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 | >6Â 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 <80Â IU and 4.68% for ALT >80Â 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) |