Antivirals and Extrahepatic Outcomes in Patients With HCV
Objective To elucidate the association between antiviral therapy and extrahepatic outcomes in individuals infected with HCV.
Methods This nationwide cohort study screened 293 480 Taiwanese residents with HCV infection and excluded those with substantial comorbidity. A total of 12 384 eligible patients who had received pegylated interferon plus ribavirin between 1 October 2003 and 31 December 2010 were enrolled in the treated cohort; they were matched 1 : 2 with 24 768 untreated controls in the propensity score and post-diagnosis treatment-free period. The incidences of end-stage renal disease (ESRD), acute coronary syndrome (ACS), ischaemic stroke and catastrophic autoimmune diseases were calculated after adjustment for competing mortality.
Results The treated and untreated cohorts were followed up for a mean (±SD) duration of 3.3 (±2.5) and 3.2 (±2.4) years, respectively, until 31 December 2011. The calculated 8-year cumulative incidences of ESRD, ACS, ischaemic stroke and autoimmune catastrophes between treated and untreated patients were 0.15% vs 1.32% (p<0.001), 2.21% vs 2.96% (p=0.027), 1.31% vs 1.76% (p=0.001) and 0.57% vs 0.49% (p=0.816), respectively. Multivariate-adjusted Cox regression revealed that antiviral treatment was associated with lower risks of ESRD (HR 0.15; 95% CI 0.07 to 0.31; p<0.001), ACS (HR 0.77; 95% CI 0.62 to 0.97; p=0.026) and ischaemic stroke (HR 0.62; 95% CI 0.46 to 0.83; p=0.001), but unrelated to autoimmune catastrophes. These favourable associations were invalid in incompletely treated patients with duration <16 weeks.
Conclusions Antiviral treatment for HCV is associated with improved renal and circulatory outcomes, but unrelated to catastrophic autoimmune diseases.
HCV infection is a global public health problem, affecting approximately 170 million people around the world. It is not only a major aetiology of liver-related morbidity and mortality, but also causally associated with a number of extrahepatic manifestations that include cryoglobulinaemia, glomerulonephritis, endothelial dysfunction, insulin resistance and aberrant autoimmunity. A large body of evidence has shown that the risks of liver-unrelated death, chronic renal failure, atherosclerotic disease, cerebral vascular accident and autoimmune disorders are significantly higher in HCV-infected patients. Strategies that can effectively attenuate these excessive risks, however, have not been elucidated.
The past two decades have witnessed a tremendous advance in the antiviral therapy for HCV infection. Interferon-free regimens composed of direct acting antiviral agents are now becoming a new paradigm. Nevertheless, pegylated interferon (Peg-IFN) plus ribavirin has been widely used as the regimen of choice for a decade, and actually brings about excellent therapeutic responses in Asian countries where the favourable IL28B is prevalent. For instance, this regimen attains an eradication rate over 70% among treatment-naïve patients in Taiwan. Empirical data have been accumulating to show that antiviral therapy is associated with risk reduction of hepatic complications.
Extrahepatic effectiveness of antiviral treatment for HCV infection has not been elucidated. Previous studies usually targeted a specific subpopulation of infected individuals. For example, Berenguer and colleagues reported that sustained viral response (SVR) to interferon plus ribavirin was associated with a lower risk of liver-unrelated mortality in patients with HIV co-infection. Our recent work demonstrated that antiviral therapy was associated with improved renal and cardiovascular outcomes in patients with diabetes mellitus (DM). A comprehensive evaluation from a general population remains unavailable. In order to fill this knowledge gap, this nationwide cohort study analysed healthcare data in the entire Taiwan population for the years 1997–2011 to clarify the association between treatment for HCV and extrahepatic outcomes.
Abstract and Introduction
Abstract
Objective To elucidate the association between antiviral therapy and extrahepatic outcomes in individuals infected with HCV.
Methods This nationwide cohort study screened 293 480 Taiwanese residents with HCV infection and excluded those with substantial comorbidity. A total of 12 384 eligible patients who had received pegylated interferon plus ribavirin between 1 October 2003 and 31 December 2010 were enrolled in the treated cohort; they were matched 1 : 2 with 24 768 untreated controls in the propensity score and post-diagnosis treatment-free period. The incidences of end-stage renal disease (ESRD), acute coronary syndrome (ACS), ischaemic stroke and catastrophic autoimmune diseases were calculated after adjustment for competing mortality.
Results The treated and untreated cohorts were followed up for a mean (±SD) duration of 3.3 (±2.5) and 3.2 (±2.4) years, respectively, until 31 December 2011. The calculated 8-year cumulative incidences of ESRD, ACS, ischaemic stroke and autoimmune catastrophes between treated and untreated patients were 0.15% vs 1.32% (p<0.001), 2.21% vs 2.96% (p=0.027), 1.31% vs 1.76% (p=0.001) and 0.57% vs 0.49% (p=0.816), respectively. Multivariate-adjusted Cox regression revealed that antiviral treatment was associated with lower risks of ESRD (HR 0.15; 95% CI 0.07 to 0.31; p<0.001), ACS (HR 0.77; 95% CI 0.62 to 0.97; p=0.026) and ischaemic stroke (HR 0.62; 95% CI 0.46 to 0.83; p=0.001), but unrelated to autoimmune catastrophes. These favourable associations were invalid in incompletely treated patients with duration <16 weeks.
Conclusions Antiviral treatment for HCV is associated with improved renal and circulatory outcomes, but unrelated to catastrophic autoimmune diseases.
Introduction
HCV infection is a global public health problem, affecting approximately 170 million people around the world. It is not only a major aetiology of liver-related morbidity and mortality, but also causally associated with a number of extrahepatic manifestations that include cryoglobulinaemia, glomerulonephritis, endothelial dysfunction, insulin resistance and aberrant autoimmunity. A large body of evidence has shown that the risks of liver-unrelated death, chronic renal failure, atherosclerotic disease, cerebral vascular accident and autoimmune disorders are significantly higher in HCV-infected patients. Strategies that can effectively attenuate these excessive risks, however, have not been elucidated.
The past two decades have witnessed a tremendous advance in the antiviral therapy for HCV infection. Interferon-free regimens composed of direct acting antiviral agents are now becoming a new paradigm. Nevertheless, pegylated interferon (Peg-IFN) plus ribavirin has been widely used as the regimen of choice for a decade, and actually brings about excellent therapeutic responses in Asian countries where the favourable IL28B is prevalent. For instance, this regimen attains an eradication rate over 70% among treatment-naïve patients in Taiwan. Empirical data have been accumulating to show that antiviral therapy is associated with risk reduction of hepatic complications.
Extrahepatic effectiveness of antiviral treatment for HCV infection has not been elucidated. Previous studies usually targeted a specific subpopulation of infected individuals. For example, Berenguer and colleagues reported that sustained viral response (SVR) to interferon plus ribavirin was associated with a lower risk of liver-unrelated mortality in patients with HIV co-infection. Our recent work demonstrated that antiviral therapy was associated with improved renal and cardiovascular outcomes in patients with diabetes mellitus (DM). A comprehensive evaluation from a general population remains unavailable. In order to fill this knowledge gap, this nationwide cohort study analysed healthcare data in the entire Taiwan population for the years 1997–2011 to clarify the association between treatment for HCV and extrahepatic outcomes.
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