Antigen-specific human monoclonal antibodies (mAbs) are key candidates for therapeutic agents. However, the availability of a suitable screening system for antigen-specific antibody-secreting cells (ASCs) is limited in humans. Here we present a unique method for detecting individual ASCs using microwell array chips, which enables the analysis of live cells on a single-cell basis and offers a rapid, efficient and high-throughput (up to 234,000 individual cells) system for identifying and recovering objective ASCs. We applied the system to detect and retrieve ASCs for hepatitis B virus and influenza viruses from human peripheral blood lymphocytes and produced human mAbs with virus-neutralizing activities within a week. Furthermore, we show that the system is useful for detecting ASCs for multiple antigens as well as for selection of ASCs secreting high-affinity antibodies on a chip. Our method can open the way for the generation of therapeutic antibodies for individual patients.

Background/Aim: The frequency of hepatocellular carcinoma (HCC) in patients with good hepatic reserve function has been increasing in Japan along with the progression of antiviral therapies and aging of the society. We evaluated the usefulness of modified albumin-bilirubin (ALBI) grade as a tool for assessment of hepatic reserve function. Materials/Methods: We enrolled 6,649 naïve HCC patients treated from 2000 to 2017 and divided them into training (Ehime Prefecture group: E group, n = 2,357) and validation (validation group: V group, n = 4,292) cohorts. Child-Pugh classification and ALBI and modified ALBI (mALBI) grading were compared using with Japan Integrated Staging (JIS), ALBI-TNM (ALBI-T), and mALBI-T scores, which were calculated based on TNM stage and each assessment tool, retrospectively. Results: In the E group, Akaike’s Information Criterion (AIC) and c-index values for mALBI-T (13,725.2/0.744) were better as compared to those of ALBI-T (13,772.6/0.733) and JIS score (13,874.7/0.720), with similar results observed in the V group (mALBI-T: 27,727.4/0.760; ALBI-T: 27,817.8/0.750; JIS: 27,807.5/0.748). Although there were some significant differences between the groups with regard to clinical background factors (age, etiology, tumor size, tumor number, treatment modalities), for all patients the AIC and c-index values of mALBI-T (45,327.1/0.755) were also better than those of ALBI-T (45,467.7/0.744) and JIS scores (45,555.8/0.739), indicating its superior stratification ability and prognostic predictive value in patients with HCC. Conclusion: The detailed stratification ability of mALBI grade for hepatic reserve function is suitable for the recent trend of HCC patients, while mALBI-T may provide a more accurate predictive value than existing total staging scoring systems.

Branched chain amino acids (BCAAs) have been shown to affect gene expression, protein metabolism, apoptosis and regeneration of hepatocytes, and insulin resistance. They have also been shown to inhibit the proliferation of liver cancer cells in vitro, and are essential for lymphocyte proliferation and dendritic cell maturation. In patients with advanced chronic liver disease, BCAA concentrations are low, whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high, conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients. Based on these basic observations, patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines, with positive effects.

Background/aim We assessed suitable factors indicating newly developed lenvatinib (LEN) treatment for unresectable hepatocellular carcinoma (u‐HCC) by investigating real‐world clinical features of patients. Materials/methods One hundred fifty two u‐HCC patients, who receive LEN treatment from March to December 2018, were enrolled. (Child‐Pugh score [CPS] 5/6/7/8 = 76/61/13/2, modified albumin‐bilirubin grade [mALBI] 1/2a/2b/3 = 53/35/60/4). Clinical features were evaluated retrospectively. Results Overall‐response rate (ORR)/disease control rate (DCR) at 1 month after starting LEN were 38.7%/86.0%, respectively. Estimated median time to progression (TTP) was 7.0 months, while median survival time was not reached within the observation period. CPS (≥7) and past history of tyrosine‐kinase inhibitor (TKI) were not significant prognostic factors. mALBI ≥2b was an only significant prognostic factor (HR 4.632, 95%CI 1.649‐13.02, P = 0.004) in Cox‐hazard multivariate analysis. In patients with Child‐Pugh A, c‐index/Akaike's information criterion (AIC) of prognostic predictive value of mALBI were superior to CPS (0.682/135.6 vs 0.652/138.7), while those of stopping LEN also showed that mALBI was better (0.575/447.3 vs 0.562/447.8). Additional analysis of patients with good mALBI (1/2a) revealed that time to stopping LEN was significantly shorter in those with the adverse event (AE) of appetite loss (any grade) than those without ( P = 0.006) and body mass index (BMI) was also lower in patients with that AE (20.3 ± 3.0 vs 23.6 ± 4.0kg/m 2 , P < 0.001), while patients with a hand‐foot skin reaction (any grade) showed good ORR/DCR (59.1%/86.4%) and longer TTP as compared to patients without ( P = 0.007). Conclusion Good hepatic function (mALBI 1/2a) is the best indication for LEN, while potential appetite loss in association with low BMI should be kept in mind in such cases.

Aim/Background: The purpose of this study was to evaluate the validity of 3 classifications for assessing liver function, the liver damage and Child-Pugh classifications and the newly proposed albumin-bilirubin (ALBI) grade, in order to examine the feasibility of evaluating hepatic function using ALBI grade with the hepatocellular carcinoma (HCC) treatment algorithm used in Japan. Methods: We analyzed the medical records of 3,495 Japanese HCC patients admitted from 2000 to 2015, which were comprised of 1,580 patients hospitalized in the Ehime Prefecture area and used as a training cohort (Ehime group), and 1,915 others who were used for validation (validation group). ALBI score used for grading ( ≤ -2.60 = grade 1, greater than -2.60 to ≤ -1.39 = grade 2, greater than -1.39 = grade 3) as well as clinical features and prognosis (Japan Integrated Staging [JIS], modified JIS, ALBI-TNM [ALBI-T] score) were retrospectively investigated. Results: For prediction of liver damage A, the values for sensitivity and specificity, positive predictive and negative predictive values, and positive and negative likelihood ratios of ALBI-1 and Child-Pugh A were similar among the 2 groups. Akaike information criterion results showed that prognosis based on ALBI grade/ALBI-T score was better than that based on liver damage/modified JIS score and Child-Pugh/JIS score (22,291.8/21,989.4, 22,379.6/22,076.0, 22,392.1/22,075.1, respectively). The cutoff values for ALBI score for indocyanine green retention rate at 15 min (ICG-R15) <10, <20, and <30% were -2.623 (area under the curve [AUC]: 0.798), -2.470 (AUC: 0.791), and -2.222 (AUC: 0.843), respectively. The distribution of ICG-R15 (<10%, 10 to <20%, 20 to <30%, and ≥ 30%) for ALBI grade 1 was similar to that for liver damage A. There were only small differences with regard to therapeutic selection with the Japanese HCC treatment algorithm between liver damage and ALBI grade. Conclusion: ALBI grade is a useful and easy classification system for assessment of hepatic function for therapeutic decision making.