Background and Aim: Tenofovir alafenamide (TAF) is a new prodrug of tenofovir, enabling treatment of patients with hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF), via more efficient delivery of tenofovir to the hepatocytes. We compared the efficacy and safety of TDF and TAF and investigated switching from TDF to TAF therapy. Methods: Consent for TDF and TAF therapy was obtained from 117 and 67 patients from August 2014 to January 2018. In total, 45 and 14 patients were administered with TDF and TAF, respectively, as naïve therapy, and 36 patients were switched from TDF to TAF. The antiviral effects and renal function safety were assessed. Results: At week 48, the antiviral effects on patients receiving TDF and TAF as naïve therapy were similar in terms of reduction of HBV DNA (À5.6 ± 1.8 logIU/ml vs À5.0 ± 1.7 log IU/ml; P = 0.34) and hepatitis B surface antigen (À0.29 ± 0.64 logIU/ml vs À0.15 ± 0.42 logIU/ml; P = 0.71) levels. A significant decrease in the estimated glomerular filtration rate (eGFR) was seen at 48-week TDF treatment (À5.34 ± 7.69 ml/min/ 1.73 m 2 ; P < 0.001). Switching from TDF to TAF did not increase the HBV DNA or hepatitis B surface antigen at 24 weeks. Although the eGFR worsened during TDF therapy (À7.32 ± 4.87 ml/min/1.73 m 2 ), it improved significantly at week 4 (+3.93 ± 6.18 ml/ min/1.73 m 2 ; P = 0.008) and week 24 (+2.89 ± 4.26 ml/min/1.73 m 2 ; P = 0.020) after switching from TDF to TAF. Conclusion: Tenofovir disoproxil fumarate and TAF showed adequate antiviral effects as naïve therapies. Furthermore, switching from TDF to TAF therapy contributed to the maintenance of the antiviral effect and recovery of renal dysfunction.

Insulin resistance in association with compensatory hyperinsulinemia and dyslipidemia may be an important pathogenetic factor underlying the development of atherothrombotic infarction.

Post-SVR WFA -M2BP is a predictive factor for the development of HCC in patients with no previous HCC history and treated with DAAs. Post-SVR AFP was predictive for HCC recurrence after DAA therapy.

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Prediction of hepatocellular carcinoma (HCC) development after sustained virological response (SVR) is clinically important, and the usefulness of noninvasive markers for prediction HCC have been reported. The aim of this study was to compare the prediction accuracy for HCC development by noninvasive markers. A total of 346 patients with chronic hepatitis C without history of HCC who achieved SVR through direct‐acting antivirals were included. Magnetic resonance elastography (MRE) and serum fibrosis markers were measured 12 weeks after the end of treatment, and the subsequent HCC development was examined. The mean observation period was 26.4 ± 7.9 months, and 24 patients developed HCC. Area under the receiver operating characteristic curve of liver stiffness by MRE, Wisteria floribunda agglutinin‐positive mac‐2 binding protein and FIB‐4 for predicting HCC within 3 years was 0.743, 0.697 and 0.647, respectively. The 1/2/3‐year rates of HCC development in patients with liver stiffness ≥3.75 KPa were 6.6%, 11.9% and 14.5%, whereas they were 1.4%, 2.5% and 2.5% in patients with liver stiffness <3.75 KPa (P < 0.001). Multivariate analysis revealed that liver stiffness ≥3.75 was an independent predictive factor for HCC development (hazard ratio, 3.51; 95% confidence interval, 1.24‐9.99). In subgroup analysis, there were 132 patients who were <73 years old and had liver stiffness <3.75 KPa, and no HCC development was observed in these patients. Diagnostic accuracy for predicting HCC development was higher in MRE than serum fibrosis markers and measurement of liver stiffness by MRE could identify patients with high and low risk of HCC development after SVR.

The assessment of liver fibrosis is essential because it correlates with mortality risk in nonalcoholic fatty liver disease (NAFLD). This study aims to examine whether serum fibrosis markers could identify candidate patients likely to have advanced fibrosis. We enrolled 352 patients with NAFLD and performed liver biopsies in 97 patients. The area under the receiver operating characteristic curve (AUROC) of liver stiffness by magnetic resonance elastography for histological advanced fibrosis was 0.910, and the optimal cutoff value was 4.07 kPa. To predict severe liver stiffness (≥4.07 kPa), the AUROC for Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA + -M2BP) and FIB-4 were 0.897 (cutoff value, 1.08) and 0.880 (cutoff value, 2.53), respectively. After stratification of patients into four age groups as quartile, the optimal cutoff values of WFA + -M2BP for predicting severe liver stiffness were similar in each group (1.09, 1.08, 1.10, and 1.12). On the other hand, those of FIB-4 increased in parallel with age (1.47, 2.19, 2.99, and 3.88). In conclusion, WFA + -M2BP was precise for estimating severe liver stiffness in NAFLD with single cutoff value independent of age. Hence, identifying high-risk cases using WFA + -M2BP from a large number of NAFLD patients is clinically significant.

Lenvatinib (LEN) is a newly approved, multikinase inhibitor for treating unresectable hepatocellular carcinoma. In the present study, we investigated the impact of three different criteria for evaluating radiological objective response (OR) on overall survival in real-world data.Methods: Consent for LEN therapy was obtained from 51 patients from April 2018 to March 2019. A total of 40 patients who received a minimal cumulative duration of 4 weeks of LEN were included in the analysis. Enhanced computed tomography scan was performed at baseline and every 4-8 weeks after LEN administration. Overall survival and OR were assessed with three different evaluations, as follows: Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria. Results:The average observation period for all participants after LEN introduction was 209.4 ± 77.5 days. The Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria identified 10 of 40 (25.0%), 15 of 40 (37.5%), and 18of 40 (45.0%) patients with OR, respectively. The median overall survival in progressive disease evaluated by each criterion was 227 days. This result was significantly shorter than OR. Furthermore, the cumulative duration of LEN administration (>150 days) represented a significant prognostic factor (HR 0.160. 95% CI 0.039-0.646, P = 0.001). Conclusion:The Response Evaluation Criteria in Solid Tumors 1.1, modified Response Evaluation Criteria in Solid Tumors, and Choi criteria were useful therapeutic evaluation methods in LEN therapy for unresectable hepatocellular carcinoma. LEN's appropriate effect evaluation and management might lead to a better prognosis.

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