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Aim Methods Results Conclusions Clinical trial registration Recent genome‐wide association studies of European populations have identified rs16906115, a single‐nucleotide polymorphism in the interleukin‐7 gene, as a predictor of immune‐related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single‐nucleotide polymorphism in a Japanese population.From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow‐up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non‐responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non‐responders.In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non‐responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis.In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome.UMIN Clinical Trials Registry with the number UMIN000043798. [ABSTRACT FROM AUTHOR]

Histology B Recommendations: b The typical histology of AIH is the chronic active hepatitis, along with characteristic to AIH histological findings, such as interface hepatitis, hepatocellular rosette, large numbers of plasma cells, and emperipolesis.52 However, all these findings have low disease specificity, making it difficult to diagnose AIH based on histology alone. SUPPORTING INFORMATION MEMO: PATHOLOGICAL FINDINGS OF ACUTE HEPATITIS PHASE AIH Some cases of acute hepatitis phase AIH have clinical presentations that resemble acute hepatitis. SUPPORTING INFORMATION MEMO: CLINICAL CHARACTERISTICS OF ACUTE HEPATITIS PHASE AIH Among AIH cases which develop like acute hepatitis, are the "acute hepatitis phase AIH" lacking any chronic findings in the liver tissue. B Recommendations: b Some cases of AIH exhibit an "acute presentation" with clinical courses and liver function test patterns that resemble acute hepatitis, severe hepatitis, or acute liver failure (fulminant hepatitis/late-onset hepatic failure (LOHF)) (recommendation grade: 1, evidence strength: B). [Extracted from the article]

Aim: The microRNA (miR) clusters miR‐183/96/182 and miR‐217/216a/216b are significantly upregulated in nonviral hepatocellular carcinoma (NBNC‐HCC). Here, we investigate the impact of each member of these clusters on the clinical outcome of NBNC‐HCC and analyze the antitumor effects of miR‐96‐5p. Methods: The association between recurrence‐free survival of 111 NBNC‐HCC patients and the levels of miR‐183‐5p, miR‐96‐5p, miR‐182‐5p, miR‐217‐5p, miR‐216a‐5p, and miR‐216b‐5p in tumor and adjacent tissues was investigated. The impact of miR‐96‐5p on apoptosis and invasion of a hepatoma cell line, HepG2, was investigated by cell counting, Transwell assay, and flow cytometry, respectively. Results: MicroRNA‐183‐5p, miR‐96‐5p, miR‐182‐5p, miR‐217‐5p, and miR‐216b‐5p were significantly upregulated in tumor tissues compared to the adjacent tissues (p = 0.0005, p = 0.0030, p = 0.0002, p = 0.0011, and p = 0.0288, respectively). By multivariate Cox regression analysis, high tumor/adjacent ratios of miR‐182‐5p (p = 0.007) and miR‐217‐5p (p = 0.008) were associated with poor recurrence‐free survival. In contrast, a low tumor/adjacent ratio of miR‐96‐5p (p < 0.001) was associated with poor recurrence‐free survival. It suggested that further upregulation of miR‐96‐5p in tumors might have an inhibitory effect on recurrence. Transfection of miR‐96‐5p mimic significantly induced apoptosis of HepG2 cells, in association with downregulation of Nucleophosmin 1 (NPM1) and a decrease of phosphorylated AKT protein. Interestingly, simultaneous knockdown of the NPM1 and AKT genes induced apoptosis. MicroRNA‐96‐5p also suppressed proliferation and invasion, which inhibited epithelial‐to‐mesenchymal transition of HCC cells. Conclusion: MicroRNA‐96‐5p as a tumor suppressor would be valuable to stratify NBNC‐HCC patients at high risk of recurrence. [ABSTRACT FROM AUTHOR]