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Cholestasis associated to Turner's syndrome can be reversed by ursodeoxycholic acid treatment
HEPATOLOGY Vol. 22, No. 4, Pt. 2, 1995 1369
AASLD ABSTRACTS
CHOLESTASIS ASSOCIATED TO TURNER'S SYNDROME CAN BE REVERSED BY URSODEOXYCHOLIC ACID TREATMENT P. Loria, F. Callea**, M. Bozzoli, A. Bagni*, M. Concari. ME. Gulcciardi, C. Carani, V. Montanini, R. Mantovani, M. Bertolotti, N. Carulli. Dipartimenti di Medicina Interna e *Scienze Moffologiche e Medico Legali, Universit/t di Modena, Italy - **Servizio di Anatomia e Istologia Patologica, Spedali Civili di Brescia, Italy.
1370
MULTIVARIATE ANALYSIS OF THE POTENTIAL FACTORS INVOLVED IN THE PRODUCTION OF CRYOGLOBULINS IN HCV
INFECTED PATIENTS..F_Lunel*, L Frangeul*r T Poynard*~ P Cresta*~L Musset*~P Cacoub*r P Loiseaa* *r JM Huraux*F P Opolon*. HSpital Piti~Salp~tri~:re 75651 Paris Codex 13. **CTS HSpital Saint Louis 75475 Paris Cedex 10, FRANCE We have shown recendy that cryoglobulinemia (CG) affe.zts 50% of the patients presenting with chronic hepatitis C. The aim of this study was to evaluate the role or influence of epidemiological, clinical virological and histological factors in the pathogenesis of CG. Patients: we have studied 130 patients with chronic HCV infection (defined on the positivity of anti HCV antibodies and HCV RNA). 80 of them had cryoglobulins detectable in their sera and 37 of them had clinical symptoms (cutaneous involvement, neuropathy or glomerulopathy). The following parameters were studied: age, sex, duration of infection, immunosuppression (AIDS, transplantation), severity of liver disease assessed by Knodell score, level of HCV RNA quantified by branched DNA (Chiron), HCV genotypes studied using the Line Probe Assay (LiPA, Innogenetics). Results: 1) using univariate analysis, the factors significandy associated with CG were the sex (female, p=0.02), the presence of cirrhosis at liver biopsy (p=0.01), the absence of immunosupression (p<0.001) the age (p--0.001), the duration of infection (p=0.003) and the KnodeU score (p=0.02), but not the level of HCV-RNA and the lb HCV subtype; 2) using multivariate analysis (logistic regression in 122 patients), the only factors significantly associated with CG were the presence of cirrhosis at liver biopsy (p=0.05), the absence of immunosupression (p=0.01) and the age (p=0.004). In conclusion: Many papers have shown that CG production was related to factors which could be in fact linked (ie severity of liver disease, age, duration of infection, genotype). In this study we suggest that age, cirrhosis and absence of immunodepression are the only factors significantly and independently associated with cryoglobulinemia.
ANTI-HCV CORE ANTIBODY LEVELS CORRESPOND TO DISEASE ACTIVITY AND PREDICTS THE THERAPY RESPONSE H. F. LOhr§. C. EIste,,~. H. P. Dien~,,-'~.G. Michel*. H. Braun*. K.-H Meyer zum Btiacbenfclde§. G. Gerken~ §I. Dept. Int. Medicinei $Pathology, Univ.Mainz, FRG. *Abbott Euro. Res, Wiesbaden, FRG. Virus-host interactions may have pathogenetic significance in chronic hepatitis. Thus the humoral immune response was evaluated as prognostic therapy prediction marker. IgG and lgM anti-HCV antibody titers and levels of circulating immune complexes were serially measured in end,point diluted sera of 18 selected chronic HCV patients that received 3 or 6 MU interferon-ot2a threetimes weekly for 6 to 12 months. The results were correlated with histology, HCV genotypes and HCVRNA levels. N'me HCV patients (genotypes la n=4; lb n=l; 2a n=l; 3a n=3) with low HCV-RNA pretreatment levels (mean 1.4x104 copies/ml) showed a long-lasting complete response with virus suppression and ALT normalization. In addition, six patients were non-responders and three partial responders (genotypes la n=2; lb n=7) characterized by significantly higher HCV-RNA pretreatment levels (mean 2.5x10 5 copie~dml). IgG and IgM subclass anti-HC34 antibodies were most immunogenei¢ in patients without response whereas IgG anti-He29 antibodies were predominant in complete responders. During treatment anti-HC34 and anti-HC29 antibody levels decreased in patients with therapy response. Two partial responders showed recurrent anti-HC34 antibody levels that proceeded disease reactivation and detectable HCVRNA. To conclude immune complexes did neither influence disease activity, HCV-RNA levels or genotypes, antibody levels nor therapy response. Anti-HCV core IgG and IgM antibodies, however, correlated with vimemia, disease activity and could serve as sensitive response predictive markers.
Cholestasis has been reported in association with Turner's syndrome (N Engl J IVied 1974; 290: 406). Aim of the present study was to investigate the presence of cholestatic features in a group of patients with the disease, and to look at the effect of treatment with ursodeoxycholic acid (UDCA). Patients and methods. We retrospectively reviewed the clinical records of 30 subjects with Turner' s syndrome, 5 of whom were also prospectively followed. In these 5 subjects, who had abnormal liver function tests, gas-liquid chromatography (GLC) of serum bile acids and liver biopsy were performed. Two of them underwent ERCP. All subjects were treated with UDCA (10mg/Kg/day) for 6 months. Results. Alkaline phosphatase was elevated in 53% (16/30) of the patients, y-GT in 42% (8/19) and serum transaminases in 37% (7/19). In the 5 patients followed prospectively AMA and viral infections markers were negative. A t GLC more than 70% of serum bile acids was constituted by chenodeoxycholic acid. A liver biopsy showed in all 5 subjects subtle but distinctive alterations consistent with a "smoldering biliopathy". The ERCP showed in 1 out of 2 subjects the presence of narrowed bile ducts. Estroprogestinic therapy worsened the eholestasis while UDCA administration determined a complete normalization of hiochemical tests. Conclusion. Tumor's syndrome is frequently associated with clinical a n d histological signs consistent with intrahepatic cholestasis. Biochemical alterations seem to be corrected by UDCA administration.
1371
449A
1372
HEPATITIS E IN DIALYSIS: FACT OR FANCY? G Macedo, AP Chaves, T Pinto, J Monteiro, F Seixas, O Pereira, B C~:rvalho, A Loureiro Nefronorte, Paredes, Portugal Hepatitis E virus (HEV), the main etiological agent of enterically transmitted non-A, non-B hepatitis, has caused epidemic outbreaks in developing countries and has been sporadically observed in industrialised countries. However, the risk factors associated with antiHEV positivity are not known yet. We studied the prevalence of HEV antibodies in a population of 71 portuguese haemodlalysis patients (35 males, aged 20-76 years old) and analysed 50 blood samples from asymptomatic volunteer blood donors (AVBD) without HBV or HCV markers. All samples were tested with HEV EIA (Abbot Diagnostic) using recombinant antigens from open reading frames 2 and 3 (SG3 and 8-5) coding respectively non structural and structural proteins from Burma virus. PCR technique was used to detect HBV DNA and HCV RNA in dialysis patients. The prevalence of HEV antibodies in our haemodialyals patients was 4,4% (3/71), whim HCV PCR positive patients were 9,8%, (7/71), and HBs Ag positive patients were 5,6% (3/71). AntiHEV was detected in 2/50 (4%) from AVBD. The values of optic dense/cutoff found in dialysis patients, were 0,8; 1,0; in AVBD, they were 1,1 and 1,5. Mean ago in HEV pos~tlve patients was 61 {being 50 in HEV negative) and the mean dialysis time was 49 months in both groups. Conclusions: 1. The prevalence of antiHEV in dialysis patients was similar to that one found in AVBD (7% x 4%, pNS). 2. All positive samples showed values of OD/cutoff that were less than two times the cutoff point, which seems to demonstrate that these values shouM be confirmed by a supplemental assay. 3. We did not observe, in our popu[etion of dialysis patients any statistical difference in age, time of dialysis and antiHCV positiveness between HEV positive or negative patients.
AASLD ABSTRACTS
CHOLESTASIS ASSOCIATED TO TURNER'S SYNDROME CAN BE REVERSED BY URSODEOXYCHOLIC ACID TREATMENT P. Loria, F. Callea**, M. Bozzoli, A. Bagni*, M. Concari. ME. Gulcciardi, C. Carani, V. Montanini, R. Mantovani, M. Bertolotti, N. Carulli. Dipartimenti di Medicina Interna e *Scienze Moffologiche e Medico Legali, Universit/t di Modena, Italy - **Servizio di Anatomia e Istologia Patologica, Spedali Civili di Brescia, Italy.
1370
MULTIVARIATE ANALYSIS OF THE POTENTIAL FACTORS INVOLVED IN THE PRODUCTION OF CRYOGLOBULINS IN HCV
INFECTED PATIENTS..F_Lunel*, L Frangeul*r T Poynard*~ P Cresta*~L Musset*~P Cacoub*r P Loiseaa* *r JM Huraux*F P Opolon*. HSpital Piti~Salp~tri~:re 75651 Paris Codex 13. **CTS HSpital Saint Louis 75475 Paris Cedex 10, FRANCE We have shown recendy that cryoglobulinemia (CG) affe.zts 50% of the patients presenting with chronic hepatitis C. The aim of this study was to evaluate the role or influence of epidemiological, clinical virological and histological factors in the pathogenesis of CG. Patients: we have studied 130 patients with chronic HCV infection (defined on the positivity of anti HCV antibodies and HCV RNA). 80 of them had cryoglobulins detectable in their sera and 37 of them had clinical symptoms (cutaneous involvement, neuropathy or glomerulopathy). The following parameters were studied: age, sex, duration of infection, immunosuppression (AIDS, transplantation), severity of liver disease assessed by Knodell score, level of HCV RNA quantified by branched DNA (Chiron), HCV genotypes studied using the Line Probe Assay (LiPA, Innogenetics). Results: 1) using univariate analysis, the factors significandy associated with CG were the sex (female, p=0.02), the presence of cirrhosis at liver biopsy (p=0.01), the absence of immunosupression (p<0.001) the age (p--0.001), the duration of infection (p=0.003) and the KnodeU score (p=0.02), but not the level of HCV-RNA and the lb HCV subtype; 2) using multivariate analysis (logistic regression in 122 patients), the only factors significantly associated with CG were the presence of cirrhosis at liver biopsy (p=0.05), the absence of immunosupression (p=0.01) and the age (p=0.004). In conclusion: Many papers have shown that CG production was related to factors which could be in fact linked (ie severity of liver disease, age, duration of infection, genotype). In this study we suggest that age, cirrhosis and absence of immunodepression are the only factors significantly and independently associated with cryoglobulinemia.
ANTI-HCV CORE ANTIBODY LEVELS CORRESPOND TO DISEASE ACTIVITY AND PREDICTS THE THERAPY RESPONSE H. F. LOhr§. C. EIste,,~. H. P. Dien~,,-'~.G. Michel*. H. Braun*. K.-H Meyer zum Btiacbenfclde§. G. Gerken~ §I. Dept. Int. Medicinei $Pathology, Univ.Mainz, FRG. *Abbott Euro. Res, Wiesbaden, FRG. Virus-host interactions may have pathogenetic significance in chronic hepatitis. Thus the humoral immune response was evaluated as prognostic therapy prediction marker. IgG and lgM anti-HCV antibody titers and levels of circulating immune complexes were serially measured in end,point diluted sera of 18 selected chronic HCV patients that received 3 or 6 MU interferon-ot2a threetimes weekly for 6 to 12 months. The results were correlated with histology, HCV genotypes and HCVRNA levels. N'me HCV patients (genotypes la n=4; lb n=l; 2a n=l; 3a n=3) with low HCV-RNA pretreatment levels (mean 1.4x104 copies/ml) showed a long-lasting complete response with virus suppression and ALT normalization. In addition, six patients were non-responders and three partial responders (genotypes la n=2; lb n=7) characterized by significantly higher HCV-RNA pretreatment levels (mean 2.5x10 5 copie~dml). IgG and IgM subclass anti-HC34 antibodies were most immunogenei¢ in patients without response whereas IgG anti-He29 antibodies were predominant in complete responders. During treatment anti-HC34 and anti-HC29 antibody levels decreased in patients with therapy response. Two partial responders showed recurrent anti-HC34 antibody levels that proceeded disease reactivation and detectable HCVRNA. To conclude immune complexes did neither influence disease activity, HCV-RNA levels or genotypes, antibody levels nor therapy response. Anti-HCV core IgG and IgM antibodies, however, correlated with vimemia, disease activity and could serve as sensitive response predictive markers.
Cholestasis has been reported in association with Turner's syndrome (N Engl J IVied 1974; 290: 406). Aim of the present study was to investigate the presence of cholestatic features in a group of patients with the disease, and to look at the effect of treatment with ursodeoxycholic acid (UDCA). Patients and methods. We retrospectively reviewed the clinical records of 30 subjects with Turner' s syndrome, 5 of whom were also prospectively followed. In these 5 subjects, who had abnormal liver function tests, gas-liquid chromatography (GLC) of serum bile acids and liver biopsy were performed. Two of them underwent ERCP. All subjects were treated with UDCA (10mg/Kg/day) for 6 months. Results. Alkaline phosphatase was elevated in 53% (16/30) of the patients, y-GT in 42% (8/19) and serum transaminases in 37% (7/19). In the 5 patients followed prospectively AMA and viral infections markers were negative. A t GLC more than 70% of serum bile acids was constituted by chenodeoxycholic acid. A liver biopsy showed in all 5 subjects subtle but distinctive alterations consistent with a "smoldering biliopathy". The ERCP showed in 1 out of 2 subjects the presence of narrowed bile ducts. Estroprogestinic therapy worsened the eholestasis while UDCA administration determined a complete normalization of hiochemical tests. Conclusion. Tumor's syndrome is frequently associated with clinical a n d histological signs consistent with intrahepatic cholestasis. Biochemical alterations seem to be corrected by UDCA administration.
1371
449A
1372
HEPATITIS E IN DIALYSIS: FACT OR FANCY? G Macedo, AP Chaves, T Pinto, J Monteiro, F Seixas, O Pereira, B C~:rvalho, A Loureiro Nefronorte, Paredes, Portugal Hepatitis E virus (HEV), the main etiological agent of enterically transmitted non-A, non-B hepatitis, has caused epidemic outbreaks in developing countries and has been sporadically observed in industrialised countries. However, the risk factors associated with antiHEV positivity are not known yet. We studied the prevalence of HEV antibodies in a population of 71 portuguese haemodlalysis patients (35 males, aged 20-76 years old) and analysed 50 blood samples from asymptomatic volunteer blood donors (AVBD) without HBV or HCV markers. All samples were tested with HEV EIA (Abbot Diagnostic) using recombinant antigens from open reading frames 2 and 3 (SG3 and 8-5) coding respectively non structural and structural proteins from Burma virus. PCR technique was used to detect HBV DNA and HCV RNA in dialysis patients. The prevalence of HEV antibodies in our haemodialyals patients was 4,4% (3/71), whim HCV PCR positive patients were 9,8%, (7/71), and HBs Ag positive patients were 5,6% (3/71). AntiHEV was detected in 2/50 (4%) from AVBD. The values of optic dense/cutoff found in dialysis patients, were 0,8; 1,0; in AVBD, they were 1,1 and 1,5. Mean ago in HEV pos~tlve patients was 61 {being 50 in HEV negative) and the mean dialysis time was 49 months in both groups. Conclusions: 1. The prevalence of antiHEV in dialysis patients was similar to that one found in AVBD (7% x 4%, pNS). 2. All positive samples showed values of OD/cutoff that were less than two times the cutoff point, which seems to demonstrate that these values shouM be confirmed by a supplemental assay. 3. We did not observe, in our popu[etion of dialysis patients any statistical difference in age, time of dialysis and antiHCV positiveness between HEV positive or negative patients.