Table 1.
Characteristics of studies included in the present systematic review on response to antiviral therapy for chronic hepatitis C and hepatocellular carcinoma occurrence.
| Article | Study design | Study population | Cases | Relative risk | ||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Author, year/ref | Study design | Study period | Follow-up duration (years) | N | Age (years) | Men (%) | Advanced fibrosisa (%) | HCV GT1 (%) | IFN | SVR rate (%) | No of SVR | No of non-SVR | No of non-IFN | SVR | Non-SVR | Non-IFN | Diagnosis method for HCC | Adjusted HR (95%CI) | Covariates | |
| Umehara Y 2017 46 | Retrospective hospital-based single | 2004–2014 | N/R | 415 | 58 | 46.0 | 25.2 | 67.5 | N/R | N/R | N/R | N/R | N/A | N/R | N/R | N/A | US/CT/MRI | Non-SVR | Ref | Age, fibrosis stage, Plt, Alb, ALT, AFP |
| SVR | 0.38 (0.15–0.99) | |||||||||||||||||||
| Tada T 2016 47 | Retrospective hospital-based single | 1994–2014 | 11.8 | 2743 | 60 | 52.6 | APRI 0.69 | 53.8 | N/R | 55.3 | 587 | 475 | 1681 | 31 | 131 | 412 | US/CT/MRI | Non-IFN | Ref | Age, sex, AST, ALT, |
| SVR | 0.28 (0.16–0.45) | Alb, T-bil, PT, Plt, | ||||||||||||||||||
| Takeuchi Y 2015 48 | Retrospective hospital-based multi | 2005–2011 | 5.4 | 1255 | 59 | 54.0 | N/R | 67.4 | Peg | 53.0 | 665 | 590 | N/A | 20 | 69 | N/A | US/CT/MRI/Angiography/Biopsy | N/R | N/R | AFP, HCV GT |
| Honda T 2015 49 | Retrospective hospital-based multi | 2004–2010 | 3.92 | 1280 | 54.2 | 52.2 | 13.9 | 67.7 | Peg | 54.8 | 701 | 579 | N/A | 9 | 41 | N/A | US/CT/MRI/Angiography/Biopsy | SVR | Ref | Age, sex, advanced fibrosis |
| Non-SVR | 4.69 (2.21–9.94) | |||||||||||||||||||
| Oze T 2014 50 | Prospective hospital-based multi | 2002–2008 | 3.08 | 2600 | 56.4 | 47.9 | 15.8 | 77.1 | Peg | 54.8 | 1425 | 1175 | N/A | 23 | 81 | N/A | US/CT/MRI/Angiography/Biopsy | Non-SVR | Ref | Age, sex, fibrosis score, Plt, T-bil, Alb, ALT, AFP |
| SVR | 0.37 (0.18–0.74) | |||||||||||||||||||
| Ogawa E 2013 51 | Prospective hospital-based multi | 2004–2009 | 3.6 | 1013 | 58 | 49.2 | 14.8 | 70.1 | Peg | 55.0 | 557 | 456 | N/A | 13 | 34 | N/A | US/CT/Biopsy | SVR | Ref | Age, sex, Plt, AFP, fibrosis |
| TVR 13 | TVR | 1.50 (0.65–3.44) | ||||||||||||||||||
| NVR 21 | NVR | 3.72 (1.69–8.18) | ||||||||||||||||||
| Arase Y 2013 44 | Retrospective hospital-based single | 1990–2009 | 8.1 | 4302 | 52 | 58.8 | 10.1 | 63.2 | N/R | 44.2 | 1900 | 2402 | N/A | 44 | 349 | N/A | US/CT/MRI/Biopsy | SVR | Ref | Age, sex, DM, alcohol intake, hepatic fibrosis |
| Non-SVR | 4.93 (3.53–6.89) | |||||||||||||||||||
| Osaki Y 2012 52 | Retrospective hospital-based single | 2002–2010 | 4.1 | 382 | 59 | 50.3 | N/R | 59.9 | Peg/others | 48.4 | 185 | 197 | N/A | 1 | 22 | N/A | US/CT/MRI | SVR | Ref | Age, ALT, AFP, Plt |
| Non-SVR | 8.41 (1.07–66.30) | |||||||||||||||||||
| Watanabe S 2011 53 | Retrospective hospital-based multi | 2004–2007 | 4.25 | 1865 | 55.6 | 56.5 | 21.7 | 79 | Peg | 53.6 | 999 | 866 | N/A | 10 | 49 | N/A | US/CT/Angiography/Biopsy | SVR | Ref | Age, sex, ALT, Plt, Alb |
| TVR | 2.06 (0.71–5.96) | |||||||||||||||||||
| NVR | 2.99 (1.04–8.60) | |||||||||||||||||||
| Takahashi H 2011 54 | Retrospective hospital-based single | 2002–2007 | 4.33 | 203 | 55.4 | 53.2 | 23.2 | 74.9 | Peg/others | 43.8 | 89 | 114 | N/A | 1 | 12 | N/A | US/CT | SVR | Ref | Age, sex, alcohol intake fibrosis, AFP, steatosis, OGTT |
| Non-SVR | 20.4 (2.1–200.9) | |||||||||||||||||||
| Asahina Y 2010 55 | Retrospective hospital-based multi | 1992–2008 | 7.5 | 2166 | 55.4 | 49.9 | 25.2 | 65.6 | Peg/others | 33.6 | 686 | 1356 | N/A | 22 | 149 | N/A | US/CT/MRI/Biopsy | SVR | Ref | Age, sex, fibrosis, steatosis, Tcho, FBS, AFP etc |
| Non-SVR | 2.6 (1.2–5.5) | |||||||||||||||||||
| Kurokawa M 2009 56 | Retrospective blood donation/ hospital-based | 2002–2005 | 3.04 | 403 | 55.8 | 63.8 | 31.3 | 64.8 | Others | 34.5 | 139 | 264 | N/A | 4 | 21 | N/A | US/CT/Angiography/Biopsy | SVR | Ref | Age, sex, fibrosis |
| Non-SVR | 3.57 (1.04–12.36) | |||||||||||||||||||
| Ikeda K 2007 57 | Prospective hospital-based multi | 1995 | 9.5 | 576 | 59.6 | 57.3 | Hepatitis | N/R | Others | 23.7 | 53 | 171 | 352 | 1 | 34 | 59 | US/CT | Non-IFN | Ref | Age, sex, alcohol intake, smoking status. HBcAb |
| SVR | 0.15 (0.02–1.09) | |||||||||||||||||||
| No response | 1.84 (1.14–2.99) | |||||||||||||||||||
| Relapse | 0.50 (0.16–1.62) | |||||||||||||||||||
| Kobayashi S 2007 58 | Retrospective hospital-based multi | 1992–2003 | 5.5 | 1124 | 52 | 60.9 | N/R | N/R | Others | 33.2 | 373 | 751 | N/A | 13 | 61 | N/A | US/CT/MRI/Angiography/Biopsy | N/R | N/R | N/A |
| Soga K 2005 59 | Retrospective hospital-based single | 1992–1996 | 7.8 | 133 | 52.5 | 47.4 | 18.4 | 52.6 | Others | 32.0 | 33 | 70 | 30 | 0 | 5 | 7 | US/CT/Angiography/Biopsy | N/R | N/R | N/A |
| Kim KI 2005 60 | Retrospective hospital-based single | N/R | SVR 2.68 | 118 | N/R | N/R | 14.4 | N/R | N/R | 26.3 | 31 | 87 | N/A | 1 | 8 | N/A | US/CT/Biopsy | N/R | N/R | N/A |
| PR 2.39 | ||||||||||||||||||||
| NR 2.45 | ||||||||||||||||||||
| Moriyama M 2003 61 | Retrospective hospital-based single | 1987–1998 | 6.46 | 654 | 48.9 | 59.5 | N/R | 53.2 | Others | 34.9 | 208 | 388 | 58 | 4 | 23 | 19 | US/CT/Angiography/Biopsy | N/R | N/R | N/A |
| Ohata K 2003 62 | Retrospective hospital-based single | 1980–1999 | 6.4 | 161 | 53 | 65.8 | 54.7 | 65.8 | N/R | 28.2 | 20 | 51 | 90 | 0 | 8 | N/R | US/CT/Angiography | N/R | N/R | N/A |
| Tazawa J 2002 63 | Retrospective hospital-based single | 1987–1995 | 5.49 | 279 | 49.4 | 68.1 | 23.7 | 48.7 | Others | 29.7 | 55 | 130 | 94 | 0 | 8 | 5 | US/CT/Angiography/Biopsy | N/R | N/R | N/A |
| Yoneyama K 2002 45 | Retrospective hospital-based single | 1984–1999 | 4.39 | 121 | 49.3 | 67.8 | N/R | 47.1 | Others | 43.8 | 53 | 68 | N/A | 1 | 9 | N/A | US/CT/MRI/Biopsy | N/R | N/R | N/A |
| Hirashima N 2002 64 | Retrospective hospital-based single | 1992–1994 | 4.9 | 153 | 51.7 | 68.6 | 30.7 | 74.5 | Others | 32.7 | 50 | 103 | N/A | 5 | 12 | N/A | US/CT/Angiography/Biopsy | N/R | N/R | Age, sex, HCV GT, RNA, ALT, stage, grade |
| Effect of IFN therapy | ||||||||||||||||||||
| 3.89 (0.53–3.34) | ||||||||||||||||||||
| Yoshida H 1999 65 | Retrospective hospital-based multi | 1986–1998 | 4.3 | 2890 | 50.2 | 62.3 | 33.2 | 44.1 | Others | 33.5 | 789 | 1568 | 490 | 10 | 79 | 59 | US/CT/MRI/Angiography/Biopsy | Non-IFN | Ref | Age, sex, fibrosis |
| SVR | 0.20 (0.10–0.39) | |||||||||||||||||||
| Non-SVR | 0.61 (0.43–0.92) | |||||||||||||||||||
| Horiike N 1998 66 | Retrospective hospital-based single | N/R | 7.6 | 149 | 47.4 | 69.8 | 22.1 | 53 | Others | 37.5 | 33 | 55 | 61 | 0 | 1 | 9 | N/R | N/R | N/R | N/A |
| Miyajima I 1998 67 | Retrospective hospital-based single | 1991–1996 | SVR2.3 | 213 | 47.2 | 63.8 | 28.6 | 66.2 | Others | 29.6 | 63 | 150 | N/A | 0 | 12 | N/A | US/CT/Angiography/Biopsy | N/R | N/R | N/A |
| Non-SVR2.5 | ||||||||||||||||||||
| Onodera H 1997 68 | Retrospective hospital-based single | 1992–1996 | SVR 129.5py | 313 | 51.6 | 51.6 | N/R | N/R | Others | 34.1 | 59 | 114 | 140 | 0 | 4 | 3 | US/CT/MRI/Angiography/Biopsy | N/R | N/R | N/A |
| Non-SVR 246.25py | ||||||||||||||||||||
| Non-IFN 333.3py | ||||||||||||||||||||
| Kuwana K 1997 69 | Retrospective hospital-based single | 1988–1994 | 4.67 | 240 | 56.2 | N/R | Excluding liver cirrhosis | N/R | Others | 19.6 | 18 | 74 | 148 | 0 | 5 | 69 | US/CT/MRI/angiography/biopsy | N/R | N/R | N/A |
AFP alpha fetoprotein, Alb albumin, ALT alanine aminotransferase, AST aspartate aminotransferase, CI confidence interval, CT computed tomography, DM diabetes mellitus, FBS fasting blood sugar, GT genotype, HCV hepatitis C virus, HR hazard ratio, IFN interferon, MRI magnetic resonance imaging, N or No number, N/R not recorded, N/A not appreciable, NVR non-viral response, OGTT oral glucose tolerance test, Peg pegylated, Plt platelet, PR partial response, PT prothrombin time, py person-years, Ref reference, RNA ribonucleic acid, SVR sustained virologic response, T-bil total bilirubin, TCho total cholesterol, US ultrasound.
aStage 3 or 4 liver fibrosis was determined by liver biopsy.