ABSTRACT
BACKGROUND: Hepatitis C virus (HCV) infection is the major cause of end-stage liver disease (LD) worldwide. The aim of this study was to assess sustained virological response (SVR) rates in a real-world cohort of patients with HCV infection treated with interferon-free direct antiviral agents (DAA). PATIENTS AND METHODS: All patients with genotypes 1, 2 or 3 HCV infection who started interferon-free treatment at a university hospital from December 2015 through July 2017 were included. The primary outcome was SVR at post-treatment week 12 by intention-to-treat (ITT) and modified ITT (mITT) analysis. RESULTS: Five hundred twenty seven patients were enrolled, 51.6% with cirrhosis. Most patients received sofosbuvir + daclatasvir + ribavirin (60.7%) and sofosbuvir + simeprevir (25.6%). Overall SVR rates were 90.5% for ITT and 96% for mITT. SVR rates were higher in non-cirrhotic (94.2% in ITT and 96.8% in mITT) versus cirrhotic patients (87.1% in ITT and 95.2% in mITT). In ITT and mITT assessments, SVR rates were higher in patients with Child-Pugh A (n = 222, 88.7% and 95.7%, respectively) versus Child-Pugh B or C (n = 40, 80% and 90%, respectively); SVR rates were higher in patients with genotype 1 (n = 405, 92.1% and 98.2%), followed by genotype 2 (n = 13, 84.6% and 92.7%) and genotype 3 (n = 109, 84.4% and 88.4%). Lower comorbidity index (p = 0.0014) and absence of cirrhosis (p = 0.0071) were associated with SVR. Among cirrhotic patients, lower Model for End-Stage Liver Disease (p = 0.0258), higher albumin (p = 0.0015), and higher glomerular filtration rate (p = 0.0366) were related to SVR. Twenty-two cirrhotic patients (8%) had clinical liver decompensation during treatment. Complications of advanced LD were responsible for discontinuation of treatment and death in 12 and 7 patients, respectively. CONCLUSION: Treatment with all-oral DAA achieved high SVR rates, particularly in patients without cirrhosis and few comorbidities. Advanced LD is associated to poor outcome, such as treatment failure and death.
Subject(s)
Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Liver Cirrhosis/complications , Administration, Oral , Adult , Aged , Aged, 80 and over , Antiviral Agents/adverse effects , Cohort Studies , Comorbidity , Dose-Response Relationship, Drug , Drug Interactions , Female , Hepatitis C, Chronic/epidemiology , Humans , Liver Cirrhosis/epidemiology , Male , Middle Aged , Safety , Treatment Failure , Treatment OutcomeABSTRACT
Despite advances in therapy, hepatitis C virus (HCV) infection remains an important global health issue. It is estimated that a significant part of the world population is chronically infected with the virus, and many of those affected may develop cirrhosis or liver cancer. The virus shows considerable variability, a characteristic that directly interferes with disease treatment. The response to treatment varies according to HCV genotype and subtype. The continuous generation of variants (quasispecies) allows the virus to escape control by antivirals. Historically, the combination of ribavirin and interferon therapy has represented the only treatment option for the disease. Currently, several new treatment options are emerging and are available to a large part of the affected population. In addition, the search for new substances with antiviral activity against HCV continues, promising future improvements in treatment. Researchers should consider the mutation capacity of the virus and the other variables that affect treatment success.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Protease Inhibitors/therapeutic use , Carcinoma, Hepatocellular , Drug Therapy, Combination , Hepacivirus/genetics , Hepatitis C, Chronic/virology , Humans , Interferon-alpha/therapeutic use , Liver Cirrhosis , Liver Neoplasms , RNA, Viral , Ribavirin/therapeutic use , Sustained Virologic Response , Viral LoadABSTRACT
A disseminação das hepatites virais é consequência de amplas e marcantes mudanças que ocorreram nas últimas três décadas do século XX, especialmente na sociedade ocidental. A emergência das hepatites virais resultou em significativa redução da qualidade de vida e sobrevida entre aqueles que contraíram a infecção. O impac¬to das hepatites virais varia de acordo com os diferentes níveis de desenvolvimento socioeconômico das populações e de fatores emer¬gentes na sua transmissão. Por fim, importantes avanços científicos e sociais foram otbtidos, mas ainda insuficientes para o controle dessas infecções. A epidemiologia das hepatites virais no Século XXI reflete tanto o impacto positivo de medidas de prevenção como o impacto negativo de padrões de transmissão históricos e emergen¬tes. As hepatites virais são doenças de dois mundos: um, no qual as novas infecções restringem-se a padrões emergentes de transmissão e o tratamento é acessível; outro, no qual tanto padrões históricos como emergentes de transmissão possibilitam novas infecções e o tratamento é pouco acessível
The spread of viral hepatitis is the result of extensive and remarkable social changes that occurred in the last three decades of the twentieth century, especially in Western society. The emergence of viral hepatitis resulted in a significant reduction in quality of life and survival among those who contracted the infection. The impact of viral hepatitis varies with the different levels of socioeconomic development of populations and emerging factors in its transmission. Finally, important scientific and social advances have been achieved, but still insufficient to control these infections. The epidemiology of viral hepatitis in the XXI century reflects both the positive impact of preventive measures and the negative impact of historical and transmission emerging patterns. Viral hepatitis is a disease of two worlds, one where new infections are restricted to emerging patterns of transmission and treatment is available, another where both historical patterns and emerging new infections allow transmission and access to treatment is restricted
Subject(s)
Hepatitis/epidemiology , Hepatitis/history , Disease Transmission, InfectiousABSTRACT
Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm3), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.
ABSTRACT
Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm 3 ), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.(AU)
Subject(s)
Hepatitis B virus , HIV , Interferon-alpha , Seroconversion , Injections, SubcutaneousABSTRACT
Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm 3 ), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.
ABSTRACT
Hepatitis C virus (HCV) infection and chronic renal diseases can be linked in two different ways. Some forms of renal disease are precipitated by HCV infection, while patients with end-stage renal disease are at increased risk for acquiring HCV infection. Patients with chronic HCV infection and renal disease have a poor prognosis. Most studies on treatment of HCV and renal diseases have been uncontrolled trials with small number of subjects. So, there is a lack of evidence-based recommendations and guidelines on the management of this condition. In this review, we will attempt to provide the most recent insights on HCV infection both as a extrahepatic manifestations and as a complication of end-stage renal patients.
ABSTRACT
BACKGROUND: Pegylated interferon (Peg-IFN) and standard interferon (IFN) play a significant role in the treatment of hepatitis C virus (HCV) infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR) rates following treatment with biosimilar standard IFN plus ribavirin (RBV) versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7%) patients with HCV genotype 2 infections. One hundred fourteen (66.3%) were treated with biosimilar standard IFN plus RBV, whist 58 (33.7%) patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172) patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58) had SVR compared to 49.1% (56/114) among those treated with biosimilar standard IFN plus RBV (p = 0.0001). CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.
Subject(s)
Antiviral Agents/administration & dosage , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Interferons/administration & dosage , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Adolescent , Adult , Aged , Cohort Studies , Drug Therapy, Combination , Female , Genotype , Humans , Interferon alpha-2 , Male , Middle Aged , RNA, Viral/analysis , Recombinant Proteins/administration & dosage , Retrospective Studies , Treatment Outcome , Viral Load , Young AdultABSTRACT
BACKGROUND: Pegylated interferon (Peg-IFN) and standard interferon (IFN) play a significant role in the treatment of hepatitis C virus (HCV) infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown. OBJECTIVE: To compare the sustained virological response (SVR) rates following treatment with biosimilar standard IFN plus ribavirin (RBV) versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection. METHODS: A retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared. RESULTS: From January 2005 to December 2010, 172 patients with a mean age of 44 +/- 9.3 years were included. There were eight (4.7%) patients with HCV genotype 2 infections. One hundred fourteen (66.3%) were treated with biosimilar standard IFN plus RBV, whist 58 (33.7%) patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172) patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58) had SVR compared to 49.1% (56/114) among those treated with biosimilar standard IFN plus RBV (p = 0.0001). CONCLUSION: In patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antiviral Agents/administration & dosage , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Interferons/administration & dosage , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Cohort Studies , Drug Therapy, Combination , Genotype , Retrospective Studies , RNA, Viral/analysis , Recombinant Proteins/administration & dosage , Treatment Outcome , Viral LoadABSTRACT
Hemodialysis patient with chronic HCV infection,who was started on monotherapy with interferon.Qualitative HCV RNA remained positive at 12 weeks of treatment; ribavirin was associated. HCV RNA was negative at week 24 and treatment was extended to 72 weeks. HCV RNA negative six months after treatment.
Subject(s)
Antiviral Agents/administration & dosage , Hepatitis C, Chronic/drug therapy , Interferons/administration & dosage , Renal Dialysis , Ribavirin/administration & dosage , Adult , Drug Therapy, Combination , Hepatitis C, Chronic/complications , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Male , RNA, Viral/analysis , Treatment OutcomeABSTRACT
Hemodialysis patient with chronic HCV infection,who was started on monotherapy with interferon.Qualitative HCV RNA remained positive at 12 weeks of treatment; ribavirin was associated. HCV RNA was negative at week 24 and treatment was extended to 72 weeks. HCV RNA negative six months after treatment.