Copyright
©The Author(s) 2017.
World J Hepatol. Mar 8, 2017; 9(7): 352-367
Published online Mar 8, 2017. doi: 10.4254/wjh.v9.i7.352
Published online Mar 8, 2017. doi: 10.4254/wjh.v9.i7.352
Table 2 Main studies highlighting the effects of hepatitis C virus antiviral therapy on patients’ mortality, fibrosis regression and risk of hepatocellular carcinoma
| Ref. | HCV genotype | Fibrosis stage | Treatment | SVR rate | Mortality (n, pts) | Survival | Other outcomes |
| Veldt et al[47], 2007 | G1: 280/474 (59%) | Ishak score 4: 120 (25%) | Duration of treatment, 26 wk (21-48) | 142/280 (50.7%) | SVR: 2/280 (0.7%) | - | SVR associated with reduction in the hazard of events (adjusted HR = 0.21, 95%CI: 0.07-0.58; P < 0.003) |
| Ishak score 5: 94 (20%) | IFN: 131 (27%) | Non-SVR: 24/280 (8.6%) | |||||
| Ishak score 6: 265 (55%) | IFN + RBV: 130 (27%) | ||||||
| PEG-IFN: 10 (2.1%) | |||||||
| PEG-IFN + RBV: 208 (43%) | |||||||
| Yoshida et al[64], 1999 | G1: 1177/2400 (49%) | F0: 45 (1.9%) | IFN-α: 84% | 789/2400 (32.8%) | - | - | Risk of HCC for IFN therapy: Adjusted risk ratio = 0.516, 95%CI: 0.358-0.742 (P < 0.001); risk of HCC for SVR pts: risk ratio = 0.197, 95%CI: 0.099-0.392 (P < 0.002) |
| G2: 496/2400 (20.6%) | F1: 665 (27.7%) | IFN-β: 14% | |||||
| F2: 896 (37.7%) | Combination of IFN-α and IFN-β: 2% | ||||||
| F3: 564 (23.5%) | |||||||
| F4: 230 (9.6%) | |||||||
| Veldt et al[41], 2004 | SVR | SVR: | Recombinant IFN α2a, α2b, or natural IFN monotherapy for 39 wk | 286 | SVR | SVR group: Comparable with the general population | 29% regression and 5% progression of fibrosis in SVR group |
| G1: 112/286 (39.2%) | F4: 15 (5.2%) | 6/286 (2.1%) | |||||
| Not specified: 174/286 (60.8%) | Non-SVR: | 3/50 (6%) | |||||
| Non-SVR | F4: 11 (22%) | ||||||
| G1: 21/50 (42%) | |||||||
| Not specified: 29/50 (58%) | |||||||
| Maruoka et al[42], 2012 | Treated (577): | Treated: | IFN (not specified) | 221/577 (38.3%) | Untreated: 37/144 (25.7%) | - | Risk ratio of overall death and liver-related death reduced to 0.173 (95%CI: 0.075-0.402) |
| G1: 383/577 (66.2%) | F0: 15 (2.6%) | Non-SVR | |||||
| G2: 144/577 (24.8%) | F1: 290 (503%) | 74/356 (20.8%) | |||||
| Untreated (144) | F2: 132 (22.9%) | SVR 10/221 (4.5%) | |||||
| F3: 82 (12.2%) | |||||||
| F4: 58 (10.1%) | |||||||
| Untreated: | |||||||
| F0: 2 (1.4%) | |||||||
| F1: 64 (44.4%) | |||||||
| F2: 32 (22.2%) | |||||||
| F3: 18 (12.5%) | |||||||
| Bruno et al[49], 2016 | G1: 88/181 (48.6%) | F4: 100% | IFN mono-therapy or IFN (pegylated or not) + RBV | 181 | 18/181 (9.9%) | - | - |
| CPT A5: 154/181 (85.1%) | |||||||
| CPT A6: 27/181 (14.9%) | |||||||
| Cardoso et al[44], 2010 | G1: 60% | F4: 54% | PEG-IFN + RBV: 252 (82%), PEG-IFN: 22 (7%), IFN ± RBV: 33 (11%) | 103/307 (33.5%) | 21/307 (6.8%) | - | - |
| G2: 8% | |||||||
| G3: 16% | |||||||
| G4: 13% | |||||||
| Tada et al[46], 2016 | G1: 1476/2743 (53.8%) | - | IFN (not specified) | 587/2267 (25.9%) | 137/2267 (6%) | - | - |
| G2: 789/2743 (28.3%) | |||||||
| Unknown: 478/2743 (17.4%) | |||||||
| Van der Meer et al[48], 2012 | G1: 340/498 (68.3%) | Ishak 4: 143/498 (27%) | IFN: 175 (33%) | 192/498 (38.5%) | SVR: 13 | - | SVR reduced all-cause mortality (HR = 0.265, 95%CI: 0.14-0.49; P < 0.001) |
| G2: 48/498 (9.6%) | Ishak 5: 101/498 (19%) | IFN + RBV: 148 (28%) | Non-SVR: 100 | ||||
| G3: 88/498 (17.7%) | Ishak 6: 22/498 (4%) | PEG-INF: 176 (33%) | |||||
| G4: 22/498 (4.4%) | PEG-IFN + RBV: 176 (33%) | ||||||
| D’Ambrosio et al[52], 2012 | G1: 11/38 (28.9%) | Only cirrhotic patients | IFN + RBV: 10/38 (26.3%) | - | - | - | SVR reduced area of fibrosis by 2.3% (P < 0.0001), with a median individual decrease of 71.8% |
| G2: 24/38 (63.2%) | PEG-IFN + RBV: | ||||||
| G3: 3/38 (7.9%) | 28/38 (73.6%) | ||||||
| Duration of treatment 24 mo (24-48) | |||||||
| Mallet et al[53], 2008 | G1: 51/96 (53.1%) | F4: 100% | IFN or PEG-IFN, with or without RBV | 39/96 (40.6%) | SVR: 4 (10.2%) | - | Regression of fibrosis (according to METAVIR score): Stage 4: 69 (71.9%); stage 3: 9 (9.4%); stage 2: 10 (10.4%); stage 1: 7 (7.3%); stage 0: 1 (1%) |
| Non-SVR: 17 (29.8%) | |||||||
| Reichard et al[56], 1999 | G1: 41/100 (41%) | F0-3: 22 | IFN alpha2b: 73 | 27/100 (27%) | - | - | Reduction of portal inflammation (P < 0.0002), piecemeal necrosis (P < 0.0004), lobular necrosis (P < 0.0005), fibrosis (P < 0.0008) after SVR |
| G2: 27/100 (27%) | F4: 4 | Human leucocyte IFN alpha: 42 | |||||
| G3: 23/100 (23%) | |||||||
| Mixed: 9/100 (9%) | |||||||
| Arif et al[57], 2003 | Naive (52): | Naive | IFN alpha2b | Naive | - | - | Reduction in fibrosis score in both groups: responders = -0.91 (P = 0.038), non-responders = -0.48 (P = 0.021) |
| G1a: 64% | 21/52 (40.4%) | ||||||
| G1b: 19% | Fibrosis score: 2.91 ± 1.64 | Duration of treatment: | |||||
| G2: 6% | 12-24 wk: 10 | Experienced | |||||
| G3: 10% | 24 wk: 56 | 18/79 (22.8%) | |||||
| G4: 1% | 36 wk: 8 | ||||||
| 48 wk: 30 | |||||||
| Experienced (79): | |||||||
| G1a: 55% | |||||||
| G1b: 26% | |||||||
| G2: 7% | |||||||
| G3: 10% | |||||||
| G4: 2% | Fibrosis score: 2.83 ± 1.62 | ||||||
| George et al[58], 2009 | G1: 75/141 (53%) | Fibrosis stage ≥ 2: 116 | IFN alpha2b + RBV: 146 (97%) | 100% | - | 1 | 39/49 (79.6%) reduction in fibrosis stage (according to Ishak score) 16/49 (32.6%) pts had 2 point or greater decrease in stage |
| G2: 49/141 (35%) | Fibrosis stage = 4: 16 | PEG-IFN alpha2a + RBV: | |||||
| G3: 14/141 (10%) | 4 (3%) | ||||||
| G4: 3/141 (2%) | According to Scheuer | ||||||
| Poynard et al[59], 2002 | - | Standard: | Standard: | Standard: | - | - | Decrease in fibrosis index score in SVR group compared with non-responders: From 0.33 ± 0.06 at baseline to 0.18 ± 0.06 at 72 wk vs from 0.41 ± 0.03 at baseline to 0.44 ± 0.03 at 72 wk (P < 0.001) |
| F0: 12 (15%) | IFN alpha2a 3 MU | 3/78 (3.8%) | |||||
| F1: 42 (54%) | TIW for 24 wk | ||||||
| F3: 24 (31%) | Reinforced: IFN alpha2a 6 MU daily for 12 d followed by thrice weekly for 22 wk, then 3 MU thrice weekly for 24 wk | Reinforced: | |||||
| F4: 0 (0%) | 14/87 (16%) | ||||||
| Reinforced: | |||||||
| F0: 16 (18%) | |||||||
| F1: 41 (47%) | |||||||
| F3: 30 (35%) | |||||||
| F4: 0 | |||||||
| Shiratori et al[60], 2000 | - | SVR: | IFN alpha2a or | 183/487 (37.6%) | - | - | SVR group: Rate of fibrosis progression -0.28 ± 0.03 unit/year (regression) |
| F0: 3 (2%) | IFN alpha2b or | ||||||
| F1: 42 (23%) | Natural IFN alpha weekly for 3 to 6 mo | ||||||
| F2: 69 (37%) | Non-SVR group: Rate of fibrosis progression: 0.02 ± 0.02 unit/year | ||||||
| F3: 45 (25%) | IFN alpha 6-7 times per wk for 8 wk | ||||||
| F4: 24 (13%) | |||||||
| Non-SVR: | P < 0.001 | ||||||
| F0: 3 (1%) | |||||||
| F1: 95 (31%) | |||||||
| F2: 109 (36%) | |||||||
| F3: 67 (22%) | |||||||
| F4: 30 (10%) | |||||||
| Maylin et al[62], 2008 | G1: 21/210 (39%) | F0-1: 121 (38%) | IFN alpha: 3 (1%) | 100% | - | - | Fibrosis stage improved in 56%, stable in 32%, deteriorated in 12%; regression of cirrhosis observed in 9 of 14 (64%) |
| G2: 55/210 (18%) | F2: 111 (35%) | IFN-lymphoblastoid: 5 (1%) | |||||
| G3: 101/210 (32%) | F3: 56 (17%) | IFN-hybrid: 9 (3%) | |||||
| G4-5: 33/210 (11%) | F4: 31 (10%) | IFN alpha2a: 18 (5%) | |||||
| IFN alpha2a + RBV: 5 (2%) | |||||||
| PEG-IFN alpha2a + RBV: 27 (8%) | |||||||
| IFN alpha2b: 22 (6%) | |||||||
| IFN alpha2b + RBV: 41 (12%) | |||||||
| PEG-IFN alpha2b + RBV: 214 (62%) |
- Citation: Ponziani FR, Mangiola F, Binda C, Zocco MA, Siciliano M, Grieco A, Rapaccini GL, Pompili M, Gasbarrini A. Future of liver disease in the era of direct acting antivirals for the treatment of hepatitis C. World J Hepatol 2017; 9(7): 352-367
- URL: https://www.wjgnet.com/1948-5182/full/v9/i7/352.htm
- DOI: https://dx.doi.org/10.4254/wjh.v9.i7.352