Factors contributing to ribavirin dose reduction due to anemia during interferon alfa2b and ribavirin combination therapy for chronic hepatitis C

Takaki, Shintaro; Tsubota, Akihito; Hosaka, Tetsuya; Akuta, Norio; Someya, Takashi; Kobayashi, Masahiro; Suzuki, Fumitaka; Suzuki, Yoshiyuki; Saitoh, Satoshi; Arase, Yasuji; Ikeda, Kenji; Kumada, Hiromitsu

doi:10.1007/s00535-003-1363-9

Cited by 81 publications

(77 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(16)(17)(18) Historically, age has been a major limitation of antiviral treatment with interferon-based therapy because of its poor tolerability, adverse effects (AEs), and poorer response in older patients. (19)(20)(21)(22)(23)(24)(25) There is a lack of efficacy and safety information on HCV therapy in older patients, primarily due to underreporting and the exclusion of elderly subjects from clinical trials. (26,27) The combination of ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, has been approved by the US Food and Drug Administration, the European Medicines Agency, and in Japan as a fixed-dose combination tablet for the treatment of HCV genotype 1.…”

mentioning

confidence: 99%

Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older

et al. 2016

View full text Add to dashboard Cite

Elderly subjects have been historically underrepresented in clinical trials involving antiviral hepatitis C therapies. The aim of this analysis was to retrospectively evaluate the safety and efficacy of ledipasvir/sofosbuvir (LDV/SOF) by age groups of <65 years versus 65 years among subjects enrolled in phase 3 trials. Four open-label phase 3 clinical trials evaluated the safety and efficacy of LDV/SOF with or without ribavirin (RBV) for the treatment of genotype 1 chronic hepatitis C virus. Sustained virological response at 12 weeks, treatment-emergent adverse events (AEs), and graded laboratory abnormalities were analyzed according to age group. Of the 2293 subjects enrolled in four phase 3 trials, 264 (12%) were 65 years of age, of whom 24 were aged 75 years. Sustained virological response at 12 weeks was achieved by 97% (1965/ 2029) of subjects aged <65 years and 98% (258/264) of subjects aged 65 years. The most common AEs in both LDV/ SOF groups that occurred in 10% of subjects were headache and fatigue. The rate of study discontinuation due to AEs was similar in the two age cohorts. The use of RBV in 1042 (45%) subjects increased the number of AEs, treatmentrelated AEs, and AEs leading to study drug modification/interruption, particularly among elderly subjects. Conclusions: LDV/SOF with or without RBV was highly effective for treatment of genotype 1 chronic hepatitis C virusin subjects aged 65 and older. Addition of RBV did not increase sustained virological response at 12 weeks rates but led to higher rates of AEs, especially in elderly subjects. (HEPATOLOGY 2016;63:1112-1119 C hronic hepatitis C viral (HCV) infection is an important cause of morbidity and mortality in infected individuals worldwide.(1) The World Health Organization estimates that the worldwide prevalence of HCV infection is 2.2%, representing 123 million people.(2) Globally, HCV accounts for 27% of liver cirrhosis and 25% of hepatocellular carcinoma cases.(3) Although the rate of HCV is decreasing overall due to attrition from mortality, (4,5) the rate of HCV-related cirrhosis is anticipated to increase by Abbreviations: AE, adverse event; CI, confidence interval; eGFR, estimated glomerular filtration rate; HCV, hepatitis C virus; LDV/SOF, ledipasvir/sofosbuvir; RAV, resistance-associated variant; RBV, ribavirin; SVR12, sustained virological response at 12 weeks

show abstract

mentioning

confidence: 99%

Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Many previous studies reported that combination therapy with PEG-IFN and RBV for 24-48 weeks was effective in treating chronic hepatitis C (11). The most frequent toxic side effect of RBV is reversible hemolytic anemia, which requires some patients to reduce or discontinue combination therapy; the mechanism underlying hemolytic anemia involves the accumulation of RBV triphosphate in erythrocytes (12).…”

Section: Discussionmentioning

confidence: 99%

Can eicosapentaenoic acid maintain the original ribavirin dose or affect the response during the treatment course of chronic hepatitis C virus (HCV) patients?

Morsy

Zaghloul²,

Mahmoud³

2016

Turk J Gastroenterol

View full text Add to dashboard Cite

“…RBV-induced hemolytic anemia (HA) is usually reversible and dose related [115,116], but may require significant dose reductions possibly affecting efficacy, and is a cause of withdrawal from therapy in 10-14% of patients [64,[117][118][119][120]. Several risk factors for RBV-induced HA have been identified, for example, age, female gender, dose and plasma concentration of RBV, baseline hemoglobin and platelets, and haptoglobin phenotype [121][122][123][124]. However, the severity of RBV-induced HA shows great variability among individuals, suggesting that the genetic background may exert a profound influence on the clinical expression of this adverse effect.…”

Section: Molecular Epidemiology Of Hcv-relatedmentioning

confidence: 99%

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

Trinks

Gadano

Argibay

2012

Epidemiology Research International

View full text Add to dashboard Cite

Hepatitis C virus (HCV) represents a major worldwide public health problem. The search for the key molecular biomarkers that may provide insight on the basis of the differences in disease progression, severity, and response to therapy is crucial for understanding the natural history of HCV, for estimating the burden of infection and for developing preventive interventions. Initially, molecular epidemiology studies have focused on studying the viral genetic diversity (genotypes, genetic variants, specific nucleotide and amino acid substitutions). However, the clinical heterogeneities of HCV infection and the imperfect predictability of the response to treatment have suggested the need to search for host genetic biomarkers. This led to the discovery of genetic polymorphisms playing a major role in the evolution of infection, as well as in treatment response and adverse effects, such asIL-28B,ITPA, andIP-10. As a consequence, nowadays the focus of molecular epidemiology studies has turned from the viral to the human genome. This paper will cover recent reports on the subject describing the most relevant viral as well as host genetic risk factors analyzed by past and current HCV molecular epidemiology studies.

show abstract

Factors contributing to ribavirin dose reduction due to anemia during interferon alfa2b and ribavirin combination therapy for chronic hepatitis C

Abstract: Because patient age of 55 years or more, and Hb levels of less than 14 g/dl are significant factors that influence ribavirin-induced hemolytic anemia, more careful monitoring is necessary during combination therapy for patients with these risk factors.

Cited by 81 publications

References 24 publications

Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older

Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older

Can eicosapentaenoic acid maintain the original ribavirin dose or affect the response during the treatment course of chronic hepatitis C virus (HCV) patients?

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

Contact Info

Product

Resources

About