The aim of this study was to assess the rate of development of hepatocellular carcinoma (HCC) in patients who achieved sustained virologic response (SVR) by direct antiviral agents (DAA). We retrospectively evaluated patients who achieved SVR by oral DAA interferon-free regimens (n = 77) (daclatasvir/asunaprevir [n = 67], ombitasvir/paritaprevir/ritonavir [n = 9], and telaprevir [n = 1]) and by pegylated-interferon plus ribavirin (Peg-IFN/RBV, n = 528). In all patients, the background was chronic hepatitis or cirrhosis caused by HCV genotype 1b. During a median follow-up period of 4.0 years, two (2.6%) of DAA-treated patients developed HCC. The 3- and 5-year cumulative HCC development rates were 1.30% and 3.03%, respectively, in the DAA group, and 1.02% and 2.19 % in the Peg-IFN/RBV group (P not significant). In patients with Fib-4 score of >3.25, the 3-year HCC development rates were 4.35% and 3.95%, whereas those of the 5 year were 9.66% and 8.37%, in the DAA and Peg-IFN/RBV group, respectively. In patients with Fib-4 score of ≤3.25, none of the DAA group developed HCC, whereas 0.48% at 3-year and 1.05% at 5-year of patients of the Peg-IFN/RBV group did. Propensity score analysis using the inverse probability of treatment weights (IPTW) also showed no significant difference in HCC development rate between the two groups. Serum AFP gradually and similarly decreased after initiation of antiviral therapy in both groups. Our data indicate that the HCC risk rate after SVR is similar regardless of whether the latter was achieved by DAA or IFN-based regimens. J. Med. Virol. 89:476-483, 2017. © 2016 Wiley Periodicals, Inc.

A prospective study based on serial liver biopsies was performed to investigate the efficacy of sodium‐glucose cotransporter 2 inhibitor for nonalcoholic fatty liver disease complicated with type 2 diabetes mellitus. Conclusion: Treatment for 24 weeks resulted in improvement in histopathologic features in all 5 patients. (Hepatology Communications 2017;1:46–52)

DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy.

Aim The aim of this study was to investigate the therapeutic potential of sodium glucose cotransporter 2 inhibitor (SGLT2I) as an effective therapeutic option for non‐alcoholic fatty liver disease (NAFLD). Methods In this prospective study, nine patients with NAFLD complicated by type 2 diabetes mellitus (DM), were introduced to the regimen of canagliflozin 100 mg once daily for 24 weeks and were evaluated by liver histology at pretreatment and at 24 weeks after the start of treatment. The primary outcome was histological improvement, defined as a decrease in NAFLD activity score of one point or more without worsening in fibrosis stage. Glucose metabolism was evaluated based on the meal tolerance test. The usefulness of extracellular and exosome microRNA‐122 (miR‐122) as early predictors of histological improvement was investigated. Results All of the nine patients achieved histological improvement. Scores of steatosis, lobular inflammation, ballooning, and fibrosis stage decreased by 78%, 33%, 22%, and 33% at 24 weeks compared to the pretreatment, respectively. Six patients showed improvement in insulin resistance, and the other three patients showed partial improvement of insulin secretion function. Six patients, who showed a decrease in both extracellular and exosome miR‐122 ratios (the ratio of miR‐122 levels at 1 day after treatment to that at baseline), showed histological improvement. Furthermore, one patient, who showed a decrease in exosome miR‐122 ratios regardless of the increase in extracellular miR‐122 ratios, also showed decreases in NAFLD activity score and fibrosis stage. Conclusion A prospective study showed that SGLT2I for NAFLD complicated by DM improved histological features in connection with glucose metabolism. This trial was registered as clinical trial UMIN000018166.

Predictors of treatment efficacy with ledipasvir plus sofosbuvir as direct-acting antiviral (DAA) regimen for HCV infection are still unclear. Retreatment efficacy of ledipasvir plus sofosbuvir for failures to prior DAA regimens, including NS5A inhibitors, are also unknown because resistance-associated variants (RAVs) in NS5A have been shown to persist up to the long-term of post-treatment. One hundred seventy-five patients with chronic HCV genotype 1 infection, without decompensated liver cirrhosis and hepatocellular carcinoma, were evaluated SVR12 by ledipasvir 90 mg plus sofosbuvir 400 mg once-daily for 12 weeks. Overall, SVR12 were 92%, based on intention to treat analysis. In failures to daclatasvir plus asunaprevir, SVR12 were 71%. The study using ultra-deep sequencing showed that ledipasvir plus sofosbuvir was effective to one case of failures to daclatasvir plus asunaprevir with multidrug RAVs (triple mutation in NS3-D168/NS5A-L31/NS5A-Y93). Multivariate analysis identified FIB4 index (<3.25), IL28B rs8099917 (TT type), and NS5A-L31 (Wild type) as significant determinants of SVR12. SVR12 rates in patients with three factors of poor response (RAVs Positive, IL28B non-TT, and FIB4 index ≥3.25) simultaneously were significantly lower than those of the other patients. Prediction of response to therapy based on combination of three predictors had high sensitivity and positive predictive values. In conclusions, this study indicated the favorable efficacy of ledipasvir plus sofosbuvir for HCV genotype 1 infection, including multidrug RAVs in Japan. Treatment efficacy could be predicted by the combination of viral and host factors. J. Med. Virol. 89:284-290, 2017. © 2016 Wiley Periodicals, Inc.