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Background: We aimed to investigate the e cacy and safety of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (u-HCC) based on whether they had previously received systemic therapy, as well as the association of atezolizumab plus bevacizumab with early alphafetoprotein (AFP) response in real-world practice.Methods: A total of 52 patients with u-HCC were treated with atezolizumab plus bevacizumab between October 2020 and April 2021. The Response Evaluation Criteria in Solid Tumors (RECIST) and modi ed RECIST were used to evaluate radiological responses.Results: The patients received atezolizumab plus bevacizumab as 1st-line (n = 23), 2nd-line (n = 16), 3rdline (n = 6), 4th-line (n = 3), 5th-line (n = 3), or 6th-line (n = 1) therapy. The objective response rate and disease control rate in all patients were 18.4% and 63.2%, respectively. Sixteen patients experienced no adverse events (AEs), whereas 4 patients discontinued therapy due to AEs. The median time to progression (TTP) was signi cantly longer among patients receiving atezolizumab plus bevacizumab as 1st-line therapy than in patients receiving atezolizumab plus bevacizumab as later-line therapy (P = 0.02).Patients with an AFP response (reduction ≥20% from baseline) at 6 weeks had a signi cantly longer TTP than those without an AFP response (P = 0.02). Conclusion:Patients who received atezolizumab plus bevacizumab as 1st-line therapy had better clinical outcome than those who received atezolizumab plus bevacizumab in later lines. The AFP response at 6 weeks could be a predictor of disease progression.

The citrus spiny whitefly Aleurocanthus spiniferus (Quaintance) is a pest of citrus plants that is native to South-East Asia. Although serious outbreaks of the tea-infesting whitefly in China, Taiwan and Japan have been attributed to this species over the last 20 years, recent research has shown different host preferences between the two whiteflies. Hence, the two pests have tentatively been differentiated as tea-infesting and citrus-infesting populations. We further compared morphological, acoustic and genomic features between the two populations in Japan. Morphological differences were recognised in the arrangement of spines, porettes and papillae on the dorsal disc and number of marginal crenulations and marginal waxy fringe of 4 th -instar nymphs, as well as wing maculation and genitalic organs of adults. In courtship behaviour, the acoustic properties of male vibratory signals also differed between the two. Furthermore, genetic analysis of mtCOI sequences (759 bp) showed that the tea-infesting population was clearly distinct from the citrus-infesting group, with high bootstrap values. The mtCOI sequence identities were 76.2% between the two populations. Genetic differentiation between the two populations was shown by the high value (0.99650) of pairwise Fst, indicating the sexual isolation of the two populations. Consequently, these two populations are regarded as different representatives, consisting of a sibling relationship, but clearly distinguished from each other as independent genomic populations. Here, we describe the tea-infesting population and propose a new scientific name, Aleurocanthus camelliae Kanmiya & Kasai sp. nov., and a new common name, camellia spiny whitefly, thus distinguishing it from A. spiniferus (Quaintance), the citrus spiny whitefly that constitutes the citrus-infesting population.

Background: Magnetic resonance elastography (MRE) has the highest diagnostic accuracy for liver fibrosis; however, the association between MRE-associated liver stiffness and the development of hepatic and extrahepatic complications as well as mortality remains unclear. Aim:In this study, we investigated the longitudinal association between MREassociated liver stiffness and complications and mortality.Methods: This retrospective study included 2373 consecutive patients with chronic liver disease. All patients received standard of care and the development of complications was assessed every 1-6 months.Results: Newly diagnosed hepatocellular carcinoma (HCC), decompensation, major adverse cardiovascular events (MACE), extrahepatic cancer and death were observed in 99, 117, 73, 77 and 170 patients respectively. In multivariable analysis, the adjusted hazard ratios (aHR) (95% confidence interval [CI]) for HCC, decompensation, MACE, extrahepatic cancer and mortality were 1.28 (1.2-1.4), 1.34 (1.3-1.4), 0.96 (0.9-1.1), 1.00 (0.9-1.1) and 1.17 (1.1-1.2), respectively, with each 1-kPa increase in liver stiffness. Similarly, the aHR (95% CI) for HCC, decompensation, MACE, extrahepatic cancer and mortality were 4.20 (2.2-8.2), 67.5 (9.2-492), 0.83 (0.4-1.7), 0.90 (0.5-1.7) and 2.90 (1.6-5.4), respectively, in patients with cirrhosis (>4.7 kPa) compared to those with minimal fibrosis (<3 kPa).Conclusions: Increased MRE-associated liver stiffness was associated with increased risk for HCC, decompensation and mortality in a dose-dependent fashion but not with MACE or extrahepatic cancer, implicating a significant role for MRE in liverrelated events and mortality; however, further studies are warranted to explore its role in MACE and extrahepatic cancer.

Lenvatinib is an approved first-line therapy for unresectable hepatocellular carcinoma (HCC), but the effect of dose modification on its efficacy is unclear. We analyzed the relationship between the relative dose intensity during the initial 4 weeks of therapy [4W-relative dose intensity (RDI)] and the efficacy of lenvatinib therapy in the real-world setting. A total of 48 consecutive patients with unresectable HCC who received lenvatinib therapy for more than 4 weeks were included. The 4W-RDI was calculated as the cumulative dose in the initial 4 weeks divided by the weight-based standard dose, and we evaluated its association with overall survival (OS) and best response by modified Response Evaluation Criteria in Solid Tumor (mRECIST). The baseline factors predicting high 4W-RDI were analyzed further. The median durations of follow-up and of therapy among the 48 participants were 7.6 and 6.6 months, respectively. The median OS was not reached. Drug interruption and/or dose reduction were necessary in 30 patients (62.5%) and the median 4W-RDI was 70% (range 22%-100%). Patients with 4W-RDI �70% had longer OS [hazard ratio (HR) 0.28, 95% confidential interval (CI):0.09-0.90, p = 0.03], and longer duration of lenvatinib therapy (HR 0.39, 95%CI:0.16-0.92, p = 0.03). Patients with 4W-RDI �70% showed higher disease control rate compared to those with 4W-RDI <70% (91.7% vs. 54.2%, p = 0.008). A baseline albumin level >3.4g/dL or ALBI score less than-2.171 were significantly associated with achieving 4W-RDI �70%. In conclusion, 4W-RDI of lenvatinib therapy is associated with favorable radiological response and longer OS.