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HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995 AASLD ABSTRACTS 403A 1185 CORRELATION BETWEEN SERUM ALPllA-I-ANTITRYIPSIN LEVELS, SEVERITY OF CIRI~OSIS AND PRESENCE OF HEPATOCELULAR CARCINOMA. H. Cheinouer 1, A. Cassall. A. S ~ I. S. Coelim-Borsus 2. R. Silva1. A. Floresl, I. Zamin jr1~..~N. Chehtauer 3, E. Ribe/roI. A. Brandio I. C. Marmn/I~ G a s t ~ Divisinn of Santa Casu l-leepital (FFFCMPA) I ,HCPA2, PUC 3, Porto Alesre, RS, Bra~l. Baclqp'oa~: Alplm-l-~ (AIAT) is an asyaloslimprctein (ASGP) which is cisumd fiem circuiatim troush binding with ASGP-recepton m tha surface ofthe hepatoq~. Seve~l studies have demmstrated that patiems with liver disorders, induding ~daosis aad ~ carcinema OtCC), have appreciablyhishar plasma omom~i;ous of ASGP than normal subjects. Aim: The pmlx~e of this study is to correlate the plasma levels of AIAT with the severity ofcirdmsis md the presmce of HCC. P ~ J Metimds: Serum samples from 79 consecutive ~ (M:F 52:27, age 14-96) with a histeiogi~ diagnesis of cirdmsis (n=70) or cirdmsis with HCC (n=9) were p r ~ coL_t,~__~and tested fur AIAT (siqle radial immmedif~iea, B~hrinswe~, Marburg - normal valum:140- 320 m~'dt). The cirrhotic petisms were classified ao=~-di~ m Chiid-Pugh criteria in Group A (n=16), Group B (n=25) and Group C (n=29). Stati'ei~ai analysis was perfaund by the mushn-wanis test (alpha=o.05). Results. Sennn AIAT levels were: I) Gro~ A = 344.5 +/- 147.1, 2) Group B = 304.2 +/- 156.3; 3) Group C = 314.1 +/- 171.0, and 4) HCC = 404.0 +/- 168.5. There wss a s',~uiflumt di~e~mee when Group A or HCC were ~q~edto Gr~ e or C (p<O.05). c~,-t,~ A Cmd-Pq~ n CWd-eqt C nCC (m46) ~ ~ (e,,'4 AIAT (ms~ +/- ~lJ ~64.5+/- 147A ~04.2+/. 156,~ 314.1 +/- ITI,O 404.0÷/. 1~.5 Cesekum: Cinhaie patiems chamified as Child-Pugh B or C have significantly lower levels of AIAT when compared with Child-Pugh A. Patimts with tiCC lmve the highast values. 1186 PREVALENCE OF HEPATITIS C VIRUS INFECTION BY ELISA II AND PCR IN ALCOHOLIC PATIENTS WITH CIRRllOSIS. H. 6"anm~l.A. eramaoLV, tame2.N, n, m2~,. e~,A, C~ns~l.n. S ' d v ~ l . s . Ceelhe-Bomes3,N, £hein~.C. Marroni 1. Gastroenterology Division of S,~ta Casa ~ (FFFCMPA) 1, Simbios (UFRGS) 2, HCPA3, PUC 4, Pone Aiesre, RS, Brazil. Intreductiea: Several repeas have danmmmted a hish prevalence of antibodies to hapatitis C vires (anti-HCV) atom8 alcoholic parians. However, fewer studies have examinedtha presaace of HCV-RNA in this pelmbtim. Aim'. To ~ the prevalmce of ami-HCV by secmd-smer~on ELISA (IELISA ID in akdmli¢ patimus with cirrhosis, and to correlate these findinss withthedetectinn ofHCV-RNA by PCR. PalimU and Me4bods: Serum samples ~rGSU 33 consecutive alceholic patients (M:F 24:9, eke 21-84 yr) with a clinical and/or histologicaldiagnosis of cinhem vnne preweaively ed__b~__~ and t_~__~ for ami-l-ICV by the ELL~A II assay (Abbott Lalxxatmies, Abbmt Park IL). Fresh senun samples were stoml at -40eC until tested for HCV-RNA by the ~ double-nested PCR (ramm ston~ time of 6 months). The p ~ were _seb~___~ to mplifi/the highly catunved 5' r,,,,U,,slated rein oftha ~ . The t~d mplified proch~t was e ~ and visuaLn~l with ahich'mn bromidestainins.PCR reaotions vame performedundercode,induplicate, with neptiveand p~tive conuols. RemdU: Amon8 the 33 patimts studied, 25 (75.8%) were ami-HCV positive by ELISA !!. HCV-RNA was detected ia 11(44%) of these 25 patimts and was not &tected in any of the ami-HCV nesatiw cases. I[USAII amt41CV pedgve (u,.~a) n (44%) 14(56%) I~ISA B m~4~'~V mS~n~(8~0 o 8(10o%) C ~ : 1) Less thaa half of the ELISA O anti-HCV positive patimts had detectable EICV-PdqA by PCR. Thase fadin~ could be related to false- pesitive ELlSA il results or to hmdequate sample storage; 2) there was a geod correlatim betwem nesative ELISA 11results and PCR. 1187 IN KIDNEY GRAFT RECIPIENTS RIBAVIRINE IS ABLE TO REDUCE HCV VIRAL LOAD P.Chossegros, S Daoud, JL Gamier, AC Marrast, P Chevallier, C.Trtpo, JL Touraine. Servicede transplantation rtnale H6pitalEdonard Herdot, INSERMU271, Lyon Chronic HCV infections are the first cause of chronic liver diseases after kidney transplantation. Progression of fibrosis is slow but a significant oecurence of cirrhosis and liver de.compensationis observed. Treatments with alpha interferon resulted in kidney rejections without durable HCV negativation.Ribavirine (RIBA) has been shown to decrease transaminases and improve histology of HCV related CAll. We have treated 7 patients with RIBA to evalual~its tolerance and efficacy in that subpopolation of patients. Anti HCV was present in each case. They were tested repeatedlypositive with PCR for more than 2 years. A cryoglobnlinemia was present in every case. Transaminases were elevated in only 2 cases at the begining of treatment. Ribavirine was given at increasing dosage starting at 400 mg/d until 800 mg/d or significantside-effects. Once the maximum dosage had been reached, the treatment was continued for 4 to 6 months. Clinical tolerance was good. There was no graft disfunction and ciclosporin dosage had never to be changed. An episode of acute rejection was observed in one case, 3 months after RIBA discontinuation. RIBA induced anemiawas the only dose-limiting side effect. Transaminases were significantly reduced during treatment. In 2 cases PCR negativation and cryoglobalinemiadisappearancewere observed concomitantly and reappeared in one case after RIBA discontinuation. The number of cases was too small to observe a significant influence of genotypes or viral load on treatment response. Histologywas improvedat the end of treatment. Condusion: RIBA is a promising treatment for kidney graft recipients. An explanationof its distinctiveaction on viral replication in those patients could result in a better managementof patients without immunosoppreasors. 1188 LEVEL OF HCV RNA IS RELATED TO GENOTYPE 1, TRANSMISSION THROUGH TRANSFUSION AND HTLV-I COINFECTION R.Chout. F. Lunel2. J. Retour, V. Ursulet. S. Vaton, D. Cales-Ouist3, A. Ranlin, J. Coulloc'h4, C. Sayada5 Laboratory of Microbiology and Department of Nephrology, Lamentin Hospital, Martinique, 2 Laboratory of Virology, La Pitie-Salpttritre Hospital, Paris. 3 STD clinic, Fort de France, Martinique. 4 InGen Laboratory, Sogaris, 5 Roche Diagnostic Systems, France Gen6types and quantitation of HCV viremia are predicitve factors of response to therapy. The aim of this study was to determine weither blood HCV RNA titre was associated with genotype, route of infection and co-infection with retrovimses (H1V and HTLV-I). Methods: 111 HCV RNA positive serum samples from renal transplant recipients, hemodialyzed patients, concomitant HCV-HIV, HCV-HTLV-I, and sexually transmitted diseases infected patients were analyzed. Genotyping was performed by Inno-LiPA TM assay (Innogenetics, Gent, Belgium). The quantitafion was carried-out with the HCV RT-PCR assay (HCV Monitor TM, Roche), based on coamplification of HCV RNA with a synthetic RNA Intemal Quanfitation Standard (IQS). Routes of transmission were : Blood transfusion (BT) (68%), intravenous drag abuse (IVDU) (11%), sexual contact without any parenteral risk factor (21%); and 42 patients presenting retroviral coinfections (12 HTLV-I, 30 HIV). Results: The genotype distribution was : la (29%), lb (59%), 2a (7%) and 3a (5%). Significant HCV viremia level was found for genotype 1(3.4x105) vs non-1 genotype (lx105) (p<0.01), but not for type lavs lb. HCV-RNA level was significantly higher in the BT group than in the others with fitres of 4.6x10 s , 1.4x10 s, and 0.4x105 respectively in BD, IVDU and STD groups (p<0.003). For retroviral coinfected patients, RNA level was higher in HTLV-I than in HIV coinfected patients: 2.7x105 vs 0.8x105 (p<0.01). Conclusions: HCV RNA level could be increased by genotype 1, and]or history of blood transfusion, and/or coinfecfion with HTLV-I. But, it could be also related to duration of infection. These data should help optimize HCV treatment regimen.

In kidney graft recipients ribavirine is able to reduce HCV viral load

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HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995 AASLD ABSTRACTS 403A

1185 CORRELATION BETWEEN SERUM ALPllA-I-ANTITRYIPSIN LEVELS, SEVERITY OF CIRI~OSIS AND PRESENCE OF HEPATOCELULAR CARCINOMA. H. Cheinouer 1, A. Cassall. A. S ~ I. S. Coelim-Borsus 2. R. Silva 1. A. Floresl , I. Zamin jr1~..~N.

Chehtauer 3, E. Ribe/ro I. A. Brandio I. C. Marmn/I~ G a s t ~

Divisinn of Santa Casu l-leepital (FFFCMPA) I ,HCPA 2, PUC 3, Porto Alesre, RS, Bra~l.

Baclqp'oa~: A l p l m - l - ~ (AIAT) is an asyaloslimprctein (ASGP) which is cisumd fiem circuiatim troush binding with ASGP-recepton m tha surface ofthe hepatoq~. Seve~l studies have demmstrated that patiems with liver disorders, induding ~daosis aad ~ carcinema OtCC), have appreciably hishar plasma omom~i;ous of ASGP than normal subjects.

Aim: The pmlx~e of this study is to correlate the plasma levels of AIAT with the severity ofcirdmsis md the presmce of HCC.

P ~ J Metimds: Serum samples from 79 consecutive ~ (M:F 52:27, age 14-96) with a histeiogi~ diagnesis of cirdmsis (n=70) or cirdmsis with HCC (n=9) were p r ~ coL_t,~__~ and tested fur AIAT (siqle radial immmedif~iea, B~hrinswe~, Marburg - normal valum:140- 320 m~'dt). The cirrhotic petisms were classified ao=~-di~ m Chiid-Pugh criteria in Group A (n=16), Group B (n=25) and Group C (n=29). St ati'ei~ai analysis was perfaund by the mushn-wanis test (alpha=o.05).

Results. Sennn AIAT levels were: I) G r o ~ A = 344.5 +/- 147.1, 2) Group B = 304.2 +/- 156.3; 3) Group C = 314.1 +/- 171.0, and 4) HCC = 404.0 +/- 168.5. There wss a s',~uiflumt di~e~mee when Group A or HCC were ~ q ~ e d t o G r ~ e or C (p<O.05).

c~,-t ,~ A Cmd-Pq~ n CWd-eqt C nCC (m46) ~ ~ (e,,'4

AIAT (ms~ +/- ~lJ ~64.5 +/- 147A ~04.2 +/. 156,~ 314.1 +/- ITI,O 404.0 ÷/. 1~.5

C e s e k u m : Cinhaie patiems chamified as Child-Pugh B or C have significantly lower levels of AIAT when compared with Child-Pugh A. Patimts with tiCC lmve the highast values.

1186 PREVALENCE OF HEPATITIS C VIRUS INFECTION BY ELISA II AND PCR IN ALCOHOLIC PATIENTS WITH CIRRllOSIS. H. 6"anm~l.A. eramaoLV, tame2.N, n, m2~,. e ~ , A , C~ns~l.n. S ' d v ~ l . s . Ceelhe-Bomes3,N, £ h e i n ~ . C . Marroni 1. Gastroenterology

Division of S,~ta Casa ~ (FFFCMPA) 1, Simbios (UFRGS) 2, HCPA 3,

PUC 4, Pone Aiesre, RS, Brazil. Intreductiea: Several repeas have danmmmted a hish prevalence of

antibodies to hapatitis C vires (anti-HCV) atom8 alcoholic parians. However, fewer studies have examined tha presaace of HCV-RNA in this pelmbtim.

Aim'. To ~ the prevalmce of ami-HCV by secmd-smer~on ELISA (IELISA ID in akdmli¢ patimus with cirrhosis, and to correlate these findinss with the detectinn of HCV-RNA by PCR.

PalimU and Me4bods: Serum samples ~rGSU 33 consecutive alceholic patients (M:F 24:9, eke 21-84 yr) with a clinical and/or histological diagnosis of c inhem vnne preweaively ed__b~__~ and t_~__~ for ami-l-ICV by the ELL~A II assay (Abbott Lalxxatmies, Abbmt Park IL). Fresh senun samples were stoml at -40eC until tested for HCV-RNA by the ~ double-nested PCR (ramm s t o n ~ time of 6 months). The p ~ were _seb~___~ to mplifi/the highly catunved 5' r,,,,U,,slated r e i n oftha ~ . The t ~ d mplified proch~t was e ~ and visuaLn~l with ahich'mn bromide stainins.PCR reaotions vame performed under code, in duplicate, with neptive and p~tive conuols.

RemdU: Amon8 the 33 patimts studied, 25 (75.8%) were ami-HCV positive by ELISA !!. HCV-RNA was detected ia 11(44%) of these 25 patimts and was not &tected in any of the ami-HCV nesatiw cases.

I[USA II amt41CV pedgve (u,.~a) n (44%) 14(56%)

I~ISA B m~4~'~V mS~n~ (8~0 o 8(10o%)

C ~ : 1) Less thaa half of the ELISA O anti-HCV positive patimts had detectable EICV-PdqA by PCR. Thase f ad in~ could be related to false- pesitive ELlSA i l results or to hmdequate sample storage; 2) there was a geod correlatim betwem nesative ELISA 11 results and PCR.

1187 IN KIDNEY GRAFT RECIPIENTS RIBAVIRINE IS ABLE TO REDUCE HCV VIRAL LOAD

P.Chossegros, S Daoud, JL Gamier, AC Marrast, P Chevallier, C.Trtpo, JL Touraine.

Service de transplantation rtnale H6pital Edonard Herdot, INSERM U271, Lyon

Chronic HCV infections are the first cause of chronic liver diseases after kidney transplantation. Progression of fibrosis is slow but a significant oecurence of cirrhosis and liver de.compensation is observed. Treatments with alpha interferon resulted in kidney rejections without durable HCV negativation. Ribavirine (RIBA) has been shown to decrease transaminases and improve histology of HCV related CAll.

We have treated 7 patients with RIBA to evalual~ its tolerance and efficacy in that subpopolation of patients. Anti HCV was present in each case. They were tested repeatedly positive with PCR for more than 2 years. A cryoglobnlinemia was present in every case. Transaminases were elevated in only 2 cases at the begining of treatment.

Ribavirine was given at increasing dosage starting at 400 mg/d until 800 mg/d or significant side-effects. Once the maximum dosage had been reached, the treatment was continued for 4 to 6 months. Clinical tolerance was good. There was no graft disfunction and ciclosporin dosage had never to be changed. An episode of acute rejection was observed in one case, 3 months after R I B A discontinuation. R I B A induced anemia was the only dose-limiting side effect.

Transaminases were significantly reduced during treatment. In 2 cases PCR negativation and cryoglobalinemia disappearance were observed concomitantly and reappeared in one case after RIBA discontinuation. The number of cases was too small to observe a significant influence of genotypes or viral load on treatment response. Histology was improved at the end of treatment.

Condusion: RIBA is a promising treatment for kidney graft recipients. An explanation of its distinctive action on viral replication in those patients could result in a better management of patients without immunosoppreasors.

1188 LEVEL OF HCV RNA IS RELATED TO G E N O T Y P E 1, TRANSMISSION T H R O U G H TRANSFUSION AND HTLV-I C O I N F E C T I O N R.Chout. F. Lunel2. J. Retour, V. Ursulet. S. Vaton, D. Cales-Ouist3, A. Ranlin, J. Coulloc'h4, C. Sayada5 Laboratory of Microbiology and Department of Nephrology, Lamentin Hospital, Martinique, 2 Laboratory of Virology, La Pitie-Salpttritre Hospital, Paris. 3 STD clinic, Fort de France, Martinique. 4 InGen Laboratory, Sogaris, 5 Roche Diagnostic Systems, France

Gen6types and quantitation of HCV viremia are predicitve factors of response to therapy. The aim of this study was to determine weither blood HCV RNA titre was associated with genotype, route of infection and co-infection with retrovimses (H1V and HTLV-I). Methods : 111 HCV RNA positive serum samples from renal transplant recipients, hemodialyzed patients, concomitant HCV-HIV, HCV-HTLV-I, and sexually transmitted diseases infected patients were analyzed. Genotyping was performed by Inno-LiPA TM assay (Innogenetics, Gent, Belgium). The quantitafion was carried-out with the HCV RT-PCR assay (HCV Monitor TM, Roche), based on coamplification of HCV RNA with a synthetic RNA Intemal Quanfitation Standard (IQS). Routes of transmission were : Blood transfusion (BT) (68%), intravenous drag abuse (IVDU) (11%), sexual contact without any parenteral risk factor (21%); and 42 patients presenting retroviral coinfections (12 HTLV-I, 30 HIV). Resu l t s : The genotype distribution was : la (29%), lb (59%), 2a (7%) and 3a (5%). Significant HCV viremia level was found for genotype 1(3.4x105) vs non-1 genotype ( lx105) (p<0.01), but not for type l a v s

lb. HCV-RNA level was significantly higher in the BT group than in the others with fitres of 4.6x10 s , 1.4x10 s, and 0.4x105 respectively in BD, IVDU and STD groups (p<0.003). For retroviral coinfected patients, RNA level was higher in HTLV-I than in HIV coinfected patients: 2.7x105 v s

0.8x105 (p<0.01). Conclusions: HCV RNA level could be increased by genotype 1, and]or history of blood transfusion, and/or coinfecfion with HTLV-I. But, it could be also related to duration of infection. These data should help optimize HCV treatment regimen.