Background
Methods
Inclusion criteria | Exclusion criteria |
---|---|
All studies
| All studies |
Published 2003–2014 | Conducted exclusively in HIV co-infected patients |
Published in English | Conducted exclusively in pediatric patients |
Conducted in patients with chronic HCV | Wrong publication type: letters, case studies, editorials and commentaries were excluded |
Conducted exclusively in patients with genotypes 2, 3, 4, 5 or 6 | |
Clinical studies
| Clinical studies |
Minimum 1 year post-treatment follow-up | <100 patients |
Report hard clinical endpoints (e.g. overall mortality, incidence of hepatocellular carcinoma) | Endpoints limited to biochemical parameters only (e.g. aminotransferase levels only) |
Health economic studies
|
Health economic studies
|
Assessing cost-effectiveness of protease inhibitors versus pegIFN plus ribavirin, pegIFN, IFN or no treatment | Assessing pegIFN plus ribavirin versus pegIFN, IFN or no treatment |
Quality of life studies
|
Quality of life studies
|
Presentation of quantitative results using a validated quality of life instrument |
Results
Clinical benefits
Hepatocellular carcinoma
Study | Setting | Sample size | Mean follow up | Study details | Key findings |
---|---|---|---|---|---|
Coverdale et al. 2004 [47] | Australia | 455 | 9 yearsa | Retrospective cohort study including 384 treated with IFN alone, (n = 71 untreated) including patients with cirrhosis | Overall 9-year incidence of HCC was 10% for untreated, 11% for non-response and 2% for SVR |
Van der Meer et al. 2013 [20] | Europe and Canada | 248 | 8.3 yearsa | Cohort of consecutive genotype 1 patients with advanced fibrosis, 24% with SVR | HR (95% CI) for HCC for SVR versus non-SVR was 0.20 (0.06–0.69) (p = 0.011) |
Van der Meer et al. 2012 [38] | Europe and Canada | 530 | 8.4 yearsa | Retrospective cohort study in patients with advanced fibrosis/cirrhosis treated with IFN, IFN plus ribavirin or pegIFN plus ribavirin, median follow up 8.4 years, 68% genotype 1 | Rate (per 100 patient years) for HCC were 0.55 (0.14–0.96) for SVR vs. 2.63 (1.83–3.82) without SVR (p < 0.001) |
Braks et al. 2007 [43] | France | 113 | 8.2 (3.1) years | Retrospective cohort study in patients with compensated cirrhosis treated with IFN or pegIFN-based treatment | Proportion of patients with HCC was 2.7% for SVR versus 31.6% for non-SVR |
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 | Adjusted HR (95% CI) for non-SVR versus SVR was 3.06 (1.12–8.39) (p = 0.029) for HCC |
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 | Adjusted HR (95% CI) for non-SVR versus SVR was 2.59 (1.13–5.97) (p = 0.025) for HCC |
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 | HR (95% CI) for HCC for non SVR versus SVR = 4.44 (1.30–15.11) (p = 0.017) |
Pellicelli et al. 2013 [27] | Italy | 172 | 5 yearsa | Retrospective-prospective study in patients with HCV genotype 1 treated with pegIFN plus ribavirin, 34% with cirrhosis | Multivariate OR (95% CI) for development of HCC for no SVR versus SVR = 3.58 (0.9–14.3) (p = 0.06) |
Hara et al. 2014 [24] | Japan | 1,125 | Not stated | Retrospective cohort study in PR-treated (SVR and non SVR) and untreated patients | HR (95% CI) for HCC for SVR versus non-SVR and untreated = 0.12 (0.03–0.48) (p = 0.003) |
Ikeda et al. 2006 [35] | Japan | 2,166 | 15 years | Retrospective cohort study in patients with HCV patients (n = 512 untreated, n = 1,654 treated with IFN-based therapy) | Crude rate of HCC at 15 years was 13.9% for all treated patients, 23.9% for untreated and 7.5% for SVR |
Imai et al. 2010 [28] | Japan | 568 | 11 years | Retrospective cohort study in consecutive HCV patients treated with IFN monotherapy | HR (95% CI) for HCC for SVR versus non-treated patients was 0.20 (0.08–0.50) (p < 0.001) for patients <60 years and 0.23 (0.08–0.64) (p = 0.005) for patients >60 years |
Imazeki et al. 2005 [46] | Japan | 459 | 8.9 (3.2) years | Retrospective cohort study in patients, inc patients with cirrhosis, treated with IFN alone (n = 355) or untreated (n = 104), n = 116 patients achieved SVR | In the total population, annual incidence of HCC was 0.5% for SVR versus 2.6% for non-responders; corresponding figures for patients with cirrhosis were 9% and 34%, respectively |
Kobayashi et al. 2007 [29] | Japan | 1,124 | 66 monthsa (range 12–197 months) | Retrospective cohort study in HCV patients treated with IFN or IFN plus ribavirin (373 with SVR, 751 without SVR) | HCC developed in 3.5% SVR patients versus 8.1% non-SVR patients. SVR HCC patients had a significantly more advanced stage of fibrosis (p < 0.001) |
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 | Annual rate of HCC development was 2.71% for untreated patients, 2.31% for non-SVR and 0.24% for SVR (p < 0.0001) |
Moriyama et al. 2005 [31] | Japan | 269 | >6 years | Retrospective study in patients with cirrhosis treated with IFN-based treatment | Mean annual incidence of HCC was 0.78% for SVR versus 0.17% for non-responders with ALT <80 IU and 4.68% for ALT >80 IU |
Ogawa et al. 2013 [25] | Japan | 1,013 | 3.6 yearsa | Prospective multicenter study in patients treated with pegIFN plus ribavirin, 70.1% had HCV genotype 1 and 14.8% had cirrhosis at baseline | HR (95% CI) for HCC relative to SVR = 1.50 (0.65–3.44) (p = 0.34) for relapse and breakthrough and 3.72 (1.69–8.18) (p = 0.001) for non-response |
Ogawa et al. 2012 [37] | Japan | 1,015 | 3.8 years (2–6 years) | Prospective multicenter study in patients treated with pegIFN plus ribavirin (n = 712 genotype 1, n = 303 genotype 2) | 6-year cumulative incidence of HCC was 3.4% for SVR versus 21.2% for non-response group (p < 0.0001) and 6.4% for transient response (ns) |
Sasaki et al. 2014 [22] | Japan | 916 | Not stated | Retrospective study of IFN-treated patients | Incidence of HCC was 3.6% in patients who achieved SVR vs. 21.2% in non-SVR patients |
Sasaki et al. 2011 [34] | Japan | 236 | 50 monthsa | N = 236 patients with IFN-based treatment, median follow up 50 months | No significant difference in incidence of HCC for SVR versus non-SVR |
Watanabe et al. 2011 [32] | Japan | 1,865 | 4.25 yearsa | Retrospective cohort study in patients treated with pegIFN plus ribavirin, n = 999 (54%) with SVR | 5 year cumulative incidence of HCC was 1.1% in patients with SVR and 7.1% in non-SVR patients (p < 0.001) |
Yoshida et al. 2004 [36] | Japan | 2,787 | >6.5 yearsa | Retrospective database analysis in HCV patients (n = 395 untreated, n = 836 SVR, and n = 1,556 non-SVR) | HR (95% CI) for HCC for non-SVR versus no treatment was 0.835 (0.625–1.125) (p = ns). |
Annual incidence of HCC in SVR was 0.05–0.40% for F0–F1 and 0.15–3.20% for F4. For non-SVR annual incidence was 0.05–1.03% for F0–F1 and 0.29–12.5% for F4 (depending on age and gender) | |||||
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 | HR (95% CI) for HCC for SVR versus non-SVR was 0.09 (0.01–0.77) (p = 0.024) |
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 | HR (95% CI) for HCC for SVR versus non-SVR = 0.38 (0.14–0.88) (p = 0.04) |
Hung et al. 2006 [30] | Taiwan | 132 | 37 monthsa (12–63 months) | Retrospective cohort study in HCV patients with cirrhosis , inc. patients with HBV or HIV coinfection, 56% genotype 1b, treated with pegIFN plus ribavirin | 4 year cumulative incidence of HCC was 28% in non-SVR versus 8% in SVR group (p = 0.0178) |
Shih et al. 2012 [48] | Taiwan | 3,988 | 34.6 monthsa | Retrospective analysis of patients with HCV monoinfection, (n = 344 patients treated with IFN-based treatment, n = 216 with SVR) | Adjusted HR (95%CI) for SVR versus untreated was 0.23 (0.06–0.94) (p = 0.041) for HCC |
Wang et al. 2011 [33] | Taiwan | 164 | 8 years | Retrospective cohort study in patients treated with pegIFN plus ribavirin | Incidence of HCC was 8.8% for patients with an SVR versus 14.3% for untreated patients (p = 0.352) |
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) | RR (95% CI) for HCC versus untreated was 0.245 (0.13–0.46) (p < 0.0001) for SVR and 0.990 (0.635–1.541) (p = 0.963) for non-SVR |
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 | HR (95% CI) for SVR versus non response was 0.19 (0.04–0.80) for HCC |
Wang et al. 2013 [21] | Not stated | 138 | 8 years | Patients (mean age 56 years) treated with PR, 80% achieved SVR | 8-year incidence of HCC was 13.5% for SVR patients, 23.5% for relapsers and 20% for non-responders (p = 0.518) |
Liver-related mortality
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) |
Overall mortality
Other complications
Study | Setting | Sample size | Mean follow-up | Study details | Outcomes assessed | Key findings |
---|---|---|---|---|---|---|
Coverdale et al. 2004 [47] | Australia | 455 | 9 yearsa | Retrospective cohort study including 384 treated with IFN alone, (n = 71 untreated) including patients with cirrhosis | Liver-related complications | Overall 9-year incidence liver-related complication rate was 25% for untreated, 25% for non-response and 2% for SVR |
Abergel et al. 2004 [73] | France | 163 | Not stated | Retrospective cohort study in patients with severe fibrosis treated with IFN alone (n = 64) or IFN plus ribavirin (n = 99) | Progression of fibrosis | Fibrosis progression rate decreased in both responders and non-responders to treatment. 33% SVR regressed from cirrhosis to severe fibrosis; corresponding figure for non-responders was 9% (p = 0.058) |
Braks et al. 2007 [43] | France | 113 | 8.2 (3.1) years | Retrospective cohort study in patients with compensated cirrhosis treated with IFN, IFN plus ribavirin or pegIFN plus ribavirin | Liver-related complications | Proportion of patients with ascites was 5.4% for SVR vs. 10.5% for non-SVR, rates of digestive hemorrhage were 2.7% vs. 5.3%, respectively |
Poynard et al. 2013 [74] | France | 933 | 6.3 years | Prospective cohort study in HCV patients, 62% genotype 1 | Regression of fibrosis, progression to cirrhosis | HR (95% CI) for regression of fibrosis at 10 years for SVR versus non-response = 4.94 (2.59–9.44) (p < 0.001) |
HR (95% CI) for progression to cirrhosis = 0.185 (0.106–0.264) for SVR and 0.173 (0.123–0.224) | ||||||
Roche et al. 2008 [75] | France | 113 | 31.4 monthsa | Open label study in with liver transplant recipients treated with IFN plus ribavirin or pegIFN plus ribavirin, 75% genotype 1 | Fibrosis stage | For SVR mean (SD) necroinflammatory grade decreased from 1.9 (0.6) to 1.0 (0.6) post-therapy and improved in 71.5% and remained stable in 26% SVR patients; corresponding figures in non-SVR patients were 51.5% and 46%, respectively |
Wiese et al. 2014 [76] | Germany | 718 | 35 years | Prospective, community-based multicenter study in women with HCV genotype 1, SVR rate of 46% in treated patients | Cirrhosis | Incidence of cirrhosis at 35 years post-infection = 6.0% for SVR vs. 15.3% for non-SVR |
Annicchiarico et al. 2012 [77] | Italy | 135 | 44.4 monthsa | Prospective study in 135 HCV patients with cirrhosis | Portal hypertension | Development of portal hypertension was 10% for SVR versus 40% for non-SVR (p < 0.0005) progression of portal hypertension was 25% for SVR vs. 48% for non-SVR (p < 0.01) |
Bruno et al. 2010 [78] | Italy | 218 | 11.4 yearsa | Retrospective cohort study in patients with compensated cirrhosis (n = 149 patients treated with IFN or IFN plus ribavirin), but no esophageal varices | Esophageal varices | Esophageal varices developed in 32% untreated patients, 39% non-SVR patients and 0% SVR patients |
D’ambrosio et al. 2011 [79] | Italy | 127 | 77 months | Prospective cohort study in initially treatment-naïve patients with compensated cirrhosis, treated with IFN plus ribavirin | Esophageal varices (development of and or progression in size/severity) | Development/progression occurred in 5% SVR patients versus 15% non-SVR patients. 8-year cumulative probability of esophageal varices was 6% for SVR vs. 30% for non-SVR (p = 0.03) |
Arase et al. 2009 [69] | Japan | 2,842 | 6.4 yearsa | Retrospective cohort study in patients treated with IFN or pegIFN plus ribavirin, 6% patients had cirrhosis at baseline | Onset of type 2 diabetes | Adjusted HR (95% CI) for the development of diabetes for non-SVR vs. SVR was 2.73 (1.77–4.20) (p < 0.001) |
Imazeki et al. 2005 [46] | Japan | 459 | 8.9 (3.2) years | Retrospective cohort study in patients, inc patients with cirrhosis, treated with IFN alone (n = 355) or untreated (n = 104), n = 116 patients achieved SVR | Hepatic failure | In the total population, annual incidence of hepatic failure was 0% for SVR and 0.5% for non-responders; corresponding figures for patients with cirrhosis were 0% and 1.0%, respectively |
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 vs. 23% for non-SVR/untreated group (p < 0.001) |
Lee et al. 2013 [80] | South Korea | 315 | 45 monthsa | Retrospective chart review, 86% patients treated, 15% with cirrhosis at baseline, SVR rate of 75% | Cirrhosis | Cumulative 5 year rate of cirrhosis was 27.6% for patients without SVR vs. 0% for patients with SVR (p < 0.01) |
Canete et al. 2013 [81] | Spain | 105 | 9.3 years | Retrospective study of paired biopsy data in HCV patients with mild-moderate fibrosis treated with IFN plus ribavirin | Progression of fibrosis | Progression of fibrosis was reported in 5.3% patients with SVR and 50% patients with non-response (p < 0.0001). Fibrosis improved in 30.5% patients with SVR and 14.6% patients with non-response |
Simo et al. 2006 [70] | Spain | 234 | 5.7 years | Retrospective cohort study in patients with HCV (without severe fibrosis) treated with IFN or IFN plus ribavirin, 79% genotype 1 | Onset of type 2 diabetes | HR (95% CI) for onset of diabetes for SVR vs. non-SVR was 0.48 (0.24–0.98) (p = 0.04) |
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 | Decompensated cirrhosis (ascites, variceal bleeding, encephalopathy) | HR (95% CI) for hepatic decompensation for SVR vs. non SVR = 0.23 (0.08–0.53) (p = 0.002) |
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 inpatient hospital episodes | Adjusted HRs (95% CI) for SVR versus non-SVR were 0.22 (0.15–0.34) for liver-related hospital episode (p < 0.01) |
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 | Cirrhosis | HR (95% CI) for development of cirrhosis vs. never treated = 0.68 (0.26–1.80) for SVR and 2.35 (1.18–4.69) for non-responders |
Hyder et al. 2013 [72] | United States | 20,486 | 5 years | Retrospective database analysis of US veterans with no history of diabetes treated between 1998–2007 | Onset of type 2 diabetes | HR (95% CI) for onset of type 2 diabetes for SVR versus non-response was 0.76 (0.70–0.82) (p < 0.0001) |
Oni et al. 2011 [71] | United States | 8,687 | >6 years | Retrospective database analysis in patients treated with pegIFN-based treatment | Onset of type 2 diabetes | Rate of new onset of diabetes was 10.2% for SVR group vs. 15% for non-SVR group |
Economic implications
Study (setting) | Patients | Interventions | Key findings |
---|---|---|---|
Morais et al. 2013 (Brazil) [86] | Treatment-naïve patients with genotype 1 with F2 fibrosis in Brazil | Boceprevir plus PR and telaprevir plus PR | In the public health system cost per SVR was BRL 50,751 for telaprevir plus PR and BRL 63,481 for boceprevir plus PR. In the private health system cost per SVR was BRL 88,508 for telaprevir plus PR and BRL 82,518 for boceprevir plus PR |
Backx et al. 2014 (UK) [85] | Treated genotype 1 patients | Patients treated with PR for a minimum of 2 months | For non-cirrhotic patients 5-year post-treatment costs were 13-fold higher for non SVR patients vs. SVR (GBP 2,530 versus GBP 190), and 56-fold higher for non-SVR patients who were retreated (GBP 10,722) |
Camma et al. 2012 (Italy) [87] | Treatment-naïve HCV genotype 1, aged 50 years with F2 fibrosis | Boceprevir- or telaprevir based triple therapy (including RGT) versus pegIFN plus ribavirin alone, time horizon of 20 years | ICER per SVR versus pegIFN plus ribavirin was EUR 56,960–85,650 for boceprevir and EUR 74,600–118,000 for telaprevir |
Yfantopoulos et al. 2012 (Greece) [88] | Treatment-naïve and treatment-experienced HCV genotype 1 | Telaprevir-based triple therapy versus boceprevir-based triple therapy | In total population, mean cost per SVR was EUR 46,635 for telaprevir and EUR 56,146 for boceprevir. For treatment-naïve population cost per SVR was EUR 38,868 and EUR 42,983, respectively. For treatment-experienced patients cost per SVR was EUR 48,966 and EUR 59,902 respectively. Telaprevir was dominant to boceprevir |
Manos et al. 2013 (United States) [89] | Chronic HCV patients treated from 2002–2007, excluding pre- and post-liver transplant antiviral treatment | PegIFN plus ribavirin | In the 5 years following treatment mean yearly total (hospital and outpatient) costs in genotype 1 patients were USD 2,504 higher for non-responders than for patients with SVR (p = 0.042) |
Quality of life
Method | Study | Value | Difference | |
---|---|---|---|---|
SVR | Non-response/relapse | |||
EQ5D | Thein et al. 2005 [93] | 0.83 | ― | ― |
Chong et al. 2003 [95] | 0.83 | 0.76c | 0.07 | |
Van Rooijen et al. 2011 [99] | 0.84 | 0.70 | 0.14 | |
SF-36 | Thein et al. 2005 [93] | 0.74–0.90 | 0.70–0.86b | 0.04–0.05 |
SF-6D | Hsu et al. 2012 [103] | 0.71 | 0.66c | 0.05 |
John-Baptiste et al. 2009 [18] | 0.71 | 0.65 | 0.06 | |
HUI3 | Thein et al. 2005 [93] | 0.77 | ― | ― |
John-Baptiste et al. 2009 [18] | 0.70 | 0.58 | 0.12 | |
Hsu et al. 2012 [103] | 0.70 | 0.57c | 0.13 | |
HUI | Chong et al. 2003 [95] | 0.77 | 0.73c | 0.04 |
TTO | John-Baptiste et al. 2009 [18] | 0.89 | 0.84 | 0.05 |
Hsu et al. 2012 [103] | 0.88 | 0.80c | 0.08 | |
SG | Thein et al. 2005 [93] | 0.86 | ― | ― |
Chong et al. 2003 [95] | 0.86 | 0.79c | 0.08 | |
VAS | Thein et al. 2005 [93] | 0.74 | ― | ― |
Chong et al. 2003 [95] | 0.74 | 0.70c | 0.04 | |
Not stated | Liu et al. 2012 [104] | 0.933–1.00a | ― | ― |
Chhatwal et al. 2013 [105] | 1.00 | ― | ― |
Discussion
Study | Details | Outcomes assessed | Key findings |
---|---|---|---|
Almasio et al. 2003 [107] | Systematic review and pooled analysis (N = 1,031 patients for cirrhosis analysis, N = 3,914 patients for HCC analysis) | HCC, progression to cirrhosis | Risk reduction for progression to cirrhosis for SVR versus no SVR = −0.22 (−0.36 to −0.08). Risk reduction for HCC = −0.097 (−0.13 to −0.07) |
Kimer et al. 2012 [51] | Systematic review and meta-analysis of 8 RCTs and 5 prospective studies (N = 3,208 patients); random effects model used. Patients treated with IFN, pegIFN or PegIFN plus ribavirin | HCC | RR (95% for HCC for SVR versus no intervention = 0.15 (0.05–0.45) |
Morgan et al. 2013 [53] | Systematic review and meta-analysis of 30 studies (N = 31,528 patients) | HCC | For patients at all stages of disease HR (95% CI) for HCC for SVR versus non-response = 0.24 (0.18–0.31) (p < 0.001) |
(18 studies included in meta-analysis) investigating impact of treatment on risk for HCC | |||
For patients with advanced liver disease HR (95% CI) for HCC for SVR versus non-response = 0.23 (0.16–0.35) (p < 0.001) | |||
Singal et al. 2010 [49] | Systematic review and meta-analysis of 20 studies (N = 4,700 patients) in treatment-naïve patients treated with IFN or IFN plus ribavirin; random effects model used | HCC | RR (95% CI) for HCC for SVR versus non-responders = 0.35 (0.26–0.46) |
Singal et al. 2010 [50] | Systematic review and meta-analysis of 26 studies (N = 13,191 patients) | HCC, hepatic decompensation, liver-related mortality | RR (95% CI) for SVR versus treatment failure were: HCC 0.21 (0.16–0.27) (p = ns) for all patients and 0.27 (0.19–0.39) (p = ns) for patients with cirrhosis. |
Liver-related mortality was 0.23 (0.10–0.52) (p = ns) for all patients and 0.13 (0.06–0.29) (p = ns) for patients with cirrhosis. RR (95% CI) Hepatic decompensation 0.16 (0.04–0.59) (p = ns) for all patients and 0.08 (0.03–0.21) (p = 0.02) for patients with cirrhosis |