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Interferon alone versus interferon plus ribavirin in the treatment of patients with acute hepatitis C: a pilot study
Poster Sessions
128
high LAM-resistant mutant rate observed in our patients and the dubious treatment benefit after YMDD mutant selection indicates that continuous LAM monotherapy should be re-evaluated.
ment tends to decrease with time depending from the emergence of YMDD variants.
~-~ ~6-]
INTERFERON ALONE VERSUS INTERFERON PLUS RIBAVIRIN IN THE TREATMENT OF PATIENTSWITH ACUTE HEPATITIS C: A PILOT STUDY
Teresa Santantonio, Emanuele Sinisi, Angela Guastadisegni, Emilio Palumbo, Giuseppe Pastore. Clinic oflnfectious Diseases,
University of Bari, Bari, Italy Early treatment of acute hepatitis C may prevent progression to chronicity. In this study the efficacy of interferon (IFN) monotherapy versus interferon plus ribavirin combination therapy was evaluated in 17 acute hepatitis C patients with high ALT levels and persistent viremia after 3 months from onset. In all patients diagnosis of acute hepatitis C was based on a welldocumented HCV seroconversion. Eleven patients were treated with IFN alone ( 5 - 3 MU tiw) and six patients received IFN plus ribavirin (800/1000 mg daily) for a total of 12 months. During therapy, patients were monthly monitored for blood count, transaminases and HCV RNA levels. Anti-HCV antibodies were measured every 6 months. All patients were followed for at least 6 months (range 6-38) after therapy discontinuation. Treatment was generally well-tolerated even if three patients reduced ribavirin therapy. At the end of therapy, 10/11 (91%) monotherapy and 5/6 (83%) combination therapy patients had normal ALT levels and undetectable HCV RNA. During follow-up, 2/10 (18%) and 1/5 (17%) patients relapsed after 1, 14 and 5 months, respectively. Anti-HCV antibodies decreased in eight sustained responders. No correlation with response was found for genotype, pretreatment viral load or interval between acute infection and start of therapy. Our data show that early treatment prevents disease chronicity in most cases and that combination therapy does not improve the response rate. However, larger studies are needed to confirm these results and to verify if a 6-month IFN course is sufficient for HCV clearance in acute hepatitis C patients.
~-~
QUALITATIVEAND QUANTITATIVEPLATELET ABNORMALITIES IN HEPATITISC VIRUS ASSOCIATED CHRONIC LIVER DISEASE
Fikry Goubran l, Abdel-Hamid Serwah 2 klaa Abdel-Hamid ] , Ahmed E1-Gohary 1, Nevene Wissa 1, Hanaa Fahmy l, Soha Younis ] .
1Clinical Pathology, Faculty of Medicine, Suez Canal University, lsmailia; 2Internal Medicine, Faculty of Medicine, Suez Canal University, lsmailia, Egypt Background: Thrombasthenia and thrombocytopenia are common findings in HCV infection. Aim of the work: to assess some quantitative and qualitative platelet abnormalities in patients with chronic HCV infection. Subjects: Included 165 patients with CLD, classified into: Group I: HCVsero positive (92), Group II: HCV-seronegative (73). Methods: Platelet counts and mean platelet volume (MPV), in vivo platelet aggregation in response to collagen, ADP and epinephrine, PF3 availability, serum platelet factor 4 (PF4) and beta thromboglobulin (BTG), platelet antibodies (PA-IgG) and bone marrow aspirate examination were performed. Results: CLD patients showed significantly reduced mean platelet counts, elevated MPV and enhanced marrow megakaryopoiesis, and increased mean PF4 and BTG levels. Patients with HCV related CLD had higher mean values for PF4 and BTG levels than other CLD patients. A statistically significant defective platelet aggregation function and PF3 availability were recorded in patients with HCV related CLD VS. those with CLD of other etiologies. Platelet antibodies were significantly more prevalent (63.3%) in patients with HCV Ab positive CLD than in HCVAb negative group (35.5%). Conclusion: we can assume that thrombocytopenia and qualitative platelet defects are common findings in CLD patients regardless of the etiology. Still, the presence of HCV infection may play a role in furtherly aggravating the condition.
PROLONGED LAMIVUDINE TREATMENT IN PATIENTSWITH CHRONI ACTIVE ANTI-HBe POSITIVE HEPATITIS
Vincenzina Fazio 2, Gioacchino Angarano 1, G. Scotto. llnfectious
Diseases O.U., University of Foggia; 2Departmentof Laboratory, Hospital of Foggia, Italy The efficacy of Lamivudine, 100 mg/die administered for one year, in norrealizing serum ALT levels and suppressing HBV DNA has been demonstrated in many studies. However frequent relapses make long-term results modest. In the present study we evaluated the efficacy of lamivudine therapy administered for a longer time in patients with chonic active anti-Hbe positive hepatitis. Methods: Thirty-four patients with chronic active anti-Hbe positive hepatitis were enrolled in the study and treated with lamivudine (100 mg) once daily for three years. Before treatment all patients had: serum ALT levels >2 times the normal levels since >6 months; HBV DNA positivity >5 pg/ml determined by the sandwich hybridization test for nucleic acid. Both ALT and HBV DNA were monitored during therapy. Results: After 12 months of therapy 24/34 patients (70.6%) showed evidence of clearance of HBV DNA and normal ALT levels; 22/34 (64.7%) and 19/34 (55.8%) patients maintained the complete response respectively after two and three years of therapy. The long-term treatment with lamivudine (>1 year) was not associated with an increase in the response in the initially non-responder patients. YMDD variant HBV emerged in 17.6% of patients in the first year, in 35.2% in the second year, in 52.9% during the third year of treatment. Lamivudine was well tolerated during the 3 years of therapy in all patients. Conclusions: These data, in patients with chronic active anti-HBe positive hepatitis, demonstrate that the Lamivudine response rate may be enhanced prolonging the treatment. However, the efficacy also of a prolonged treat-
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EFFECT OF COMBINED LAMIVUDINE AND INTERFERON ALPHA TREATMENT ON THE T-CELL RESPONSE TO HBV CORE PEPTIDES IN PATIENTSWITH CHRONIC HEPATITIS B VIRUS INFECTION
Mhairi Cavers I , Marion Aw 2, Umesh Shalma ~, Lorenzo D'Antiga 2, Roger William 1, Alison Moorat 3 , Martin Greensmith3, Mark Atldns 3, Giorgina Mieli-Vergani2, Diego Vergani 1. llnstitute of Hepatology,
University College London, London; 2Departmentof Child Health, King's College Hospital, London; 3Glaxo-WellcomeResearch and Development, Greenford, Middlesex, UK Background: Lamivudine treatment in adult patients with chronic hepatitis B virus (CHBV) infection dramatically reduces viral antigenaemia concomitantly with an increase in a proliferative CD4 positive T-cell response to HBV nucleocapsid antigens and peptides (Boni et al 1998), both changes subsiding on Lamivudine removal. Aim: To investigate CD4 positive T-cell proliferative responses in paediattic patients undergoing an 8 week viral load-reducing Lamivudine treatment followed by a 44 week immunostimulatory interferon alpha treatment. Methods/Patients: PBMC were obtained at 11 different time points (1 pretreatmem, 4 during lamivudine, 6 during IFN alfa treatment) over the one year treatment period, from 10 HbeAg positive patients (aged 4-14), 7 of whom had acquired the infection vertically and 3 horizontally. Proliferation of PBMC was assessed against 20-mer synthetic HBV peptides spanning the whole core sequence, tetanus toxoid as recall antigen and phytohemagglutinin as a polyclonal T cell stimulator. HBV DNA tests were performed by hybridisation assay.
128
high LAM-resistant mutant rate observed in our patients and the dubious treatment benefit after YMDD mutant selection indicates that continuous LAM monotherapy should be re-evaluated.
ment tends to decrease with time depending from the emergence of YMDD variants.
~-~ ~6-]
INTERFERON ALONE VERSUS INTERFERON PLUS RIBAVIRIN IN THE TREATMENT OF PATIENTSWITH ACUTE HEPATITIS C: A PILOT STUDY
Teresa Santantonio, Emanuele Sinisi, Angela Guastadisegni, Emilio Palumbo, Giuseppe Pastore. Clinic oflnfectious Diseases,
University of Bari, Bari, Italy Early treatment of acute hepatitis C may prevent progression to chronicity. In this study the efficacy of interferon (IFN) monotherapy versus interferon plus ribavirin combination therapy was evaluated in 17 acute hepatitis C patients with high ALT levels and persistent viremia after 3 months from onset. In all patients diagnosis of acute hepatitis C was based on a welldocumented HCV seroconversion. Eleven patients were treated with IFN alone ( 5 - 3 MU tiw) and six patients received IFN plus ribavirin (800/1000 mg daily) for a total of 12 months. During therapy, patients were monthly monitored for blood count, transaminases and HCV RNA levels. Anti-HCV antibodies were measured every 6 months. All patients were followed for at least 6 months (range 6-38) after therapy discontinuation. Treatment was generally well-tolerated even if three patients reduced ribavirin therapy. At the end of therapy, 10/11 (91%) monotherapy and 5/6 (83%) combination therapy patients had normal ALT levels and undetectable HCV RNA. During follow-up, 2/10 (18%) and 1/5 (17%) patients relapsed after 1, 14 and 5 months, respectively. Anti-HCV antibodies decreased in eight sustained responders. No correlation with response was found for genotype, pretreatment viral load or interval between acute infection and start of therapy. Our data show that early treatment prevents disease chronicity in most cases and that combination therapy does not improve the response rate. However, larger studies are needed to confirm these results and to verify if a 6-month IFN course is sufficient for HCV clearance in acute hepatitis C patients.
~-~
QUALITATIVEAND QUANTITATIVEPLATELET ABNORMALITIES IN HEPATITISC VIRUS ASSOCIATED CHRONIC LIVER DISEASE
Fikry Goubran l, Abdel-Hamid Serwah 2 klaa Abdel-Hamid ] , Ahmed E1-Gohary 1, Nevene Wissa 1, Hanaa Fahmy l, Soha Younis ] .
1Clinical Pathology, Faculty of Medicine, Suez Canal University, lsmailia; 2Internal Medicine, Faculty of Medicine, Suez Canal University, lsmailia, Egypt Background: Thrombasthenia and thrombocytopenia are common findings in HCV infection. Aim of the work: to assess some quantitative and qualitative platelet abnormalities in patients with chronic HCV infection. Subjects: Included 165 patients with CLD, classified into: Group I: HCVsero positive (92), Group II: HCV-seronegative (73). Methods: Platelet counts and mean platelet volume (MPV), in vivo platelet aggregation in response to collagen, ADP and epinephrine, PF3 availability, serum platelet factor 4 (PF4) and beta thromboglobulin (BTG), platelet antibodies (PA-IgG) and bone marrow aspirate examination were performed. Results: CLD patients showed significantly reduced mean platelet counts, elevated MPV and enhanced marrow megakaryopoiesis, and increased mean PF4 and BTG levels. Patients with HCV related CLD had higher mean values for PF4 and BTG levels than other CLD patients. A statistically significant defective platelet aggregation function and PF3 availability were recorded in patients with HCV related CLD VS. those with CLD of other etiologies. Platelet antibodies were significantly more prevalent (63.3%) in patients with HCV Ab positive CLD than in HCVAb negative group (35.5%). Conclusion: we can assume that thrombocytopenia and qualitative platelet defects are common findings in CLD patients regardless of the etiology. Still, the presence of HCV infection may play a role in furtherly aggravating the condition.
PROLONGED LAMIVUDINE TREATMENT IN PATIENTSWITH CHRONI ACTIVE ANTI-HBe POSITIVE HEPATITIS
Vincenzina Fazio 2, Gioacchino Angarano 1, G. Scotto. llnfectious
Diseases O.U., University of Foggia; 2Departmentof Laboratory, Hospital of Foggia, Italy The efficacy of Lamivudine, 100 mg/die administered for one year, in norrealizing serum ALT levels and suppressing HBV DNA has been demonstrated in many studies. However frequent relapses make long-term results modest. In the present study we evaluated the efficacy of lamivudine therapy administered for a longer time in patients with chonic active anti-Hbe positive hepatitis. Methods: Thirty-four patients with chronic active anti-Hbe positive hepatitis were enrolled in the study and treated with lamivudine (100 mg) once daily for three years. Before treatment all patients had: serum ALT levels >2 times the normal levels since >6 months; HBV DNA positivity >5 pg/ml determined by the sandwich hybridization test for nucleic acid. Both ALT and HBV DNA were monitored during therapy. Results: After 12 months of therapy 24/34 patients (70.6%) showed evidence of clearance of HBV DNA and normal ALT levels; 22/34 (64.7%) and 19/34 (55.8%) patients maintained the complete response respectively after two and three years of therapy. The long-term treatment with lamivudine (>1 year) was not associated with an increase in the response in the initially non-responder patients. YMDD variant HBV emerged in 17.6% of patients in the first year, in 35.2% in the second year, in 52.9% during the third year of treatment. Lamivudine was well tolerated during the 3 years of therapy in all patients. Conclusions: These data, in patients with chronic active anti-HBe positive hepatitis, demonstrate that the Lamivudine response rate may be enhanced prolonging the treatment. However, the efficacy also of a prolonged treat-
~-~
EFFECT OF COMBINED LAMIVUDINE AND INTERFERON ALPHA TREATMENT ON THE T-CELL RESPONSE TO HBV CORE PEPTIDES IN PATIENTSWITH CHRONIC HEPATITIS B VIRUS INFECTION
Mhairi Cavers I , Marion Aw 2, Umesh Shalma ~, Lorenzo D'Antiga 2, Roger William 1, Alison Moorat 3 , Martin Greensmith3, Mark Atldns 3, Giorgina Mieli-Vergani2, Diego Vergani 1. llnstitute of Hepatology,
University College London, London; 2Departmentof Child Health, King's College Hospital, London; 3Glaxo-WellcomeResearch and Development, Greenford, Middlesex, UK Background: Lamivudine treatment in adult patients with chronic hepatitis B virus (CHBV) infection dramatically reduces viral antigenaemia concomitantly with an increase in a proliferative CD4 positive T-cell response to HBV nucleocapsid antigens and peptides (Boni et al 1998), both changes subsiding on Lamivudine removal. Aim: To investigate CD4 positive T-cell proliferative responses in paediattic patients undergoing an 8 week viral load-reducing Lamivudine treatment followed by a 44 week immunostimulatory interferon alpha treatment. Methods/Patients: PBMC were obtained at 11 different time points (1 pretreatmem, 4 during lamivudine, 6 during IFN alfa treatment) over the one year treatment period, from 10 HbeAg positive patients (aged 4-14), 7 of whom had acquired the infection vertically and 3 horizontally. Proliferation of PBMC was assessed against 20-mer synthetic HBV peptides spanning the whole core sequence, tetanus toxoid as recall antigen and phytohemagglutinin as a polyclonal T cell stimulator. HBV DNA tests were performed by hybridisation assay.