Hepatology Research最新文献

{"title":"Metabolic dysfunction-associated steatotic liver disease (SLD) and alcohol-associated liver disease, but not SLD without metabolic dysfunction, are independently associated with new onset of chronic kidney disease during a 10-year follow-up period.","authors":"Kazuma Mori, Marenao Tanaka, Tatsuya Sato, Yukinori Akiyama, Keisuke Endo, Toshifumi Ogawa, Toru Suzuki, Hiroki Aida, Wataru Kawaharata, Kei Nakata, Itaru Hosaka, Araya Umetsu, Nagisa Hanawa, Masato Furuhashi","doi":"10.1111/hepr.14097","DOIUrl":"https://doi.org/10.1111/hepr.14097","url":null,"abstract":"<p><strong>Aims: </strong>The new nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We aimed to elucidate the relationship between each category of SLD and chronic kidney disease (CKD).</p><p><strong>Methods: </strong>We investigated the effects of various SLDs on the development of CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or positive for urinary protein, during a 10-year period in 12 138 Japanese subjects (men / women, 7984/4154; mean age, 48 years) who received annual health examinations including abdominal ultrasonography.</p><p><strong>Results: </strong>The prevalences of SLD without metabolic dysfunction (SLD-MD[-]), MASLD, MetALD, and ALD were 1.7%, 26.3%, 4.9%, and 1.9%, respectively. During the follow-up period, 1963 subjects (16.2%) (men / women, 1374 [17.2%]/589 [14.2%]) had new onset of CKD. Multivariable Cox proportional hazard model analyses after adjustment of age, sex, eGFR, current smoking habit, diabetes mellitus, hypertension, and dyslipidemia showed that the hazard ratios (HR [95% confidence interval]) for the development of CKD in subjects with MASLD (1.20 [1.08-1.33], p = 0.001) and those with ALD (1.41 [1.05-1.88], p = 0.022), but not those with MetALD (1.11 [0.90-1.36], p = 0.332), were significantly higher than the HR in subjects with non-SLD. Interestingly, subjects with SLD-MD[-] had a significantly lower HR (0.61 [0.39-0.96], p = 0.034) than that in subjects with non-SLD. The addition of the novel classification of SLDs into traditional risk factors for the development of CKD significantly improved the discriminatory capacity.</p><p><strong>Conclusions: </strong>MASLD and ALD, but not SLD-MD[-], are independently associated with the development of CKD.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901574","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":"High serum gamma-glutamyltransferase level after hepatitis C virus elimination is a risk factor for the development of hepatocellular carcinoma.","authors":"Miyako Murakawa, Mina Nakagawa, Hisaaki Nishimura, Shun Kaneko, Masato Miyoshi, Fukiko Kawai-Kitahata, Sayuri Nitta, Jun Tsuchiya, Taro Shimizu, Keiya Watakabe, Tomohiro Mochida, Kento Inada, Yasuhiro Iizuka, Hideki Sakai, Yuki Sakurai, Ayako Sato, Seishin Azuma, Takahiro Kawamura, Chiaki Maeyashiki, Masayuki Kurosaki, Fumihiko Kusano, Hideki Watanabe, Hitoshi Kurata, Yuko Karakama, Takeo Fujiwara, Yuki Nagata, Toshihiro Tanaka, Sei Kakinuma, Ryuichi Okamoto, Yasuhiro Asahina","doi":"10.1111/hepr.14094","DOIUrl":"https://doi.org/10.1111/hepr.14094","url":null,"abstract":"<p><strong>Aim: </strong>Gamma-glutamyltransferase (GGT) is known as an oxidative stress marker, induced by alcohol consumption and metabolic disorders, and is reported as a predictor of hepatocellular carcinoma (HCC) development after hepatitis C virus (HCV) elimination. However, it is not clear whether GGT serves simply as a surrogate marker for overlapping metabolic diseases or reflects HCV-specific carcinogenicity. We investigated the association between GGT and hepatocarcinogenesis after achieving a sustained viral response (SVR), accounting for drinking habits or diabetes, and examined predisposing factors associated with GGT levels after SVR.</p><p><strong>Methods: </strong>This is a prospective, multicenter, and observational study using the database of 1001 patients after HCV eradication with direct-acting antiviral agents. The association of GGT at SVR with cumulative HCC development was examined in a multivariate analysis using Cox proportional hazard models after adjustment for covariates including alcohol and diabetes. The association between oxidative stress markers or genetic factors and GGT levels was analyzed.</p><p><strong>Results: </strong>High GGT levels at SVR were associated with HCC development (HR] 2.38, 95% CI 1.10-5.17). This association was also significant when restricted to patients without alcohol consumption or diabetes (HR 8.38, 95% CI 2.87-24.47). GGT levels were correlated with serum growth differentiation factor 15 levels, a marker of mitochondrial dysfunction. Single-nucleotide polymorphisms of ZNF827 and GDF15 were associated with high GGT levels.</p><p><strong>Conclusions: </strong>High GGT levels at SVR were associated with HCC development after accounting for alcohol consumption and diabetes. GGT levels are influenced by genetic predisposition and may reflect mitochondrial dysfunction after HCV eradication.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787909","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":"Improved survival outcome of curative liver resection for Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma in the era of tyrosine kinase inhibitors.","authors":"Yoh Asahi, Tatsuhiko Kakisaka, Toshiya Kamiyama, Tatsuya Orimo, Shingo Shimada, Akihisa Nagatsu, Takeshi Aiyama, Yuzuru Sakamoto, Kazuki Wakizaka, Shunsuke Shichi, Hirofumi Kamachi, Akinobu Taketomi","doi":"10.1111/hepr.14098","DOIUrl":"https://doi.org/10.1111/hepr.14098","url":null,"abstract":"<p><strong>Aim: </strong>This study was undertaken to evaluate the outcome of curative liver resection, (LR) of Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (BCLC-C HCC) after tyrosine kinase inhibitors (TKIs) became approved as a treatment option for recurrent lesions.</p><p><strong>Methods: </strong>Sixty-seven patients with BCLC-C HCC who underwent curative LR were enrolled in this study. The patients were classified into two groups according to whether LR was performed before (n = 24) or after (n = 43) TKI approval (\"beforeTKI\" and \"afterTKI\" group, respectively).</p><p><strong>Results: </strong>There was no difference in the median disease-free survival time after LR between the beforeTKI and afterTKI groups (5.6 and 7.1 months, respectively; p = 0.435). However, the median survival time after LR was longer in the afterTKI than beforeTKI group (42.7 and 14.9 months, respectively; p = 0.022). Univariate and multivariate analyses showed that the date of LR was the only independent factor affecting postresection survival. When the patients were limited to those with recurrence, there were no differences in the recurrence pattern or progression of HCC at the time of recurrence between the two groups. The only difference in the treatment distribution was the administration of TKIs (14 of 34 patients in afterTKI group and only 1 of 19 patients in beforeTKI group, p < 0.001).</p><p><strong>Conclusion: </strong>These data suggest that TKI therapy for recurrent BCLC-C HCC is associated with improved overall survival. Thus, LR could be a promising option for BCLC-C HCC in the current era of TKI therapy.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765927","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":"Molecular biological role of epithelial splicing regulatory protein 1 in intrahepatic cholangiocarcinoma.","authors":"Takahiro Haruna, Mitsuhiro Kudo, Kousuke Ishino, Junji Ueda, Yukako Shintani-Domoto, Daigo Yoshimori, Takenori Fuji, Yoko Kawamoto, Kiyoshi Teduka, Taeko Kitamura, Hiroshi Yoshida, Ryuji Ohashi","doi":"10.1111/hepr.14096","DOIUrl":"https://doi.org/10.1111/hepr.14096","url":null,"abstract":"<p><strong>Aim: </strong>Epithelial splicing regulatory protein 1 (ESRP1) regulates tumor progression and metastasis through the epithelial‒mesenchymal transition by interacting with zinc finger E-box binding 1 (ZEB1) and CD44 in cancers. However, the role of ESRP1 in intrahepatic cholangiocarcinoma (iCCA) remains unclear.</p><p><strong>Methods: </strong>Three iCCA cell lines (HuCCT-1, SSP-25, and KKU-100) were analyzed using small interfering RNA to investigate the molecular biological functions of ESRP1 and ZEB1. The association between clinicopathological features and the expression of ESRP1 and ZEB1 in iCCA tissues was analyzed immunohistochemically. Proteomic analysis was performed to identify molecules related to ESRP1 expression.</p><p><strong>Results: </strong>ESRP1 expression was upregulated in HuCCT-1 and SSP-25 cells. Cell migration and invasion were enhanced, and the expression of ZEB1 and CD44s (CD44 standard) isoforms were upregulated in the ESRP1 silencing cells. Moreover, ESRP1 silencing increased the expression of N-cadherin and vimentin, indicating the presence of mesenchymal properties. Conversely, ZEB1 silencing increased the expression of ESRP1 and CD44v (CD44 variant) isoforms. Immunohistochemical analysis revealed that a lower ESRP1-to-ZEB1 expression ratio was associated with poor recurrence-free survival in patients with iCCA. Flotillin 2, a lipid raft marker related to epithelial‒mesenchymal transition, was identified as a protein related to the interactive feedback loop in proteomic analysis.</p><p><strong>Conclusions: </strong>ESRP1 suppresses tumor progression in iCCA by interacting with ZEB1 and CD44 to regulate epithelial‒mesenchymal transition.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734009","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":"What we know and need to know about Fontan-associated liver disease.","authors":"Kunimaro Furuta","doi":"10.1111/hepr.14095","DOIUrl":"https://doi.org/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}