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Carbohydrate-deficient transferrin (CDT) evaluation in the insurance industry
H E P A T O L O G Y V o l . 22, N o . 4, P t .
1145
2, 1 9 9 5
AASLD
A CLASSIFICATION OF LARGE VEIN THROMBOSIS OCCURRING IN PATIENTS WITH CIRRHOSIS AND PORTAL HYPERTENSION Y. Bayraklar, F. Balkanci, M. Bayraklar, B. Kayhan, S. Dundar, S. Arslan, D.H. Van Thiel, B. Uzunalimoqlu. Hacettepe University School of Medicine, Ankara, Turkey; Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
ABSTRACTS
1146
COMPARISON OF THE PREVALENCE OF AUTOANTIBODIES IN CHRONIC HEPATITIS C PATIENTS WITH THOSE OF AUTOANTIBODIES IN AUTOIMMUNE HEPATITIS PATIENTS Y. Bayraktar, M. Bayraktar, A. Gurakar, T. Hassanein, D~H. Van Thiel. Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma
Venous stasis, vascular wall injury and/or a deficiency of one or more naturally existing anti-coagnlants can lead to venous thrombosis. Only a few studies report the prevalence and type of large vein thrombosis seen in patients with liver disease. Most of these occur in cases with hepatic cancer or advanced liver cirrhosis and are limited to the portal vein. In this study, the incidence of venous thrombosis of one or more large veins in patients seen over an 8 year period from 1986 to 1994 was determined. A total of 1,512 patients were evaluated. 96 of these (6%) were found to have a large vessel thrombosis. The large vein thrombosis was limited to the abdominal cavity and was confirmed by either inferior or superior venacavography, hepatic venography or portography with digital subtraction angiography. Other studies such as computed tomography, liver biopsy and findings at surgery were confirmatory in many. These patients were studied intensively in an attempt to deiermine the etiology of the venous thrombosis. The venous disease could be classified as follows: Type I - involvement of the portal vein and/er its tributaries; Type II - involvement of the hepatic veins (Budd-Chiari syndrome); Type 11I - isolated fuvolvement of inferior vena eava at any level; Type IV combined involvementof the hepatic veins and the inferior vena cava; and, Type V combined involvementof the hepatic veins, inferior vena cava and portal vein and/or its tributaries. The underlying disorder responsible for the venous thrombosis was Behcet's disease in 16, chronic liver disease in 6, estrogen treatment in 5, congenital hepatic fibrosis in 4, hepatocellular carcinoma in 4, an antiphospholipid syndrome in 3, different malignancies in 3 and miscellaneuns disorders in 8. Despite a full clinical, radiographic, biochemical and serologic evaluation, no etiologic factor for the large vein thrombosis was found in 48 (50%). 43 (22%) were classified as type I, 22 (11%) as type II, 1 (0.5%) as type III, 24 (12%) as type IV and 7 (3.5%) as type V. In all 24, but 1, with inferior vena caval thrombosis, hepatic venous involvementwas present also. The extent of the eaval thrombosis appeared to have a major impact on the clinical enurse and survival of the cases. The azygous system and collaterals in the abdominal wall were important rootes for decompressing the dotted venous system in many.
1147
CARBOHYDRATE-DEFICIENT TRANSFERRIN (CDT) EVALUATION IN THE INSURANCE INDUSTRY. Pamela Bean'. Marv Susan Su~hin'. Palrieia Necessaryt. Sam Niedbala*. and M¢lkon S. Agopian*. "Specialty Laboratories, Inc., Santa Monica, CA 90404-3900; tLabOne, Overland Park, KS 66215; tSTC Diagnostics, Bethlehem, PA 18018-1799. In this study, we evaluated the utility of quantitating serum CDT using two methods: the well-established isoclectric foeusing/immunoblotting/laser densitometry (IEF/IB/LD) procedure and the newly developed STC kit. The former method separates CDT isoforms in a gradient of ampholytes under conditions of partial iron saturation; the latter procedure uses ion exchange chromatography followed by quantitation of eluted CDT isoforms in an enzyme immunoassay. Linearity data, precision data and interference studies performed for both tests support the clinical utility of these procedures in the diagnosis of alcohol abuse. Both assays measure CDT as a ratio of CDT to total serum transferrin (Tf). However, only IEF/IB/LD identifies false-positive results due to T f genetic D variants. One hundred thirty-two serum specimens submitted by insurance applicants were evaluated for CDT once (50/132) or twice (82/132) by the STC kit (LabOne) prior to testing by IEFflB/LD. Using a cutoff of 9 densitometry units (DU) for IEFfIB/LD (established for maximum clinical utility at 95% specificity based on ROC data) and 3% CDT/total "If for the STC kit, 30% (40/132) of the specimens were CDT+ and 48% (64/132) were CDT- by both methods. Four percent (5/132) of the sera tested CDT+ by IEF/IB/LD only; 11% (14/132) of the sera tested CDT+ by the STC kit only. Seven percent (9/132) of the specimens CDT-Y by the STC kit showed values in the indeterminate range (7 to 9 DU) for IEF/IB/LD. Of the two specimens identified as T f genetic D variants, one tested CDT+ by the STC kit only. All specimens CDT+ by STC had abnormal liver function test results. In summary, these data show that 93% (64/69) of the specimens CDT- by the STC kit, remain CDT- when evaluated by IEF/IB/LD. For CDT+ specimens, the best results are obtained when using the STC kit as a screening procedure, followed by IEFflB/LD as a confirmatory test.
393A
Hepatitis C virus (BCV) infection leads to chronic liver disease in 70% of individuals infected with the virus. HCV is associated with various autoimmune disorders. The only treatment for chronic hepatitis C is Interferon (IFN). The rationale for the use of IFN is that it is both an antiviral agent and upregnlates cellular immune mechanisms. This latter action is not specific and accordingly the cellular immune system is diffusely activated and can lead to the development of new autoimmane diseases in treated subjecLs. To determine the prevalence of abnormal autoantibodies in patients with chronic HCV and to estimate the prevalence of new onset autoimmune disease, the records of 201 patients with HCV were reviewed. 161 patients had chronic HCV defined by the presence of detectable anti-HCV or HCV-RNA by PeR. Each was also negative for HBsAg and had a liver biopsy consistent with chronic liver disease. 41 patients withpntative autoimmanehepatitis diagnosed on the basis of classical autoantibodies, tissue typing and the absence of anti-HCV and HCV/RNA in serum were reviewed also. The records of both groups were reviewed for the following autoimmune antibody: anti-nuclear antibody (ANA), antimitochondrial antibody (AMA), anti-liver-kidney microsomal antibody (LKM), anti-smooth muscle antibody (ASMA) and anti-microsomal antibody (AMS). The rate of ANA and ASMA positivity was 63-65% in both groups; AMA was positive in 4% of group I and 19% of group Ili LKM was absent in all HCV cases and present in 4% of group II cases; AMS positivity was present in 17 and 10% respectively. No significant differences in the IFN response rate was noted between those with HCV and antibodies and those withoot antibodies. 15 of the IFN-treated patients developed clinical manifestations of new onset autoimmune disease during their IFN treatment. None were managed by discontinuing the IFN. Most required some form of specific treatment. It can be concluded that: 1) ANA and ASMA are positive at the same frequency in both groups; 2) anti-LKM antibodies are frequently absent in patients with HCV infection; 3) newly developed autoimmune conditions develop during IFN treatment; 4) bet they do not require interruption of IFN therapy; and, 5) but do require additional therapy specific for the putative autoimmune disease.
1148
SERUM ~/-GLUTAMYL-TRANSPEPTI DASE ISOENZYMES IN CIRRHOSIS AND HEPATOCELLULAR CARCINOMA. _M. Bellini, S. Marchi, *R. Ginrdani, "t3. Fabfini. F. Costa. E. Taminn, G. Amatn, A Ricclfiuti. M. Rueen. P. Ciccorossi, C. Belcati and G. Mzltinri ClJnica Medica I and *Laboratotio Analisi Cliniehe; Universi~ di Pisa, Pisa, Italy Senan ~-glutamyltranspeptidase (GGT) is a sensitive but non-specific index of liver disease. Separation of G G T isoenzymes (iso-GG'D could improve the specificity. We have used a Rapid Electropboresis system (REP) (Helena Laboratories, Italy) on agarose gel in order to identify i s ~ G G T in: -fifty healthy volunteers (I-IV): 24 f and 26 m; mean age + SD: 32.96 _+ 4.59; mean total G G T value 5: SD; 15.20 + 9,13 U/L; -thirty-six patients with posthepatitic cirrhosis (PHC): 22 f and 14 m; mean age SD: 67.05 =i=11.31; mean total G G T value + SD: 76.42 + 54.16 U/L; -eigtheen patients with bepatoeellular carcinoma gdCC): 5 f and 13 m; mean age + SD: 61.5 + 7~54; mean total G G T value ± SD: 106.7 _+81.31 U/L. Ten fractions (0a, 0b, la, lb, 2a, 2b, 3a, 3b, 4a, 4b) were identified in HV and in PHC patients; an eleventh fraction (2c) was detected in HCC patients. A significant difference (p<0.05) has been observed in: la, 3b and 4b between HV and PHC patients; la, 2c and 4b between HV and HCC patients; In, 2c, 3a and 3b between PHC and HCC patients. HCC patients showed a typical pattern characterized by a lower la fraction and a higher 2c fraction. The peculiar 2c fraction was revealed in 15/18 HCC patients (83.3%): with a sensitivity of 83.3%, a specificity of 88.4% and an accuracy rate as a whole of 87.5%. Serum ct-fetoprotein levels showed no significant correlation with 2c values. In conclusion separation of iso-GGT could be proposed as a useful test in the follow up of chronic liver disease, particularly in the diagnosis of HCC. +
-
-
-
1145
2, 1 9 9 5
AASLD
A CLASSIFICATION OF LARGE VEIN THROMBOSIS OCCURRING IN PATIENTS WITH CIRRHOSIS AND PORTAL HYPERTENSION Y. Bayraklar, F. Balkanci, M. Bayraklar, B. Kayhan, S. Dundar, S. Arslan, D.H. Van Thiel, B. Uzunalimoqlu. Hacettepe University School of Medicine, Ankara, Turkey; Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
ABSTRACTS
1146
COMPARISON OF THE PREVALENCE OF AUTOANTIBODIES IN CHRONIC HEPATITIS C PATIENTS WITH THOSE OF AUTOANTIBODIES IN AUTOIMMUNE HEPATITIS PATIENTS Y. Bayraktar, M. Bayraktar, A. Gurakar, T. Hassanein, D~H. Van Thiel. Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma
Venous stasis, vascular wall injury and/or a deficiency of one or more naturally existing anti-coagnlants can lead to venous thrombosis. Only a few studies report the prevalence and type of large vein thrombosis seen in patients with liver disease. Most of these occur in cases with hepatic cancer or advanced liver cirrhosis and are limited to the portal vein. In this study, the incidence of venous thrombosis of one or more large veins in patients seen over an 8 year period from 1986 to 1994 was determined. A total of 1,512 patients were evaluated. 96 of these (6%) were found to have a large vessel thrombosis. The large vein thrombosis was limited to the abdominal cavity and was confirmed by either inferior or superior venacavography, hepatic venography or portography with digital subtraction angiography. Other studies such as computed tomography, liver biopsy and findings at surgery were confirmatory in many. These patients were studied intensively in an attempt to deiermine the etiology of the venous thrombosis. The venous disease could be classified as follows: Type I - involvement of the portal vein and/er its tributaries; Type II - involvement of the hepatic veins (Budd-Chiari syndrome); Type 11I - isolated fuvolvement of inferior vena eava at any level; Type IV combined involvementof the hepatic veins and the inferior vena cava; and, Type V combined involvementof the hepatic veins, inferior vena cava and portal vein and/or its tributaries. The underlying disorder responsible for the venous thrombosis was Behcet's disease in 16, chronic liver disease in 6, estrogen treatment in 5, congenital hepatic fibrosis in 4, hepatocellular carcinoma in 4, an antiphospholipid syndrome in 3, different malignancies in 3 and miscellaneuns disorders in 8. Despite a full clinical, radiographic, biochemical and serologic evaluation, no etiologic factor for the large vein thrombosis was found in 48 (50%). 43 (22%) were classified as type I, 22 (11%) as type II, 1 (0.5%) as type III, 24 (12%) as type IV and 7 (3.5%) as type V. In all 24, but 1, with inferior vena caval thrombosis, hepatic venous involvementwas present also. The extent of the eaval thrombosis appeared to have a major impact on the clinical enurse and survival of the cases. The azygous system and collaterals in the abdominal wall were important rootes for decompressing the dotted venous system in many.
1147
CARBOHYDRATE-DEFICIENT TRANSFERRIN (CDT) EVALUATION IN THE INSURANCE INDUSTRY. Pamela Bean'. Marv Susan Su~hin'. Palrieia Necessaryt. Sam Niedbala*. and M¢lkon S. Agopian*. "Specialty Laboratories, Inc., Santa Monica, CA 90404-3900; tLabOne, Overland Park, KS 66215; tSTC Diagnostics, Bethlehem, PA 18018-1799. In this study, we evaluated the utility of quantitating serum CDT using two methods: the well-established isoclectric foeusing/immunoblotting/laser densitometry (IEF/IB/LD) procedure and the newly developed STC kit. The former method separates CDT isoforms in a gradient of ampholytes under conditions of partial iron saturation; the latter procedure uses ion exchange chromatography followed by quantitation of eluted CDT isoforms in an enzyme immunoassay. Linearity data, precision data and interference studies performed for both tests support the clinical utility of these procedures in the diagnosis of alcohol abuse. Both assays measure CDT as a ratio of CDT to total serum transferrin (Tf). However, only IEF/IB/LD identifies false-positive results due to T f genetic D variants. One hundred thirty-two serum specimens submitted by insurance applicants were evaluated for CDT once (50/132) or twice (82/132) by the STC kit (LabOne) prior to testing by IEFflB/LD. Using a cutoff of 9 densitometry units (DU) for IEFfIB/LD (established for maximum clinical utility at 95% specificity based on ROC data) and 3% CDT/total "If for the STC kit, 30% (40/132) of the specimens were CDT+ and 48% (64/132) were CDT- by both methods. Four percent (5/132) of the sera tested CDT+ by IEF/IB/LD only; 11% (14/132) of the sera tested CDT+ by the STC kit only. Seven percent (9/132) of the specimens CDT-Y by the STC kit showed values in the indeterminate range (7 to 9 DU) for IEF/IB/LD. Of the two specimens identified as T f genetic D variants, one tested CDT+ by the STC kit only. All specimens CDT+ by STC had abnormal liver function test results. In summary, these data show that 93% (64/69) of the specimens CDT- by the STC kit, remain CDT- when evaluated by IEF/IB/LD. For CDT+ specimens, the best results are obtained when using the STC kit as a screening procedure, followed by IEFflB/LD as a confirmatory test.
393A
Hepatitis C virus (BCV) infection leads to chronic liver disease in 70% of individuals infected with the virus. HCV is associated with various autoimmune disorders. The only treatment for chronic hepatitis C is Interferon (IFN). The rationale for the use of IFN is that it is both an antiviral agent and upregnlates cellular immune mechanisms. This latter action is not specific and accordingly the cellular immune system is diffusely activated and can lead to the development of new autoimmane diseases in treated subjecLs. To determine the prevalence of abnormal autoantibodies in patients with chronic HCV and to estimate the prevalence of new onset autoimmune disease, the records of 201 patients with HCV were reviewed. 161 patients had chronic HCV defined by the presence of detectable anti-HCV or HCV-RNA by PeR. Each was also negative for HBsAg and had a liver biopsy consistent with chronic liver disease. 41 patients withpntative autoimmanehepatitis diagnosed on the basis of classical autoantibodies, tissue typing and the absence of anti-HCV and HCV/RNA in serum were reviewed also. The records of both groups were reviewed for the following autoimmune antibody: anti-nuclear antibody (ANA), antimitochondrial antibody (AMA), anti-liver-kidney microsomal antibody (LKM), anti-smooth muscle antibody (ASMA) and anti-microsomal antibody (AMS). The rate of ANA and ASMA positivity was 63-65% in both groups; AMA was positive in 4% of group I and 19% of group Ili LKM was absent in all HCV cases and present in 4% of group II cases; AMS positivity was present in 17 and 10% respectively. No significant differences in the IFN response rate was noted between those with HCV and antibodies and those withoot antibodies. 15 of the IFN-treated patients developed clinical manifestations of new onset autoimmune disease during their IFN treatment. None were managed by discontinuing the IFN. Most required some form of specific treatment. It can be concluded that: 1) ANA and ASMA are positive at the same frequency in both groups; 2) anti-LKM antibodies are frequently absent in patients with HCV infection; 3) newly developed autoimmune conditions develop during IFN treatment; 4) bet they do not require interruption of IFN therapy; and, 5) but do require additional therapy specific for the putative autoimmune disease.
1148
SERUM ~/-GLUTAMYL-TRANSPEPTI DASE ISOENZYMES IN CIRRHOSIS AND HEPATOCELLULAR CARCINOMA. _M. Bellini, S. Marchi, *R. Ginrdani, "t3. Fabfini. F. Costa. E. Taminn, G. Amatn, A Ricclfiuti. M. Rueen. P. Ciccorossi, C. Belcati and G. Mzltinri ClJnica Medica I and *Laboratotio Analisi Cliniehe; Universi~ di Pisa, Pisa, Italy Senan ~-glutamyltranspeptidase (GGT) is a sensitive but non-specific index of liver disease. Separation of G G T isoenzymes (iso-GG'D could improve the specificity. We have used a Rapid Electropboresis system (REP) (Helena Laboratories, Italy) on agarose gel in order to identify i s ~ G G T in: -fifty healthy volunteers (I-IV): 24 f and 26 m; mean age + SD: 32.96 _+ 4.59; mean total G G T value 5: SD; 15.20 + 9,13 U/L; -thirty-six patients with posthepatitic cirrhosis (PHC): 22 f and 14 m; mean age SD: 67.05 =i=11.31; mean total G G T value + SD: 76.42 + 54.16 U/L; -eigtheen patients with bepatoeellular carcinoma gdCC): 5 f and 13 m; mean age + SD: 61.5 + 7~54; mean total G G T value ± SD: 106.7 _+81.31 U/L. Ten fractions (0a, 0b, la, lb, 2a, 2b, 3a, 3b, 4a, 4b) were identified in HV and in PHC patients; an eleventh fraction (2c) was detected in HCC patients. A significant difference (p<0.05) has been observed in: la, 3b and 4b between HV and PHC patients; la, 2c and 4b between HV and HCC patients; In, 2c, 3a and 3b between PHC and HCC patients. HCC patients showed a typical pattern characterized by a lower la fraction and a higher 2c fraction. The peculiar 2c fraction was revealed in 15/18 HCC patients (83.3%): with a sensitivity of 83.3%, a specificity of 88.4% and an accuracy rate as a whole of 87.5%. Serum ct-fetoprotein levels showed no significant correlation with 2c values. In conclusion separation of iso-GGT could be proposed as a useful test in the follow up of chronic liver disease, particularly in the diagnosis of HCC. +
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