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Does HBsAg carriage modify ethanol metabolism ?
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H B V A N D H C V IN P E R I P H E R A L BLOOD M O N O N U C L E A R CELLS OF P A T I E N T S U N D E R G O I N G C H R O N I C H E M O D I A L Y S I S Ch. M~ller, Ch. O e s t e r r e i c h e r r F. Pfeffel~ J. H a m m e r r O. Traindl, G. S u n d e r - P l a s s m a n n , J. Kovarik. University Clinic for Internal M e d i c i n e III and IV, Vienna, Austria. C h r o n i c dialysis is associated with a state of i ~ u n o d e f i c i e n c y w h i c h c a n result in undetectable levels of antibodies a g a i n s t H B V or HCV. T h e r e fore, d i r e c t d e t e c t i o n of v i r u s in the form of e i t h e r v i r a l a n t i g e n s or v i r a l g e n o m e s is n e c e s sary. However, a low viral titer in serum can fall below t h e d e t e c t i o n limit of PCR-based assays. As p e r i p h e r a l b l o o d m o n o n u c l e a r cells (PMNC) are known to be susceptible to infection of both H B V and HCV, d e t e c t i o n of viral genomes in t h o s e cells could u n c o v e r some h i d d e n infection. We i n v e s t i g a ted 67 patients on c h r o n i c h e m o d i a l y s i s (34m, 33f) by PCR for t h e p r e s e n c e of H B V or H C V g e n o m e s in s e r u m as w e l l as in PMNC. In 5 p a t i e n t s H B V - D N A in PMNC was t h e o n l y m a r k e r of H B V i n f e c t i o n as both H B s A g and H B V - D N A in s e r u m was negative; in addition, those patients were also a n t i - H B c negative. In 9 patients HCV-RNA was positive in serum; in 5 of t h o s e p a t i e n t s if w a s also found in PMNC. 1 patient had no H C V - R N A in serum, but was positive for H C V - R N A in PMNC. Of the i0 patients who had H C V - R N A p r e s e n t either in serum and/or in PMNC, 4 patients w e r e n e g a t i v e for anti-HCV. Thus, in 9% of patients u n d e r g o i n g c h r o n i c h e m o d i a l y s i s we found evidence of infection with HBV or HCV by d e t e c t i o n of viral g e n o m e s in PMNC without the p r e s e n c e of detectable viremia, a n t i g e n e m i a or specific viral antibodies in serum.
Papers read by title
DOES HBSAG CARRIAGE MODIFY ETHANOL METABOLISM ? 1'2B. Nalpas, 3p. Letteron, 4 M L Mancini, 5_.j. Guechot 1.2p.Berthelot !~bC.Br~chot, 5C.Pourcel. 1Unit~ d'H~patologie H6p. N e ~ R M ~ 4 , U-4"~'~-163I'nstitut Pasteur, 5Lab Biochimie H6p St Antoine, 6U-370. It has been shown that chronic HBsAg carriage increases monooxygenases activities As alcohol is in part oxydized via microsomal pathways, one could suspect that an on-going HBV infection could modify ethanol metabolism rate. Therefore we measured the plasma ethanol disappearance in transgenic HBsAg positive mice after an acute and a chronic alcohol administration Methods : 1. After an overnight fast, ethanol (5 g/k bw) was administered intra-gastrically to 8 naive male mice (4 HBs pos, 4 HBs neg) Blood was collected via the retro-orbitary plexus at hours 1, 2, 4 and 6 : 2 . 2 2 male mice (10 HBs pos, 12 HBs neg) were alcohol-fed over an 8-week period. Alcohol was given diluted in tap-water at increasing concentration (5 to 30%) At day 57 the 22 mice were submitted to the same protocol than naive mice. Blood ethanol concentrations were measured using a kit from Sigma Results : In naive mice the ethanol elimination rate constant (k) was similar in HBs pos and HBs neg mice (-0.13+0.08 vs -0.12+0 04, NS) Chronically alcoholized mice displayed an increase in k, as compared to naive mice, however there was still no difference between HBs pos and HBs neg mice (-0.20+010 vs -0 22+011). Our data suggest that chronic HBsAg carriage does not interact with ethanol metabolism
DETECTION OF SERUM HCV-RNA IN ANTI-HCV POSITIVE SUBJECTS WITH NORMAL ALT LEVEL CORRELATES WITH LIVER HCV-RNA AND LIVER HISTOLOGY.
HEPATITIS C TRANSYLVANIA,
1.2B.Nalpas, -3R.Romeo, 1-~.Pol, 4-V.Thiers, -5F.Carnot, 1-.~P.Berthelot 1.3C.Br~chot. 1Li~, Hop. Necker; 21nserm U-99 and 3U-370: 4Hybridotest, Inst. Pasteur; 5Lab. d'Anatomopathologie, Hop. Laennec.
A . N e a m t u I , D. Badea 2 D. State 3 , P. Szanto 1 , O. Chira 1 , D.
Although anti-HCV positivity is mostly associated to an on-going infection when serum ALT is increased, the signification of anti-HCV remains unclear when ALT level is persistently normal To shed some light on this point we looked for HCV-RNA in the serum and the liver and analyzed liver histology in 14 anti-HCV positive subjects who had repeatedly normal ALT values over a follow-up period of 3 months at least; this protocol was approved by the local ethical comittee and all the 14 subjects gave their informed consent. Mean ALT level at time of the biopsy was 15.2+-8.7 I.U/I (upper normal limit 45).The presumed duration of the infection, which could be evaluated in 9/14, was 13.8+5.6 years (range 8-22) Results: Twelve anti-HCV positive with ELISA 2 were positive by RIBA3 and 2 were undetermined. Serum HCV-RNA was positive by PCR in 6 subjects HCV-RNA was positive in the liver in all cases where positive in the serum and never when serum was negative Liver histology was normal in all HCV-RNA negative subjects (Mean Knodell score 1.3, range 0-2): minor lesions (Mean Knodell score 24, range 1-4) were present in the 5 of the 6 HCV-RNA positive subjects while the sixth had a score of 8 Conclusions: Our data indicate that in anti-HCV positive subjects with repeatedly normal ALT values " 1. HCV-RNA is negative and liver histology is normal in more than a half, even if RIBA3 is positive, demonstrating that HCV can be eradicated. 2. only minor liver alterations are usually found in HCV-RNA positive subjects • 3. there is a complete correlation between serum and liver HCV-RNA on one hand, and between HCV-RNA status and liver histology on the other. Therefore combination of serum HCV-RNA and ALT level determinations are reliable tools to appreciate HGV status and to decide to perform a liver biopsy
VIRUS (HCV) ROMANIA
INFECTION
IN
1 t~:~ V'/~ R. Cozgarea 1 . 1I tUniversity of Medicine, Cluj, 2 Sanofi Diagnostics Pasteur Bucharest, 3 University of Medicine Bucharest, Romania. Data on HCV infection are still limited in Romania. We evaluated the prevalence of antibodies to HCV (antiHCV) in blood donors, high-risk groups, chronic hepatitis (CH) patients (pts), liver cirrhosis (LC) pts and hepatocellular carcinoma (HCC) pts. Sere from 712 subjects have been tested for antiHCV by ELISA 2 nd generation (Sanofi Diagnostics Pasteur kits}. The results are 9resented in table:
V o l u n t e e r blood d o n o r s Chronic haemodialysis Multitransfused Multiple heterosexual p a r t n e r s CH - adults - children LC HCC
Number tested 232 82 54 49 84 46 156 9
antiHCV+ n % 12 5.2 66 80.5 19 35 13 26.5 38 45.2 3 6.5 84 53.8 5 55.5
Prevalence of antiHCV in Romanian blood donors was 5.2%. High prevalence of antiHCV was also noticed in chronically haemodialysed, HCC, LC, CH adult patients. In children with CH the prevalence of anti HCV was 6.5%.
H B V A N D H C V IN P E R I P H E R A L BLOOD M O N O N U C L E A R CELLS OF P A T I E N T S U N D E R G O I N G C H R O N I C H E M O D I A L Y S I S Ch. M~ller, Ch. O e s t e r r e i c h e r r F. Pfeffel~ J. H a m m e r r O. Traindl, G. S u n d e r - P l a s s m a n n , J. Kovarik. University Clinic for Internal M e d i c i n e III and IV, Vienna, Austria. C h r o n i c dialysis is associated with a state of i ~ u n o d e f i c i e n c y w h i c h c a n result in undetectable levels of antibodies a g a i n s t H B V or HCV. T h e r e fore, d i r e c t d e t e c t i o n of v i r u s in the form of e i t h e r v i r a l a n t i g e n s or v i r a l g e n o m e s is n e c e s sary. However, a low viral titer in serum can fall below t h e d e t e c t i o n limit of PCR-based assays. As p e r i p h e r a l b l o o d m o n o n u c l e a r cells (PMNC) are known to be susceptible to infection of both H B V and HCV, d e t e c t i o n of viral genomes in t h o s e cells could u n c o v e r some h i d d e n infection. We i n v e s t i g a ted 67 patients on c h r o n i c h e m o d i a l y s i s (34m, 33f) by PCR for t h e p r e s e n c e of H B V or H C V g e n o m e s in s e r u m as w e l l as in PMNC. In 5 p a t i e n t s H B V - D N A in PMNC was t h e o n l y m a r k e r of H B V i n f e c t i o n as both H B s A g and H B V - D N A in s e r u m was negative; in addition, those patients were also a n t i - H B c negative. In 9 patients HCV-RNA was positive in serum; in 5 of t h o s e p a t i e n t s if w a s also found in PMNC. 1 patient had no H C V - R N A in serum, but was positive for H C V - R N A in PMNC. Of the i0 patients who had H C V - R N A p r e s e n t either in serum and/or in PMNC, 4 patients w e r e n e g a t i v e for anti-HCV. Thus, in 9% of patients u n d e r g o i n g c h r o n i c h e m o d i a l y s i s we found evidence of infection with HBV or HCV by d e t e c t i o n of viral g e n o m e s in PMNC without the p r e s e n c e of detectable viremia, a n t i g e n e m i a or specific viral antibodies in serum.
Papers read by title
DOES HBSAG CARRIAGE MODIFY ETHANOL METABOLISM ? 1'2B. Nalpas, 3p. Letteron, 4 M L Mancini, 5_.j. Guechot 1.2p.Berthelot !~bC.Br~chot, 5C.Pourcel. 1Unit~ d'H~patologie H6p. N e ~ R M ~ 4 , U-4"~'~-163I'nstitut Pasteur, 5Lab Biochimie H6p St Antoine, 6U-370. It has been shown that chronic HBsAg carriage increases monooxygenases activities As alcohol is in part oxydized via microsomal pathways, one could suspect that an on-going HBV infection could modify ethanol metabolism rate. Therefore we measured the plasma ethanol disappearance in transgenic HBsAg positive mice after an acute and a chronic alcohol administration Methods : 1. After an overnight fast, ethanol (5 g/k bw) was administered intra-gastrically to 8 naive male mice (4 HBs pos, 4 HBs neg) Blood was collected via the retro-orbitary plexus at hours 1, 2, 4 and 6 : 2 . 2 2 male mice (10 HBs pos, 12 HBs neg) were alcohol-fed over an 8-week period. Alcohol was given diluted in tap-water at increasing concentration (5 to 30%) At day 57 the 22 mice were submitted to the same protocol than naive mice. Blood ethanol concentrations were measured using a kit from Sigma Results : In naive mice the ethanol elimination rate constant (k) was similar in HBs pos and HBs neg mice (-0.13+0.08 vs -0.12+0 04, NS) Chronically alcoholized mice displayed an increase in k, as compared to naive mice, however there was still no difference between HBs pos and HBs neg mice (-0.20+010 vs -0 22+011). Our data suggest that chronic HBsAg carriage does not interact with ethanol metabolism
DETECTION OF SERUM HCV-RNA IN ANTI-HCV POSITIVE SUBJECTS WITH NORMAL ALT LEVEL CORRELATES WITH LIVER HCV-RNA AND LIVER HISTOLOGY.
HEPATITIS C TRANSYLVANIA,
1.2B.Nalpas, -3R.Romeo, 1-~.Pol, 4-V.Thiers, -5F.Carnot, 1-.~P.Berthelot 1.3C.Br~chot. 1Li~, Hop. Necker; 21nserm U-99 and 3U-370: 4Hybridotest, Inst. Pasteur; 5Lab. d'Anatomopathologie, Hop. Laennec.
A . N e a m t u I , D. Badea 2 D. State 3 , P. Szanto 1 , O. Chira 1 , D.
Although anti-HCV positivity is mostly associated to an on-going infection when serum ALT is increased, the signification of anti-HCV remains unclear when ALT level is persistently normal To shed some light on this point we looked for HCV-RNA in the serum and the liver and analyzed liver histology in 14 anti-HCV positive subjects who had repeatedly normal ALT values over a follow-up period of 3 months at least; this protocol was approved by the local ethical comittee and all the 14 subjects gave their informed consent. Mean ALT level at time of the biopsy was 15.2+-8.7 I.U/I (upper normal limit 45).The presumed duration of the infection, which could be evaluated in 9/14, was 13.8+5.6 years (range 8-22) Results: Twelve anti-HCV positive with ELISA 2 were positive by RIBA3 and 2 were undetermined. Serum HCV-RNA was positive by PCR in 6 subjects HCV-RNA was positive in the liver in all cases where positive in the serum and never when serum was negative Liver histology was normal in all HCV-RNA negative subjects (Mean Knodell score 1.3, range 0-2): minor lesions (Mean Knodell score 24, range 1-4) were present in the 5 of the 6 HCV-RNA positive subjects while the sixth had a score of 8 Conclusions: Our data indicate that in anti-HCV positive subjects with repeatedly normal ALT values " 1. HCV-RNA is negative and liver histology is normal in more than a half, even if RIBA3 is positive, demonstrating that HCV can be eradicated. 2. only minor liver alterations are usually found in HCV-RNA positive subjects • 3. there is a complete correlation between serum and liver HCV-RNA on one hand, and between HCV-RNA status and liver histology on the other. Therefore combination of serum HCV-RNA and ALT level determinations are reliable tools to appreciate HGV status and to decide to perform a liver biopsy
VIRUS (HCV) ROMANIA
INFECTION
IN
1 t~:~ V'/~ R. Cozgarea 1 . 1I tUniversity of Medicine, Cluj, 2 Sanofi Diagnostics Pasteur Bucharest, 3 University of Medicine Bucharest, Romania. Data on HCV infection are still limited in Romania. We evaluated the prevalence of antibodies to HCV (antiHCV) in blood donors, high-risk groups, chronic hepatitis (CH) patients (pts), liver cirrhosis (LC) pts and hepatocellular carcinoma (HCC) pts. Sere from 712 subjects have been tested for antiHCV by ELISA 2 nd generation (Sanofi Diagnostics Pasteur kits}. The results are 9resented in table:
V o l u n t e e r blood d o n o r s Chronic haemodialysis Multitransfused Multiple heterosexual p a r t n e r s CH - adults - children LC HCC
Number tested 232 82 54 49 84 46 156 9
antiHCV+ n % 12 5.2 66 80.5 19 35 13 26.5 38 45.2 3 6.5 84 53.8 5 55.5
Prevalence of antiHCV in Romanian blood donors was 5.2%. High prevalence of antiHCV was also noticed in chronically haemodialysed, HCC, LC, CH adult patients. In children with CH the prevalence of anti HCV was 6.5%.