Clinical Effect of Lenvatinib Re-Administration after Transcatheter Arterial Chemoembolization in Patients with Intermediate Stage Hepatocellular Carcinoma

The present study clarified the prognosis of intermediate-stage hepatocellular carcinoma (HCC) patients who received lenvatinib (LEN) followed by transcatheter arterial chemoembolization (TACE) on demand. We retrospectively evaluated 88 intermediate-stage HCC patients who received LEN. The median age was 74 (range: 47–92) years old, 67 patients were male, and 82 were classified as Child-Pugh A. LEN was administered until disease progression or discontinuation due to adverse events (AEs). The mean duration of LEN treatment was 7.0 months. The response and disease control rates were 51.1% and 89.8%, respectively. The median progression-free survival and overall survival (OS) after the initiation of LEN were 6.8 months and 29.9 months, respectively. The OS in patients for whom LEN was re-administered after TACE (TACE-LEN) was better than that in patients who received other therapies (e.g., only TACE, TACE-other therapy, or only other therapy) even with propensity score matching (p = 0.008). A Cox proportional hazard analysis showed that TACE-LEN was most strongly associated with the OS (hazard ratio: 0.083, 95% confidence interval: 0.019–0.362, p = 0.001). LEN was administered for approximately 11.1 months after TACE. In intermediate-stage HCC patients who can tolerate LEN without discontinuation due to AEs, TACE-LEN may prolong the prognosis

The co-existence of NS5A and NS5B resistance-associated substitutions is associated with virologic failure in Hepatitis C Virus genotype 1 patients treated with sofosbuvir and ledipasvir

<div><p>Objective</p><p>The present study aimed to reveal the factors associated with virologic failure in sofosbuvir and ledipasvir (SOF/LDV)-treated patients, and identify baseline NS5A or NS5B resistance-associated substitutions (RASs).</p><p>Methods</p><p>Four hundred ninety-three patients with Hepatitis C Virus (HCV) genotype 1b infection were treated with SOF/LDV; 31 had a history of interferon (IFN)-free treatment with daclatasvir and asunaprevir. The effect of baseline RASs on the response to SOF/LDV therapy was analyzed.</p><p>Results</p><p>Overall, a sustained virologic response at 12 weeks (SVR12) was achieved in 476 patients (96.6%). The SVR12 rates in the patients with IFN-free treatment-naïve and retreatment were 97.6% and 80.6%, respectively. HCV elimination was not achieved in 17 patients, 11 (including 5 with IFN-free retreatment) of whom had virologic failure. Eight patients had coexisting NS5A RASs of Q24, L28 and/or R30, L31, or Y93 and one patient had coexisting NS5A RASs of P32L and A92K. Interestingly, 10 and 8 patients had NS5B A218S and C316N RAS respectively. According to a multivariate analysis, coexisting NS5A RASs, NS5A P32 RAS, NS5B A218 and/or C316 RASs, and γ-glutamyltranspeptidase were associated with virologic failure. In the naïve patients, all patients without NS5B A218 and/or C316 RAS achieved an SVR12. Notably, the SVR12 rates of patients with coexisting NS5A and NS5B RASs were significantly lower (83.3%).</p><p>Conclusions</p><p>Although SOF/LDV therapy resulted in a high SVR12 rate, coexisting NS5A and NS5B RASs were associated with virologic failure. These results might indicate that the coexisting baseline RASs influence the therapeutic effects of SOF/LDV.</p></div

The sustained virologic response (SVR) 12 rate in the patients with co-existing NS5A and NS5B RASs.

<p>The interferon (IFN) free-naïve patients with coexisting resistance-associated substitutions (RASs) of Q24, L28, and/or R30, L31, or Y93 and NS5B A218 and/or C316 had a significantly lower sustained virologic response (SVR) 12 rate in comparison to the patients without these RASs.</p

The reasons for the discontinuation of sofosbuvir/lediprevir.

<p>The reasons for the discontinuation of sofosbuvir/lediprevir.</p

The virologic response rates (intention-to-treat analysis).

<p>The sustained virologic response (SVR) 12 rates of the IFN-free treatment-naïve patients and IFN-free retreatment patients were 97.6% and 80.6% respectively.</p

The baseline resistance-associated substitutions (RASs) and virologic failure in patients treated with sofosbuvir and ledipasvir.

<p>The baseline resistance-associated substitutions (RASs) and virologic failure in patients treated with sofosbuvir and ledipasvir.</p

The multivariate logistic regression analysis of factors associated with virologic failure in patients treated with sofosbuvir and ledipasvir.

<p>The multivariate logistic regression analysis of factors associated with virologic failure in patients treated with sofosbuvir and ledipasvir.</p