Background: We aimed to explore the relative dose intensity (RDI) and post-regorafenib treatments in regorafenib therapy. Methods: The medical records of 38 patients treated with regorafenib between July 2017 and June 2019 at our institution were collected. The RDI of regorafenib for the first month (1M-RDI) was calculated. Results: The overall survival (OS) and progression-free survival (PFS) were 12.4 and 3.7 months. The objective response rate and disease control rate were 13.2% and 71.1%. The median total dose of regorafenib in the first month was 2080 mg (240–3360 mg), and the median 1M-RDI was 61.9% (7.1–100%). Patients with 1M-RDI ≥ 50% showed significantly longer OS and PFS than patients with 1M-RDI < 50% (HR 0.19, 95% CI 0.08–0.48, p = 0.0004 and HR 0.2, 95% CI 0.08–0.52, p = 0.0008). A 1M-RDI ≥ 50% (HR 0.18, 95% CI 0.06–0.55, p = 0.002) and hand–foot skin reaction (HR 0.03, 95% CI 0.008–0.16, p < 0.0001) were independently associated with OS. Post-regorafenib therapies were performed in 19 (86.4%) of 22 patients who had stopped regorafenib due to disease progression. Conclusion: A 1M-RDI ≥ 50% is clinically significant. Post-regorafenib therapies are commonly performed in real-world practice.

Background: Recent advances in the development of tyrosine kinase inhibitors (TKIs) have enabled patients with unresectable hepatocellular carcinoma (HCC) to receive multiple TKIs in sequence. The aim of this study was to identify predictors of good candidates for second-line treatment after disease progression during sorafenib treatment. Methods: This is a retrospective cohort study of 190 consecutive HCC patients who were treated with sorafenib in our hospital. Three criteria of good candidates for second-line TKI at the time of disease progression during sorafenib treatment were defined as follows: criterion 1 was the same as the inclusion criteria of the regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE) study, criterion 2 was the inclusion criteria of the RESORCE study plus Child–Pugh score 5, and criterion 3 was the inclusion criteria of the RESORCE study plus albumin–bilirubin (ALBI) grade 1. Factors at baseline and at week 4 during sorafenib treatment were used to predict patients fulfilling each of these three criteria. Results: The distribution of patients was 29%, 13%, and 6% in criteria 1, 2, and 3, respectively. Significant factors for meeting criterion 1 was the combination of baseline albumin >3.7 g/dL (odds ratio (OR) 2.7) plus degree of decrease in albumin (Δalbumin) at week 4 <0.2 g/dL (OR 2.6), or the combination of baseline ALBI score <−2.33 (OR 2.5) and ΔALBI at week 4 <0.255 (OR 4.9). For criterion 2, the value of baseline albumin and ALBI score was identical to criterion 1; however, Δalbumin (<0.1 g/dL) and ΔALBI score (3.8 g/dL) and ALBI (<−2.55) became stricter, as did Δalbumin (<0.1 g/dL) and ΔALBI (11) was selected as an additional predictor (OR 5.4). Conclusion: Predictors to satisfy the RESORCE study inclusion criteria were as follows: preserved liver function at baseline, as reflected by albumin or ALBI score, and small deterioration of liver function early during sorafenib therapy, as reflected by Δalbumin or ΔALBI at week 4. Liver function at baseline and degree of change in liver function during sorafenib treatment need to be stricter for better outcomes of liver function with disease progression.

Background: A test to narrow down patients who require esophagogastroduodenoscopy (EGD) with a high probability of having gastroesophageal varices (GEV) and a high-risk of liver-related events is an unmet need. Methods: The measurement of serum fibrosis markers and EGD was performed in 166 consecutive chronic hepatitis C patients. The correlation between the grades of GEV and fibrosis markers and the subsequent occurrence of liver-related and fibrosis markers were examined. Results: Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA⁺–M2BP) levels increased according to the grade of GEV (3.4 (0.2–18.6) for no GEV, 7.9 (1.8–20.0) for small GEV, and 11.4 (4.0–20.0) for large GEV; p < 0.001). The diagnostic accuracy of the WFA⁺–M2BP was superior compared to other serum fibrosis markers, and WFA⁺–M2BP was an independent predictor of GEV in the multivariate analysis. Furthermore, the cumulative incidence of liver-related events at one year was 2.3% in patients with WFA⁺–M2BP levels ≤ 7.0 and 37.5% in patients with WFA⁺–M2BP levels > 7.0 (p < 0.001). WFA⁺–M2BP > 7.0 was a significant predictive factor for liver-related events (Hazard ratio 6.7, p = 0.004) independent of Child–Pughclass. Conclusions: WFA⁺–M2BP could be used to estimate the presence and grade of GEV and is linked to liver-related events in chronic hepatitis C patients.

Identification of high-risk patients for hepatocellular carcinoma (HCC) after sustained virological responses (SVR) is necessary to define candidates for long-term surveillance. In this study, we examined whether serum markers after 1 year of SVR could predict subsequent HCC development. Total 734 chronic hepatitis C patients without a history of HCC who achieved SVR with direct-acting antivirals were included. The regular surveillance for HCC started from 24 weeks after the end of treatment (SVR24). Factors at SVR24 and 1 year after SVR24 were analyzed for predicting HCC development. During the mean observation period of 19.7 ± 10 months, 24 patients developed HCC. At SVR24, Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA±M2BP) ≥ 1.85 and α-fetoprotein (AFP) ≥ 6.0 ng/mL were independent factors of HCC development. However, at 1 year after SVR24, WFA±M2BP ≥ 1.85 was associated with subsequent HCC development (hazard ratio: 23.5, 95% confidence interval: 2.68–205) but not AFP. Among patients with WFA±M2BP ≥ 1.85 at SVR24, 42% had WFA±M2BP < 1.85 at 1 year after SVR24 (WFA±M2BP declined group). Subsequent HCC development was significantly lower in the declined group than in the non-declined group (1 year HCC rate: 0% vs. 9.4%, p = 0.04). In conclusion, WFA^±M2BP but not AFP could identify high and no-risk cases of HCC at 1 year after SVR. Therefore, it was useful as a real-time monitoring tool to identify the candidates for continuous surveillance for HCC.