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Page 2 of 7 Örmeci. Hepatoma Res 2019;5:11 I http://dx.doi.org/10.20517/2394-5079.2019.14

decompensation and occurrence or recurrence rates after radical treatment of HCC are not fully understood.

Recently several studies reported unexpectedly high occurrence or recurrence rates of HCC after DAAs
treatment for HCV and curative treatment for HCC [1,7,8] .

In a retrospective study, 344 patients with liver cirrhosis were treated with DAAs. 285 of those patients did
not have a history of HCC, but 59 patients did. SVR rate was 91%. Six months after follow-up, 26 patients
were shown to have HCC (7.6%). HCC occurred in 9 out of 285 (3.2%) patients without a history of HCC,
while recurrence of HCC developed in 17 (28.8%) patients with a previous history of HCC. Besides, disease
free survival was short as a median of 376 days in this group. They postulated that SVR after the treatment
with DAAs was not associated with the reduced risk of HCC occurrence. However this study had several
gaps such as historical control was used instead of normal control group, absence of information in detail
about surgical resection of HCC for 59 patients with a history of HCC preceding the treatment of DAAs, and
radiological control was performed in 6 months rather than 3 months. There were different HCC treatment
modalities such as ablation, resection, and percutaneous ethanol injection. In addition, there were differences
in terms of confounding factors between the treatment groups, and DAAs were started as a median of 376 days after
the curative treatment of HCC. Normally HCC recurrence occurs at a rate of 20% after curative treatment of
HCC. Unexpected increased rate of HCC recurrence (28.8%) may be a missed diagnosis of remnant HCC in
[1]
several cases .
In another similar study, 58 patients with HCV-related early HCC who achieved complete response after
curative HCC treatment [resection n: 20; ablation n: 32; Trans Arterial Chemo Embolization (TACE) n: 6]
were treated with DAAs after 11.2 months. SVR rate was 97.5%. Median follow-up time was 5.7 (0.4-14.6)
months. Sixteen patients (27.6%) had unexpected recurrence of HCC in a median of 3.5 (1.1-8) months. It
is difficult to definitely estimate early recurrence of HCC due to small sample size of study, high clinical,
[7]
biological, and epidemiological heterogeneity of early HCC .
In a meta-analysis which included 30 observational studies, 31,538 patients were treated for IFN-based
regimen. SVR occurred in 10,853 patients (34.4%). Overall HCC occurrence was 5.5%. A hundred forty-five
out of 9,185 patients (1.5%) with SVR developed HCC while 990 out of 16,312 patients (6.2%) had HCC. No
matter if the patient had varying degrees of fibrosis or advanced liver disease, SVR was associated with 54%
reduction in all causes of mortality, histologic improvement, risk for progression of liver disease, liver related
[8]
mortality, and HCC .

[9]
Ravi et al. reported 6 out of 66 HCV patients with HCC (9.1%) after the treatment of DAAs during 6 months
[10]
follow-up. Cardoso et al. reported that HCC occurrence rate was 7.4% in 54 patients with cirrhotic HCV
[11]
treated with DAAs after 12 months of follow-up. Yang et al. compared the 81 patients who had liver
transplantation in terms of HCC occurrence. The patients receiving DAAs in pre-liver transplantation
showed 27.8% of HCC while those who did not take DAAs demonstrated 9.5% (6/63) of HCC. Among
17,487 patients who were treated with DAAs, 624 of them had HCC. 142 patients with HCC received liver
transplantation. 482 patients still had HCC. Overall SVR was found 91% in non-HCC, 74% in HCC, 94% in
transplanted due to HCC. It was concluded that the patients who had transplantation due to HCV and HCC
[12]
can successfully be treated with DAAs with high SVR rates .

In a large retrospective cohort study comparing 2,400 chronic hepatitis C patients treated with IFN and 490
untreated patients, all patients had a liver biopsy, and they were followed up for a mean of 4.3 years. HCC
occurred in 89 treated and 59 untreated patients. It was found that both F2 and F3 patients had less HCC in
treated group compared to untreated group (P = 0.0128 for F2; P = 0.0011 for F3 patients). Predictive factors
for less HCC occurrence were SVR, normal Alanine Aminotransferase (ALT) levels, and less than two times