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Douhara et al. DAA therapy for patients with CHC

In the IFN era, liver fibrosis was improved after SVR With regard to the effect on HCC reoccurrence, the PEG-
in patients with CHC [4-6] . Shiratori et al. reported that IFN + RBV combination therapy reduced HCC occurrence
[3]
[15]
the resolution of hepatic fibrosis was achieved in 0.283 if SVR was achieved [12-14] . In Italy, Bruno et al. reported
stages per year. However, whether anti-fibrotic effects that the SVR to IFN-α was associated with improved
occurred with DAA therapy was unclear. In our study, outcomes in HCV-related cirrhosis. Moreover, IFN
platelet count, T-bil and albumin were unchanged, likely itself has an anti-tumor effect [16] , and low-dose and
because the observed period was only six month after long-term maintenance administration of PEG-IFNα-2α
the end of DAA treatment. However, AST and ALT, decreased the incidence of HCC in non-SVR patients [17] .
which showed that liver inflammation was significantly On the other hand, DAA has no direct anti-tumor effect,
decreased, as well as the FIB4-index, which is a and the suppressive effect of DAA on HCC occurrence
. In a
remains controversial in western countries
[18-21]
calculated hepatic fibrosis marker, were significantly Japanese retrospective cohort study, the HCC risk
decreased after SVR24.
rate after SVR was similar regardless of whether it was
achieved by DAA or IFN-based regimens [22] . In our
IFN-based treatment for CHC has multiple adverse study, during a median follow-up period of 10.4 ± 3.7
events, such as influenza like syndrome, interstitial months, one elderly patient (3.0%) with an HCC history
pneumonia, cytopenia, depression, etc. Conversely, developed multiple HCC recurrence after SVR24.
DAA therapy rarely has adverse events compared to Patients without HCC history did not develop HCC in
IFN-based treatment. ASV, an NS3/4 protease inhibitor, this observed period.
is more likely to result in liver function test disorder .
[7]
In our study, 2 patients in the DCV + ASV group (n = This study has several limitations. First, this was a
13) had liver function disorder [Grade 1, n = 1 (7.7%); single-center study with a limited number of patients.
Grade 3, n = 1 (7.7%)]. One patient withdrew from DAA Therefore, the statistical power was low. Second, all
therapy. Another patient decreased their dosage of patients in this study were Japanese. Thus, applying
ASV. Fortunately, these two patients achieved SVR24. these results to other ethnic groups is difficult. Third,
the criteria of liver function for DAA therapy in Japan
RBV + PEG-IFN therapy was used for patients with CHC. are only CPS grade A. Therefore, the efficacy and
It is known that ribavirin triggers hemolytic anemia . In safety of DAA therapy in patients with CPS grades from
[8]
our study, the SOF + RBV group (n = 6) had anemia B to C are unknown.
in 5 patients [Grade 1, n = 2 (33.3%); Grade 2, n = 3
(50%)]. If anemia developed, we decreased the dosage In conclusion, DAA therapy achieved a high SVR rate
of RBV. After the end of DAA treatment, anemia was and a good serological response. However, one patient
naturally improved without blood transfusion or iron pill had multiple HCC recurrence in our small cohort study.
These findings indicate that careful follow-up may be
administration.
essential after DAA therapy.
IFN is one of the cytokines in response to several DECLARATIONS
pathogens, such as virus, bacteria, parasite and tumor.
So, IFN therapy activated immune systems that help to Authors’ contributions
eradicate HCV. The previous report indicated that IFN
therapy for CHC triggered sarcoidosis via activating Designed the report: A. Douhara
immune system [9-11] . Sarcoidosis is a granulomatous Attending doctors for patients: A. Douhara, H. Ogawa,
autoimmune disease of unknown etiology that may E. Shioyama, M. Yoshikawa, S. Ueda
affect many organs. Until now, IFN was thought to be Discussed the pathogenesis: A. Douhara, H. Ogawa,
S. Nakatani, T. Ozutsumi, E. Shioyama, M. Yoshikawa,
involved in the onset of sarcoidosis. In the other hands, S. Ueda
DAA itself don’t influence immune system. Moreover, Organized the report: S. Ueda
HCV is known to have several systemic autoimmune Wrote the paper: A. Douhara
disorder, such as cryoglobulinemia, Sjögren’s syndrome,
diabetes mellitus, thyroiditis, membranoproliferative Financial support and sponsorship
glomerulonephritis, etc. Interestingly, in our study, the
SOF + LDV group (n = 14) had a patient with lung and None.
renal sarcoidosis that was induced after DAA therapy. Conflicts of interest
Our case indicated that the eradication of HCV itself
might have induced sarcoidosis via an acute change in There are no conflicts of interest.
immune status. In speculation, HCV decrease with the
very short periods may trigger acute change in immune Patient consent
status. In our institution, we obtained informed consent from
Hepatoma Research ¦ Volume 3 ¦ October 17, 2017 219