinking history (LDH) questionnaire. In addition, clinical status, transient elastography and biochemistry values were analysed and registered. Patients were defined as having either significant or non-significant fibrosis. Significant fibrosis was defined as either an elastography value of ≥ 17.3 kPa or the presence of clinical signs of cirrhosis. Patients were divided into two groups depending on their alcohol consumption patterns; no/low alcohol consumption (one drink or unit/d) and moderate/high alcohol consumption (≥ 1 drink or unit/d). LDH data were calculated to estimate lifetime alcohol intake (LAI), current alcohol intake, drinks per year before and after diagnosis of PSC. We also calculated the number of episodes of binge-drinking (defined as consuming ≥ 5 drinks per occasion) in total, before and after the diagnosis of PSC.
RESULTS: The mean LAI was 3882 units of alcohol, giving a mean intake after onset of alcohol consumption of 2.6 units per week. Only 9% of patients consumed alcohol equal to or more than one unit per day. Current alcohol intake in patients with significant fibrosis (n = 26) was less than in patients without significant fibrosis (n = 70), as shown by lower values of phosphatidylethanol (B-PEth) (0.1 μmol/L vs 0.33 μmol/L, respectively, P = 0.002) and carbohydrate-deficient transferrin (CDT) (0.88% vs 1.06%, respectively, P = 0.02). Self-reported LAI was similar between the two groups. Patients with significant fibrosis reduced their alcohol intake after diagnosis from 103 to 88 units per year whereas patients without fibrosis increased their alcohol intake after PSC diagnosis from 111 to 151 units/year. There were no correlations between elastography values and intake of alcohol (units/year) (r = -0.036).
CONCLUSION: PSC patients have low alcohol consumption. The lack of correlation between fibrosis and alcohol intake indicates that a low alcohol intake is safe in these patients.
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Chrostek L, Cylwik B, Gruszewska E, Panasiuk A, Szmitkowski M. N-Latex CDT results in liver diseases. Alcohol Alcohol 2012; 47:428-32. [PMID: 22582186 DOI: 10.1093/alcalc/ags053] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
AIMS The aim of this study was to test whether liver diseases of alcoholic and non-alcoholic origin cause false-positive carbohydrate-deficient transferrin (CDT) results when the particle-enhanced immunonephelometry for CDT assays is used and to assess the effect of liver disease severity on N-Latex CDT results. METHODS Blood was sampled from 245 newly admitted patients suffering from liver diseases: alcoholic and non-alcoholic cirrhosis (AC), chronic viral (B and C) and non-viral hepatitis, toxic and autoimmune hepatitis (AIH), hepatocellular carcinoma and primary biliary cirrhosis (PBC). CDT was determined by particle-enhanced imunononephelometry using the N-Latex CDT test. RESULTS There were significant differences in %CDT levels between liver diseases of various etiologies. The %CDT level in AC was higher than that in chronic hepatitis (non-viral and viral C). In turn, the %CDT level in chronic hepatitis C was lower than that in toxic hepatitis. The frequency of false-positive %CDT results in liver diseases of non-alcoholic origin was 13/146, and was highest in AIH (4/14). There were no CDT-positive results in PBC and chronic hepatitis B. The frequency of CDT-positive results in alcoholic liver diseases was 24/59 in cirrhosis and 10/34 in hepatitis. Serum levels of %CDT in cirrhotic patients are correlated with the severity of the disease assessed by the Child-Pugh score. CONCLUSION We concluded that the liver diseases affect the relative but not absolute values of CDT when using the assay with the monoclonal antibodies directed against CDT. The CDT results from N-Latex CDT test reflect the severity of liver dysfunction.
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Affiliation(s)
- Lech Chrostek
- Department of Biochemical Diagnostics, Medical University, Waszyngtona 15A, 15-269 Bialystok, Poland.
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Ireland J, Cheng DM, Samet JH, Bridden C, Quinn E, Saitz R. Operating characteristics of carbohydrate-deficient transferrin (CDT) for identifying unhealthy alcohol use in adults with HIV infection. AIDS Care 2011; 23:1483-91. [PMID: 21732900 DOI: 10.1080/09540121.2011.565019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Unhealthy alcohol use (the spectrum of risky use through dependence) is common in HIV-infected persons, yet it can interfere with HIV medication adherence, may lower CD4 cell count, and can cause hepatic injury. Carbohydrate-deficient transferrin (CDT), often measured as %CDT, can detect heavy drinking but whether it does in people with HIV is not well established. We evaluated the operating characteristics of %CDT in HIV-infected adults using cross-sectional data from 300 HIV-infected adults with current or past alcohol problems. Past 30-day alcohol consumption was determined using the Timeline Followback (TLFB), a validated structured recall questionnaire, as the reference standard. Sensitivity and specificity of %CDT (at manufacturer's cut-off point of 2.6%) for detecting both "at-risk" (≥4 drinks in a day or >7 drinks per week for women, ≥5 drinks in a day or >14 per week for men) and "heavy" drinking (≥4 drinks in a day for women, ≥5 drinks in a day for men on at least seven days) were calculated. Receiver operating characteristic (ROC) curves were estimated to summarize the diagnostic ability of %CDT for distinguishing "at risk" and "heavy" levels of drinking. Exploratory analyses that stratified by gender and viral hepatitis infection were performed. Of 300 subjects, 103 reported current consumption at "at-risk" amounts, and 47 reported "heavy" amounts. For "at-risk" drinking, sensitivity of %CDT was 28% (95% confidence interval (CI) 19%, 37%), specificity 90% (95% CI 86%, 94%); area under the ROC curve (AUC) was 0.59. For "heavy" drinking, sensitivity was 36% (95% CI 22%, 50%), specificity 88% (95% CI 84%, 92%); AUC was 0.60. Sensitivity appeared lower among women and those with viral hepatitis; specificity was similar across subgroups. Among HIV-infected adults, %CDT testing yielded good specificity, but poor sensitivity for detecting "at-risk" and "heavy" alcohol consumption, limiting its clinical utility for detecting unhealthy alcohol use in this population.
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Affiliation(s)
- Julia Ireland
- Department of Family Medicine, Boston Medical Center, Boston University School of Medicine, MA, USA.
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Wolff F, Mesquita M, Corazza F, Demulder A, Willems D. False positive carbohydrate-deficient transferrin results in chronic hemodialysis patients related to the analytical methodology. Clin Biochem 2010; 43:1148-51. [PMID: 20599878 DOI: 10.1016/j.clinbiochem.2010.06.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2010] [Revised: 06/02/2010] [Accepted: 06/03/2010] [Indexed: 10/19/2022]
Abstract
OBJECTIVES Chronic kidney disease stage V is associated with a metabolic acidosis, a disturbance also observed in heavy alcohol consumption. Carbohydrate-deficient transferrin is considered the most accurate biomarker for identifying chronic alcohol abuse. We tested whether increased CDT results occurred in patients on dialysis therapy. DESIGN AND METHODS One hundred twenty-two samples from HD patients were analyzed by three different analytical methods and the results were compared with those obtained in 48 healthy volunteers. RESULTS On the basis of the upper 97.5th percentile, positive CDT results were found in 25.4%, 9.8% and 12.3% of the HD patients with particle-enhanced immunonephelometry, capillary electrophoresis and HPLC, respectively. A significant correlation between CDT values and transferrin concentration was found for the particle-enhanced immunonephelometric test (r: -0.311; p: 0.0009). CONCLUSIONS A high rate of positive CDT results was observed in HD patients with the particle-enhanced immunonephelometry and seems to be related to the low transferrin concentration.
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Affiliation(s)
- Fleur Wolff
- Laboratory of Clinical Chemistry, Brugmann University Hospital, Brussels, Belgium.
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Carbohydrate deficient transferrin and forensic medicine. Clin Chim Acta 2009; 406:1-7. [DOI: 10.1016/j.cca.2009.05.020] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2009] [Revised: 05/19/2009] [Accepted: 05/20/2009] [Indexed: 11/24/2022]
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Marti U, Joneli J, Caslavska J, Thormann W. Determination of carbohydrate-deficient transferrin in human serum by two capillary zone electrophoresis methods and a direct immunoassay: Comparison of patient data. J Sep Sci 2008; 31:3079-87. [DOI: 10.1002/jssc.200800314] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Arndt T, van der Meijden BB, Wielders JP. Atypical serum transferrin isoform distribution in liver cirrhosis studied by HPLC, capillary electrophoresis and transferrin genotyping. Clin Chim Acta 2008; 394:42-6. [DOI: 10.1016/j.cca.2008.03.033] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2008] [Revised: 03/27/2008] [Accepted: 03/27/2008] [Indexed: 01/08/2023]
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HPLC evaluation of clinical and pharmacological factors reported to cause false-positive carbohydrate-deficient transferrin (CDT) levels. Clin Chim Acta 2008; 389:164-6. [DOI: 10.1016/j.cca.2007.11.020] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2007] [Revised: 11/22/2007] [Accepted: 11/22/2007] [Indexed: 11/23/2022]
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Arndt T, Guessregen B, Hallermann D, Nauck M, Terjung D, Weckesser H. Forensic analysis of carbohydrate-deficient transferrin (CDT) by HPLC—Statistics and extreme CDT values. Forensic Sci Int 2008; 175:27-30. [PMID: 17560061 DOI: 10.1016/j.forsciint.2007.05.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2006] [Revised: 04/23/2007] [Accepted: 05/02/2007] [Indexed: 11/29/2022]
Abstract
BACKGROUND Carbohydrate-deficient transferrin (CDT) is the most specific serum marker of chronic alcohol abuse so far. There is little knowledge about extreme CDT values of >20% and the more >30% CDT. METHODS Serum CDT/transferrin ratios from 19,236 serum samples sent to our laboratory for routine CDT analysis were determined by HPLC. About 75% of these serum samples were from traffic or employment medicine investigations. A CDT value frequency histogram was computed and extreme CDT values were clinically validated. RESULTS Fourteen thousand four hundred and sixty-one CDT results were normal (< or =1.7%) and 4775 increased (1.8-36.9% CDT). Most frequent normal and increased results were 0.9% CDT (n=1964) and 1.8% CDT (n=356). CA. 70% of the pathological results were between 1.8% and 5.0% CDT, ca. 88% between 1.8% and 10.0% CDT, and 98% between 1.8% and 20.0%. CDT values >20.0% appeared in 79 cases and results >30.0% in two cases (33.8% and 36.9%). In each case of CDT values >20%, chronic alcohol abuse was the underlying cause as confirmed by anamnestic exploration. CONCLUSIONS CDT/transferrin ratios are usually <20%. Higher values can appear in rare cases. CDT results >30% can be due to alcohol abuse but should be considered as remarkable single observations. Visualization of the transferrin isoform patterns by HPLC allows the detection of pathological transferrin isoform patterns and of genetic transferrin variants. This is essential for a reliable interpretation of (extreme) CDT values. CDT analysis by immunoassays without physico-chemical confirmatory analysis is no longer acceptable.
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Affiliation(s)
- Torsten Arndt
- Bioscientia GmbH, Konrad Adenauer Strasse 17, D-55218 Ingelheim, Germany.
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Rainio J, De Paoli G, Druid H, Kauppila R, De Giorgio F, Bortolotti F, Tagliaro F. Post-mortem stability and redistribution of carbohydrate-deficient transferrin (CDT). Forensic Sci Int 2008; 174:161-5. [PMID: 17475426 DOI: 10.1016/j.forsciint.2007.03.020] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2006] [Revised: 03/22/2007] [Accepted: 03/25/2007] [Indexed: 10/23/2022]
Abstract
Post-mortem diagnosis of chronic alcohol abuse is a challenge for forensic experts due to the lack of pathognomonic morphological findings and often also inadequate background information. Objective methods demonstrating chronic excessive alcohol consumption would therefore be a useful tool for forensic pathologists. In clinical practice, several markers of chronic alcohol abuse have recently been introduced, among which carbohydrate-deficient transferrin (CDT) is the most accepted, but the use of these markers in autopsy has not yet been established. We examined post-mortem stability and possible post-mortem redistribution of CDT and compared two analytical methods, capillary zone electrophoresis and high-performance liquid chromatography. According to our results, CDT remains stable for an appreciable time after death. The results further indicate that CDT is not subject to major post-mortem redistribution.
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Affiliation(s)
- Juha Rainio
- Institute of Legal Medicine, Catholic University of Sacred Heart School of Medicine, Rome, Italy
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Abstract
PURPOSE OF REVIEW This review aims to acquaint the reader with advances in 2006 in the epidemiology, genetics, detection, pathogenesis and treatment of alcoholic liver disease. RECENT FINDINGS Important discoveries have been made in pathogenesis and mechanism of disease, with great emphasis on the many pathways leading to oxidative stress, and the novel mechanism of endoplasmic reticulum stress that is proving to be important in the pathogenesis of many liver diseases. The reliability of ethyl glucuronide and other biomarkers for the detection of alcohol abuse is being better established. There have been no treatment advances for alcoholic liver disease but, on balance, steroids are still favored for carefully selected patients with alcoholic hepatitis. Many compounds tested in rodents may now be available for consideration for clinical trials. Criteria for patient selection and refusal for liver transplantation are being established but the 6 months abstinence rule still holds. SUMMARY Insights are being made into the pathogenesis of alcoholic liver disease but safe and effective therapies for both alcoholic hepatitis and alcoholic cirrhosis have yet to be discovered.
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Affiliation(s)
- Adrian Reuben
- Liver Service, Division of Gastroenterology and Hepatology, And Liver Transplant Program, Medical University of South Carolina, Charleston, South Carolina, USA.
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Arndt T, Erkens M, Holtkamp K, Keller T, Gressner AM. High prevalence of increased trisialotransferrin concentrations in patients with anorexia nervosa: Implications for determination of carbohydrate-deficient transferrin. Clin Chim Acta 2007; 379:150-3. [PMID: 17291470 DOI: 10.1016/j.cca.2007.01.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2006] [Revised: 01/10/2007] [Accepted: 01/10/2007] [Indexed: 11/25/2022]
Abstract
BACKGROUND Carbohydrate-deficient transferrin (asialo-+monosialo-+disialotransferrin, CDT) is currently the most specific laboratory marker of chronic alcohol abuse. We tested whether previous findings of false-positive CDT results for anorexia nervosa patients have been due to invalid CDT analysis methods or anorexia nervosa by itself. METHODS Serum CDT from 49 anorexia nervosa patients, 14 bulimia nervosa patients and 22 healthy controls (all adolescent, female and age-matched) was determined in a retrospective study by HPLC (Clin-Rep-CDT-in-serum-online, cut-off > or =1.8%, Recipe), by capillary electrophoresis (Capillarys-CDT, cut-off > or =1.3%, Sebia) and (due to limited surplus serum volume for a subset of 18 anorexia nervosa patients with increased trisialotransferrin detected by HPLC) by immunoassay based on anion-exchange CDT and non-CDT fractionation (%CDT-TIA, cut-off > or =2.6% CDT, Bio-Rad). RESULTS HPLC and capillary electrophoresis: No false-positive CDT results were obtained. Asialo- and monosialotransferrin were not detected and disialotransferrin (CDT) was in each case clearly below the test-specific cut-offs. Trisialotransferrin (a non-CDT isoform) was increased (cut-off > or =5.0% for HPLC) in 33 anorexia patients, 2 bulimia patients and 2 controls. %CDT-TIA: 8 false-positive CDT results of > or =2.6% out of the 18 samples tested (CDT-range/mean/median 2.6-4.6/3.2/2.8%). CONCLUSIONS Anorexia nervosa does not cause by itself increased CDT results. False-positive CDT values from the past are most likely due to an incomplete separation of trisialotransferrin from CDT and thus overdetermination of CDT. Immunological CDT testing without confirmatory analysis by HPLC or CE is no longer acceptable.
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Affiliation(s)
- Torsten Arndt
- Bioscientia Institut fuer Medizinische Diagnostik GmbH, D-55218 Ingelheim, Germany.
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Arndt T, Keller T. Carbohydrate-deficient transferrin and anorexia nervosa. Psychiatry Res 2006; 144:245-6; author reply 247-8. [PMID: 16945425 DOI: 10.1016/j.psychres.2006.07.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2006] [Accepted: 07/27/2006] [Indexed: 11/30/2022]
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