Author
Fernando L. Gonçales
Bio: Fernando L. Gonçales is an academic researcher from State University of Campinas. The author has contributed to research in topics: Hepatitis C & Ribavirin. The author has an hindex of 17, co-authored 42 publications receiving 8445 citations.
Topics: Hepatitis C, Ribavirin, Hepatitis C virus, Hepatitis, Viral hepatitis
Papers
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TL;DR: In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferonAlfa- 2b plus Ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interfer on alfa -2b plus ribvirin or pegin terferonalfa-3a alone.
Abstract: Background Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Methods A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 μg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. Results A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) th...
6,523 citations
TL;DR: Early, sustained suppression of HCV replication portends an SVR, and cessation of treatment may be contemplated in patients without a > or = 2 log10 reduction in HCV RNA after 12 weeks.
542 citations
Leipzig University1, Odense University Hospital2, Université libre de Bruxelles3, Universidade Federal do Estado do Rio de Janeiro4, University Health Network5, Nottingham University Hospitals NHS Trust6, Ege University7, Ankara University8, Université de Montréal9, Universidade Federal do Rio Grande do Sul10, Federal University of Rio de Janeiro11, Hannover Medical School12, University of Plymouth13, University of New South Wales14, Cairo University15, Örebro University16, Ain Shams University17, Dokuz Eylül University18, Karolinska University Hospital19, Federal University of São Paulo20, Carlos III Health Institute21, University of Copenhagen22, State University of Campinas23, University of São Paulo24, Medical University of Vienna25, Masaryk University26, University of Manitoba27, Istanbul University28, University of British Columbia29, Aalborg University30, Katholieke Universiteit Leuven31, University of Western Ontario32, University of Düsseldorf33, University of Zurich34, University of Calgary35, Geneva College36, Queen Elizabeth II Health Sciences Centre37, Dalhousie University38, Monash University39, University College London40, Goethe University Frankfurt41, University of St. Gallen42, Université catholique de Louvain43, Medical University of Graz44, University of Melbourne45, Charles University in Prague46, Ghent University Hospital47, University of Hasselt48, Ghent University49, Copenhagen University Hospital50, University of Antwerp51, Karolinska Institutet52
TL;DR: In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use, and Diagnosis, treatment and transplant levels also differed considerably between countries.
Abstract: Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6,358,000 cases in 2008 and Brazil with 2,106,000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
277 citations
Pierre-and-Marie-Curie University1, University of Milan2, University of Barcelona3, University of Miami4, Northwestern University5, University of São Paulo6, University of Iowa7, Charité8, Penn State Milton S. Hershey Medical Center9, University Health Network10, State University of Campinas11, University of Palermo12, Schering-Plough13
TL;DR: Peginterferon alfa-2b plus weight-based ribavirin is effective and safe in patients who failed interferonAlfa/ribavirin therapy andGenotype, baseline viral load, and fibrosis stage were predictors of response.
243 citations
Hannover Medical School1, Örebro University2, University College London3, Cairo University4, Ankara University5, Ghent University Hospital6, Ege University7, Karolinska Institutet8, Karolinska University Hospital9, Leipzig University10, Université de Montréal11, Universidade Federal do Estado do Rio de Janeiro12, Universidade Federal do Rio Grande do Sul13, Odense University Hospital14, Federal University of Rio de Janeiro15, University of Plymouth16, University of New South Wales17, Ain Shams University18, Dokuz Eylül University19, Federal University of São Paulo20, Carlos III Health Institute21, University of Copenhagen22, State University of Campinas23, University of São Paulo24, Medical University of Vienna25, Masaryk University26, University of Manitoba27, Istanbul University28, University of British Columbia29, Aalborg University30, Katholieke Universiteit Leuven31, University of Western Ontario32, University of Düsseldorf33, Université libre de Bruxelles34, University of Zurich35, University of Calgary36, Queen Elizabeth II Health Sciences Centre37, Monash University38, Nottingham University Hospitals NHS Trust39, Goethe University Frankfurt40, University of St. Gallen41, University Health Network42, Université catholique de Louvain43, Medical University of Graz44, University of Melbourne45, Charles University in Prague46, University of Antwerp47, University of Hasselt48, Copenhagen University Hospital49, Geneva College50
TL;DR: It is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030), however, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment.
Abstract: The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
188 citations
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TL;DR: How PEGylation can result in drugs that are often more effective and safer, and which show improved patient convenience and compliance are reviewed.
Abstract: Protein and peptide drugs hold great promise as therapeutic agents. However, many are degraded by proteolytic enzymes, can be rapidly cleared by the kidneys, generate neutralizing antibodies and have a short circulating half-life. Pegylation, the process by which polyethylene glycol chains are attached to protein and peptide drugs, can overcome these and other shortcomings. By increasing the molecular mass of proteins and peptides and shielding them from proteolytic enzymes, pegylation improves pharmacokinetics. This article will review how PEGylation can result in drugs that are often more effective and safer, and which show improved patient convenience and compliance.
3,142 citations
TL;DR: This document has been approved by the AASLD, the Infectious Diseases Society of America, and the American College of Gastroenterology.
3,013 citations
TL;DR: The institution of blood-screening measures in developed countries has decreased the risk of transfusion-associated hepatitis to a negligible level, but new cases continue to occur mainly as a result of injection-drug use and, to a lesser degree, through other means of percutaneous or mucous-membrane exposure.
Abstract: Hepatitis C virus (HCV) infects an estimated 170 million persons worldwide and thus represents a viral pandemic, one that is five times as widespread as infection with the human immunodeficiency virus type 1 (HIV-1). The institution of blood-screening measures in developed countries has decreased the risk of transfusion-associated hepatitis to a negligible level, but new cases continue to occur mainly as a result of injection-drug use and, to a lesser degree, through other means of percutaneous or mucous-membrane exposure. Progression to chronic disease occurs in the majority of HCV-infected persons, and infection with the virus has become the main indication . . .
2,966 citations
TL;DR: Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype, and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribvirin was statistically inferior to low-dose Ribavirin.
Abstract: BACKGROUND:
Treatment with pegylated interferon (peginterferon) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. OBJECTIVE:
To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or standard dose of ribavirin. DESIGN:
Randomized, double-blind trial. SETTING:
99 international centers. PATIENTS: 1311 patients with chronic hepatitis C. PATIENTS:
1311 patients with chronic hepatitis C. INTERVENTION:
Peginterferon-?2a, 180 ?/wk, for 24 or 48 weeks plus a low-dose (800 mg/d) or standard weight-based dose (1000 or 1200 mg/d) of ribavirin. Measurement: Sustained virologic response: undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up. RESULTS:
Overall and in patients infected with HCV genotype 1, 48 weeks of treatment was statistically superior to 24 weeks and standard-dose ribavirin was statistically superior to low-dose ribavirin. In patients with HCV genotype 1, absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2% (95% CI, 3.6% to 18.9%) and 11.9% (CI, 4.7% to 18.9%), respectively, between standard- and low-dose ribavirin. Sustained virologic response rates for peginterferon-alpha2a and standard-dose ribavirin for 48 weeks were 63% (CI, 59% to 68%) overall and 52% (CI, 46% to 58%) in patients with HCV genotype 1. In patients with HCV genotypes 2 or 3, the sustained virologic response rates in the 4 treatment groups were not statistically significantly different. CONCLUSION:
Treatment with peginterferon-?2a and ribavirin may be individualized by genotype. Patients with HCV genotype 1 require treatment for 48 weeks and a standard dose of ribavirin; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks.
2,954 citations
TL;DR: Because there is no vaccine and no post-exposure prophylaxis for HCV, the focus of primary prevention efforts should be safer blood supply in the developing world, safe injection practices in health care and other settings, and decreasing the number of people who initiate injection drug use.
Abstract: Hepatitis C virus (HCV) is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. The complexity and uncertainty related to the geographic distribution of HCV infection and chronic hepatitis C, determination of its associated risk factors, and evaluation of cofactors that accelerate its progression, underscore the difficulties in global prevention and control of HCV. Because there is no vaccine and no post-exposure prophylaxis for HCV, the focus of primary prevention efforts should be safer blood supply in the developing world, safe injection practices in health care and other settings, and decreasing the number of people who initiate injection drug use.
2,865 citations