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Table 3. Molecular risk factors of carcinogenesis in patients treated with DAA
Molecular risk factors of carcinogenesis in patients treated with DAA
Cirrhosis
Reduced interferon production
Decreased micro-RNA-122 levels
T-cell dysfunction
Hyporesponsive NK cells
Rapid decrease of chronic inflammation
DAA: direct acting antiviral; NK: natural killer

In patients waiting for a liver transplant because due to HCV-associated cirrhosis and HCC, the moment of
DAA treatment commencement should be decided depending on the patient’s position on the list, expected
waiting time, and liver disease stage.

In patients with HCC treated with radical methods: transplantation, resection or embolization, treatment
with DAAs should be considered after they have remained clinically stable and relapse-free for 6 months.

Patients with cirrhosis and history of HCC, who completed treatment with DAA, regardless of their SVR
status, should be carefully monitored every 3-6 months, with an abdominal ultrasound and, in some cases,
[12]
also abdominal CT and MRI .

HCC RECURRENCE IN PATIENTS TREATED WITH DAA
Recurrence is seen in some patients treated for HCC subsequently treated effectively with DAA [Table 4].
At times, it may be aggressive and rapidly lead to death. In 2017 and 2018, a number of often contradictory
reports from different centres were published.

The main cause of recurrence is a simultaneous rapid clearance of HCV and liver tissue-resident memory
[13]
T-cells, which reduces local immunosuppression and promotes recurrent carcinogenesis . HCC recurrence
after effective treatment HCV proteins are known modulators of intracellular signalling pathways, which may
induce carcinogenesis in infected individuals. The expression of treatment-induced, mutated viral proteins
also plays a role in HCC recurrence. Despite viral clearance, the ongoing oncogenesis does not cease, and the
tumour develops further spreading to other sites as metastases.

HCC RECURRENCE IN PATIENTS TREATED WITH DAA - SIGNIFICANT PUBLICATIONS
[14]
In a retrospective study by Nagata et al. , patients with HCV and a history of HCC were treated either
with INF (n = 60) or with DAA (n = 83), with the mean follow up of 7.5 years. The recurrence rates were
comparable in patients treated with IFN and DAA (47% at 5 years post-SVR vs. 22.9% at 3 years post-SVR,
respectively).

[15]
In a prospective study in Italy, Cabibbo et al. studied patients with history of HCC treated with DAA,
demonstrating HCC recurrence in 20.38% of patients treated with DAA. Previous HCC recurrence prior to
treatment with DAA and tumour size above 2.5 cm at baseline were associated with higher risk of recurrence.

In 2018, Singal published a large meta-analysis of 793 patients who completed HCC treatment in the USA and
Canada and were treated for HCV with DAA (n = 304) or untreated (n = 489). There were 128 (42%) cases of
relapse in patients treated with DAA and 228 (58.9%) cases of relapse in those untreated for HCV infection,
which clearly indicates the beneficial role of DAAs in preventing HCC relapse in individuals with chronic
[16]
hepatitis C. The only factor significantly correlated with relapse was the baseline HCC stage (BCLC) .