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Örmeci. Hepatoma Res 2019;5:11 I http://dx.doi.org/10.20517/2394-5079.2019.14 Page 3 of 7

[13]
of the upper normal limits for aspartate aminotransferase (AST) levels . In another retrospective study,
463 patients with HCV cirrhosis were treated with the combination of PEG interferon and Ribavirin. Three
hundred of 463 patients had SVR (64.8%). Development of HCC was seen in 3 and 9 patients with SVR and
non-SVR, respectively. It was found that SVR group had less HCC (1%) compared to non-SVR group (5.5%)
[14]
(P = 0.005) after 36.1 months follow-up .

[15]
Innes et al. reported that 857 patients with HCV infection were treated with IFN-based or IFN free
regimens to compare the occurrence of HCC in both groups. Patients were followed up for 2.4 years,
and 46 patients out of 857 had HCC. Incidence of HCC occurrence was two-fold high [(2.53 vs. 1.26 per
100 person years) P = 0.21] in patients who took IFN free regimen. However, those patients were more
thrombocytopenic, were at the higher Child Pugh stages, had more treatment experiences and were older
than the patients who took IFN-based regimens. When confounding factors were corrected, there was no
difference between two treatment regimens in terms of HCC occurrence. Adjusted (HR: 1.15, 95%CI: 0.49-
2.71; P= 0.744).

[16]
Similarly, Telep et al. presented US administrative claims data which contained 4,887 patients who were
curatively treated for HCC and HCV infection. Those patients were treated with IFN-based or IFN free
treatment regimens. The latter patients were followed up for 182 days while the former were followed up 349
days. The patients in the IFN free treatment regimen had cirrhosis more frequently (95.7% vs. 88.2%), more
liver necrosis (34.8% vs. 9.8%), more portal hypertension (58% vs. 35.3%) and were older than the patients who
took IFN-based treatment regimen. Statistical difference could not be shown after adjusting the confounding
factors (HR: 0.97; 95%CI: 0.49-1.92) between two treatment regimen groups in terms of HCC occurrence
after following three, six and twelve months periods.

In a large retrospective cohort study, Group A (n = 3534, PEG IFN treated group) and Group B (n = 834,
Sofosbuvir and Simeprevir or Sofosbuvir and Ledipasvir treatment group), Group C (n = 8468) untreated
group were compared for occurrence of HCC in patients with liver cirrhosis. There were not statistical
differences for basic characteristics among the groups. Mean follow-up time was 2,719.2 days for IFN-treated
persons and 396.4 days for DAAs-treated persons. It was found that there was no association between HCC
[17]
occurrence rates and DAAs treatment compared to IFN treatment .

In an Italian multi-centric study, 328 patients with HCV related early HCC followed up for the recurrence
of HCC. Median time for the recurrence of HCC was 31 months (26-38) in the group of active hepatitis,
72 months in the group of SVR by Interferon free therapies, 82.3 months in group of SVR by Interferon
based therapies. There were statistical differences between active hepatitis and entire SVR groups. However
there was not a difference between Interferon free or Interferon based treatment groups. In the multivariate
analysis, serum bilirubin, creatinine and alpha-feto protein (AFP) levels were found to be an independent
[18]
predictor for recurrence of HCC .
In a well-designed prospective large cohort study, 143 consecutive HCV infected patients who had complete
response after curative treatment of HCC with stage Barcelona Clinic Liver Cancer (BCLC) 0/A were treated
with DAAs. Those patients were followed up for a mean of 9.1 (3-19) months. SVR rate was 96%. The 6-,
12- and 18-month HCC recurrence rates in the whole cohort were 12%, 26.6% and 29.1%, respectively. The
6-, 12- and 18-month HCC recurrence rates in patients without prior history of HCC recurrences and in
those with prior history of HCC recurrences were 9.2%, 20.9%, 24.2% and 18.5%, 39.7%, 39.7% respectively.
Predictive factors for the recurrence of HCC were prior history of HCC and tumor size bigger than 2.5 cm in
[19]
diameter .

Sixty-eight consecutive cirrhotic patients with HCV and HCC under remission were treated with DAAS (n
= 23) or not treated (n = 45). SVR rate reached 96%. Median time between HCC remission and initiation of