Hepatology Research最新文献

{"title":"Elevated nuclear expression of ZHX1 correlates with poor prognosis in hepatocellular carcinoma (HCC): Comparison of nuclear and cytoplasmic distribution of the ZHX family in HCC cells","authors":"Yu-Hong Ma,&nbsp;Shinya Maekawa,&nbsp;Shinichi Takano,&nbsp;Tatsuya Yamaguchi,&nbsp;Takeshi Ishida,&nbsp;Shinya Takaoka,&nbsp;Masaru Muraoka,&nbsp;Yasuyuki Komiyama,&nbsp;Hitomi Takada,&nbsp;Yuichiro Suzuki,&nbsp;Mitsuaki Sato,&nbsp;Jianglin Fan,&nbsp;Nobuyuki Enomoto","doi":"10.1111/hepr.14100","DOIUrl":"10.1111/hepr.14100","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The role of the zinc fingers and homeoboxes family (ZHX1–3), transcriptional repressors, through their subcellular localization in hepatocellular carcinoma (HCC), is not fully understood. The present study aimed to examine the differential nuclear and cytoplasmic expression of ZHXs in HCC tissues.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Immunohistochemistry was utilized to detect the expression of ZHXs in 54 liver tissues from HCC (<i>n</i> = 33), hepatitis C (<i>n</i> = 16), and the normal liver tissue surrounding hepatic metastasis of colorectal cancer (<i>n</i> = 5). Next-generation sequencing and digital polymerase chain reaction identified gene mutations associated with HCC. Kaplan–Meier curves were constructed to evaluate the relationship between ZHX expression and survival. The results were validated using data from The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses were undertaken to identify independent prognostic factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High nuclear expression of ZHX1 was associated with poor overall survival (OS), while high nuclear expression of ZHX2 correlated with higher recurrence. Conversely, patients with high cytoplasmic expression of ZHX3 had lower recurrence and better OS. Hepatitis B virus-associated HCC was related to high cytoplasmic expression of ZHX1, which was marginally related to telomerase reverse transcriptase (TERT) promoter mutation-negative HCC. In contrast, low nuclear expression of ZHX3 was associated with TERT promoter mutation-positive HCC and HCC patients over 70 years old.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results suggest that the expression and localization of different ZHXs may be related to HCC progression, potentially inferring genetic backgrounds such as TERT promoter mutation. Further studies on the relationship between HCC and ZHXs will enhance our understanding and control of HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 1","pages":"79-93"},"PeriodicalIF":3.9,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106917","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":"Efficacy of steroid therapy for improving native liver survival after pediatric acute liver failure with immune activation","authors":"Hiroshi Oue,&nbsp;Eitaro Hiejima,&nbsp;Hideaki Okajima,&nbsp;Tatsuya Okamoto,&nbsp;Eri Ogawa,&nbsp;Elena Yukie Uebayashi,&nbsp;Etsuro Hatano,&nbsp;Takenori Suga,&nbsp;Yotaro Hanami,&nbsp;Kazushige Ashina,&nbsp;Shinichi Kai,&nbsp;Tsuyoshi Sogo,&nbsp;Ayano Inui,&nbsp;Takeshi Matsubara,&nbsp;Kaoru Sakai,&nbsp;Motoko Yanagita,&nbsp;Hironori Haga,&nbsp;Sachiko Minamiguchi,&nbsp;Yosuke Yamada,&nbsp;Hiroshi Nihira,&nbsp;Kazushi Izawa,&nbsp;Takahiro Yasumi,&nbsp;Junko Takita","doi":"10.1111/hepr.14107","DOIUrl":"10.1111/hepr.14107","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case–control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the “Steroid group”), and seven steroid-free patients who also met the criteria (“Nonsteroid group”) were enrolled. Patients in the “Steroid group” were categorized as “responders” or “nonresponders” according to treatment outcome. Clinical and histological data were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; <i>p =</i> 0.0052). Nonresponders were significantly younger, with higher Model for End-stage Liver Disease and pediatric end-stage liver disease scores, higher prothrombin time – international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 1","pages":"138-148"},"PeriodicalIF":3.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017278","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":"Hepatitis B surface antigen glycan isomer as a new potential biomarker in patients with hepatitis B virus infection","authors":"Taiki Okumura,&nbsp;Takeji Umemura","doi":"10.1111/hepr.14106","DOIUrl":"10.1111/hepr.14106","url":null,"abstract":"&lt;p&gt;It is estimated that over 254 million people worldwide are infected with HBV, causing roughly 1.1 million deaths annually&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; as HBV infection progresses to liver cirrhosis and HCC.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; Nucleoside/nucleotide analogs and pegylated interferon are currently available antiviral regimens for managing chronic HBV infection. However, it remains difficult to eradicate the cccDNA of HBV in hepatocyte nuclei. Thus, serological biomarkers such as HBsAg, HBV DNA, and HBcrAg have been established to estimate HBV replication activity, predict therapeutic responses, and assess the risk of HCC development.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Although the currently available quantitative HBsAg assay has been proven to correlate with serum HBV DNA and intrahepatic cccDNA levels,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; it cannot distinguish HBsAg in terms of HBV virions and noninfectious SVPs. Hepatitis B virus envelope proteins include three distinct types of HBsAg: S-HBsAg, M-HBsAg, and L-HBsAg. The HBV particles in a patient's blood include infectious Dane particles containing viral DNA and SVPs. The SVPs are composed mainly of S-HBsAg and are 1000 times more abundant than Dane particles, which are composed primarily of M-HBsAg protein. To accurately assess disease status, HBV virions must be closely monitored and clearly distinguished from SVPs.&lt;/p&gt;&lt;p&gt;Hepatitis B surface antigens are heavily glycosylated with N-glycans and O-glycans.&lt;span&gt;&lt;sup&gt;7, 8&lt;/sup&gt;&lt;/span&gt; Whole-glycan structural analyses have revealed that the PreS2 domain on M-HBs, but not on L-HBs, contain a highly conserved O-glycosylated site in genotype C.&lt;span&gt;&lt;sup&gt;9, 10&lt;/sup&gt;&lt;/span&gt; A recombinant monoclonal antibody against this HBsAgGi was then generated using an O-glycosylated PreS2 peptide. Unlike conventional HBsAg testing, which recognizes the entirety of viral particles, HBsAgGi specifically identifies infectious HBV particles containing M-HBsAg, that is, Dane particles containing DNA and RNA. Hepatitis B antigen glycan isomer testing is now commercially available and can be measured in patient serum with an enzyme-linked immunosorbent assay kit featuring a monoclonal antibody to O-glycosylated PreS2 on M-HBsAg. Evidence on the clinical utility of HBsAgGi is now growing.&lt;/p&gt;&lt;p&gt;Recent studies have described correlations of HBsAgGi with other HBV-associated markers along with HBsAgGi kinetics. We earlier reported that serum HBsAgGi had stronger correlations with serum HBV DNA than did total HBsAg after excluding patients under NA therapy (&lt;i&gt;r&lt;/i&gt; = 0.4332 vs. 0.3927).&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt; Murata et al. showed that serum HBsAgGi was significantly associated with HBcrAg at baseline (&lt;i&gt;r&lt;/i&gt; = 0.452, &lt;i&gt;p&lt;/i&gt; = 0.001) and after 48 weeks of NA therapy (&lt;i&gt;r&lt;/i&gt; = 0.388, &lt;i&gt;p&lt;/i&gt; = 0.007).&lt;span&gt;&lt;sup&gt;12&lt;/sup&gt;&lt;/span&gt; Similarly, Kozuka et al. showed that serum HBsAgGi was significantly associated with iTACT-HBcrAg at baseline (&lt;i&gt;r&lt;/i&gt; = 0.56 &lt;i&gt;p&lt;/i&gt; &lt; 0.001) a","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"54 10","pages":"874-876"},"PeriodicalIF":3.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008747","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":"Trajectories of hepatic steatosis and incidence of cardiovascular disease over a 29-year follow-up","authors":"Ming-Whei Yu,&nbsp;Wan-Jung Wu,&nbsp;Chih-Lin Lin,&nbsp;Chun-Jen Liu,&nbsp;Wei-Ya Peng,&nbsp;Pin-Yu Huang,&nbsp;Yi-Wen Huang,&nbsp;Jui-Ting Hu,&nbsp;Hung-Chuen Chang,&nbsp;Jyh-Ming Liou","doi":"10.1111/hepr.14101","DOIUrl":"10.1111/hepr.14101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To examine the dynamic change in hepatic steatosis status during repeated assessments over time, and its potential impact on the risk of developing cardiovascular disease (CVD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We assessed trajectories of hepatic steatosis and other metabolic disorders in 3134 middle-aged adults undergoing longitudinal assessment of ultrasonography during a pre-baseline period (1993–2009) in a population-based cohort study of liver health. Subsequently, we determined the association of hepatic steatosis trajectories with the incidence of CVD among 2185 CVD-free individuals, followed until 2021. Metabolic risk factors and cardiovascular events (including coronary heart disease and stroke) were determined through medical examination and linkage with nationwide health databases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified three discrete trajectories of hepatic steatosis according to changing pattern over time through group-based trajectory modeling: “stable, non-steatosis” (<i>n</i> = 1298), “intermittent” (<i>n</i> = 921), and “persistent steatosis” (<i>n</i> = 915). During the pre-baseline period, hepatic steatosis trajectories were associated with trajectories of developing diabetes and hypertension, and persistent steatosis (vs. other trajectories) was associated with higher risks and rapidly progressive disease patterns. At a median 13.6 years of follow-up, 629 CVD events occurred. A persistent (vs. non-steatosis: HR 1.44, 95% CI 1.17–1.76), but not intermittent, steatosis pattern predicted the future risk of CVD, after adjustment for age, sex, smoking, and obesity. This association was independent of genetic background, and remained after accounting for pre-baseline body-mass index, other cardiometabolic risk factors, Framingham risk score, medications, and hepatic fibrosis score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The persistence of hepatic steatosis is associated with trajectories of metabolic disorder development and increased risk of CVD. These data have important implications for practice and further research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 1","pages":"46-57"},"PeriodicalIF":3.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999773","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":"Significance of changes in tumor markers in patients treated with durvalumab plus tremelimumab combination therapy as a surrogate marker for tumor response to unresectable hepatocellular carcinoma","authors":"Shinsuke Uchikawa,&nbsp;Tomokazu Kawaoka,&nbsp;Serami Murakami,&nbsp;Ryoichi Miura,&nbsp;Yuki Shirane,&nbsp;Yusuke Johira,&nbsp;Masanari Kosaka,&nbsp;Yasutoshi Fujii,&nbsp;Hatsue Fujino,&nbsp;Atsushi Ono,&nbsp;Eisuke Murakami,&nbsp;Daiki Miki,&nbsp;C. Nelson Hayes,&nbsp;Masataka Tsuge,&nbsp;Shiro Oka","doi":"10.1111/hepr.14104","DOIUrl":"10.1111/hepr.14104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>When evaluating response to immune checkpoint inhibitor therapy, the tumor sometimes initially swells before shrinking and ultimately responding, also called pseudo-progression. In this study, we analyzed whether tumor markers were useful for reflecting the treatment response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thirty-three patients who were treated with durvalumab plus tremelimumab combination therapy (Dur + Tre) were enrolled. Their functional reserve was Child–Pugh grade A. Their tumor markers α-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP), or AFP-Lectin 3 fraction (AFP-L3) were positive. Tumor markers were evaluated before treatment and at 1, 4, and 8 weeks after the start of treatment. The first radiological evaluation was carried out at 4 weeks and the second evaluation at 8–12 weeks. The responders included those with complete response and partial response and the nonresponders included those with stable disease (SD) and progression disease at best response evaluated by Response Evaluation Criteria in Solid Tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the responder group, the change ratio of AFP, DCP, and AFP-L3 specifically decreased at 8 weeks. In the nonresponder group, the change ratio of DCP specifically increased at 4 weeks. The optimal cut-off value to divide responders and nonresponders at 4 weeks was approximately −40%. The ratio of responders was 72.7% in the patients whose AFP or DCP decreased over 40% at 4 weeks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The change in tumor markers is a more useful predicter of tumor response to Dur + Tre than imaging evaluation alone.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 1","pages":"149-154"},"PeriodicalIF":3.9,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141995654","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":"Genetic alteration of SLCO1B3 defines constitutional indocyanine green excretory defect in patients who underwent hepatectomy","authors":"Meguri Tanimoto,&nbsp;Yujiro Nishioka,&nbsp;Yoshinori Inagaki,&nbsp;Takashi Kokudo,&nbsp;Takeaki Ishizawa,&nbsp;Junichi Arita,&nbsp;Nobuhisa Akamatsu,&nbsp;Junichi Kaneko,&nbsp;Kiyoshi Hasegawa","doi":"10.1111/hepr.14099","DOIUrl":"10.1111/hepr.14099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Constitutional indocyanine green (ICG) excretory defects must be distinguished when assessing liver function. The absence of OATP1B3 expression due to homogenous alterations in the <i>SLCO1B3</i> gene has been recently reported to induce ICG excretory defects; however, its association with the clinical examinations and the clinical implications of heterogeneous <i>SLCO1B3</i> gene alteration remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>OATP1B3 expression was evaluated in 49 patients who underwent hepatectomy after evaluation of the ICG retention rate at 15 min (ICGR15) and technetium-99 m-galactosyl serum albumin (99mTc-GSA) hepatic scintigraphy. Additionally, alterations in <i>SLCO1B3</i> were analyzed in patients without OATP1B3 expression. Subsequently, 59 patients who underwent hepatectomy for colorectal liver metastasis (CRLM) were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 49 patients, 6 (12%) had absent OATP1B3 expression. They had significantly higher ICGR15 value (74.7% vs. 23.5%; <i>p</i> &lt; 0.0001), better modified albumin–bilirubin (ALBI) grade (≤grade 2A, 100% vs. 42%; <i>p</i> = 0.010), more normal 99mTc-GSA hepatic scintigraphy (100% vs. 28%; <i>p</i> = 0.0003), and better pathological liver fibrosis (F0–1, 100% vs. 49%; <i>p</i> = 0.027) compared to those with OATP1B3 expression. Three available frozen blocks of cases without OATP1B3 expression showed homozygous alterations in <i>SLCO1B3</i>. Of 59 patients with CRLM in normal liver background, five (8.5%) had heterozygous insertion in <i>SLCO1B3</i>, however they had no difference in ICGR15 values or other clinical findings compared to the other patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Constitutional ICG excretory defects may be defined by the complete absence of OATP1B3 expression. The modified ALBI grade and 99mTc-GSA hepatic scintigraphy were useful for detecting constitutional ICG excretory defects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 1","pages":"106-114"},"PeriodicalIF":3.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971004","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":"What can we create by adding robotic assistance to conventional laparoscopic liver resection?","authors":"Zenichi Morise","doi":"10.1111/hepr.14103","DOIUrl":"10.1111/hepr.14103","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"54 9","pages":"783-785"},"PeriodicalIF":3.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971007","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":"Reply to Letter to the Editor: Regarding the “Hepatitis B surface antigen glycan isomer is a predictor of the development of hepatocellular carcinoma during nucleoside/nucleotide analog therapy”","authors":"Ritsuzo Kozuka,&nbsp;Masaru Enomoto","doi":"10.1111/hepr.14105","DOIUrl":"10.1111/hepr.14105","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"54 12","pages":"1238-1239"},"PeriodicalIF":3.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971006","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":"Interleukin-33 and liver natural killer cells: A novel perspective on antitumor activity in liver fibrosis","authors":"Yuki Imaoka,&nbsp;Masahiro Ohira,&nbsp;Kouki Imaoka,&nbsp;Tomoaki Bekki,&nbsp;Ryosuke Nakano,&nbsp;Takuya Yano,&nbsp;Yuka Tanaka,&nbsp;Toshihiro Nakayama,&nbsp;Miho Akabane,&nbsp;Tetsuya Tajima,&nbsp;Shinichiro Yokota,&nbsp;Sheri M. Krams,&nbsp;Olivia M. Martinez,&nbsp;Carlos O. Esquivel,&nbsp;Kazunari Sasaki,&nbsp;Hideki Ohdan","doi":"10.1111/hepr.14102","DOIUrl":"10.1111/hepr.14102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Liver fibrosis, heralding the potential progression to cirrhosis and hepatocellular carcinoma (HCC), compromises patient survival and augments post-hepatectomy recurrence. This study examined the detrimental effects of liver fibrosis on the antitumor functions of liver natural killer (NK) cells and the interleukin-33 (IL-33) signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our investigation, anchored in both human physiologies using living and deceased donor livers and the carbon tetrachloride (CCl₄)-induced mouse fibrosis model, aimed to show a troubling interface between liver fibrosis and weakened hepatic immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The Fibrosis-4 (FIB-4) index emerged as a salient, non-invasive prognostic marker, and its elevation correlated with reduced survival and heightened recurrence after HCC surgery even after propensity matching (<i>n</i> = 385). We established a strong correlation between liver fibrosis and liver NK cell dysfunction by developing a method for extracting liver NK cells from the liver graft perfusate. Furthermore, liver fibrosis ostensibly disrupted chemokines and promoted IL-33 expression, impeding liver NK cell antitumor activities, as evidenced in mouse models. Intriguingly, our results implicated IL-33 in diminishing the antitumor responses of NK cells. This interrelation, consistent across both mouse and human studies, coincides with clinical data suggesting that liver fibrosis predisposes patients to an increased risk of HCC recurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study revealed a critical relationship between liver fibrosis and compromised tumor immunity, emphasizing the potential interference of IL-33 with NK cell function. These insights advocate for advanced immunostimulatory therapies targeting cytokines, such as IL-33, aiming to bolster the hepatic immune response against HCC in the context of liver fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 1","pages":"115-129"},"PeriodicalIF":3.9,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141971005","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":"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,&nbsp;Marenao Tanaka,&nbsp;Tatsuya Sato,&nbsp;Yukinori Akiyama,&nbsp;Keisuke Endo,&nbsp;Toshifumi Ogawa,&nbsp;Toru Suzuki,&nbsp;Hiroki Aida,&nbsp;Wataru Kawaharata,&nbsp;Kei Nakata,&nbsp;Itaru Hosaka,&nbsp;Araya Umetsu,&nbsp;Nagisa Hanawa,&nbsp;Masato Furuhashi","doi":"10.1111/hepr.14097","DOIUrl":"10.1111/hepr.14097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We investigated the effects of various SLDs on the development of CKD, defined as estimated glomerular filtration rate (eGFR) &lt;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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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], <i>p</i> = 0.001) and those with ALD (1.41 [1.05–1.88], <i>p</i> = 0.022), but not those with MetALD (1.11 [0.90–1.36], <i>p</i> = 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], <i>p</i> = 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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MASLD and ALD, but not SLD-MD[−], are independently associated with the development of CKD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 1","pages":"34-45"},"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}