Page 225 - Read Online

Douhara et al. DAA therapy for patients with CHC

(%) SVR 24 Table 4: HCC development after DAA therapy, n = 33
100
13/13 14/14 6/6 HCC development n (%)
HCC pre-treatment (+)
75 HCC occurrence (+) 1 (3.0)
HCC occurrence (-) 0
HCC history(-)
50 DCV + ASV
0
SOF + LDV HCC occurrence (+) 32 (97)
HCC occurrence (-)
SOF + RBV
25 Observed periods after DAA, month 10.4 ± 3.7
Patients without HCC history did not develop HCC in these
observed periods. One elderly patient (3.0%) had multiple HCC
0
DCV + ASV SOF + LDV SOF + RBV recurrence after SVR24. HCC: hepatocellular carcinoma; DAA:
direct-acting antiviral agents
GT 1 GT 2
Figure 2: SVR24 rate with GT1 or GT2. All patients achieved HCC recurrence after SVR24 [Figure 4]. Before the start
SVR24 regardless of GT1 or GT2. SVR: sustained virological of DAA treatment, transarterial chemoembolization
response; DCV: daclatasvir; ASV: asunaprevir; SOF: sofosbuvir;
LDV: ledipasvir; RBV: ribavirin (TACE) was performed twice. Then, DAA treatment
was initiated after a complete response was achieved.
CE-CT after 3 months from the end of DAA treatment
Table 2: Virological response before and 24 weeks following showed local and distant HCC recurrence. Common
therapy
hepatic artery angiography showed multiple HCC.
24 weeks Thus, a 3rd TACE was performed for HCC recurrence.
Characteristics Baseline P
off therapy
AST (IU/L) 43 ± 20 22 ± 5 0.000 DISCUSSION
ALT (IU/L) 46 ± 29 17 ± 5 0.000
T-bil (mg/dL) 0.8 ± 0.3 0.8 ± 0.3 0.094
Albumin (g/dL) 4.1 ± 0.3 4.3 ± 0.2 0.081 IFN-based therapy for CHC should not be used for
3
4
Platelet (10 x/mm ) 14.4 ± 4.5 15.1 ± 4.3 0.125 elderly patients and autoimmune diseases because of
AFP (ng/mL) 11.1 ± 19.0 6.0 ± 13.1 0.000 adverse effects and the mechanism of IFN. On the other
FIB4-index 3.6 ± 2.6 2.6 ± 1.3 0.000 hand, DAA therapy can be used for these patients with
AST, ALT, AFP and FIB4-index were significantly decreased. relative safety. However, as DAA therapy is relatively
However, T-bil, albumin and platelet count were not significantly new, it is unclear whether DAA therapy ameliorates
changed after SVR24. AST: aspartate aminotransferase; ALT: hepatic fibrosis and suppresses the development of
alanine aminotransferase; T-bil: total bilirubin; AFP: alpha-
fetoprotein HCC. Thus, the purpose of this retrospective cohort
study was to elucidate changes in liver function and
ledipasvir (LDV) developed sarcoidosis after SVR24 fibrotic markers before and after DAA therapy using
[Figure 3]; after the end of DAA treatment, renal SVR24, adverse events and HCC development.
dysfunction occurred. Renal biopsy revealed renal The effect for SVR24 was very high in this cohort study.
sarcoidosis. Moreover, chest X-P showed bilateral hilar The SVR rate of DCV + ASV is known to be slightly
lymphadenopathy while the ophthalmologic examination lower than SOF + LDV. We checked the resistance
showed iritis. Eradication of HCV or DAA treatment itself associated substitution (RAS) before DCV + ASV
might trigger the onset of sarcoidosis. administration. All DCV + ASV patients didn’t have
Y93 mutation, which was key mutation involving for
HCC development non-SVR. In our speculation, the reasons of the high
With regard to HCC development, patients without an SVR24 rate of DCV + ASV group may be wild type of
HCC history did not develop HCC in these observed RAS and the small number of patients (DCV + ASV,
periods [Table 4]. One elderly patient (3.0%) had multiple n = 13).

Table 3: Adverse events during and after DAA therapy
Adverse events DCV + ASV n = 13 SOF + LDV n = 14 SOF + RBV n = 6
Grade1, 2 (33.3%)
Anemia 0 0
Grade 2, 3 (50%)
Grade1, 1 (7.7%)
Liver function test disorder 0 0
Grade3, 1 (7.7%)
Pruritus 1 (7.7%) 0 0
Sarcoidosis 0 1 (7.1%) 0
Liver function disorder was found in only the DCV + ASV group. Anemia was found in only the SOF + RBV group. One patient treated with
SOF + LDV developed sarcoidosis after SVR24. DCV: daclatasvir; ASV: asunaprevir; SOF: sofosbuvir; RBV: ribavirin; LDV: ledipasvir;
SVR: sustained virological response
Hepatoma Research ¦ Volume 3 ¦ October 17, 2017 217