Hepatology Research最新文献

{"title":"What we know and need to know about Fontan-associated liver disease","authors":"Kunimaro Furuta","doi":"10.1111/hepr.14095","DOIUrl":"10.1111/hepr.14095","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the associations of interlukin-7 genetic variants with toxicity and efficacy of immune checkpoint inhibitors: A replication study of a Japanese population, based on the findings of a European genome-wide association study.","authors":"Hideaki Miyamoto, Yasuteru Kondo, Ei Itobayashi, Masayoshi Uehara, Atsushi Hiraoka, Masatoshi Kudo, Satoru Kakizaki, Tatehiro Kagawa, Satoshi Miuma, Takanori Suzuki, Kazuhiro Sugi, Koichi Suyama, Toru Beppu, Hidenori Toyoda, Hitoshi Yoshiji, Haruki Uojima, Shiho Miyase, Kaori Inoue, Akihiro Tamori, Takanori Ito, Shigeo Shimose, Goki Suda, Tsuguru Hayashi, Masaya Onishi, Satoshi Narahara, Takehisa Watanabe, Masaaki Iwatsuki, Satoshi Fukushima, Yasuhito Tanaka","doi":"10.1111/hepr.14092","DOIUrl":"https://doi.org/10.1111/hepr.14092","url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Clinical trial registration: </strong>UMIN Clinical Trials Registry with the number UMIN000043798.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance of gamma-glutamyl transferase elevation in patients with Fontan-associated liver disease.","authors":"Tomomi Kogiso, Yuri Ogasawara, Makiko Taniai, Eriko Shimada, Kei Inai, Katsutoshi Tokushige, Yousuke Nakai","doi":"10.1111/hepr.14093","DOIUrl":"https://doi.org/10.1111/hepr.14093","url":null,"abstract":"<p><strong>Aim: </strong>In patients with Fontan-associated liver disease (FALD), gamma-glutamyl transferase (GGT) levels are often elevated, however, its clinical importance is unclear. We investigated the relationship between the clinical course of FALD and GGT levels.</p><p><strong>Methods: </strong>We enrolled 145 patients with FALD who underwent right-heart catheterization (RHC) and visited our department. Ursodeoxycholic acid (UDCA) was administered to 62 of the patients. Patients with GGT levels <50 and ≥50 U/L were compared. Follow-up RHC was undertaken in 76 patients. Cases in which GGT levels decreased by ≥10% or <50 U/L were defined as improved (n = 33).</p><p><strong>Results: </strong>Patients with GGT levels ≥50 U/L had significantly lower levels of albumin and higher levels of alanine transaminase (ALT) but no significant differences in RHC factors. Over a 4.6-year period, 43.4% showed improvement in GGT levels. Improved cases had significantly lower total bilirubin (1.1 vs. 1.6 mg/dL), AST (22 vs. 28 U/L), and ALT (18 vs. 27 U/L) levels than nonimproved cases (n = 29, p < 0.05), and the change in platelet count (-0.5 vs. -3.0 × 10^-4/μL) was significantly lower in the latter (p = 0.03). The improvement rate was significantly higher in UDCA-treated cases (55.2%) with GGT levels ≥50 U/L compared to cases not treated with UDCA (18.2%, p = 0.04).</p><p><strong>Conclusion: </strong>In cases of FALD with no improvement in GGT level, the platelet count decreased over time, suggesting progression of fibrosis. Physicians should be aware of the importance of a high GGT level in patients with FALD.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib radiofrequency ablation sequential therapy offers survival benefits for patients with unresectable hepatocellular carcinoma at intermediate stage and the liver reserve of Child-Pugh A category: A multicenter study.","authors":"Ying Zhang, Kazushi Numata, Kento Imajo, Haruki Uojima, Akihiro Funaoka, Satoshi Komiyama, Katsuaki Ogushi, Makoto Chuma, Kuniyasu Irie, Shigehiro Kokubu, Masato Yoneda, Takashi Kobayashi, Hisashi Hidaka, Taito Fukushima, Satoshi Kobayashi, Manabu Morimoto, Tatehiro Kagawa, Nobuhiro Hattori, Tsunamasa Watanabe, Shigeru Iwase, Shin Maeda","doi":"10.1111/hepr.14089","DOIUrl":"https://doi.org/10.1111/hepr.14089","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to evaluate the efficacy and safety of lenvatinib radiofrequency ablation (RFA) sequential therapy for certain hepatocellular carcinoma (HCC) patients.</p><p><strong>Methods: </strong>One hundred and nineteen patients with unresectable HCC in the intermediate stage with Child-Pugh A were retrospectively recruited in a multicenter setting. Those in the lenvatinib RFA sequential therapy group received lenvatinib initially, followed by RFA and the retreatment with lenvatinib. The study compared overall survival (OS), progression-free survival (PFS), tumor response, and adverse events (AEs) between patients undergoing sequential therapy and lenvatinib monotherapy.</p><p><strong>Results: </strong>After propensity score matching, 25 patients on sequential therapy and 50 on monotherapy were evaluated. Independent factors influencing OS were identified as sequential therapy, modified albumin-bilirubin (mALBI) grade, and relative dose intensity (%) with hazard ratios (HRs) of 0.381 (95% confidence interval [CI], 0.186-0.782), 2.220 (95% CI, 1.410-3.493), and 0.982 (95% CI, 0.966-0.999), respectively. Stratified analysis based on mALBI grades confirmed the independent influence of treatment strategy across all mALBI grades for OS (HR, 0.376; 95% CI, 0.176-0.804). Furthermore, sequential therapy was identified as an independent factor of PFS (HR, 0.382; 95% CI, 0.215-0.678). Sequential therapy significantly outperformed monotherapy on survival benefits (OS: 38.27 vs. 18.96 months for sequential therapy and monotherapy, respectively, p = 0.004; PFS: 13.80 vs. 5.32 months for sequential therapy and monotherapy, respectively, p < 0.001). Sequential therapy was significantly associated with complete response by modified Response Evaluation Criteria in Solid Tumors (odds ratio, 63.089). Ten of 119 patients experienced grade 3 AEs, with no AE beyond grade 3 observed.</p><p><strong>Conclusion: </strong>Lenvatinib RFA sequential therapy might offer favorable tolerability and potential prognostic improvement compared to lenvatinib monotherapy.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141491649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutritional management for acute liver failure","authors":"Tokio Sasaki,&nbsp;Keisuke Kakisaka,&nbsp;Hidekatsu Kuroda,&nbsp;Takayuki Matsumoto","doi":"10.1111/hepr.14090","DOIUrl":"10.1111/hepr.14090","url":null,"abstract":"<p>Acute liver failure (ALF) induces increased energy expenditure and disrupts the metabolism of essential nutrients. Hepatic encephalopathy is a complication of ALF with a poor prognosis and mainly involves the metabolic disturbance of amino acids in its pathogenesis. In this review, we discuss the nutritional management for ALF in consideration of the pathophysiology of ALF with respect to the impairment of hepatocyte function. It is known that enteral nutrition is recommended for patients with ALF, while parenteral nutrition is recommended for patients who cannot tolerate enteral nutrition. As ALF leads to a hypermetabolic state, the energy intake is recommended to cover 1.3 times the resting energy expenditure. Because of the high risk of hypoglycemia associated with disturbances in glucose metabolism, substantial glucose intake is recommended. Along with the deterioration of glucose metabolism, protein metabolism is also disrupted. As patients with ALF have increased systemic protein catabolism together with decreased protein synthesis, appropriate amounts of amino acids or protein under monitoring serum ammonia levels are recommended. In conclusion, nutritional management based on the understanding of nutritional pathophysiology is a pivotal therapeutic approach for patients with ALF. The approach should be individualized in the acute phase, the recovery phase, and the pretransplant phase.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytokine release syndrome following durvalumab and tremelimumab in advanced hepatocellular carcinoma: A case report with cytokine and damage-associated molecular pattern analysis.","authors":"Tomomi Ozaki, Sae Yumita, Sadahisa Ogasawara, Makoto Fujiya, Takahiro Tsuchiya, Ryohei Yoshino, Midori Sawada, Teppei Akatsuka, Ryo Izai, Chihiro Miwa, Takuya Yonemoto, Kentaro Fujimoto, Hidemi Unozawa, Kisako Fujiwara, Ryuta Kojima, Hiroaki Kanzaki, Keisuke Koroki, Masanori Inoue, Kazufumi Kobayashi, Masato Nakamura, Soichiro Kiyono, Naoya Kanogawa, Takayuki Kondo, Ryo Nakagawa, Shingo Nakamoto, Naoya Kato","doi":"10.1111/hepr.14088","DOIUrl":"https://doi.org/10.1111/hepr.14088","url":null,"abstract":"<p><p>Cytokine release syndrome (CRS) is a systemic inflammatory syndrome that causes fatal circulatory failure due to hypercytokinemia, and subsequent immune cell hyperactivation caused by therapeutic agents, pathogens, cancers, and autoimmune diseases. In recent years, CRS has emerged as a rare, but significant, immune-related adverse event linked to immune checkpoint inhibitor therapy. Furthermore, several previous studies suggested that damage-associated molecular patterns (DAMPs) could be involved in malignancy-related CRS. In this study, we present a case of severe CRS following combination therapy with durvalumab and tremelimumab for advanced hepatocellular carcinoma, which recurred during treatment, as well as an analysis of cytokine and DAMPs trends. A 35-year-old woman diagnosed with hepatocellular carcinoma underwent a partial hepatectomy. Due to cancer recurrence, she started a combination of durvalumab and tremelimumab. Then, 29 days post-administration, she developed fever and headache, initially suspected as sepsis. Despite antibiotics, her condition worsened, leading to disseminated intravascular coagulation and hemophagocytic syndrome. The clinical course and elevated serum interleukin-6 levels led to a CRS diagnosis. Steroid pulse therapy was administered, resulting in temporary improvement. However, she relapsed with increased interleukin-6, prompting tocilizumab treatment. Her condition improved, and she was discharged on day 22. Measurements of inflammatory cytokines interferon-γ, tumor necrosis factor-α, and DAMPs, along with interleukin-6, using preserved serum samples, confirmed marked elevation at CRS onset. CRS can occur after the administration of any immune checkpoint inhibitor, with the most likely trigger being the release of DAMPs associated with tumor collapse.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: A treatment dilemma-Authors' reply.","authors":"Jun-Zhe Yi, Ning Lyu, Ming Zhao","doi":"10.1111/hepr.14091","DOIUrl":"https://doi.org/10.1111/hepr.14091","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in alanine aminotransferase and body composition and metabolic factors among individuals receiving medical health checkups.","authors":"Saori Onishi, Akira Fukuda, Masahiro Matsui, Kosuke Ushiro, Tomohiro Nishikawa, Akira Asai, Soo Ki Kim, Hiroki Nishikawa","doi":"10.1111/hepr.14087","DOIUrl":"https://doi.org/10.1111/hepr.14087","url":null,"abstract":"<p><strong>Aim: </strong>To examine the relationship between changes in alanine aminotransferase (ALT) and those in body composition and metabolic factors in participants receiving medical health checkups (4350 men [mean age 52.5 years] and 5398 women [mean age 50.5 years]) METHODS: We divided the participants into four types based on their ALT value at baseline and 1 year: A, ALT ≤30 (baseline) and ≤30 (1 year); B, ALT ≥31 (baseline) and ≤30 (1 year); C, ALT ≤30 (baseline) and ≥31 (1 year); and D, ALT ≥31 (baseline) and ≥31 (1 year). The change in each body composition-related parameter (waist circumference, fat mass, fat-free mass, fat mass to fat-free mass ratio, etc.) after 1-year was defined as Δ.</p><p><strong>Results: </strong>The mean changes in waist circumference (cm) in the four types (A, B, C, and D) were -0.33, -1.54, 0.66, and -0.29 (overall p < 0.0001) in men, and -0.19, -0.90, 0.30, and 0.090 (overall p < 0.0001) in women. The mean changes in fat mass (kg) in the four types were -0.027, -0.86, 0.62, and 0.092 (overall p < 0.0001) in men, and 0.0067, -0.48, 0.39, and 0.063 (overall p < 0.0001) in women. The mean changes in fat-free mass (kg) in the four types were -0.028, -0.55, 0.42, and -0.034 (overall p < 0.0001) in men, and -0.0091, -0.34, 0.12, and -0.045 (overall p = 0.0012) in women. The mean changes in fat mass to fat-free mass ratio in the four types were -0.00042, -0.0120, 0.00837, and 0.00171 (overall p < 0.0001) in men, and -0.00013, -0.00817, 0.00730, and 0.00628 (overall p < 0.0001) in women.</p><p><strong>Conclusion: </strong>A decrease in ALT to ≤30 IU/L may be associated with improved body composition balance, but caution should be exercised for the decrease in muscle mass.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic arterial infusion therapy for advanced hepatocellular carcinoma after systemic treatment failure: A treatment dilemma","authors":"Teh‐Ia Huo, Shu‐Yein Ho","doi":"10.1111/hepr.14082","DOIUrl":"https://doi.org/10.1111/hepr.14082","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141529779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regarding the “Hepatitis B surface antigen glycan isomer is a predictor of the development of hepatocellular carcinoma during nucleoside/nucleotide analog therapy”","authors":"Wei Huang, Yan Zheng","doi":"10.1111/hepr.14080","DOIUrl":"https://doi.org/10.1111/hepr.14080","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141527065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}