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Myocardial function in HGV chronic infection
204
Pupers reud by title
ROUTINE DIAGNOSTIC TESTS FOR THE DETECTION AND QUANTITATION OF HEPATITIS C VIRUS RNA S. Soviero, S. Barmat. L. Chena. K. Hasselbrina. M. Hinchev. L. Isopi. C. Kazanecki. S. McDonald, D. Ost, D. Petersen. and S. Turri, 2. Xue. JQ Yana. A. Yoder. K. Gutekunst. Roche Molecular Systems, 1080 US Highway 202, Branchburg, NJ USA Detection and accurate quantitation of Hepatitis C Virus (HCV) viral RNA in patient specimens has been shown to be useful in both disease prognosis and monitoring of patients on antiviral therapy. It is widely accepted that viremia should be confirmed using a PCR-based test prior to consideration of enrolling patients in a therapeutic regimen. Once viremia has been confirmed, baseline viral load is often used to help guide the initial treatment regimen. It has now become routine practice to monitor viremia at 1 to 3 months to determine early clearance of RNA. We describe in this report the performance of a second generation family of RT-PCR tests for the direct detection and quantitation of HCV RNA in serum or plasma. The AMPLICOR” HCV and COBAS AMPLICORTM HCV Tests are qualitative tests for detection of HCV RNA. The COBAS AMPLICOR Test fully automates the amplification and detection reactions. Both tests have an improved sample preparation method that increases the sensitivity to approximately 100 copies/ml. In addition, modifications to the amplification reagent have resulted in improved amplification efficiency of all HCV genotypes. The AMPLICOR HCV MONITORTM and COBAS AMPLICOR HCV MONITORTM are quantitative tests for determination of viral load in patient specimens. The COBAS AMPLICOR Test fully automates amplification, detection, and determination of copy number. Both of the second generation MONITOR tests also include new master mix that allows for equivalent amplification of all HCV genotypes over a linear dynamic range of approximately 1000 to IO’ copies/ml. The tests are highly reproducible with CV’s ranging from 20 - 35%. When compared to ALT determinations an excellent correlation is seen. In fact, changes in HCV RNA levels occur at earlier timepoints than changes in ALT, indicating viral load to be a more sensitive measure of response to therapy. An algorithm for incorporation of qualitative and quantitative HCV RNA testing into routine patient management will be discussed.
INTERFERON
TREATMENT
ON THE CARBOHYDRATE
METABOLISM
OF PATIENTS WITH CHRONIC HEPATITIS-C. E.NemesBnszkv.
M.Pusztav. A.Cseoreqi
Department of Gastroenterology,
Natl. Inst. Rheumatology,
Budapest, Hungary Background: A broad spectrum of side effects of long-term interferon therapy is well-known, but only a few cases have been reported up till now on its impact on diabetes mellitus. This association is suggested to be one of the manifestations of autoimmune extrahepatic disorders of HCV infection. Results: 64 patients with chronic HCV infection (without cirrhosis) were enrolled; 8 were diabetics, 6 had impaired glucose tolerance. (IGT) and 40 had normal CH metabolism. 32 cases were given long-term alphainterferon therapy (either Intron-A, Schering AG. or Roferon-A, H.LaRoche were administered). Of the 32 patients 3 were diabetic (NIDDM) and one had IGT before the interferon treatment. Normal CH metabolism was found in 28 patients. In the course of the 6-month-interferon therapy one diabetic patients’s CH metabolism did not change. Deterioration of CH metabolism was observed in 2 diabetic patients, who required hospitalization for insulin treatment. One patient’s IGT turned to a manifested diabetes mellitus. Of the 28 patients (with normal CH metabolism) 9 cases developed IGT. No deterioration of the CH-methabolism was observed in 19 patients. Conclusion: Interferon therapy occasionally has deleterious effect on the CH metabolism. Our data also support the view that this is a reversible impact. Presented data emphasize the necessity of a thorough follow-up of patients - including controlling the CH-metabolism as well - throughout patients are on interferon treatment.
AMANTADINE AND INTERFERON TREATMENT OF CHRONIC HEPATITIS C PATIENTS - PRELIMINARY ANALYSIS Z. Ben-Ari. R. Zemel*. A. Kazatzker*. V. Manhaim. R. Tur-Kasna, Liver Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva and *FMRC, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Treatment of chronic hepatitis C (I-ICV) infection with alphainterferon (IFN) has limited efficacy with 30% of treated patients achieving a sustained response. Amantadine-HCl (AMA) was recently reported to have a possible effect on chronic HCV patients who failed IFN therapy. We initiated a trial to investigate the safety and efficacy of combination therapy with IFN and AMA in chronic HCV patients who were not treated previously. Seven patients (6 males, 1 female, median age 39 years, range 19-49) with histological proven chronic HCV, serum ALT>2x and HCV RNA positive have been enrolled since August 1997 (an ongoing study). Patients were treated open-label with AMA 100 mg p.o. b.i.d. and IFN 3 MU thrice weekly for 6 months. Blood samples were collected for analysis of ALT and HCV RNA prior to treatment and every 3 months. All patients have completed a 3-month course with no major side effects. All patients had evidence of biochemical response, 4/7 have normal ALT levels. In one patient, HCV RNA already disappeared, and in two, it significantly decreased. These preliminary results suggest that the combination therapy of AMA and IFN may be of benefit in chronic “naive” HCV-infected patients. We are studying this combination effect in other patients and over longer periods of time.
MYOCARDIAL FUNCTION IN HGV CHRONIC INFECTION Taliani G. Ciavarella GM *. Lino S *. Malamti U*. Caltini G *, Badolato MC, Osso A. Furlan C, Ferretti G. De Bat C. Department of Infectious and Tropical Diseases and *Department of Clinical Pathophysiology, University of Rome “La Sapienza”, Italy Myocardial involvement has been recently reported in patients with hepatitis C virus chronic infection. To investigate whether hepatitis G virus (HGV), another members of the flaviviridae family, could be associated to changes in myocardial function, we have examined 12 patients (mean age 44 +13 yr, range 27 to 66 yr ) with hepatitis G (I-IGV) viremia and chronically raised ALT levels and 15 control subjects matched for age, sex and body surface area. HGV was detected by nested PCR employing primers from the NS3 and 5’noncoding region followed by “P-hybridization with an internal probe. All subjects undenvent echocardiography (Hewlett-Packard Sonos 1000, probe 2.5-3.5 MHz) and all measurements were performed according to the American Society of Echocardiography guidelines. Overall, HGV infected patients showed a significant reduction of end-diastolic left ventricle volume (94*24 ml versus 119*30 ml ; p< 0.05) with a reduction of left ventricular compliance, defined as end diastolic volume minus end systolic volume/pulse pressure ratio, (1.41*0.4 ml/mmHg vs 1.7iO.4 ml/mmHg ; p
Pupers reud by title
ROUTINE DIAGNOSTIC TESTS FOR THE DETECTION AND QUANTITATION OF HEPATITIS C VIRUS RNA S. Soviero, S. Barmat. L. Chena. K. Hasselbrina. M. Hinchev. L. Isopi. C. Kazanecki. S. McDonald, D. Ost, D. Petersen. and S. Turri, 2. Xue. JQ Yana. A. Yoder. K. Gutekunst. Roche Molecular Systems, 1080 US Highway 202, Branchburg, NJ USA Detection and accurate quantitation of Hepatitis C Virus (HCV) viral RNA in patient specimens has been shown to be useful in both disease prognosis and monitoring of patients on antiviral therapy. It is widely accepted that viremia should be confirmed using a PCR-based test prior to consideration of enrolling patients in a therapeutic regimen. Once viremia has been confirmed, baseline viral load is often used to help guide the initial treatment regimen. It has now become routine practice to monitor viremia at 1 to 3 months to determine early clearance of RNA. We describe in this report the performance of a second generation family of RT-PCR tests for the direct detection and quantitation of HCV RNA in serum or plasma. The AMPLICOR” HCV and COBAS AMPLICORTM HCV Tests are qualitative tests for detection of HCV RNA. The COBAS AMPLICOR Test fully automates the amplification and detection reactions. Both tests have an improved sample preparation method that increases the sensitivity to approximately 100 copies/ml. In addition, modifications to the amplification reagent have resulted in improved amplification efficiency of all HCV genotypes. The AMPLICOR HCV MONITORTM and COBAS AMPLICOR HCV MONITORTM are quantitative tests for determination of viral load in patient specimens. The COBAS AMPLICOR Test fully automates amplification, detection, and determination of copy number. Both of the second generation MONITOR tests also include new master mix that allows for equivalent amplification of all HCV genotypes over a linear dynamic range of approximately 1000 to IO’ copies/ml. The tests are highly reproducible with CV’s ranging from 20 - 35%. When compared to ALT determinations an excellent correlation is seen. In fact, changes in HCV RNA levels occur at earlier timepoints than changes in ALT, indicating viral load to be a more sensitive measure of response to therapy. An algorithm for incorporation of qualitative and quantitative HCV RNA testing into routine patient management will be discussed.
INTERFERON
TREATMENT
ON THE CARBOHYDRATE
METABOLISM
OF PATIENTS WITH CHRONIC HEPATITIS-C. E.NemesBnszkv.
M.Pusztav. A.Cseoreqi
Department of Gastroenterology,
Natl. Inst. Rheumatology,
Budapest, Hungary Background: A broad spectrum of side effects of long-term interferon therapy is well-known, but only a few cases have been reported up till now on its impact on diabetes mellitus. This association is suggested to be one of the manifestations of autoimmune extrahepatic disorders of HCV infection. Results: 64 patients with chronic HCV infection (without cirrhosis) were enrolled; 8 were diabetics, 6 had impaired glucose tolerance. (IGT) and 40 had normal CH metabolism. 32 cases were given long-term alphainterferon therapy (either Intron-A, Schering AG. or Roferon-A, H.LaRoche were administered). Of the 32 patients 3 were diabetic (NIDDM) and one had IGT before the interferon treatment. Normal CH metabolism was found in 28 patients. In the course of the 6-month-interferon therapy one diabetic patients’s CH metabolism did not change. Deterioration of CH metabolism was observed in 2 diabetic patients, who required hospitalization for insulin treatment. One patient’s IGT turned to a manifested diabetes mellitus. Of the 28 patients (with normal CH metabolism) 9 cases developed IGT. No deterioration of the CH-methabolism was observed in 19 patients. Conclusion: Interferon therapy occasionally has deleterious effect on the CH metabolism. Our data also support the view that this is a reversible impact. Presented data emphasize the necessity of a thorough follow-up of patients - including controlling the CH-metabolism as well - throughout patients are on interferon treatment.
AMANTADINE AND INTERFERON TREATMENT OF CHRONIC HEPATITIS C PATIENTS - PRELIMINARY ANALYSIS Z. Ben-Ari. R. Zemel*. A. Kazatzker*. V. Manhaim. R. Tur-Kasna, Liver Institute, Rabin Medical Center, Beilinson Campus, Petah Tikva and *FMRC, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Treatment of chronic hepatitis C (I-ICV) infection with alphainterferon (IFN) has limited efficacy with 30% of treated patients achieving a sustained response. Amantadine-HCl (AMA) was recently reported to have a possible effect on chronic HCV patients who failed IFN therapy. We initiated a trial to investigate the safety and efficacy of combination therapy with IFN and AMA in chronic HCV patients who were not treated previously. Seven patients (6 males, 1 female, median age 39 years, range 19-49) with histological proven chronic HCV, serum ALT>2x and HCV RNA positive have been enrolled since August 1997 (an ongoing study). Patients were treated open-label with AMA 100 mg p.o. b.i.d. and IFN 3 MU thrice weekly for 6 months. Blood samples were collected for analysis of ALT and HCV RNA prior to treatment and every 3 months. All patients have completed a 3-month course with no major side effects. All patients had evidence of biochemical response, 4/7 have normal ALT levels. In one patient, HCV RNA already disappeared, and in two, it significantly decreased. These preliminary results suggest that the combination therapy of AMA and IFN may be of benefit in chronic “naive” HCV-infected patients. We are studying this combination effect in other patients and over longer periods of time.
MYOCARDIAL FUNCTION IN HGV CHRONIC INFECTION Taliani G. Ciavarella GM *. Lino S *. Malamti U*. Caltini G *, Badolato MC, Osso A. Furlan C, Ferretti G. De Bat C. Department of Infectious and Tropical Diseases and *Department of Clinical Pathophysiology, University of Rome “La Sapienza”, Italy Myocardial involvement has been recently reported in patients with hepatitis C virus chronic infection. To investigate whether hepatitis G virus (HGV), another members of the flaviviridae family, could be associated to changes in myocardial function, we have examined 12 patients (mean age 44 +13 yr, range 27 to 66 yr ) with hepatitis G (I-IGV) viremia and chronically raised ALT levels and 15 control subjects matched for age, sex and body surface area. HGV was detected by nested PCR employing primers from the NS3 and 5’noncoding region followed by “P-hybridization with an internal probe. All subjects undenvent echocardiography (Hewlett-Packard Sonos 1000, probe 2.5-3.5 MHz) and all measurements were performed according to the American Society of Echocardiography guidelines. Overall, HGV infected patients showed a significant reduction of end-diastolic left ventricle volume (94*24 ml versus 119*30 ml ; p< 0.05) with a reduction of left ventricular compliance, defined as end diastolic volume minus end systolic volume/pulse pressure ratio, (1.41*0.4 ml/mmHg vs 1.7iO.4 ml/mmHg ; p