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Iliescu et al. Hepatoma Res 2018;4:3 I http://dx.doi.org/10.20517/2394-5079.2017.48 Page 3 of 10

of the 278 patients underwent a Fibromax evaluation, resulting in 173 patients with F4 degree of fibrosis
(cirrhotic patients) and 105 patients with F3 degree of fibrosis. None of the patients underwent liver biopsy
for liver evaluation, due to its invasive character and susceptibility of associated complications.

The follow-up time was 14 months (since January 2016 until March 2017). Screening for liver cancer in the
subjects included in the study was periodically performed by assessment of alpha-fetoprotein (AFP) levels
and abdominal ultrasonography; both parameters were determined before starting the IFN-free therapy,
monthly (during therapy), and also every three months afterwards.

According to the protocol of evaluation, the liver assessment was started by performing an AFP determination
as well as an abdominal ultrasonography at the beginning of the therapy. If AFP levels were found high
(twice the normal value) or ultrasonography abnormalities were spotted, a computed tomography (CT) scan
or contrast-enhanced ultrasonography (CEUS) would be performed, in order to obtain more information.
CT was not routinely performed as a first-hand screening method for HCC on all patients, at the beginning
of the study, due to the potential risk related to ionizing radiation exposure and contrast-induced injury,
and also because the use of CT-scan in all the patients was not considered to be cost-effective. Moreover,
the AASLD and EASL-EORTC surveillance and diagnostic algorithms in HCC state that only cirrhotic
patients are considered candidates for surveillance, and surveillance should be performed with ultrasound
every 6 months. It is also worth mentioning that ultrasound examination of all the individuals included
in the study was done by highly experienced personnel, with extensive experience in the field of hepatic
imaging. Patients with HCC diagnosed in this stage were not included in the study and did not receive any
form of IFN-free treatment, as the presence of HCC represents a contraindication for the therapy. AFP
and liver enzymes were also determined at week 4 and week 8 of therapy. At the end of treatment (EOT)
(week 12), the evaluation protocol included AFP and abdominal ultrasonography. Any abnormality in these
parameters would impose a CT scan for further investigation, as well as a magnetic resonance imaging
(MRI) (if the CT scan turned out to be inconclusive).

RESULTS
We prospectively collected and analyzed data from 278 patients infected with HCV genotype 1b, 37.76% of
which (105 individuals) had F3 degree of fibrosis, while 173 of the subjects (meaning approximately 62.24%)
were already in the F4 cirrhosis stage. They were all treated with DAAs (paritaprevir/ombitasvir/ritonavir
and dasabuvir, with or without ribavirin) for 12 weeks. Most of the participants (53.24%) were females; the
percent of liver cirrhosis among women was 60.8%. The male population included 46.76% of the subjects,
with a similar percent of 63.8% cirrhotic participants among the male population. The numeric distribution
of patients by gender and degree of fibrosis are shown in Figure 1.

The mean age was 60.29 ± 11.9 years. The follow up time was 14 months (from January 2016 to March
2017). Before starting the therapy, 69.3% of the cirrhotic patients and 26.7% of the patients with F3 degree
of liver fibrosis presented higher than normal levels of AFP, with blood values up to 70 ng/mL. The mean
AFP level, at the initiation of therapy, was 13.39 ± 11.18 ng/mL. Contrast-enhanced ultrasonography was
performed for 79% of patients. Neither CEUS nor the CT scan revealed any HCC nodules at the beginning
of therapy. The distribution of patients with high AFP levels, according to gender, fibrosis and means of
further evaluation are shown in Figure 2.

During the 4th week of treatment, 5 participants presented elevated levels of AFP. All of them had previously
been classified as cirrhotic (F4 on Fibromax evaluation). Abdominal CT scan was therefore performed on
all 5 patients, showing single HCC nodules in 2 subjects and multiple HCC nodules in the other three.
Furthermore, the CT scan identified signs of portal vein thrombosis (PVT) in 2 of the 5 patients (1 patient