Hepatology Research最新文献

{"title":"Involvement of the ADAMTS13–von Willebrand factor axis in acute kidney injury in mice with liver cirrhosis","authors":"Masayoshi Takami,&nbsp;Norihisa Nishimura,&nbsp;Kosuke Kaji,&nbsp;Nobuyuki Yorioka,&nbsp;Hiroyuki Masuda,&nbsp;Hiroaki Takaya,&nbsp;Koh Kitagawa,&nbsp;Shinya Sato,&nbsp;Tadashi Namisaki,&nbsp;Hitoshi Yoshiji","doi":"10.1111/hepr.14181","DOIUrl":"10.1111/hepr.14181","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Hepatorenal syndrome-induced acute kidney injury (AKI) comprises AKI and liver cirrhosis (LC) and is a risk factor for poor prognoses of patients with LC. Decreased a disintegrin-like metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) activity and increased von Willebrand factor (vWF) antigen levels are associated with LC progression and portal hypertension. We investigated the role of the ADAMTS13–vWF axis in AKI using an LC mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Wild-type and ADAMTS13-deficient (Adamts13^−/−) 129+Ter/Sv mice comprised the negative control and AKI groups. AKI was induced by intraperitoneal carbon tetrachloride, a single injection of a double dose of carbon tetrachloride, and lipopolysaccharide administration. Wild-type and vWF-deficient C57/B6J mice comprised a secondary animal model. Effects of ADAMTS13 alterations on liver and kidney injuries, and the role of vWF in AKI in the cirrhotic mouse model were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AKI groups of wild-type and Adamts13^−/− mice showed increased serum aspartate aminotransferase/alanine aminotransferase and blood urea nitrogen/creatinine levels. Significantly greater changes in Adamts13^−/− mice were observed. Blood flow in the liver and kidney was significantly decreased in the AKI group of Adamts13^−/− mice. The AKI group of Adamts13^−/− mice also demonstrated inflammatory changes, including increased F4/80-positive cells and renal injury markers in the kidney. Oxidative stress markers were increased in Adamts13^−/− mice after AKI induction. Conversely, vWF-deficient mice were protected from liver and kidney damage, and showed reduced tissue blood flow, inflammation, and oxidative stress responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>An imbalanced ADAMTS13–vWF axis may play a critical role in AKI progression with LC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 6","pages":"844-858"},"PeriodicalIF":3.9,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14181","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984361","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":"Cachexia is an independent predictor of mortality in patients with cirrhosis","authors":"Takao Miwa,&nbsp;Goki Suda,&nbsp;Ryosuke Tateishi,&nbsp;Tatsunori Hanai,&nbsp;Masatsugu Ohara,&nbsp;Yasuhiro Hagiwara,&nbsp;Shinji Unome,&nbsp;Kazuya Okushin,&nbsp;Mina Nakagawa,&nbsp;Naoya Sakamoto,&nbsp;Masahito Shimizu","doi":"10.1111/hepr.14183","DOIUrl":"10.1111/hepr.14183","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Cachexia is a systemic response syndrome characterized by disabling wasting during disease progression. This study aimed to elucidate factors associated with cachexia in patients with cirrhosis and to examine the impact of cachexia on patient survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicenter retrospective cohort study included patients with cirrhosis admitted to two distinct institutes in Japan. Cachexia was diagnosed according to the criteria proposed by the Asian Working Group for Cachexia. Factors associated with cachexia and the prognostic impact of cachexia were assessed using logistic regression and Cox proportional hazards regression, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 723 patients enrolled (median [interquartile range] age, 71 [64–77] years; 456 [63%] were male; and 390 [54%] had viral hepatitis), 200 (28%) met the criteria for cachexia diagnosis, with the prevalence increasing with Child–Pugh class from A (17%) to B (40%) and C (66%). Multivariable logistic regression analysis revealed that age and indices of liver function reserve, including Child–Pugh score, were associated with cachexia, whereas sex, etiology of cirrhosis, and complications with hepatocellular carcinoma (HCC) were not. During a median follow-up period of 3.2 years, 264 (37%) patients died. Multivariable Cox regression analyses showed that cachexia was independently associated with increased mortality (adjusted hazard ratio, 1.62; 95% confidence interval, 1.24–2.12), along with factors related to liver function, HCC, and alcohol-associated liver disease as the etiology. [Correction added on 22 May 2025, after first online publication: The adjusted hazard ratio and confidence interval in the Results section of Abstract have been changed from ‘1.59; 95% and 1.43–1.77’ to ‘1.62; 95% and 1.24–2.12’.]</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Cachexia is associated with poor liver function in patients with cirrhosis and is an independent prognostic factor.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 6","pages":"859-867"},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017694","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":"Weighted prevalence and associated risk factors of hepatitis E virus antibodies among pregnant women in rural Burkina Faso using dried blood spot samples","authors":"Chanroth Chhoung,&nbsp;Serge Ouoba,&nbsp;Moussa Lingani,&nbsp;Ko Ko,&nbsp;Zayar Phyo,&nbsp;Ulugbek Khudayberdievich Mirzaev,&nbsp;Yayoi Yoshinaga,&nbsp;Golda Ataa Akuffo,&nbsp;Aya Sugiyama,&nbsp;Tomoyuki Akita,&nbsp;Shingo Fukuma,&nbsp;Halidou Tinto,&nbsp;Kazuaki Takahashi,&nbsp;Junko Tanaka","doi":"10.1111/hepr.14180","DOIUrl":"10.1111/hepr.14180","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To estimate the weighted prevalence of hepatitis E virus (HEV) antibodies and risk factors among pregnant women in Burkina Faso and to evaluate the efficiency of dried blood spots (DBS) in detecting HEV antibodies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We first evaluated the efficiency of DBS detecting HEV antibodies by comparing 62 DBS with matched serum samples using recomWell IgG and IgM kits (Mikrogen Diagnostik). Anti-HEV immunoglobulin G (IgG) and immunoglobulin M (IgM) were identified in 491 DBS samples collected from pregnant women in Burkina Faso using recomWell kits. HEV RNA was tested using HEV nested polymerase chain reaction among HEV-antibodies positive. The survey-weighted method was applied for prevalence calculations and risk factors analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The detection of anti-HEV IgG and anti-HEV IgM in DBS samples revealed a sensitivity of 96.7% and 76.7% and a specificity of 100% and 93.8% compared to serum samples, respectively. Among 491 pregnant women tested, the weighted prevalence of anti-HEV IgG was 18.6%, and anti-HEV IgM was 2.5%, with no HEV RNA detected. A significant age-related increase was observed in the prevalence of anti-HEV IgG (<i>p</i> &lt; 0.001), while no significant was found for anti-HEV IgM-positivity (<i>p</i> = 0.1451). Multiparity was significantly associated with anti-HEV IgG-positivity, while women aged 25–34 years were at higher risk of anti-HEV IgM-positivity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study revealed that DBS is a reliable alternative for HEV seroepidemiological studies, especially in resource-limited settings, although further investigation is needed for anti-HEV IgM detection. The weighted prevalence of anti-HEV IgG was 18.6% and anti-HEV IgM was 2.5%, highlighting the ongoing burden of HEV infection, particularly in high-risk groups like pregnant women in rural Burkina Faso.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 6","pages":"795-806"},"PeriodicalIF":3.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14180","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963356","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":"Grip strength is a strong indicator of osteoporosis in both women and men with chronic liver disease","authors":"Tatsuki Ichikawa,&nbsp;Satoshi Miuma,&nbsp;Mio Yamashima,&nbsp;Shinobu Yamamichi,&nbsp;Makiko Koike,&nbsp;Yusuke Nakano,&nbsp;Hiroyuki Yajima,&nbsp;Osamu Miyazaki,&nbsp;Tomonari Ikeda,&nbsp;Takuma Okamura,&nbsp;Naohiro Komatsu,&nbsp;Sayuri Sugio,&nbsp;Miruki Yoshino,&nbsp;Hisamitsu Miyaaki","doi":"10.1111/hepr.14179","DOIUrl":"10.1111/hepr.14179","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Osteoporosis (Op) and sarcopenia are common complications of chronic liver disease. We sought to identify clinical screening indicators for Op, and evaluated their relationship with bone and muscle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>We retrospectively evaluated 495 patients (264 women) with chronic liver disease who underwent a bone mineral density evaluation at their first outpatient visit. Bone mineral density was measured in the lumbar spine (mean of L2–L4) and femoral neck using dual-energy X-ray absorptiometry. The relationship between Op and various clinical factors was examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Op was diagnosed in 156 patients (31.5%). Sex, age, steatotic liver disease, fibrosis-4 index, body mass index, and grip strength (GS) were associated with Op. In logistic multivariate analysis, Op was associated with older age (&gt;68 years in women and &gt;69 years in men), low body mass index (&lt;20), and low GS (&lt;18 kg in women and &lt;28 kg in men). Factors associated with Op were analyzed in 254 patients whose body composition was evaluated. Op was associated with older age, low GS, and low skeletal muscle (&lt;86 cm²) in women, and only low skeletal muscle (&lt;116 cm²) in men. Combined Op and sarcopenia was observed in 19.6% of patients. Sarcopenia was associated with Op in both sexes. The number of patients with a low GS increased with age in both sexes. However, the number of patients with low bone mineral density increased with age in women, but not in men.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Low GS is an indicator of Op in both sexes. Overlooked Op in chronic liver disease should be screened using GS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 6","pages":"830-843"},"PeriodicalIF":3.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970114","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":"Potential indications for liver transplant in Child–Pugh A and Model for End-stage Liver Disease exception for hepatocellular carcinoma in Japan","authors":"Ryoichi Goto,&nbsp;Tsuyoshi Shimamura,&nbsp;Tomoaki Nakajima,&nbsp;Koji Ogawa,&nbsp;Kazunari Tanaka,&nbsp;Takao Shimizu,&nbsp;Ryosuke Minami,&nbsp;Takeshi Matsui,&nbsp;Noriyuki Akutsu,&nbsp;Shigeru Sasaki,&nbsp;Tatsuhiko Kakisaka,&nbsp;Norio Kawamura,&nbsp;Masaaki Watanabe,&nbsp;Akinobu Taketomi","doi":"10.1111/hepr.14178","DOIUrl":"10.1111/hepr.14178","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In 2019, expanded criteria for hepatocellular carcinoma (HCC), known as 5-5-500 (size ≤5 cm, number ≤5, alpha-fetoprotein ≤500 ng/mL), as well as Model for End-stage Liver Disease (MELD) exception, were implemented in Japan. In the present study, we evaluated liver transplantation indications and the Japanese allocation policy for HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adults with HCC were evaluated between January 2013 and December 2017 in a multicenter study in Japan. The patients were aged ≤65 years, in line with the limits of Japanese transplant center limits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>HCC patients (<i>n</i> = 289) were classified as Child–Pugh A (74%), B (18%), or C (8%). Of these, 178 (62%) and 185 (64%) met the Milan and 5-5-500 criteria, respectively. The respective 1- and 5-year overall survival rates of patients who met the criteria were 100% and 88.1% in Child–Pugh A, 91.7% and 30.6% in B, and 72.9% and 0% in C without access to liver transplantation. For Child–Pugh A patients, we developed a risk score using the Child–Pugh score, des-gamma-carboxy prothrombin, tumor-node-metastasis stage grade, as well as albumin-bilirubin and albumin-bilirubin tumor-node-metastasis stage , which predicted worse prognosis. Additionally, we showed the characteristics of patients who achieved MELD exception points high enough to receive an organ: survival at least 2 years after waitlist registration, relatively good liver functional reserve, and sufficient tumor control with multiple treatments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High-risk patients, identified by our scoring system and albumin-bilirubin tumor-node-metastasis stage ≥2 in Child–Pugh A, should be considered for liver transplantation eligibility. The allocation policy for HCC should be revised based on precise evaluations on a regular basis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 6","pages":"896-907"},"PeriodicalIF":3.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063517","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":"Comparison between Japan and Korea in liver transplantation: Focusing on a higher deceased donation rate in Korea.","authors":"Soo Ryang Kim, Soo Ki Kim, Akira Asai, Hiroki Nishikawa","doi":"10.1111/hepr.14177","DOIUrl":"https://doi.org/10.1111/hepr.14177","url":null,"abstract":"<p><p>Over the past 30 years, liver transplantations (LTs) and deceased-donor LTs (DDLTs) have been higher in Korea than in Japan. In 2019, the number of DDLT reached 88 (22.3% of LTs) in Japan and 391 (24.7% of LTs) in Korea. The deceased-donor rate (per million population) was 0.70 in Japan and 7.56 in Korea. Presently, Korea is one of the Asian countries with the highest rate of DDLT. Factors conducive to the deceased donation rate in Korea encompass the socio-legal system, including the Korean Network for Organ Sharing, Korean Organ Donation Agency, the healthcare system and public awareness. During 2009-2019, two major indications of DDLT were hepatitis B cirrhosis and alcoholic liver disease in Korea, and acute liver failure and metabolic diseases in Japan. For living-donor LT, two major indications were hepatitis B cirrhosis and neoplastic diseases in Korea, and biliary atresia and neoplastic diseases in Japan. During the COVID-19 pandemic, the indications for DDLT in Korea were alcoholic liver disease and hepatitis B cirrhosis with a higher rate of alcoholic liver disease than during the pre-pandemic period. In 2021, the 5-year survival rate of DDLT was 66.5% in Korea compared with 82.6% in Japan, whereas that rate of living-donor LT in Korea reached 80.8% compared with 79.4% in Japan. To promote LT in Japan and Korea, mutual understanding and intercommunication between the two countries is crucial.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990180","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":"Vascular endothelial growth factor released from lenvatinib-resistant hepatocellular carcinoma promotes malignant behavior and drug resistance through tumor-associated macrophages","authors":"Yukako Takehara,&nbsp;Yuhei Waki,&nbsp;Yuji Morine,&nbsp;Yu Saito,&nbsp;Hiroki Teraoku,&nbsp;Yuma Wada,&nbsp;Shinichiro Yamada,&nbsp;Tetsuya Ikemoto,&nbsp;Mitsuo Shimada","doi":"10.1111/hepr.14173","DOIUrl":"https://doi.org/10.1111/hepr.14173","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Lenvatinib is one of the molecularly targeted drugs used worldwide in hepatocellular carcinoma (HCC) treatment, but the acquisition of drug resistance is a major problem. The mechanisms that make HCC lenvatinib-resistant (LR) in the tumor microenvironment are largely unknown. Here, we examined the impact of LR HCC cells on tumor-associated macrophages (TAMs) regarding tumor progression and drug resistance, focusing on vascular endothelial growth factor (VEGF) secretion by LR HCC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Hepatocellular carcinoma cells were cultured with lenvatinib to obtain cells with approximately 4-fold lenvatinib resistance. Monocyte-derived macrophages were cultured in the conditioned medium (CM) of LR HCC to induce LR TAMs. Secretion of VEGF by naïve HCC cells, LR HCC cells, TAMs, and LR TAMs was assessed. The macrophage phenotype and VEGFR2 expression in both TAMs were evaluated. Additionally, the effects of inhibiting VEGF secretion in LR HCC cells on the TAM malignant potential were investigated. Tumor-associated macrophages induced by VEGF-inhibited LR HCC were defined as modified LR TAMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Secretion of VEGF was elevated in LR HCC. Lenvatinib-resistant TAMs had increased expression of M2-like macrophage markers and increased expression of VEGFR2 compared with naïve HCC-derived TAMs. Lenvatinib-resistant TAM-CM promoted malignant behaviors and lenvatinib resistance in naïve HCC cells and LR HCC cells. However, the modified LR TAMs did not increase M2 polarization markers or decreased VEGFR2 expression. The elevated VEGF secretion in LR TAMs was not seen in modified LR TAMs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Increased VEGF secretion from LR HCC promoted malignant behaviors and lenvatinib resistance through LR TAMs in the tumor microenvironment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 5","pages":"752-762"},"PeriodicalIF":3.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902870","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":"Pemafibrate improves liver biochemistry and GLOBE scores in patients with primary biliary cholangitis: Nationwide, multicenter study by the Japanese Red Cross Liver Study Group","authors":"Keiji Tsuji,&nbsp;Nobuharu Tamaki,&nbsp;Masayuki Kurosaki,&nbsp;Nami Mori,&nbsp;Shintaro Takaki,&nbsp;Kazuki Ohya,&nbsp;Toshie Mashiba,&nbsp;Hironori Ochi,&nbsp;Haruhiko Kobashi,&nbsp;Chikara Ogawa,&nbsp;Michiko Nonogi,&nbsp;Hideo Yoshida,&nbsp;Takehiro Akahane,&nbsp;Masahiko Kondo,&nbsp;Toyotaka Kasai,&nbsp;Hideki Fujii,&nbsp;Yasushi Uchida,&nbsp;Hirotaka Arai,&nbsp;Kaoru Tsuchiya,&nbsp;Namiki Izumi","doi":"10.1111/hepr.14172","DOIUrl":"https://doi.org/10.1111/hepr.14172","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor-α modulator, on patients with primary biliary cholangitis (PBC) complicated by dyslipidemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In total, 61 patients with PBC (Add-on group: 33 patients on ursodeoxycholic acid [UDCA] + pemafibrate combination therapy; Switch group: 28 patients who switched from UDCA + other fibrates to UDCA + pemafibrate combination therapy) were included in the study. Changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and GLOBE scores were retrospectively analyzed from 6 months before to 12 months after treatment. The POISE criteria were also used to evaluate the treatment efficacy after 12 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After 12 months of UDCA + pemafibrate combination therapy, AST significantly decreased from 45 ± 3 to 28 ± 3 U/L (<i>p</i> &lt; 0.05), ALT from 49 ± 5 to 32 ± 5 U/L (<i>p</i> &lt; 0.005), GGT from 155 ± 223 to 91 ± 182 U/L (<i>p</i> &lt; 0.005), and ALP from 1.4 ± 0.9 to 0.9 ± 0.8 × upper limit of normal (<i>p</i> &lt; 0.0005) in all patients. ALT, GGT, and ALP levels were significantly lower after 12 months of UDCA + pemafibrate combination therapy in both the Add-on and Switch groups. After 12 months of combination therapy, the mean GLOBE score of all patients significantly decreased from 0.37 to 0.01 (<i>p</i> &lt; 0.05) and the percentage of patients with a GLOBE score of 0.3 or higher decreased.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In patients with PBC who showed an inadequate response to prior therapy, pemafibrate add-on or switch therapy improved liver biochemistry and GLOBE scores. Pemafibrate may be useful as a second-line drug when UDCA alone is inadequate, or as an alternative after combination therapy with other fibrates.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 5","pages":"675-684"},"PeriodicalIF":3.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902864","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":"Serum alpha-fetoprotein/hepatocyte growth factor ratio as a novel biomarker predicting the prognosis of acute alcoholic hepatitis","authors":"Hiroki Inada,&nbsp;Katsuya Nagaoka,&nbsp;Kenyu Hashimoto,&nbsp;Toshinori Toyota,&nbsp;Satoshi Narahara,&nbsp;Sotaro Kurano,&nbsp;Takayuki Tokunaga,&nbsp;Kentaro Tanaka,&nbsp;Yoko Yoshimaru,&nbsp;Etsuko Iio,&nbsp;Takehisa Watanabe,&nbsp;Hiroko Setoyama,&nbsp;Yasuhito Tanaka","doi":"10.1111/hepr.14174","DOIUrl":"10.1111/hepr.14174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Acute alcoholic hepatitis (AAH) can be fatal, particularly when it progresses to severe alcoholic hepatitis. There are several prognostic markers, but none specifically reflects liver regenerative capacity. This study investigated the serum alpha-fetoprotein (AFP)/hepatocyte growth factor (HGF) ratio as a novel prognostic indicator for AAH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A single-center retrospective analysis was conducted on 20 AAH patients, including 12 with severe alcoholic hepatitis, hospitalized between April 2007 and September 2023. Serum AFP and HGF levels were measured at diagnosis, and the AFP/HGF ratio was calculated. Prognostic performance was assessed using receiver operating characteristic analysis, Kaplan–Meier survival analysis, and a validation cohort of 67 non-alcohol-related liver failure cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Receiver operating characteristic analysis demonstrated excellent prognostic performance for the AFP/HGF ratio, with an area under the curve of 0.97. Patients with high AFP/HGF ratios (≥1.86) had significantly longer overall survival than those with low ratios (&lt;1.86; <i>p</i> &lt; 0.001). The median survival time for the low-ratio group was 55 days. In severe alcoholic hepatitis patients, a high AFP/HGF ratio was also associated with significantly longer overall survival (<i>p</i> = 0.013). At diagnosis, surviving patients had significantly higher AFP/HGF ratios when compared with subsequently deceased patients (<i>p</i> = 0.005). In the non-AAH cohort, no significant difference was observed between groups, but survivors showed a trend toward higher AFP/HGF ratios.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The AFP/HGF ratio is a novel and highly specific prognostic marker for AAH, reflecting liver regenerative capacity. It may guide early therapeutic decisions and improve outcomes, particularly for high-risk AAH patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 6","pages":"922-931"},"PeriodicalIF":3.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017695","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":"Multicenter observational study to characterize fibroblast growth factor receptor 2 fusions or rearrangements in patients with advanced/metastatic cholangiocarcinoma","authors":"Tomoyuki Satake,&nbsp;Chigusa Morizane,&nbsp;Hiroyuki Isayama,&nbsp;Akio Katanuma,&nbsp;Masato Endo,&nbsp;Noritoshi Kobayashi,&nbsp;Yasushi Kojima,&nbsp;Shoji Kubo,&nbsp;Saburo Matsubara,&nbsp;Takeshi Shiraishi,&nbsp;Takashi Ohta,&nbsp;Tadashi Uwagawa,&nbsp;Shingo Kobayashi,&nbsp;Takatoshi Sahara,&nbsp;Setsuo Funasaka,&nbsp;Hiroki Ikezawa,&nbsp;Takuji Okusaka","doi":"10.1111/hepr.14176","DOIUrl":"10.1111/hepr.14176","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>We conducted this observational study to investigate patterns of fibroblast growth factor receptor 2 (<i>FGFR2</i>) fusions or rearrangements, and how they relate to other characteristics of patients with unresectable advanced cholangiocarcinoma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients aged 20 years or older with intrahepatic cholangiocarcinoma (ICC) or perihilar cholangiocarcinoma (PHC) had tumor samples assessed for <i>FGFR2</i> fusions or rearrangements by a break-apart fluorescence in situ hybridization probe kit analyzed at a central laboratory; multivariate analyses using a logistic regression model were conducted to investigate the relationship between <i>FGFR2</i> fusions or rearrangements and patients' baseline characteristics; two cut-off values (<i>p</i>-values of 0.15 and 0.05) were used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 453 patients observed, 25 (5.5%) had <i>FGFR2</i> fusions or rearrangements, corresponding with 7.4% (23/306) of patients with ICC and 1.4% (2/144) of patients with PHC. Of 426 evaluable patients, <i>FGFR2</i> fusions or rearrangements were associated with hepatitis C antibodies (odds ratio [OR] 6.901; <i>p</i> &lt; 0.05); patients who had PHC versus ICC (OR 0.273; <i>p</i> &lt; 0.05) or were men (OR 0.431; <i>p</i> &lt; 0.15) were less likely to have <i>FGFR2</i> fusions or rearrangements. Of 252 evaluable patients with ICC, <i>FGFR2</i> fusions or rearrangements were associated with hepatitis C antibodies (OR 9.500; <i>p</i> &lt; 0.05); patients who were men (OR 0.419; <i>p</i> &lt; 0.05) or were aged ≥65 years (OR 0.406; <i>p</i> &lt; 0.15) were less likely to have <i>FGFR2</i> fusions or rearrangements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This large observational study helps to characterize factors associated with <i>FGFR2</i> fusions or rearrangements. Further study is warranted to explore differences in prevalence among different geographic populations and patients with PHC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 7","pages":"1005-1014"},"PeriodicalIF":3.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981341","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}