screening strategies for hepatitis c: models derived from the national hepatitis surveillance...

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HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995 AASLD ABSTRACTS 385A 1113 SCREENING STRATEGIES FOR HEPATITIS C: MODELS DERIVED FROM THE NATIONAL HEPATITIS SURVEILLANCE PROGRAM (NHSP). A, Jakiche, K. Lanane, D. Su~,ano. W. Wen~. W.D. Carev. Dept of Gastroenterology and Hepatology, The Cleveland Clinic Foundation, Cleveland, Ohio, and Sobering-Plough Corporation, Kenilworth, New Jersey. Background: Most viral hepatitis C (VHC) cases are asymptomatic and remain undetected for years. Many with VHC suffer significant morbidity and mortality within two decades of infection. Early detection may improve the outcome and reduce disease transmission through treatment, and education of lifestylebehavior changes. Using the database of the NftSP we sought to evaluate the performance characteristics and cost of multiple scxeening strategies for VHC. Methods: 13,997 healthy individuals were screened for viral hepatitis in 40 centers throughout the U.S.. Serum samples, patient demographics, and risk profile were availableon 9,269 subjects. Risk factors (RF) for VHC identified in logistic regression models were designated as major if odds ratio (OR)~4, or minor if OR<4. A mathematicalpredictive equation (MPE) was derived to predict probabilityof VHC [P=l/l+exp-(Po+PJ?]. Four sereening strategies were evaluated, lst:probability 10% in the MPE. 2nd: any major RF or two or more minor RF. ~ two or more minor risk factors. 4th : ALT followed by anti-HCV for elevated ALT. The performance characteristics of each strategy were determined from the database. The estimated cost/case is based on the cost of blood testing (ALT & anti-HCV in strate~ 4, anli-HCV in other strategies). Results: Major RF included Hx of IVDU, and Hx of sex with an IVDU. Minor RF identified were Hx of transfusion, male gender, and age 30-49. Characteristics of the screening strategic ~reeented: Screening Prevalence Pos P.V. Sensitivity Specificity Cost/case strategies % % % % detected Strategy 1 12 30 57 91 $165 Strategy 2 29 18 67 74 $222 Strategy 3 25 16 52 77 $285 Strategy 4 12 37 59 92 $842 Conclusion: 1) Use of RF in the clinical decision making on screening for VHC limits blood testing to less than 30% of the population, and detects up to 67% of cases. 2) The performance characteristics of RF and MPE are comparable to screening with ALT but much less cosily. Those with significant risk for VHC should be screened with anti-HCV rather than ALT. 3) These results need to be validated prospectively on selected populations. 1114 ASSESSMENT AND MEDICAL FOLLOW-UP OF INTRAVENOUS DRUG USERS (IVDU) POSITIVE FOR HEPATITIS C VIRUS (HCV) 1N NORTH EAST ENGLAND. AM Brind (1), MA Seffaty (2), A Lawrie (2), JP Watson(l), S Johnson (l), E Gilvarr~ 2) and MF Bassendine10. 0)Freeman Hospital, NE7 7DN, (2)Plummer Court, Regional Drug Dependency Unit, NE1 6UR, Newcastle-upon Tyne, UK. IVDUs are at high risk of HCV infection but there have been few studies in this group in the UK. We found 38% HCVAb positive by ELISA 1 (ORTHO) but have now extended our study to all clients who satisfied DSM IV criteria for opioid dependence or abuse attending the regional drug dependency unit during 1993, n=202. Clients were counselled about HCV infection, 103 either refused or were thought unsuitable for screening. There was in no difference between tested and non-tested clients in age [32.5 vs 31.9], sex [64 male:35 female vs 71 male:32 female] or needle sharing [82/99 vs 76/103] but more of the tested clients were currently using IV drugs [64/99 vs 40/103 p<0.005]. 67/99 (67%) of those tested were positive by ELISA 2 (ORTHO) confirmed by RIBA 2 (ORTHO) and referred to the Liver clinic. 28 attended at least once and 21 more than once. 22 had abnormal liver function tests but only 11 attended for liver biopsy. All had chronic hepatitis, median histological activity according to Scheuer s classification.was 3, range 1-10. 50% of those tested were genotype la by INNO-LIPA (1NNOGENETICS). We found the prevalence of HCV infection in IVDUs is high, 67%. 27,976 IVDUs were registered in the UK in 1993, considered to be 20% of the total. By extrapolation it is likely that at least 100,000 IVDUs in the UK have chronic HCV. Uptake and attendance for medical follow-up is poor. Preventative measures to reduce spread of infection are required to tackle this epidemic. 1115 INTRAHEPATIC CHOLESTASIS OF PREGNANCY (ICP) I N MULTIPLE PREGNANCIES (MP) ~, Aber~el. S. Froment, P. Kuder, J.F Viallard*, D. Lemery §, M. Canis ", B. Jacquetin §, M.A. Bruhat ", G. Bommelaer. Service d'Hdpatogastroentdrologie, § et " Services de Gyndco- Obstdtrique, H6tel Dieu ; * Laboratoire de Biochlmie, Faeultd de M6decine, Clermont Ferrand, France. It is generally believed that ICP may induce prematurity in 40% of the cases and perinatal mortality i n less that 1% of the pregnancies. In a recent Chilian study (Am J Obstet Gyneeol, 1994, 170, 890-5), the prematurity % was 12,1 (3,9% in the control group, p<0,05) and the perinatal mortality was 18 %0 (13 %0 in the control group, p=NS). Aim : To evaluate this risks in the two maternity-hospitals of our city with special reference to MP. Methods : 28 women with pruritus and transaminases elevation who delivered between Ian 90 and Sept 94 were studied. Women with ICP were separated in two groups : singleton pregnancy (SP) (n=lT), and MP (n=ll, 23 neonates). Results : SP (n=17) MP (n=ll) Premature labor 8 (47%) 8 (73%) Prematurity (< 37th week) 7 (42%) 8 (73%) Prematurity (< 35 th week) 4 (23%) 4 (36%) Perinatal mortality 0 0 Caesarean delivery 4 (23%) 4 (36%) The prevalence of ICP in the MP of our hospital was 11/250 (4,4 %) and 17/10750 (0,16%) in SP (p<0,00001). The relative risk of prematurity was 5 in SP (42% in ICP vs 9 %in SP of our center) and 3 in MP ( 73% vs 25% in the group of MP of our center), Conclusion : I) ICP in MP is 28 times more prevalent than in SP and suggest that ICP is an estrogen related disease ; 2) Prematurity is still very high in ICP in our hospital ; 3) There is no perlnatal mortality in this study, particulary in MP. 1116 PROGRESS IN PAEDIATRIC LIVER TRANSPLANTATION - THE BIRMINGHAM EXPERIENCE. OA Achillece. D ~lhlbot. BK Gunson. AD Mayer. P MeMaster, DA Kelly*, JAC Buckels. Liver & Hepatobiliary Unit, Queen Elizabeth Hospital and *Liver Unit Children's Hospital, B'mninglmm, United Kingdom. In January 1995 the 200th paediatrlc liver transplant was performed at our institution. The background, techniques and outcome of this group were reviewed against time and the results summarised below. 1988-1986 1987- 1990 1991- 1995 N 11 67 122 Median recipient age/years 11.9 1.75 2.85 Median recipient weight/kg 32.0 11.4 13.0 Whole liver grafts/% 100 47.8 32.3 Reduced liver grafts/% 0 52.2 63.8 Split liver grsfln/% 0 0 g. 9 Outcome Regrafd% 0 31.3 8.9 Death/% 54.5 33.8 26.3 The three periods of time illustrate the changes that have occurred st our institution. Firstly, the numbers transplanted have increased to a now steady 30 per year. The age and weight of the recipient has fallen in common with other centres. With the demand of children dying whilst on the waiting list, the reduced liver program was developed. The regraft rate 198%1990 was increased but the mortality was reduced. Further improvement in mortality occurred in 1991-1995 as a result of a dedicated paediatrie hepstelogy unit and improvement in regraft rate was produced by a refined surgical approach. It is anticipated that the split program will be developed further to expand the program and also reduce death whilst on the wai~lg list.

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HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995 AASLD ABSTRACTS 385A

1113 SCREENING STRATEGIES FOR HEPATITIS C: MODELS DERIVED FROM THE NATIONAL HEPATITIS SURVEILLANCE PROGRAM (NHSP). A, Jakiche, K. Lanane, D. Su~,ano. W. Wen~. W.D. Carev. Dept of Gastroenterology and Hepatology, The Cleveland Clinic Foundation, Cleveland, Ohio, and Sobering-Plough Corporation, Kenilworth, New Jersey.

Background: Most viral hepatitis C (VHC) cases are asymptomatic and remain undetected for years. Many with VHC suffer significant morbidity and mortality within two decades of infection. Early detection may improve the outcome and reduce disease transmission through treatment, and education of lifestyle behavior changes. Using the database of the NftSP we sought to evaluate the performance characteristics and cost of multiple scxeening strategies for VHC. Methods: 13,997 healthy individuals were screened for viral hepatitis in 40 centers throughout the U.S.. Serum samples, patient demographics, and risk profile were available on 9,269 subjects. Risk factors (RF) for VHC identified in logistic regression models were designated as major if odds ratio (OR)~4, or minor if OR<4. A mathematical predictive equation (MPE) was derived to predict probability of VHC [P=l/l+exp-(Po+PJ?]. Four sereening strategies were evaluated, lst:probability

10% in the MPE. 2nd: any major RF or two or more minor RF. ~ two or more minor risk factors. 4th : ALT followed by anti-HCV for elevated ALT. The performance characteristics of each strategy were determined from the database. The estimated cost/case is based on the cost of blood testing (ALT & anti-HCV in strate~ 4, anli-HCV in other strategies). Results: Major RF included Hx of IVDU, and Hx of sex with an IVDU. Minor RF identified were Hx of transfusion, male gender, and age 30-49. Characteristics of the screening strategic ~reeented:

Screening Prevalence Pos P.V. Sensitivity Specificity Cost/case strategies % % % % detected Strategy 1 12 30 57 91 $165

Strategy 2 29 18 67 74 $222

Strategy 3 25 16 52 77 $285

Strategy 4 12 37 59 92 $842

Conclusion: 1) Use of RF in the clinical decision making on screening for VHC limits blood testing to less than 30% of the population, and detects up to 67% of cases. 2) The performance characteristics of RF and MPE are comparable to screening with ALT but much less cosily. Those with significant risk for VHC should be screened with anti-HCV rather than ALT. 3) These results need to be validated prospectively on selected populations.

1114 ASSESSMENT AND MEDICAL FOLLOW-UP OF INTRAVENOUS DRUG USERS (IVDU) POSITIVE FOR HEPATITIS C VIRUS (HCV) 1N NORTH EAST ENGLAND. AM Brind (1), MA Seffaty (2), A Lawrie (2), JP Watson (l), S Johnson (l), E Gilvarr~ 2) and MF Bassendine 10. 0)Freeman Hospital, NE7 7DN, (2)Plummer Court, Regional Drug Dependency Unit, NE1 6UR, Newcastle-upon Tyne, UK.

IVDUs are at high risk of HCV infection but there have been few studies in this group in the UK. We found 38% HCVAb positive by ELISA 1 (ORTHO) but have now extended our study to all clients who satisfied DSM IV criteria for opioid dependence or abuse attending the regional drug dependency unit during 1993, n=202. Clients were counselled about HCV infection, 103 either refused or were thought unsuitable for screening. There was in no difference between tested and non-tested clients in age [32.5 vs 31.9], sex [64 male:35 female vs 71 male:32 female] or needle sharing [82/99 vs 76/103] but more of the tested clients were currently using IV drugs [64/99 vs 40/103 p<0.005]. 67/99 (67%) of those tested were positive by ELISA 2 (ORTHO) confirmed by RIBA 2 (ORTHO) and referred to the Liver clinic. 28 attended at least once and 21 more than once. 22 had abnormal liver function tests but only 11 attended for liver biopsy. All had chronic hepatitis, median histological activity according to Scheuer s classification.was 3, range 1-10. 50% of those tested were genotype l a by INNO-LIPA (1NNOGENETICS).

We found the prevalence of HCV infection in IVDUs is high, 67%. 27,976 IVDUs were registered in the UK in 1993, considered to be 20% of the total. By extrapolation it is likely that at least 100,000 IVDUs in the UK have chronic HCV. Uptake and attendance for medical follow-up is poor. Preventative measures to reduce spread of infection are required to tackle this epidemic.

1115 INTRAHEPATIC CHOLESTASIS OF PREGNANCY (ICP) I N MULTIPLE PREGNANCIES (MP) ~, Aber~el . S. Froment, P. Kuder, J.F Viallard*, D. Lemery §,

M. Canis ", B. Jacquetin §, M.A. Bruhat ", G. Bommelaer . Service d'Hdpatogastroentdrologie, § et " Services de Gyndco- Obstdtrique, H6tel Dieu ; * Laboratoire de Biochlmie, Faeul td de M6decine, Clermont Ferrand, France.

It is generally believed that ICP may i n d u c e prematurity in 40% of the cases and perinatal mortality i n less that 1% of the pregnancies. In a recent Chilian s tudy (Am J Obstet Gyneeol, 1994, 170, 890-5), the prematurity % was 12,1 (3,9% in the control group, p<0,05) and the perinatal mortality was 18 %0 (13 %0 in the control group, p=NS). Aim : To evaluate this risks in the two m a t e r n i t y - h o s p i t a l s of our city with special reference to MP. M e t h o d s : 28 women with pruritus and t r a n s a m i n a s e s elevation who delivered between Ian 90 and Sept 94 w e r e studied. Women with ICP were separated in two groups : singleton pregnancy (SP) (n=lT), and MP (n=l l , 23 neona tes ) . R e s u l t s : SP (n=17) MP (n=l l ) Premature labor 8 (47%) 8 (73%) Prematurity (< 37th week) 7 (42%) 8 (73%) Prematurity (< 35 th week) 4 (23%) 4 (36%) Perinatal mortal i ty 0 0 Caesarean delivery 4 (23%) 4 (36%) The prevalence of ICP in the MP of our hospital was 11/250 (4,4 %) and 17/10750 (0,16%) in SP (p<0,00001). The r e l a t i v e risk of prematurity was 5 in SP (42% in ICP vs 9 %in SP of our center) and 3 in MP ( 73% vs 25% in the group of MP of our center), C o n c l u s i o n : I) ICP in MP is 28 times more prevalent t h a n in SP and suggest that ICP is an estrogen related disease ; 2) Prematurity is still very high in ICP in our hospital ; 3) There is no perlnatal mortality in this study, p a r t i c u l a r y in MP.

1116 PROGRESS IN PAEDIATRIC LIVER TRANSPLANTATION - THE BIRMINGHAM EXPERIENCE. OA Achillece. D ~lhlbot. BK Gunson. AD Mayer. P MeMaster, DA Kelly*, JAC Buckels. Liver & Hepatobiliary Unit, Queen Elizabeth Hospital and *Liver Unit Children's Hospital, B'mninglmm, United Kingdom.

In January 1995 the 200th paediatrlc liver transplant was performed at our institution. The background, techniques and outcome of this group were reviewed against time and the results summarised below.

1988-1986 1987- 1990 1991- 1995

N 11 67 122 Median recipient age/years 11.9 1.75 2.85 Median recipient weight/kg 32.0 11.4 13.0

Whole liver grafts/% 100 47.8 32.3 Reduced liver grafts/% 0 52.2 63.8 Split liver grsfln/% 0 0 g. 9

Outcome Regrafd% 0 31.3 8.9 Death/% 54.5 33.8 26.3

The three periods of time illustrate the changes that have occurred s t our institution. Firstly, the numbers transplanted have increased to a now steady 30 per year. The age and weight of the recipient has fallen in common with other centres. With the demand of children dying whilst on the waiting list, the reduced liver program was developed. The regraft rate 198%1990 was increased but the mortality was reduced. Further

improvement in mortality occurred in 1991-1995 as a resul t of a dedicated paediatrie hepstelogy unit and improvement in regraft rate was produced by a refined surgical approach. It is anticipated that the split program will be developed further to expand the program and also reduce death whilst on the wai~lg list.