Exosomal microRNAs (miRNAs) have been investigated as potential novel biomarkers, and miR‑122 and miR‑21 were shown to be important in hepatocellular carcinoma (HCC). We analyzed the importance of serum exosomal miRNA expression levels in HCC patients that underwent transarterial chemoembolization (TACE). Seventy‑five HCC patients who underwent TACE as the initial treatment in Nagasaki University Hospital were enrolled. Exosomal miRNAs were isolated from serum samples collected before and after TACE. Exosomal miR‑122 expression levels significantly decreased after TACE (P=0.012), while the exosomal miR‑21 expression levels did not significantly change. The expression levels of exosomal miR‑122 before TACE were shown to correlate significantly with aspartate aminotransferase (r=0.31, P=0.004) and alanine aminotransferase (r=0.33, P=0.003) levels, tumor diameter (r=0.29, P=0.010) and Child‑Pugh score (r=‑0.28, P=0.013). The median survival time for all patients was 47 months, and neither of the investigated exosomal miRNAs were shown to be independent factors associated with the disease‑specific survival. According to the median relative expression of miR‑122 after TACE/before TACE (miR‑122 ratio) in liver cirrhosis patients (n=57), the patients with a higher miR‑122 ratio had significantly longer disease‑specific survival, compared with that of the patients with the lower miR‑122 ratio (P=0.0461). Multivariate Cox proportional hazards regression analysis of clinical parameters revealed that a lower exosomal miR‑122 ratio (HR 2.720; 95% confidence interval, 1.035‑8.022; P=0.042) is associated with the disease‑specific survival. Taken together, our results demonstrate that the exosomal miR‑122 level alterations may represent a predictive biomarker in HCC patients with liver cirrhosis treated with TACE.

Background: Lenvatinib is currently available as the first-line treatment for advanced unresectable hepatocellular carcinoma. We evaluated the relationship between its relative dose intensity (RDI) and response in clinical settings. Methods: From March 2018 to May 2019, 93 patients were administered lenvatinib at the Nagasaki University Hospital and its related facilities. Among these, 81 patients (66 men, 15 women, median age 72.0) who received lenvatinib were analyzed retrospectively. Results: Fourteen patients were Child–Pugh grade B, and 15 had received other systemic therapy. According to Response Evaluation Criteria in Solid Tumors (RECIST), the objective response (OR) rate was 17.3%. The overall survival (OS) was significantly better in the OR group (p = 0.011). There was a significant difference in RDI between the OR and non-OR groups (p < 0.05). The area under the receiver operating characteristics curve for OR prediction by the 4, 8, 12, and 16-week RDI were 0.666, 0.747, 0.731, and 0.704, respectively. In the 8-week RDI ≥67.0% group, OS was significantly better than in the 8-week RDI <67.0% group (p = 0.003). Conclusions: Because a sufficient RDI is required to achieve an OR, it is strongly recommended that lenvatinib should be administered to patients with good hepatic function and status.

Background: Atezolizumab plus bevacizumab therapy has high response rates in patients with unresectable hepatocellular carcinoma (HCC). The hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) has been reported to be useful as an imaging biomarker for detecting β-catenin mutations. We evaluated whether the pretreatment of the hepatobiliary phase of EOB-MRI could predict the therapeutic effect of lenvatinib and atezolizumab plus bevacizumab. Methods: This study included 68 patients (lenvatinib group (n = 33) and atezolizumab plus bevacizumab group (n = 35)). The visual assessment and relative enhancement ratio (RER) of the largest HCC lesions were evaluated using the hepatobiliary phase of EOB-MRI. Results: The hyperintensity type (RER ≥ 0.9) was 18.2% in the lenvatinib group and 20.0% in the atezolizumab plus bevacizumab group. In the lenvatinib group, progression-free survival (PFS) was not different between the heterogeneous and homogenous types (p = 0.688) or between the hyperintensity and hypointensity types (p = 0.757). In the atezolizumab plus bevacizumab group, the heterogeneous type had significantly shorter PFS than the homogenous type (p = 0.007), and the hyperintensity type had significantly shorter PFS than the hypointensity type (p = 0.012). Conclusions: The hepatobiliary phase of EOB-MRI was useful for predicting the therapeutic effect of atezolizumab plus bevacizumab therapy on unresectable HCC.

Endoscopic management of esophagogastric varices in Japan