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Page 4 of 7 Örmeci. Hepatoma Res 2019;5:11 I http://dx.doi.org/10.20517/2394-5079.2019.14

DAAs was 7.2 months, while between the time of starting of DAAs and HCC recurrence was 13.0 months.
Recurrence rate was 1.7/100 person-months among treated patients vs. 4.2/100 person-months in not treated
patients. HCC recurrence rate was significantly lower in patients who were treated with DAAs compared to
[20]
untreated group .
[21]
Mettke et al. compared DAAs treated (n = 158), and untreated control patients (n = 184) in terms of HCC
occurrence. Treated and untreated control patients were followed up for a mean of 440 (91-408) days and a
mean of 592 (90-1000) days, respectively. HCC occurred in treated and untreated patients at rates of 2.9% (n
= 6) and 4.48% (n = 14). They concluded that DAAs therapies do not change the short time occurrence of de
novo HCC; however, it reduces HCC developing risk after 1.5 years.

[22]
In a prospective study of Calvaruso et al. , in 2,249 patients with HCV related cirrhosis (Child Pugh A
90.5%, Child Pugh B 9.5%) were treated with DAAs. SVR occurred in 95.2% (2140/2249; Child Pugh A 95.9%,
Child Pugh B 88.3%; P < 0.001). Patients were followed-up for a median of 14 (6-24) months. In Child Pugh A
patients who maintained SVR, HCC developed in 2.1% of the cases while HCC was seen in 6.6% of those cases
without SVR. Accordingly, in Child Pugh B patients who maintained SVR, HCC developed in 7.8% of the cases
while HCC was observed in 12.4% of those cases without SVR (P < 0.001). The predictive factors for occurrence
of HCC were the absence of SVR, serum albumin levels less than 3.5 g/dL, platelet level < 120 × 10 /L.
9

Patients with 218 Stage-1 and 226 Stage-2 were treated with PEG-IFN and ribavirin. Patients with SVR had
less esophageal varices compared to non-SVR patients (HR 0.23; 95%CI: 0.11-0.48; P < 0.001). However, there
was no difference in terms of the progression of esophageal varices between the groups (HR 458; 95%CI:
[23]
0.33-1.03; P= 0.7). SVR was found to be associated with reduced risk of HCC .
In a multicenter retrospective study, 22,500 patients (39% cirrhotic) were treated with DAAs based regimens.
The patients were followed up for 20 months; 19,500 of them had SVR (group A) and 2,982 did not have SVR.
A hundred eighty-three patients (0.9%) with HCC were detected in Group A, while HCC occurred in 88
patients (3.4%) in Group B. (HR 0.28; 95%CI: 0.22-0.36; P < 0.0001). Even if SVR occurred, the patients over
65 years of age and patients with advanced fibrosis or cirrhosis were associated to increased rates of HCC
development. In this study, there were several comorbid conditions like alcohol use (61.4%), drug addiction
(54.2%), and diabetes mellitus (43.6%) which all may facilitate HCC development. SVR was associated with
[24]
76% reduced risk of HCC occurrence .
In a prospective study, 3,917 patients who included stage F3 fibrosis and CP-A cirrhosis were treated with
DAAs based regimen. They were followed up with a mean of 536.2 ± 197.6 days after the start of DAAs.
Overall incidence of HCC was found to be 0.97% patients/year, 95%CI: 0.73-1.26. HCC incidence of cirrhotic
patients was found to be 1.18% patients/year. When patients were stratified according to the stage of liver
disease at baseline, HCC incidence rates during the first year of follow-up were 0.46x100 patients/year
(95%CI: 0.12-1.17) in patients with fibrosis F3, 1.49´100 patients/year (95%CI: 1.03-2.08) in CTP-A cirrhosis
and 3.61 100 patients/year (95%CI: 1.86-6.31) in CTP-B cirrhosis. HCC incidence rates in the second year
of follow-up declined to 0% in F3, to 0.20´100 patients/year (95%CI: 0.05-0.51) in CTP-A cirrhosis and to
0.69´100 patients/year (95%CI: 0.08-2.49) in CTP-B cirrhosis and these differences were statistically significant
[25]
(Mantel-Cox test, P = 0.00008) .

In a retrospective study 421 patients who had HCV infection with or without cirrhosis were treated with
DAAs therapy. Thirty-three per cent of patients had active or a history of HCC. Twenty-nine out of 421
patients resulted in failed SVR. Twenty-one per cent of patients who had HCC did not have SVR while, SVR
failed in 12% of patients without HCC. Twenty-seven out of 29 patients who failed SVR resulted in active
period of HCC. If DAAs treatments were given in an inactive period of HCC or after transplantation, SVR
[26]
was excellent similar to those without HCC (P < 0.0001) .