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

In a retrospective study 1,170 patients with HCV were treated with DAAs for 12-24 weeks. The patients were
followed up for 1.3 years. Twenty-two patients had HCC during the follow-up. Cumulative incidences of
HCC were 1.8% and 2.3% at 1 year and two years respectively. However, SVR was associated with reduced
risk of HCC occurrence in 1.4% and 1.8% at 1 year and two years respectively. Non-SVR, hypoalbuminemia,
[27]
thrombocytopenia, high AFP levels are risk factors for the development of HCC .

The occurrence and recurrence rate of HCC is lower among patients who receive DAAs treatment compared
to those who are not treated. HCV infection should be treated as early as possible in order to reduce the
progression of parenchymal damage. Occurrence of SVR after treatment with both DAAs and Interferon
is strongly associated with reduced developing or recurrence of HCC in patients with all fibrotic stages and
advanced liver diseases compared to those patients who had no SVR. Occurrence of SVR does not exclude
the development of HCC. However, reduced recurrence (0.4%-2%) of HCC may take a longer time than the
patients who had active HCV infection. The patients who had SVR should be followed up periodically in
every 3 or 6 months. Presence of active HCC reduces of SVR with the treatment of DAAs. The patients with
HCV infection and active stage of HCC should be treated for HCV infection after curative treatment of HCC
and/or after liver transplantation.

In our recently published multi-centric study, 200 patients with chronic hepatitis C were treated with the fixed
dose combination of Sofosbuvir and Ledipasvir for 12 weeks. Thirty-five out of 200 patients had a history of
HCC. Nineteen of those 35 patients had curative treatment at the beginning of anti-viral therapy. Median
follow-up time was 22.1 months (15.7-30.3 months). Overall HCC occurrence was detected in 18 (9.0%) out of
200 patients. Recurrence of HCC was detected in 12 out of 16 (75%) patients who had non-curative treatments,
while it was detected in 5 out of 19 (26.3%) patients who had curative treatments. This study also has several
limitations. There is no control group, treatment modalities are different, time period between the beginning
[28]
of anti-viral therapy and the time for recurrence of HCC varies between 3-14 months .
Seventy-one million people are still infected with HCV infection in the world. DAAs are very effective with
more than 95% of SVR rates. World Health Organization and some countries like Japan, Egypt, Mongolia,
and Turkey have an elimination program for HCV infection. It may be an important problem to have a
claim without evidence that DAAs treatment for HCV infection is associated with the occurrence and
recurrence of HCC.

In conclusion, unexpected results concerning high occurrence and recurrence rates of HCC after the
treatment of HCV infection with DAAs and complete curative treatment are heterogenic and incompatible
in retrospective studies due to clinic, biologic, epidemiologic differences and methodological biases. In
most of the studies which are HCV-related, occurrence and recurrence of HCC are retrospective and small
case groups. Confounding factors such as age, sex, fibrotic stages, genotypes, Plt, AFP, serum albumine and
bilirubine levels, number of liver cirrhosis are different between comparative groups. Curative treatment
modalities such as radical surgery and Radio Frequency Ablation, TACE, Trans Arterial Radio Embolization
of HCC are different. Prognosis of these modalities are different. Most of the articles did not describe
pathological examinations, lymphatic and vascular infiltration of the tumor. Follow-up times are also
different in similar studies. In order to make more precise decisions for occurrence or recurrence of HCC
after DAAs treatment, we need to do large prospective randomized studies.

DECLARATIONS
Authors’ contributions
Prof. Necati Örmeci contributed solely to the article.

Availability of data and materials
Not applicable.