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Table 3 Summary of clinical studies reporting the impact of SVR on all-cause and liver-related mortality

From: Achieving sustained virologic response in hepatitis C: a systematic review of the clinical, economic and quality of life benefits

Study Setting Sample size Mean follow up Study details Outcomes assessed Key findings
Selzner et al. 2009 [59] Canada 446 68 monthsa Retrospective cohort study in liver transplant recipients treated with IFN-based therapy Overall survival Actuarial 5-year survival rates were 96% for SVR and 69% for non-response (p < 0.0001)
Tanaka et al. 2013 [60] Canada 245 5.7 years Retrospective single center study in liver transplant recipients undergoing treatment (agents not stated) All cause mortality HR for all cause mortality for SVR versus non-response = 0.091 (0.04–0.21) (p < 0.001). HR for all cause mortality for relapse versus non-response = 0.19 (0.06–0.63) (p = 0.006)
Van der Meer et al. 2012 [38] Europe and Canada 530 8.4 years Retrospective cohort study in patients with advanced fibrosis/cirrhosis treated with IFN, IFN plus ribavirin or pegIFN plus ribavirin, 68% genotype 1 All cause mortality HR for all cause mortality for SVR versus non-SVR was 0.25–0.26 (p < 0.001)
Van der Meer et al. 2012 [61] Europe and Canada 248 8.3 yearsa Retrospective cohort study in patients with HCV genotype 1 with cirrhosis, treated with IFN-based treatment, 88% treatment-naïve at baseline All cause mortality Unadjusted HR (95% CI) for all cause mortality for SVR 0.20 (0.06–0.64) (p = 0.007)
Aguilera et al. 2012 [62] France 114 Not stated liver transplant recipients treated with pegIFN plus ribavirin Overall survival For patients with F0–F1, 10 year survival was 100% for SVR versus 76% for non-response (p = 0.024). For patients with F3–F4, 7-year survival was 85% for SVR versus 72% for non-response (p = ns)
Cardoso et al. 2010 [42] France 307 3.5 yearsa Retrospective analysis in patients with bridging fibrosis or cirrhosis treated with IFN, pegIFN or pegIFN plus ribavirin Liver-related mortality Adjusted HR (95% CI) for non-SVR versus SVR was 3.71 (1.05–13.05) (p = 0.041) for liver-related mortality
Kutala et al. 2013 [63] France 484 4.5 yearsa Retrospective study in patients with advanced fibrosis, SVR rate was 30% in treated patients All cause mortality 5 year survival rate was 100% in those with SVR vs. 54% for those without SVR (p < 0.0001), HR (95% CI) for mortality for non-SVR versus SVR was 6.8 (2.5–20.5)
Bruno et al. 2007 [44] Italy 883 96.1 months Retrospective database analysis in patients treated with IFN monotherapy with no cirrhosis or decompensation, 73.5% genotype 1 Liver-related mortality Adjusted HR (95% CI) for non-SVR versus SVR was 6.97 (1.70–28.42) (p = 0.0007) for liver-related mortality
Calvaruso et al. 2013 [23] Italy 444 69 monthsa (range 24–130 months) Prospective cohort study in PR-treated patients with compensated cirrhosis, 83% genotype 1, 24% with SVR Liver-related mortality HR (95% CI) for liver related death for no SVR versus SVR = 6.56 (2.06–20.92) (p = 0.001)
Hara et al. 2014 [24] Japan 1,125 Not stated Retrospective cohort study in PR-treated (SVR and non SVR) and untreated patients All cause mortality HR (95% CI) for all cause mortality for SVR vs non-SVR and untreated = 0.08 (0.01–0.55) (p = 0.011)
Imazeki et al. 2003 [58] Japan 459 8.2 (2.9) years Retrospective cohort study in consecutive patients with CHC (335 treated with IFN and 104 untreated) All-cause mortality, liver-related mortality Adjusted RR (95%CI) for all cause mortality for SVR versus untreated was 0.22 (0.07–0.71) (p = 0.0114). Adjusted RR (95% CI) for liver-related death was 0.03 (0.003–0.28) (p = 0.0017)
Kasahara et al. 2004 [57] Japan 2,954 6.0 (2.2) years Retrospective cohort study in HCV patients with stage F0–F4 fibrosis, (n = 2,698 treated with IFN alone, n = 256 untreated) All cause mortality, liver-related mortality RR (95% CI) for all cause mortality versus untreated was 0.14 (0.06–0.35) (p < 0.001) for SVR and 0.78 (0.43–1.39) (p = 0.394) for non-response. RR (95% CI) for liver-related mortality versus no treatment was 0.04 (0.01–0.30) (p = 0.002) for SVR and 1.02 (0.54–1.90) (p = 0.962)
Maruoka et al. 2012 [40] Japan 721 9.9 (5.3) years Retrospective cohort study in patients treated with monotherapy (n = 577, of which n = 221 (38.3%) achieved SVR and n = 144 untreated patients Overall mortality, liver-related mortality Annual liver-related mortality rate was 2.52% for untreated patients, 1.26% for non-SVR and 0.1% for SVR. Multivariate HR for all cause mortality versus untreated was 0.84 (0.50–1.42) for non-SVR and 0.17 (0.08–0.40) for SVR
Uenishi et al. 2008 [64] Japan 209 4.1 yearsa Retrospective cohort study in patients who underwent curative surgery for early stage HCC (n = 139 had no antiviral treatment, remainder treated with pegIFN plus ribavirin) Tumor-free survival and recurrence of HCC Tumor-free survival rate at 5 years was 54% for SVR group versus 23% for non-SVR/untreated group (p < 0.001)
Velosa et al. 2011 [39] Portugal 130 6.4 (4.0) years Retrospective cohort study in patients with cirrhosis treated with IFN, IFN plus ribavirin or pegIFN plus ribavirin Liver-related mortality Liver-related mortality rate during follow up was 21% for non-SVR versus 0% for SVR
Aleman et al. 2013 [26] Sweden 351 5.3 years Prospective multicenter study in patients with HCV-related cirrhosis treated with pegIFN plus ribavirin, 50% genotype 1 All cause mortality, liver-related mortality HR (95% CI) for liver-related mortality for SVR versus non-SVR = 0.18 (0.05–0.45) (p = 0.001)
HR (95% CI) all cause mortality for SVR versus non SVR = 0.36 (0.18–0.68) (p = 0.003)
Shih et al. 2012 [48] Taiwan 3,988 57.7 monthsa Retrospective analysis of patients with HCV monoinfection, (n = 344 patients treated with IFN-based treatment, n = 216 with SVR) Liver-related mortality Adjusted HR (95%CI) for SVR versus untreated was 0.19 (0.05–0.77) (p = 0.02) for liver-related mortality
Yu et al. 2006 [45] Taiwan 1,619 5.2 years Prospective study in patients with or without cirrhosis (n = 562 untreated and n = 1,057 treated with IFN or IFN plus ribavirin) Overall morality RR (95% CI) for overall mortality versus untreated control was 0.37 (0.14–0.99) (p = 0.047) for SVR and 1.32 (0.57–3.07) (p = 0.524)
Innes et al. 2012 [56] United Kingdom 1,215 5.3 years Retrospective cohort study in previously naïve patients, 36% genotype 1, treated with IFN-based therapy, 14% patients with cirrhosis at baseline Liver-related mortality Adjusted HR (95% CI) for SVR versus non-SVR was 0.22 (0.09–0.58) for liver-related mortality (p < 0.01)
Backus et al. 2011 [65] United States 22,942 3.8 yearsa Retrospective database analysis in n = 12,166 genotype 1, n = 2,904 genotype 2, and 1,794 genotype 3 patients treated with pegIFN plus ribavirin All cause mortality Adjusted HR (95% CI) for all cause mortality for SVR versus non SVR in HCV genotype 1 was 0.70 (0.59–0.83) (p < 0.0001)
Cozen et al. 2013 [66] United States 358 10 years Retrospective database analysis in patients with HCV treated with IFN monotherapy or pegIFN plus ribavirin, 69% genotype 1 and 7.3% with cirrhosis at baseline All cause mortality HR (95% CI) for death or liver transplant vs. never treated patients = 0.23 (0.07–0.75) for SVR and 0.56 (0.24–1.32) for non-responder
Dieperink et al. 2014 [67] United States 536 7.5 yearsa Retrospective chart review of treated patients, 70% genotype 1, SVR rate of 41% All cause mortality, liver-related mortality or transplant HR (95% CI) for all cause mortality for SVR vs. non-SVR = 0.47 (0.26–0.85) (p < 0.012)
HR (95% CI) for liver-related death or transplant for SVR vs. non-SVR = 0.23 (0.08–0.66) (p = 0.007)
Morgan et al. 2010 [41] United States 140 78.6 (15.9) months Prospective analysis from the HALT-C trial in patients with advanced fibrosis treated with pegIFN plus ribavirin and achieving SVR All cause mortality, liver-related mortality, liver transplantation HR (95% CI) for SVR versus non response was 0.17 (0.06–0.46) for all cause mortality or transplant and 0.12 (0.03–0.48) for liver-related mortality or transplant
Singal et al. 2013 [68] United States 242 5 years Retrospective single center study in patients treated with pegIFN plus ribavirin, 68% genotype 1, 31% with histological cirrhosis All cause mortality HR for mortality for SVR versus non-response = 0.11 (0.03–0.47)
  1. aMedian follow up.
  2. ALT, alanine aminotransferase; CI, confidence interval; HCC, hepatocellular carcinoma; HR, hazard ratio; IFN, interferon; ns, not significant; SVR, sustained virologic response.