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Papers by Juan Antonio Verjano Esteban
Journal of Hepatology, 2002
The aim of this study was to propose a method, to develop, assess and validate the busine ss oppo... more The aim of this study was to propose a method, to develop, assess and validate the busine ss opportunities that arise in the premises ...
Dialogo Familia Colegio, 2009
Advances in Differential Equations
Advances in Differential Equations
Antiviral Therapy
Objective To investigate the efficacy of early antiviral treatment for hepatitis C virus (HCV) re... more Objective To investigate the efficacy of early antiviral treatment for hepatitis C virus (HCV) recurrence in HIV/HCV-coinfected patients undergoing liver transplantation for end-stage liver disease. Methods Open prospective trial of early treatment of HCV recurrence in consecutive HIV/HCV-coinfected patients transplanted at a tertiary hospital in Barcelona between 2002 and 2004. All patients had indication for liver transplantation, no previous CDC class C HIV-associated opportunistic events, a CD4+ T-cell count >100 cells/fxl, and undetectable plasma HIV RNA on highly active antiretroviral therapy. Treatment with pegylated interferon-a2b (1.5 μg/kg/week) and ribavirin (800–1000 mg/day) was given for 24 to 48 weeks, as soon as HCV recurrence was histologically documented. Results Of six patients who underwent transplant, five patients surviving the early post-transplantation period developed HCV recurrence, presenting as severe cholestatic hepatitis in three, and were started on ...
Journal of Clinical Microbiology, 1999
We describe a rapid and reproducible method for assessment of the hepatitis C virus (HCV) load in... more We describe a rapid and reproducible method for assessment of the hepatitis C virus (HCV) load in serum samples. The method combines Taqman technology (Roche) and the ABI Prism 7700 (Perkin Elmer) real-time sequence detection system. We have optimized a single-tube reverse transcription-PCR (RT-PCR) that contains a dual-labeled fluorogenic probe to quantify the 5′ noncoding region (5′ NCR) of HCV. The probe contains a fluorescent reporter at the 5′ end and a fluorescent quencher at the 3′ end. The use of such a probe combined with the 5′-3′ nuclease activity of Taq polymerase allows direct quantitation of the PCR product by the detection of a fluorescent reporter released in the course of the exponential phase of the PCR. For accurate quantitation of the number of copies of HCV in samples containing unknown quantities, we have used serial dilutions of a synthetic 5′ NCR RNA standard of HCV that was previously quantified with an isotopic tracer. The method has a 5-log dynamic range (...
Journal of Virology, 1992
Sequencing of multiple recombinant clones generated from polymerase chain reaction-amplified prod... more Sequencing of multiple recombinant clones generated from polymerase chain reaction-amplified products demonstrated that the degree of heterogeneity of two well-conserved regions of the hepatitis C virus (HCV) genome within individual plasma samples from a single patient was consistent with a quasispecies structure of HCV genomic RNA. About half of circulating RNA molecules were identical, while the remaining consisted of a spectrum of mutants differing from each other in one to four nucleotides. Mutant sequence diversity ranged from silent mutations to appearance of in-frame stop codons and included both conservative and nonconservative amino acid substitutions. From the relative proportion of essentially defective sequences, we estimated that most circulating particles should contain defective genomes. These observations might have important implications in the physiopathology of HCV infection and underline the need for a population-based approach when one is analyzing HCV genomes.
Journal of Virology, 1997
We have analyzed the population of hepatitis C virus (HCV) sequences in paired liver and serum sa... more We have analyzed the population of hepatitis C virus (HCV) sequences in paired liver and serum samples from four patients with chronic hepatitis C. Sequences from three different biopsy specimens from a liver explant from one patient were compared with each other and with the circulating sequences. Our results demonstrate that the circulating quasispecies does not necessarily reflect the viral population replicating in the liver and that this is not due to a macroscopic anatomic compartmentalization of HCV replication. This finding has important implications for the pathogenesis and natural history of chronic HCV infection.
Journal of virology, 2014
Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed... more Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-α), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV. Importance: Viral drug resistance is usually attributed to the presence of amino acid substitutions in the protein targeted by the drug. In the present study with HCV, we show that high viral replicative fitness c...
The American Journal of Gastroenterology, 2007
The influence of glucose abnormalities on the efficacy of antiviral treatment is unknown. This st... more The influence of glucose abnormalities on the efficacy of antiviral treatment is unknown. This study investigated whether glucose abnormalities (impaired fasting glucose and type 2 diabetes) influence the response to antiviral therapy with interferon plus ribavirin in patients with chronic hepatitis C. A total of 178 treatment-naïve patients with chronic hepatitis C treated with combination therapy were retrospectively studied. SVR was assessed after completing treatment. Fasting plasmatic glucose was measured prior to therapy. Compared with nonresponders (N = 111), patients with SVR (N = 67) had lower plasma glucose (94.1 +/- 12.7 vs 104.4 +/- 25.8 mg/dL, P= 0.001) and a lower prevalence of glucose abnormalities (24.24%vs 44.14%, P= 0.012). The SVR rate was 45.13% in patients with normoglycemia (N = 113), 28.26% in patients with impaired fasting glucose (N = 46), and 15.78% in type 2 diabetic patients (N = 19) (P < 0.001). Multivariate logistic regression identified genotype 1 (OR 1.55, 95% CI 1.01-2.41, P= 0.05), gamma-glutamyltranspeptidase level (OR 6.41, 95% CI 1.86-22.07, P= 0.003), and presence of glucose abnormalities (OR 2.33, 95% CI 1.04-5.20, P= 0.039) as being independently associated with the absence of an SVR. In addition, patients with glucose abnormalities (N = 65) showed a lower virological response rate when compared with a subgroup of normoglycemic patients (N = 65) matched for sex, age, and liver fibrosis (24.6%vs 44.6%, P= 0.001). Glucose abnormalities are an independent predictor of poor virological response to combined therapy in hepatitis C virus infected patients.
The American Journal of Gastroenterology, 2008
Lecture Notes in Computer Science, 2001
Nucleic Acids Research, 2004
New England Journal of Medicine, 1996
Journal of Virology, 2000
The quasispecies nature of the hepatitis C virus (HCV) is thought to play a central role in maint... more The quasispecies nature of the hepatitis C virus (HCV) is thought to play a central role in maintaining and modulating viral replication. Several studies have tried to unravel, through the parameters that characterize HCV circulating quasispecies, prognostic markers of the disease. In a previous work we demonstrated that the parameters of circulating viral quasispecies do not always reflect those of the intrahepatic virus. Here, we have analyzed paired serum and liver quasispecies from 39 genotype 1b-infected patients with different degrees of liver damage, ranging from minimal changes to cirrhosis. Viral level was quantified by real-time reverse transcription-PCR, and viral heterogeneity was characterized through the cloning and sequencing of 540 HCV variants of a genomic fragment encompassing the E2-NS2 junction. Although in 95% of patients, serum and liver consensus HCV amino acid sequences were identical, quasispecies complexity varied considerably between the viruses isolated f...
Journal of Hepatology, 2002
The aim of this study was to propose a method, to develop, assess and validate the busine ss oppo... more The aim of this study was to propose a method, to develop, assess and validate the busine ss opportunities that arise in the premises ...
Dialogo Familia Colegio, 2009
Advances in Differential Equations
Advances in Differential Equations
Antiviral Therapy
Objective To investigate the efficacy of early antiviral treatment for hepatitis C virus (HCV) re... more Objective To investigate the efficacy of early antiviral treatment for hepatitis C virus (HCV) recurrence in HIV/HCV-coinfected patients undergoing liver transplantation for end-stage liver disease. Methods Open prospective trial of early treatment of HCV recurrence in consecutive HIV/HCV-coinfected patients transplanted at a tertiary hospital in Barcelona between 2002 and 2004. All patients had indication for liver transplantation, no previous CDC class C HIV-associated opportunistic events, a CD4+ T-cell count >100 cells/fxl, and undetectable plasma HIV RNA on highly active antiretroviral therapy. Treatment with pegylated interferon-a2b (1.5 μg/kg/week) and ribavirin (800–1000 mg/day) was given for 24 to 48 weeks, as soon as HCV recurrence was histologically documented. Results Of six patients who underwent transplant, five patients surviving the early post-transplantation period developed HCV recurrence, presenting as severe cholestatic hepatitis in three, and were started on ...
Journal of Clinical Microbiology, 1999
We describe a rapid and reproducible method for assessment of the hepatitis C virus (HCV) load in... more We describe a rapid and reproducible method for assessment of the hepatitis C virus (HCV) load in serum samples. The method combines Taqman technology (Roche) and the ABI Prism 7700 (Perkin Elmer) real-time sequence detection system. We have optimized a single-tube reverse transcription-PCR (RT-PCR) that contains a dual-labeled fluorogenic probe to quantify the 5′ noncoding region (5′ NCR) of HCV. The probe contains a fluorescent reporter at the 5′ end and a fluorescent quencher at the 3′ end. The use of such a probe combined with the 5′-3′ nuclease activity of Taq polymerase allows direct quantitation of the PCR product by the detection of a fluorescent reporter released in the course of the exponential phase of the PCR. For accurate quantitation of the number of copies of HCV in samples containing unknown quantities, we have used serial dilutions of a synthetic 5′ NCR RNA standard of HCV that was previously quantified with an isotopic tracer. The method has a 5-log dynamic range (...
Journal of Virology, 1992
Sequencing of multiple recombinant clones generated from polymerase chain reaction-amplified prod... more Sequencing of multiple recombinant clones generated from polymerase chain reaction-amplified products demonstrated that the degree of heterogeneity of two well-conserved regions of the hepatitis C virus (HCV) genome within individual plasma samples from a single patient was consistent with a quasispecies structure of HCV genomic RNA. About half of circulating RNA molecules were identical, while the remaining consisted of a spectrum of mutants differing from each other in one to four nucleotides. Mutant sequence diversity ranged from silent mutations to appearance of in-frame stop codons and included both conservative and nonconservative amino acid substitutions. From the relative proportion of essentially defective sequences, we estimated that most circulating particles should contain defective genomes. These observations might have important implications in the physiopathology of HCV infection and underline the need for a population-based approach when one is analyzing HCV genomes.
Journal of Virology, 1997
We have analyzed the population of hepatitis C virus (HCV) sequences in paired liver and serum sa... more We have analyzed the population of hepatitis C virus (HCV) sequences in paired liver and serum samples from four patients with chronic hepatitis C. Sequences from three different biopsy specimens from a liver explant from one patient were compared with each other and with the circulating sequences. Our results demonstrate that the circulating quasispecies does not necessarily reflect the viral population replicating in the liver and that this is not due to a macroscopic anatomic compartmentalization of HCV replication. This finding has important implications for the pathogenesis and natural history of chronic HCV infection.
Journal of virology, 2014
Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed... more Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-α), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV. Importance: Viral drug resistance is usually attributed to the presence of amino acid substitutions in the protein targeted by the drug. In the present study with HCV, we show that high viral replicative fitness c...
The American Journal of Gastroenterology, 2007
The influence of glucose abnormalities on the efficacy of antiviral treatment is unknown. This st... more The influence of glucose abnormalities on the efficacy of antiviral treatment is unknown. This study investigated whether glucose abnormalities (impaired fasting glucose and type 2 diabetes) influence the response to antiviral therapy with interferon plus ribavirin in patients with chronic hepatitis C. A total of 178 treatment-naïve patients with chronic hepatitis C treated with combination therapy were retrospectively studied. SVR was assessed after completing treatment. Fasting plasmatic glucose was measured prior to therapy. Compared with nonresponders (N = 111), patients with SVR (N = 67) had lower plasma glucose (94.1 +/- 12.7 vs 104.4 +/- 25.8 mg/dL, P= 0.001) and a lower prevalence of glucose abnormalities (24.24%vs 44.14%, P= 0.012). The SVR rate was 45.13% in patients with normoglycemia (N = 113), 28.26% in patients with impaired fasting glucose (N = 46), and 15.78% in type 2 diabetic patients (N = 19) (P < 0.001). Multivariate logistic regression identified genotype 1 (OR 1.55, 95% CI 1.01-2.41, P= 0.05), gamma-glutamyltranspeptidase level (OR 6.41, 95% CI 1.86-22.07, P= 0.003), and presence of glucose abnormalities (OR 2.33, 95% CI 1.04-5.20, P= 0.039) as being independently associated with the absence of an SVR. In addition, patients with glucose abnormalities (N = 65) showed a lower virological response rate when compared with a subgroup of normoglycemic patients (N = 65) matched for sex, age, and liver fibrosis (24.6%vs 44.6%, P= 0.001). Glucose abnormalities are an independent predictor of poor virological response to combined therapy in hepatitis C virus infected patients.
The American Journal of Gastroenterology, 2008
Lecture Notes in Computer Science, 2001
Nucleic Acids Research, 2004
New England Journal of Medicine, 1996
Journal of Virology, 2000
The quasispecies nature of the hepatitis C virus (HCV) is thought to play a central role in maint... more The quasispecies nature of the hepatitis C virus (HCV) is thought to play a central role in maintaining and modulating viral replication. Several studies have tried to unravel, through the parameters that characterize HCV circulating quasispecies, prognostic markers of the disease. In a previous work we demonstrated that the parameters of circulating viral quasispecies do not always reflect those of the intrahepatic virus. Here, we have analyzed paired serum and liver quasispecies from 39 genotype 1b-infected patients with different degrees of liver damage, ranging from minimal changes to cirrhosis. Viral level was quantified by real-time reverse transcription-PCR, and viral heterogeneity was characterized through the cloning and sequencing of 540 HCV variants of a genomic fragment encompassing the E2-NS2 junction. Although in 95% of patients, serum and liver consensus HCV amino acid sequences were identical, quasispecies complexity varied considerably between the viruses isolated f...