Table 2. Summary of antiviral treatments on the clinical outcomes and HCC incidence in patients with HCV infection.
| Trial name or First author | Antiviral regimens | Number of patients (Treat group vs. non-treat group) | Study population | Period of Follow-up | Biological response (BR), Treat group vs. non-treat group | Virological response (VR), Treat group vs. non-treat group | Incidence of HCC and liver cirrhosis complication | Endpoint | Conclusion | References (published year) |
|---|---|---|---|---|---|---|---|---|---|---|
| Bernardinello E, et al./TVVH Study Group. | beta-IFN 6 Million units(MU) tiw for 6 months followed by 3 MU tiw for 6 months | 61 (38 vs. 23) | CHC patients with cirrhosis | 5 years | Normalization of ALT: 5/38 (13%) vs. 2/23 (9%) | Negative of serum HCV-RNA 4/38 (11%) vs. 0/23 | The cumulative probability of liver decompensation at 60 months was 24% in treated and 35% in untreated cases.HCC developed in 2 treated and in 1 untreated patient.No significant reduction of cirrhosis related clinical events in treated patients. | Liver decompensation (variceal bleeding, ascites or hepatic encephalopathy), and HCC incidence | beta-IFN therapy does not improve either in BR or VR or reduction of cirrhosis related clinical events in CHC cirrhotic patients. | 16 (1999) |
| Valla DC, et al. | IFN-alpha 2b 3MU tiw for 48 weeks | 99 (47 vs. 52) | CHC patients with biopsy-prove compensated cirrhosis | 160+/− 57 weeks | End-of-treatment (EOT)-BR was not observed in any control but in 6/47 treated patients (P < 0.02); SBR in 2 treated patients. | SVR in 2 treated patients | HCC developed in 9 controls and 5 treated patients; decompensation of cirrhosis occurred in 5 controls and 7 treated patients. Seven controls and 10 treated patients died. | Decompensation of cirrhosis, death, and HCC incidence. | A 48-week course of IFN therapy can induce EOT-BR, but fail to achieve sustained response and improve the 3-year outcome in patients with compensated HCV-related cirrhosis. | 17 (1999) |
| Nishiguchi S, et al. | IFN-alpha 6 MU tiw for 12–24 weeks | 90 (45 vs. 45) | CHC with compensated cirrhosis | 2–7 years | ALT <80 IU/L: 19 vs. 9(P < 0.011). Mean ALT is comparable, but lower AFP, higher albumin, and improved histology in IFN group. | EOT-VR: 16 in IFN treated patients. HCV RNA disappeared: 7/45 (16%) vs. 0/45 (P = 0.018) | HCC was detected in 2 IFN-alpha patients and 17 controls. The risk ratio of IFN-alpha treatment versus symptomatic treatment was 0.067 (0.009–0.530; P = 0.010 Cox’s proportional hazards). | HCC incidence | IFN-alpha improved liver function and decreased incidence of HCC in CHC cirrhotic patients. | 18 (1995) |
| Di Bisceglie AM, et al./ HALT-C Trial Investigators | PEG-IFN alfa–2a 90 μg per week for 3.5 years. | 1050 (517 vs. 533); 622 with non-cirrhotic fibrosis and 428 with cirrhosis | CHC patients (Ishak fibrosis scores ≥3) who did not have a SVR to initial PEG-IFN and ribavirin | 3.5/ median 6.1(maximum, 8.7) yr | The level of serum aminotransferases, and histologic necroinflammatory scores all decreased significantly with treatment (P < 0.001). | The level of serum HCV RNA decreased significantly with treatment (P < 0.001) | After a 3.5 yr of follow-up, no significant difference between the groups in the rate of any primary outcome.After a 6.1 yr (median) of follow-up, HCC incidence: 37 of 515(7.2%) vs. 51/ 533 (9.6%; P = 0.24).After 7 years, the cumulative incidences of HCC in patients with cirrhosis: 7.8% vs. 24.2% (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.24–0.83). Treated patients with a ≥2-point decrease in the histologic activity index, based on a follow-up biopsy, had a lower incidence of HCC than those with unchanged or increased scores (2.9% vs. 9.4%; P = 0.03). | Death, HCC, hepatic decompensation, or an increase in the Ishak fibrosis score of 2 or more points. | Long-term therapy with PEG-IFN did not reduce disease progression rate in CHC patients with advanced fibrosis or cirrhosis, who failed to respond to initial treatment with PEG-IFN and ribavirin after a 3.5 yr of follow-up, but reduce the HCC risk in patients with cirrhosis who received PEG-IFN treatment after a 7 yr of follow-up. | 4 (2008) |
| Bruix J, et al./EPIC3 Study Group | PEG-IFN alfa−2b 0.5 μg/kg/week | 626(311 vs. 315) | CHC compensated cirrhosis without HCC and had failed to respond to IFN alfa plus ribavirin | 5 yr | Not available (NA) | NA | The time to disease progression was significantly longer for patients received PEG-IFN alfa-2b compared with controls (HR, 1.564; 95% CI: 1.130–2.166).Variceal bleeding was reported in 10 controls and 1 treated patient.No significant difference in time to first clinical event or decrease in the development of HCC with therapy. | Liver decompensation (variceal bleeding, Child-Pugh class C, ≧grade 2 hepatic encephalopathy, ascites requiring therapeutic paracentesis, and/or additional therapy), HCC, death, or liver transplantation | Maintenance therapy with PEG-IFN alfa-2b does not prevent HCC. There is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension. | 9 (2011) |
Five RCTs, including a total of 1,926 CHC patients with cirrhosis or advanced fibrosis, were identified to examine the impact of antiviral agents on patients with HCV infection. After a >2 years of follow-up, IFN-treated CHC patients had a better liver function tests, liver histology, and slower liver disease progression than non-IFN-treated controls. Moreover, IFN-treated CHC cirrhotic patients had a lower HCC incidence than non-IFN-treated controls after a >5-year of follow-up.