Page 293 - Read Online

Harrod et al. Hepatoma Res 2019;5:28 I http://dx.doi.org/10.20517/2394-5079.2019.15 Page 5 of 13

SVR may significantly improve a given patient´s clinical liver function, making them eligible for a
therapeutic procedure. A recent multicentre study showed that 24% of the 122 patients with decompensated
[52]
cirrhosis could be delisted due to improvement after HCV eradication . Three patients with HCC that
were originally listed for liver transplantation improved such that they were able to undergo resection or
SIRT after achieving SVR.

Secondly, with some studies showing decreased SVR rates in the presence of active HCC, consideration
should be given to treating the HCC with LRTs prior to DAA initiation. One retrospective study
demonstrated that failure to achieve SVR rates was higher in patients with active HCC when
[37]
compared to patients with inactive or resected HCCs or in patients with no HCC . Similarly, a large
prospective national multicentre study showed that successfully treated HCCs (resection, ablation, or
chemoembolization) do not influence subsequent SVR rates with DAA therapy. DAA therapy was given at
[53]
least 6 months after successful treatment (i.e., complete response) of the HCC . As radiological response
following LRT does not always accurately predict pathologic necrosis - and in some cases this may be
overestimated - this underscores the importance of this time window before pursuing HCV treatment.
Conversely, preliminary data from the HCV-TARGET study comparing SVR rates of cirrhotic patients with
HCC with those of patients without HCC, again showed significantly inferior SVR rates in the former, but
also showed no difference in SVR rates between those patients with active HCC versus those with complete
[38]
response to LRTs . In another study of 62 patients, who were started on DAAs just after radiological
documentation of complete response to treatment (mainly radiofrequency ablation, TACE, microwave
[54]
ablation, and percutaneous ethanol injection), the SVR rate was only 64.5% . Importantly, 42% had HCC
recurrence, and in most cases within the following 6 months after initiation of DAAs, suggesting the
presence of residual HCC despite documentation of radiological response. Hence, in this case the presence
of viable HCC could have contributed to the low SVRs.

Finally, in cases where LRTs fail to achieve complete necrosis of the tumour, DAA metabolite distribution
to viable HCC areas may be compromised through multiple mechanisms. Impaired blood supply will
impair penetration into the HCV-infected tumour tissue, particularly with procedures that include
vascular embolization such as TACE. Altered tissue architecture may also have an impact on tissue
penetration, as LRTs induce fibrosis, which seems to be particularly accentuated with SIRT [37,55] . There may,
therefore, be a role for re-treatment of HCCs in an attempt to achieve a complete response before initiating
DAAs. In reality, however, many physicians commence HCV treatment prior to HCC treatment, with an
unmet need in research into this area.

In summary, the evidence is variable and further trials in this area may help to confirm the best approach
where an HCC in chronic HCV cases is amenable to LRT. Until more evidence is available, it may be
prudent to treat an active HCC with LRTs and achieve a complete and sustained response before initiating
DAAs, in order to improve SVR rate. Where a patient is anatomically a candidate for LRT but is not
suitable due to poor liver function, one might consider treating the HCV in order to improve the patient´s
clinical condition.

DAAs and liver transplantation
There is also much speculation regarding timing of HCV treatment in patients with HCC, particularly
[35]
in those for which liver transplantation is being considered [Table 1]. Where no guidelines exist that
prevent the transplantation of HCV-viraemic organs into HCV-negative recipients, limited data is available
into this practice and so it is not generally accepted. In liver transplantation specifically, outcomes of HCV-
viraemic organs into HCV-positive recipients do not appear to negatively impact patient or graft survival,
[35]
therefore many centres have adopted this practice . Treatment of HCV prior to transplantation may