Hepatitic C virus carriers with normal alt activity: Viremia, genotype, histology and effect of...
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HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995 AASLD ABSTRACTS 343A 945 HEPATITIS C VIRUS (HCV) GENOTY'PES AND CLINICAL COURSE OF ANTI-HCV POSITIVE CIRRHOSIS. L Benve~nu, P Pontisso, D Cavalletto, L Chemello, and A Alberti. Cliniea Medica II, University of Padova, ITALY Hepatitis C virus (HCV) infection is a major cause of chronic liver disease woddwide and greatly contributes to the etiology of cirrhosis and of hepatocellular carcinoma. HCV exists as a fanuly of distinct genotypes and it has been suggested that the Course of liver disease may depend on the infecting virus strain. We have therefore investigate the relation between the HCV genotype (Stmmonds's classification) and liver disease activity and stage in 429 consecutive patients with chronic hepatitis C, including 109 patients with cirrhosis who had been followed up prospectively for 4 to 10 years allowing to assess whether the HCV genotype has a significant influence on disease outcome and development of hepatocellular carcinoma. Results. HCV-I was detected in 194 patients - 147/320 (46%) without cirrhosis and 47/109(43%) with cirrhosis- being mainly HCV-Ib. HCV-2 was found in 133 patients - 103/320 (32%) without cirrhosis and 30/109 (275) with cirrhosis - being mainly HCV-2a. HCV-3 was detected in 34 patients - 32/320 (10%) without cirrhosis and 2/109 (2%) with cirrhosis. Infection with the simultaneous presence of more than one genotype (HCV-I/HCV-2, HCV-I/HCV-3) was observed only in cirrhotic patients (6 out of 109 - 5.5%). After adjustment for age and sex, no significant differences in prevalence of HCV-I and HCV-2 between non-cirrhotic and cirrhotic patients were noted. The latter, however. were more frequently found HCV-RNA negative (p < 0.02), or with mixed genotypes infection (p < 0.005) and more rarely infected by HCV-3 (p < 0.005). During prospective follow-up. 21 (19.2%) of patients with cirrhosis deteriorated according to Child's stage, 5 (4.5%) underwent liver transplant. 23 (21.l%) developed HCC and 24 (22%) died for complications of l~ver disease, the overall incidence of at least one of these events being 385% (42/109 cases). The cumulative probability of developing each or at least one of the above events (Kaplan-Meier method and log-rank test) did not differ in relation to the genotype of infecting HCV, with the exception of patients with mixed genotvpes infection who showed a significantly higher risk of death. Independently of clinical events. patients with HCV, Ib showed a significantly higher probability of maintaining elevated/fluctuating levels of ALT during follow-up. These results do not indicate major differences in liver disease severity among patients infected by different HCV types. In patients with cirrhosis infection with HCV-I or HCV-2 had similar prognosis and progression to HCC, while patients with mixed genotypes had higher risk of death for liver disease. 946 HEPATITIS C VIRUS CARRIERS WITH NORMAL ALT ACTIVITY:VIREMIA, GENOTYPE, HISTOLOGY AND EFFECT OF INTERFERON THERAPY. I AreiasL I PedrotoL T FreitasI. R Cerqueira~,.~ TeixeiraL L Pinh02. B Justica 2. A M Saraiva'. Dept of Gastroenterology 1 and Hematology ~, Hospital Geral de Santo Ant6nio, Oporto, Portugal. Chronic HCV infection in patients with persistently normal ALT activity is under investigation. AIM - To assess the level of viremia, HCV genotype histological activity and the effect of interferon recombinant alpha 2b in these patients, compared with a control group. METHODS - We have studied 14 patients with persistently normal ALT levels. HCV RNA was quantifiedby bDNA (Quantiplex TM HCV RNA, Chiton Corporation, Emeryville, USA), and HCV genotype by LIPA. The levels of viremia and HCV genotype of these patients were compared with a homogeneous control group of 20 patients with chronic hepatitis C histologically proven but with elevated ALT values. Eight (57%) of the 14 patients were treated by IFN 3 MU TIW for 6 months and were evaluated at the end'of treatment, and six months later: RESULTS - Thirteen (92.8%) patients had chronic hepatitis and 1 (7.2%) had minimal lesions. Mean Knodell score was 3.4+_2.5(1-9): Table 1. Levels of viremia and genotypes in patients (n=14) end controls (n=20) ALT levels* HCV RNA Genotype (%) CR (%) SR (%) (UL/L) (Eq/rnlxJO 5) Treated group (n=t4) 19_+8 21_+3 la (36) 9/14 (64) '3/9 (33) lb (50) 3a (14) Control group (n=20) 1245:11 38-+5 la (35) 12/20 (60) 7)12 (58) lb (65) *mean-+SD CONCLUSIONS - In HCV carders with persistently normal ALT activity: (1) Histological liver injury is frequent; (2) when compared to patents with abnormal ALT activity, HCV genotypes are not significantlydifferent, butthe level of viremia is lower; (3) IFN lowers levels of viremia, improves liver histology, but falls HCV eradication. 947 GENOMIC CHARACTERIZATION OF HCV IN VIREMIC PATIENTS WITH NORMAL ALT. P Pontissot MG Euvoletto~M GerottotL De Moliner~ S Tisminetzky~ L Chemello~C Casarin~F Baralle*and A Alberti Cliniea Medica 2, University of Padova,*ICGEB Trieste,Italy Hepatitis C viremia may be detected in patients with normal ALT profile and in 20-30% of cases with sustained biochemical response to IFN. We have studied 24 HCVcarriers with persistently normal ALT and 20 viremic long-term responders to interferon (IFN), defined on the basis of biochemical profile. They derived from i14 patients who mantained persistently normal ALT after IFN for at least 12 months. HCV genotype was assessed by type-specific probe hybridization of the 5'UTR. In HCV carriers 33% were infected by type i, 63% by type 2 and 4% by type 3. Among sustained responders viremia persisted in 2/18 (11%) with type i, in 20/47 (42%) with type 2 and in none of the 23 cases with type 3. Viremic levels were quantified before and after therapy by a commercial kit (Amplicor HCV Monitor, Roche Molecular Systems) and 5'UTR amplified products were analyzed by direct sequencing. In viremic sustained responders 71% of patients with type 2 showed a mixture of two virus populations, defined by simultaneous presence of T/C at position -119 or -165 or -94, or of A/G at -109. Simultaneous T/C at -119 was also observed in HCV carriers with type 2. In treated patients the mixed population was often detected after therapy, at the time of ALT normality and disappeared in coincidence with hepatitis relapse, occurring at long term follow-up with an ALT flare. Levels of viremia were significantly higher in sera with mixed type 2 populations compared to those with a single viral strain and increased up to 20 times in those in whom a mixed population appeared after treatment, while ALT were normal. These findings indicate that genotype 2 may frequently associate with normal ALT, both in HCV carriers and in viremic patients with sustained biochemical response to interferon. Quantitative and qualitative variations of circulating viral particles can influence biochemical activity of liver disease. 948 LICHEN PLANUS AND HEPATITIS C VIRUS (HCV)-RELATED CHRONIC HEPATITIS : ROLE OF HCV GENOTYPES. JM. Pawlotskv 1. H. Benchik~-.~ Pelletl, J. Duval-!-. D. Dhumeaux 3. J. Revuz2, M. Bagot2 Departments of 1Bacteriology and Virology, 2Derrnatology, 3Hepatology and Gastroenterology, H6pital Henri Mondor, Universit~ Paris XII, Crdteil, France. A relationship between lichen planus (LP) and chronic hepatitis C has been recently suggested, but the prevalence of HCV markers varies widely in patients with LP from one study to another. The aim of this study was to determine whether the occurrence of LP in patients with chronic hepatitis C could be associated with peculiar HCV genotypes. Methods. Two groups of patients were studied : (i) the LP group included 10 patients with LP and chronic hepatitis C (6M, 4F, mean age 61_+9 yr), and (ii) the control group included 98 patients with chronic hepatitis C without signs of LP (64M, 34F, mean age 47+14 yr). HCV genotype was determined in all patients by means of a slight modification of the Inno-LiPA method (Innogenetics, Gent, Belgium). The characteristics of LP were analyzed in the patients of LP group. Results. The prevalences of HCV genotypes in the two groups are given in the table : LP group (n=10) Control group (n=98) t a 1/10 19/98 (19%) lb 4/10 42/98 (43%) 2a 1/10 8/98 (8%) 3a 1/10 19/98 (19%) 4a 2/10 7/98 (7%) mixed 1/10 3/98 I3% / The distribution of HCV genotypes did not differ among the two groupsl Four patients in the LP group had cutaneous LP, 2 had mucosal LP and 4 had both cutaneous and mucosal LP. Localization and severity of LP were independent of HCV genotype. Conclusions. Like other extra-hepatic immunologic manifestations frequently associated with chronic hepatitis C (Pawlotsky et al., Ann Intern Med 1995;122:169-173), LP can be observed in patients infected by any of the main HCV genotypes present in industrialized countries. Therefore, the inconstant emergence of LP in patients with chronic hepatitis C is not related to specific HCV genotypes. In patients with both LP and chronic HCV infection, evaluation of HCV replication in skin and mucosal lesions is needed to better understand the mechanism underlying the association.
Transcript of Hepatitic C virus carriers with normal alt activity: Viremia, genotype, histology and effect of...
HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995 AASLD ABSTRACTS 343A
945 HEPATITIS C VIRUS (HCV) GENOTY'PES AND CLINICAL COURSE OF ANTI-HCV POSITIVE CIRRHOSIS. L Benve~nu, P Pontisso, D Cavalletto, L Chemello, and A Alberti. Cliniea Medica II, University of Padova, ITALY
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease woddwide and greatly contributes to the etiology of cirrhosis and of hepatocellular carcinoma. HCV exists as a fanuly of distinct genotypes and it has been suggested that the Course of liver disease may depend on the infecting virus strain. We have therefore investigate the relation between the HCV genotype (Stmmonds's classification) and liver disease activity and stage in 429 consecutive patients with chronic hepatitis C, including 109 patients with cirrhosis who had been followed up prospectively for 4 to 10 years allowing to assess whether the HCV genotype has a significant influence on disease outcome and development of hepatocellular carcinoma. Results. HCV-I was detected in 194 patients - 147/320 (46%) without cirrhosis and 47/109(43%) with cirrhosis- being mainly HCV-Ib. HCV-2 was found in 133 patients - 103/320 (32%) without cirrhosis and 30/109 (275) with cirrhosis - being mainly HCV-2a. HCV-3 was detected in 34 patients - 32/320 (10%) without cirrhosis and 2/109 (2%) with cirrhosis. Infection with the simultaneous presence of more than one genotype (HCV-I/HCV-2, HCV-I/HCV-3) was observed only in cirrhotic patients (6 out of 109 - 5.5%). After adjustment for age and sex, no significant differences in prevalence of HCV-I and HCV-2 between non-cirrhotic and cirrhotic patients were noted. The latter, however. were more frequently found HCV-RNA negative (p < 0.02), or with mixed genotypes infection (p < 0.005) and more rarely infected by HCV-3 (p < 0.005). During prospective follow-up. 21 (19.2%) of patients with cirrhosis deteriorated according to Child's stage, 5 (4.5%) underwent liver transplant. 23 (21.l%) developed HCC and 24 (22%) died for complications of l~ver disease, the overall incidence of at least one of these events being 385% (42/109 cases). The cumulative probability of developing each or at least one of the above events (Kaplan-Meier method and log-rank test) did not differ in relation to the genotype of infecting HCV, with the exception of patients with mixed genotvpes infection who showed a significantly higher risk of death. Independently of clinical events. patients with HCV, Ib showed a significantly higher probability of maintaining elevated/fluctuating levels of ALT during follow-up. These results do not indicate major differences in liver disease severity among patients infected by different HCV types. In patients with cirrhosis infection with HCV-I or HCV-2 had similar prognosis and progression to HCC, while patients with mixed genotypes had higher risk of death for liver disease.
946 H E P A T I T I S C VIRUS C A R R I E R S WITH N O R M A L ALT ACTIVITY:VIREMIA, GENOTYPE, HISTOLOGY AND EFFECT OF INTERFERON THERAPY. I AreiasL I PedrotoL T Freitas I. R Cerqueira~,.~ TeixeiraL L Pinh0 2. B Justica 2. A M Saraiva '. Dept of Gastroenterology 1 and Hematology ~, Hospital Geral de Santo Ant6nio, Oporto, Portugal.
Chronic HCV infection in patients with persistently normal ALT activity is under investigation. AIM - To assess the level of viremia, HCV genotype histological activity and the effect of interferon recombinant alpha 2b in these patients, compared with a control group. METHODS - We have studied 14 patients with persistently normal ALT levels. HCV RNA was quantified by bDNA (Quantiplex TM HCV RNA, Chiton Corporation, Emeryville, USA), and HCV genotype by LIPA. The levels of viremia and HCV genotype of these patients were compared with a homogeneous control group of 20 patients with chronic hepatitis C histologically proven but with elevated ALT values. Eight (57%) of the 14 patients were treated by IFN 3 MU TIW for 6 months and were evaluated at the end'of treatment, and six months later: RESULTS - Thirteen (92.8%) patients had chronic hepatitis and 1 (7.2%) had minimal lesions. Mean Knodell score was 3.4+_2.5 (1-9): Table 1. Levels of viremia and genotypes in patients (n=14) end controls (n=20)
ALT levels* HCV RNA Genotype (%) CR (%) SR (%) (UL/L) (Eq/rnlxJO 5)
Treated group (n=t4) 19_+8 21_+3 la (36) 9/14 (64) '3/9 (33) lb (50) 3a (14)
Control group (n=20) 1245:11 38-+5 la (35) 12/20 (60) 7)12 (58) lb (65)
*mean-+SD
CONCLUSIONS - In HCV carders with persistently normal ALT activity: (1) Histological liver injury is frequent; (2) when compared to patents with abnormal ALT activity, HCV genotypes are not significantly different, butthe level of viremia is lower; (3) IFN lowers levels of viremia, improves liver histology, but falls HCV eradication.
947 GENOMIC CHARACTERIZATION OF HCV IN VIREMIC PATIENTS WITH NORMAL ALT. P Pontissot MG Euvoletto~M GerottotL De Moliner~ S Tisminetzky~ L Chemello~C Casarin~F Baralle*and A Alberti Cliniea Medica 2, University of Padova,*ICGEB Trieste,Italy
Hepatitis C viremia may be detected in patients with normal ALT profile and in 20-30% of cases with sustained biochemical response to IFN. We have studied 24 HCVcarriers with persistently normal ALT and 20 viremic long-term responders to interferon (IFN), defined on the basis of biochemical profile. They derived from i14 patients who mantained persistently normal ALT after IFN for at least 12 months. HCV genotype was assessed by type-specific probe hybridization of the 5'UTR. In HCV carriers 33% were infected by type i, 63% by type 2 and 4% by type 3. Among sustained responders viremia persisted in 2/18 (11%) with type i, in 20/47 (42%) with type 2 and in none of the 23 cases with type 3. Viremic levels were quantified before and after therapy by a commercial kit (Amplicor HCV Monitor, Roche Molecular Systems) and 5'UTR amplified products were analyzed by direct sequencing. In viremic sustained responders 71% of patients with type 2 showed a mixture of two virus populations, defined by simultaneous presence of T/C at position -119 or -165 or -94, or of A/G at -109. Simultaneous T/C at -119 was also observed in HCV carriers with type 2. In treated patients the mixed population was often detected after therapy, at the time of ALT normality and disappeared in coincidence with hepatitis relapse, occurring at long term follow-up with an ALT flare. Levels of viremia were significantly higher in sera with mixed type 2 populations compared to those with a single viral strain and increased up to 20 times in those in whom a mixed population appeared after treatment, while ALT were normal. These findings indicate that genotype 2 may frequently associate with normal ALT, both in HCV carriers and in viremic patients with sustained biochemical response to interferon. Quantitative and qualitative variations of circulating viral particles can influence biochemical activity of liver disease.
948 LICHEN PLANUS AND HEPATITIS C VIRUS (HCV)-RELATED CHRONIC HEPATITIS : ROLE OF HCV GENOTYPES. JM. Pawlotskv 1. H. Benchik~-.~ Pelletl, J. Duval-!-. D. Dhumeaux 3. J. Revuz 2, M. Bagot 2 Departments of 1 Bacteriology and Virology, 2Derrnatology, 3Hepatology and Gastroenterology, H6pital Henri Mondor, Universit~ Paris XII, Crdteil, France.
A relationship between lichen planus (LP) and chronic hepatitis C has been recently suggested, but the prevalence of HCV markers varies widely in patients with LP from one study to another. The aim of this study was to determine whether the occurrence of LP in patients with chronic hepatitis C could be associated with peculiar HCV genotypes.
Methods. Two groups of patients were studied : (i) the LP group included 10 patients with LP and chronic hepatitis C (6M, 4F, mean age 61_+9 yr), and (ii) the control group included 98 patients with chronic hepatitis C without signs of LP (64M, 34F, mean age 47+14 yr). HCV genotype was determined in all patients by means of a slight modification of the Inno-LiPA method (Innogenetics, Gent, Belgium). The characteristics of LP were analyzed in the patients of LP group.
Results. The prevalences of HCV genotypes in the two groups are given in the table :
LP group (n=10) Control group (n=98) t a 1/10 19/98 (19%) lb 4/10 42/98 (43%) 2a 1/10 8/98 (8%) 3a 1/10 19/98 (19%) 4a 2/10 7/98 (7%) mixed 1/10 3/98 I3% /
The distribution of HCV genotypes did not differ among the two groupsl Four patients in the LP group had cutaneous LP, 2 had mucosal LP and 4 had both cutaneous and mucosal LP. Localization and severity of LP were independent of HCV genotype.
Conclusions. Like other extra-hepatic immunologic manifestations frequently associated with chronic hepatitis C (Pawlotsky et al., Ann Intern Med 1995;122:169-173), LP can be observed in patients infected by any of the main HCV genotypes present in industrialized countries. Therefore, the inconstant emergence of LP in patients with chronic hepatitis C is not related to specific HCV genotypes. In patients with both LP and chronic HCV infection, evaluation of HCV replication in skin and mucosal lesions is needed to better understand the mechanism underlying the association.
