- Email: [email protected]
Long-term results of interferon therapy in HBeAg positive chronic hepatitis B
$66 P2Cl/163
Posters 2
]
I~2 cl/16s I
IRON AND CHRONIC HEPATITIS C: INFLUENCE OF IRON STORES ON at-INTERFERON RESPONSE AND EFFECT OF IRON DEPLETION
DE NOVO HEPATITIS C VIRUS INFECTION IN A HEMODIALYSIS UNIT: INCIDENCE AND RISK FACTORS.
A.Piperno, tLD'Alba*, L.Roffi, S.Fargion*, M.Pozzi, A.L.Fracanzani*, C.Nicoli, V.Arosio, G.Mancia, G.Fiorelli*. Istituto di Scienze Biomediche S.Gerardo, Monza, *Istituto di Medicina Interna e Fisiopatologia Medica, Milano; Universiut di Milano To better understand the relations between iron and hepatitis C virus infection, we analyzed the response to at-interferon and iron depletion therapy in 59 patients with chronic hepatitis C. Forty-two patients (group A) thoroughly underwent to recombinant at-interferon treatment whereas 17 patients (group B) were firstly submitted to phlebotomy treatment up to iron depletion. In group A, 13 were responders at 12th month and 29 were non-responders to at-interferon. The percentage of patients with increased transferrin saturation frs), serum ferritin (SF) and liver iron concentration CLIC) was significantly higher in non-responders than in responders (TS: 52% vs 15%. p= 0.027; SF: 76% vs 30%, p= 0.0075; LIC: 57% vs 0%, p=0.002). An increased LIC value indicates a 100% probabiliD' of no response to or-interferon whereas a normal LIC value does not allow to predict either negative or positive response. Serum ALT significantly decreased after phlebotomy treatment in patients of group B (197+92 vs 85+39 U/L, p<0.001) as well as in twelve non-responder patients of group A that were then submitted to iron depletion therapy (198+89 vs 107+81 U/L, p<0.001). In no cases HCV RNA disappeared in the serum after iron depletion. Subsequently, in 14 iron depleted patients (7 in group A and 7 in group B) or-interferon treatment was performed. None of the patients in the two groups showed any change of serum ALT after six months of atinterferon therapy. In conclusion increased liver iron is a negative prognostic factor for at-interferon response in chronic hepatitis C. Iron depletion therapy has a favcurable effect on serum ALT in almost all the patients treated, probably by reducing the generation of reactive oxygen species, but does not improve the response to at-interferon.
X Fores, P Ferndndez-Llama', D Maluenda, S Ampurdan~, E Olmedo, JM Sdnchez-Tapias, J LOpez-Pedrot*, J Rod,s. Liver Unit and Nephrology DepL* Hospital Clinic i Provincial, Barcelona, Spain. Chronic hepatiEs C virus infac~on is frequent in hamodialyzed patients, but the mechanisms of transmission, including Iransfuslon ~ HCV screened blood, are not well defined. The incidence and risk factors for hopattds C seroconversion were prospectively assesed in a hernodlalysis unit, where 25% of patients are anli-HCV seropesi~e. 77 anti-HCV negalive (ELISA II) patients who started hemodlalysis for end-stage renal failure from January 1991 to September 1992 (median age 59 years, range 20 to 88), were followed for a mean period of 25 months (range 15 to 36).HCV infected and non-infectedpaints were not treated aparL ALT levels and anti-HCV (ELISA II or III) were determinedevery 6 months. ELISA positive sere were tested by RIBA II and PCR for HCV-RNK Blood ~nsfusion, surgical procedures, hospital admissions and other factors possibly associated with hepatitis C virus Iransmissionwere registered. Seroconversionto anti-HCV was observed in 6 patients (7.8%) during follow-up (RIBA II was posi~e in 2 and indeterminatein 2, PCR disclosed viremia in 4 patients). Seroconversion was preceded by a mild and ITansientincrease in ALT values in all six patients. No differences were found between patients who seroconvertedand patients who did not in terms of time on hemodialysis (mean 27.5 SD 5; mean 25.4 SD 6 months respectively) and amount of blood transfused (mean 5.6 SD 2 and mean 7.3 SD 4 units, respectively). These observations suggest that in patients on hamodialysis acquisition of infection by HCV is relaUvelycommon and does not seam related to blood Iransfusion.
[ P2C1/164 ]
P2Cl/166
]
SUPPLEMENTARY ANTI-HBV ACTIVITY OF TWO HUMAN ANTIHBs MONOCLONALS
LONG-TERM RESULTS OF INTERFERON THERAPY IN HBaAg POSITIVE CHRONIC HEPATITIS B
RA Hei[tinkl~ RA de Man 2, HGM Niesters ~, SW Schalm2. Department of Virology, Erasmus University Rotterdam and 2 Department of Internal Medicine II, Academic Hospital Dijkzigt, Rotterdam, The Netherlands.
X Foms, FX L6pez-Labrador,J Costa, A Mas, A Vitella, JM Sdnchez-Tapias, MT Jim(~nez de Ante, J Rod~. Liver unit and Microbiology Dept. Hospital Clinic i Provincial, Barcelona, Spain. Long-term results of interferon treatment in HSeAg positive chronic hepatitis B are not well known. We anelized 40 conseculJvepatients with HBeAg positive chronic acl~e hepa~s B Ireated with alfa interferon between 1987 and 1991 and followed for a mean penod of 46 months (range 24 to 72) after therapy. All showed stable HBV-DNA levels (dot-blot)and moderately elevated ALT (less than 6 times above normal values, mean ALT: 131 UI/L, SD 72 Ul/L) during a 6 months period before therapy. During treatment HBeAg became negative in 6 patients (15%) and HBV-DNA disappeared in 12 (30%). During follow-up, HBaAg disappeared in 21 additional patients but it reappeared in 2; consecuentiy, 25 patients (62%) were HBeAg negate at the end of follow-up. 19 of them seroconverted to anti-HBe and ALl" normalized in 16. During follow-up HBV-DNA became negative in 13 additional patients, but it reappeared in 5; consecuentiy, HBV-DNA remained positive in 20 patients (50%) at the end of follow-up (15 HBeAg positive and 5 anll-HBe positive, all with abnormal AL'r). Loss of HBeAg with reappearanceof HBV -DNA and abnormal ALT occurred in 5 patients; all had lost HBV-DNA during treatment.Termination of viral replicalJon and clearence of HBeAg occurred spontaneously during follow-up in 13 of the 28 patients (46%) who did not clear HBV-DNA during interferon b"eatmenLThese observatioms indicate that the outcome of HBeAg positive chronic hepatitis B after interferon Ireatment is very heterogeneous.Complete inactivation of the disease occured in about one half of the patients, even in those who did not respond immediately to therapy. However, viral replication and liver disease persisted in the remaining patients, often in the absence of HBeAg. Careful follow-up is mandatory alter interferon therapy in patients with chronic hepatitis 8.
Discovery of new viruses (HIV, HCV) have strongly stimulated the search for monoclonal antibodies (McAb) for prophylactic use of anti-HBs in hepatitis B-positive liver transplant recipients. Two human McAb with anti-hepatitis B activity, constructed by the Central Laboratory for the Red Cross Blood Transfusion Services of The Netherlands were investigated seperately and simultaneously in a 'neutralization in solution' assay. In this assay monoclonal antibodies are mixed with HBsAg and incubated at room temperature for 2 hours. The mixture is assayed for residual activity of HBsAg in a standard radio irnmunoessay (Austria II, Abbott Laboratories). A panel of HBsAg subtypes was used as well as HBsAg and purified Dane paricles from liver transplant patients. Residual binding of Dane particles in the Austria II was determined semi-quantitiatively by dot spot hybridization after extraction of DNA from the beads. One of the McAb (9H9) is directed against comformational epitopes anti-'a' like) but had limited 'neutralizing' capacity (80-90%) against all HBsAg subtypes; the other (4-7B), active against linear epitopes, has full neutralization capacity against all HBsAg subtypes except one (adw4). However the latter monoclonal antibody gave excellent results with HBsAg in serum of a patient with an HBsAg/'a' escape-mutant after transplantation. This assay may be used to select an antibody panel to treat liver transplant recipients post operatively.
Posters 2
]
I~2 cl/16s I
IRON AND CHRONIC HEPATITIS C: INFLUENCE OF IRON STORES ON at-INTERFERON RESPONSE AND EFFECT OF IRON DEPLETION
DE NOVO HEPATITIS C VIRUS INFECTION IN A HEMODIALYSIS UNIT: INCIDENCE AND RISK FACTORS.
A.Piperno, tLD'Alba*, L.Roffi, S.Fargion*, M.Pozzi, A.L.Fracanzani*, C.Nicoli, V.Arosio, G.Mancia, G.Fiorelli*. Istituto di Scienze Biomediche S.Gerardo, Monza, *Istituto di Medicina Interna e Fisiopatologia Medica, Milano; Universiut di Milano To better understand the relations between iron and hepatitis C virus infection, we analyzed the response to at-interferon and iron depletion therapy in 59 patients with chronic hepatitis C. Forty-two patients (group A) thoroughly underwent to recombinant at-interferon treatment whereas 17 patients (group B) were firstly submitted to phlebotomy treatment up to iron depletion. In group A, 13 were responders at 12th month and 29 were non-responders to at-interferon. The percentage of patients with increased transferrin saturation frs), serum ferritin (SF) and liver iron concentration CLIC) was significantly higher in non-responders than in responders (TS: 52% vs 15%. p= 0.027; SF: 76% vs 30%, p= 0.0075; LIC: 57% vs 0%, p=0.002). An increased LIC value indicates a 100% probabiliD' of no response to or-interferon whereas a normal LIC value does not allow to predict either negative or positive response. Serum ALT significantly decreased after phlebotomy treatment in patients of group B (197+92 vs 85+39 U/L, p<0.001) as well as in twelve non-responder patients of group A that were then submitted to iron depletion therapy (198+89 vs 107+81 U/L, p<0.001). In no cases HCV RNA disappeared in the serum after iron depletion. Subsequently, in 14 iron depleted patients (7 in group A and 7 in group B) or-interferon treatment was performed. None of the patients in the two groups showed any change of serum ALT after six months of atinterferon therapy. In conclusion increased liver iron is a negative prognostic factor for at-interferon response in chronic hepatitis C. Iron depletion therapy has a favcurable effect on serum ALT in almost all the patients treated, probably by reducing the generation of reactive oxygen species, but does not improve the response to at-interferon.
X Fores, P Ferndndez-Llama', D Maluenda, S Ampurdan~, E Olmedo, JM Sdnchez-Tapias, J LOpez-Pedrot*, J Rod,s. Liver Unit and Nephrology DepL* Hospital Clinic i Provincial, Barcelona, Spain. Chronic hepatiEs C virus infac~on is frequent in hamodialyzed patients, but the mechanisms of transmission, including Iransfuslon ~ HCV screened blood, are not well defined. The incidence and risk factors for hopattds C seroconversion were prospectively assesed in a hernodlalysis unit, where 25% of patients are anli-HCV seropesi~e. 77 anti-HCV negalive (ELISA II) patients who started hemodlalysis for end-stage renal failure from January 1991 to September 1992 (median age 59 years, range 20 to 88), were followed for a mean period of 25 months (range 15 to 36).HCV infected and non-infectedpaints were not treated aparL ALT levels and anti-HCV (ELISA II or III) were determinedevery 6 months. ELISA positive sere were tested by RIBA II and PCR for HCV-RNK Blood ~nsfusion, surgical procedures, hospital admissions and other factors possibly associated with hepatitis C virus Iransmissionwere registered. Seroconversionto anti-HCV was observed in 6 patients (7.8%) during follow-up (RIBA II was posi~e in 2 and indeterminatein 2, PCR disclosed viremia in 4 patients). Seroconversion was preceded by a mild and ITansientincrease in ALT values in all six patients. No differences were found between patients who seroconvertedand patients who did not in terms of time on hemodialysis (mean 27.5 SD 5; mean 25.4 SD 6 months respectively) and amount of blood transfused (mean 5.6 SD 2 and mean 7.3 SD 4 units, respectively). These observations suggest that in patients on hamodialysis acquisition of infection by HCV is relaUvelycommon and does not seam related to blood Iransfusion.
[ P2C1/164 ]
P2Cl/166
]
SUPPLEMENTARY ANTI-HBV ACTIVITY OF TWO HUMAN ANTIHBs MONOCLONALS
LONG-TERM RESULTS OF INTERFERON THERAPY IN HBaAg POSITIVE CHRONIC HEPATITIS B
RA Hei[tinkl~ RA de Man 2, HGM Niesters ~, SW Schalm2. Department of Virology, Erasmus University Rotterdam and 2 Department of Internal Medicine II, Academic Hospital Dijkzigt, Rotterdam, The Netherlands.
X Foms, FX L6pez-Labrador,J Costa, A Mas, A Vitella, JM Sdnchez-Tapias, MT Jim(~nez de Ante, J Rod~. Liver unit and Microbiology Dept. Hospital Clinic i Provincial, Barcelona, Spain. Long-term results of interferon treatment in HSeAg positive chronic hepatitis B are not well known. We anelized 40 conseculJvepatients with HBeAg positive chronic acl~e hepa~s B Ireated with alfa interferon between 1987 and 1991 and followed for a mean penod of 46 months (range 24 to 72) after therapy. All showed stable HBV-DNA levels (dot-blot)and moderately elevated ALT (less than 6 times above normal values, mean ALT: 131 UI/L, SD 72 Ul/L) during a 6 months period before therapy. During treatment HBeAg became negative in 6 patients (15%) and HBV-DNA disappeared in 12 (30%). During follow-up, HBaAg disappeared in 21 additional patients but it reappeared in 2; consecuentiy, 25 patients (62%) were HBeAg negate at the end of follow-up. 19 of them seroconverted to anti-HBe and ALl" normalized in 16. During follow-up HBV-DNA became negative in 13 additional patients, but it reappeared in 5; consecuentiy, HBV-DNA remained positive in 20 patients (50%) at the end of follow-up (15 HBeAg positive and 5 anll-HBe positive, all with abnormal AL'r). Loss of HBeAg with reappearanceof HBV -DNA and abnormal ALT occurred in 5 patients; all had lost HBV-DNA during treatment.Termination of viral replicalJon and clearence of HBeAg occurred spontaneously during follow-up in 13 of the 28 patients (46%) who did not clear HBV-DNA during interferon b"eatmenLThese observatioms indicate that the outcome of HBeAg positive chronic hepatitis B after interferon Ireatment is very heterogeneous.Complete inactivation of the disease occured in about one half of the patients, even in those who did not respond immediately to therapy. However, viral replication and liver disease persisted in the remaining patients, often in the absence of HBeAg. Careful follow-up is mandatory alter interferon therapy in patients with chronic hepatitis 8.
Discovery of new viruses (HIV, HCV) have strongly stimulated the search for monoclonal antibodies (McAb) for prophylactic use of anti-HBs in hepatitis B-positive liver transplant recipients. Two human McAb with anti-hepatitis B activity, constructed by the Central Laboratory for the Red Cross Blood Transfusion Services of The Netherlands were investigated seperately and simultaneously in a 'neutralization in solution' assay. In this assay monoclonal antibodies are mixed with HBsAg and incubated at room temperature for 2 hours. The mixture is assayed for residual activity of HBsAg in a standard radio irnmunoessay (Austria II, Abbott Laboratories). A panel of HBsAg subtypes was used as well as HBsAg and purified Dane paricles from liver transplant patients. Residual binding of Dane particles in the Austria II was determined semi-quantitiatively by dot spot hybridization after extraction of DNA from the beads. One of the McAb (9H9) is directed against comformational epitopes anti-'a' like) but had limited 'neutralizing' capacity (80-90%) against all HBsAg subtypes; the other (4-7B), active against linear epitopes, has full neutralization capacity against all HBsAg subtypes except one (adw4). However the latter monoclonal antibody gave excellent results with HBsAg in serum of a patient with an HBsAg/'a' escape-mutant after transplantation. This assay may be used to select an antibody panel to treat liver transplant recipients post operatively.