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Table 2 Summary of clinical studies reporting the impact of SVR on HCC

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

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)

  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.