Hepatology Research最新文献

{"title":"Circulating and hepatic levels of growth differentiation factor 15 in patients with metabolic dysfunction-associated steatotic liver disease","authors":"Mikkel Parsberg Werge,&nbsp;Josephine Grandt,&nbsp;Mira Thing,&nbsp;Liv Eline Hetland,&nbsp;Elias Badal Rashu,&nbsp;Anne-Sofie Houlberg Jensen,&nbsp;Anders Ellekær Junker,&nbsp;Michael Martin Richter,&nbsp;Søren Møller,&nbsp;Flemming Bendtsen,&nbsp;Lea Mørch Harder,&nbsp;Gianluca Mazzoni,&nbsp;Birgitte Martine Viuff,&nbsp;Henning Hvid,&nbsp;Cesar Augusto Prada-Medina,&nbsp;Sebastian Beck Jørgensen,&nbsp;Kristian Moss Bendtsen,&nbsp;Jonas Kildegaard,&nbsp;Mogens Vyberg,&nbsp;Reza Serizawa,&nbsp;Elisabeth Douglas Galsgaard,&nbsp;Nicolai Jacob Wewer Albrechtsen,&nbsp;Lise Lotte Gluud","doi":"10.1111/hepr.14148","DOIUrl":"https://doi.org/10.1111/hepr.14148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Increased growth differentiation factor 15 (GDF15) may reflect impaired metabolic health and an inflammatory state in metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the role of GDF15 in histologically verified MASLD in a meal test (discovery) cohort (<i>n</i> = 20) and a prospective (validation) cohort with 2 years of follow-up (<i>n</i> = 276).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants were evaluated clinically and histologically in both cohorts. Fibrosis severity was classified as no/mild (F0/F1) or significant (F2–4). Plasma GDF15 was measured by enzyme-linked immunosorbent assays and the SOMAScan platform. Hepatic GDF15 mRNA expression was analyzed by RNA in situ hybridization and bulk RNA-sequencing. In addition, we used data from public single-nucleus RNA-sequencing datasets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In both cohorts, plasma GDF15 was increased in MASLD compared with healthy controls (<i>p</i> &lt; 0.0001) with the highest levels in patients with significant fibrosis (area under the curve 0.83; 95% confidence interval [CI], 0.76–0.91). The GDF15 levels were unaffected by a standardized meal and there was no difference in peripheral or hepatic venous concentrations. After 2 years, the increase in GDF15 levels was reduced in patients treated with glucagon-like peptide receptor agonists (GLP-1-RA) compared to patients receiving lifestyle advice (−28%; 95% CI, −44 to −8; <i>p</i> = 0.01). Plasma GDF15 was associated with circulating insulin-like growth factor 1 and related proteins. Hepatic GDF15 mRNA was mainly expressed in hepatocytes and in cholangiocytes in fibrotic areas and was increased in MASLD (<i>p</i> = 0.02) with the highest expression in the group with steatohepatitis (<i>p</i> = 0.009).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Increased hepatic and circulating GDF15 are found in MASLD. Treatment with GLP-1-RA may reduce GDF15, possibly reflecting beneficial metabolic and inflammatory effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"492-504"},"PeriodicalIF":3.9,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762290","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":"Prediction of intrahepatic covalently closed circular DNA levels in patients with resolved hepatitis B virus infection: Impact of serum antibody to hepatitis B core antigen titers","authors":"Sung Kwan Bae,&nbsp;Junichi Arita,&nbsp;Nobuhisa Akamatsu,&nbsp;Akihiko Ichida,&nbsp;Yujiro Nishioka,&nbsp;Akinori Miyata,&nbsp;Takuya Kawahara,&nbsp;Yoshinori Inagaki,&nbsp;Yoshikuni Kawaguchi,&nbsp;Junichi Kaneko,&nbsp;Sumihito Tamura,&nbsp;Yasuhito Tanaka,&nbsp;Hiroshi Yotsuyanagi,&nbsp;Kyoji Moriya,&nbsp;Kiyoshi Hasegawa","doi":"10.1111/hepr.14146","DOIUrl":"https://doi.org/10.1111/hepr.14146","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The correlation between intrahepatic covalently closed circular DNA (cccDNA) levels and serum hepatitis B virus (HBV) markers in patients with resolved HBV infection (hepatitis B surface antigen [HBsAg]-negative and antibody to hepatitis B core antigen [anti-HBc]-positive) is unclear. We therefore examined the utility of anti-HBc titers as a surrogate marker of intrahepatic cccDNA levels in patients with resolved HBV infections.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Among 1005 patients who underwent hepatectomy between 2010 and 2018, a retrospective review was performed in 114 patients (76 with resolved HBV infection and 38 HBsAg-positive) with frozen specimens of the background liver. Clinical, biochemical, and virological data, including intrahepatic cccDNA levels, were retrospectively evaluated. Intrahepatic cccDNA levels were measured using droplet digital polymerase chain reaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Intrahepatic cccDNA levels positively correlated with serum HBsAg levels (<i>r</i> = 0.609, <i>p</i> &lt; 0.001) and anti-HBc titers (<i>r</i> = 0.542, <i>p</i> &lt; 0.001). An intrahepatic cccDNA level of 22.2 copies/μg was the optimal cut-off for HBsAg positivity, with a sensitivity of 86.8% and specificity of 89.5%. Of the 76 cases with resolved HBV infection, 8 had high levels of intrahepatic cccDNA (≥22.2 copies/μg). Multivariate analyses showed that anti-HBc ≥ 11.0 sample/cut-off (S/CO) was an independent risk factor for high intrahepatic cccDNA levels (odds ratio, 12.6; 95% confidence interval, 2.4–66.156; <i>P</i> = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Anti-HBc titers were positively correlated with intrahepatic cccDNA levels. Even in patients with resolved HBV infection, anti-HBc ≥ 11.0 S/CO was considered to indicate high intrahepatic cccDNA levels, comparable to those in HBsAg-positive cases. In this group, careful monitoring is required during immunosuppressive therapy to prevent HBV reactivation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"471-478"},"PeriodicalIF":3.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762010","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":"Immune-related adverse event detection in liver cancer patients treated with immune checkpoint inhibitors: Nationwide exploratory survey in Japan","authors":"Masako Shomura,&nbsp;Haruka Okabe,&nbsp;Maya Sakakibara,&nbsp;Naho Yaguchi,&nbsp;Sachiko Takahira,&nbsp;Emi Sato,&nbsp;Koichi Shiraishi,&nbsp;Yoshitaka Arase,&nbsp;Kota Tsuruya,&nbsp;Shunji Hirose,&nbsp;Yusuke Mishima,&nbsp;Tatehiro Kagawa","doi":"10.1111/hepr.14144","DOIUrl":"10.1111/hepr.14144","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This study aimed to comprehensively assess the incidence of immune-related adverse events (irAEs) and the detection systems in place for patients with liver cancer undergoing treatment with immune checkpoint inhibitors (ICIs), using a self-administered anonymous questionnaire. The questionnaire was designed to gather crucial insights into the management of irAEs in these patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A self-administered anonymous questionnaire was sent to 456 liver disease collaborative base hospitals and cancer care coordination base hospitals in Japan.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Responses were received from 112 facilities, indicating a response rate of 25%. The region with the highest response rate was Kanto (22%, 24 sites), followed by Kyushu (19%, 21 sites), Chubu (14%, 15 sites), and Kinki (14%, 15 sites). The number of patients with hepatocellular carcinoma (HCC) who received ICI treatment varied, with a mean ± SD of 20.4 ± 19.4 cases per year per facility. The number of full-time physicians who provided ICI treatment for HCC was 4.2 ± 3.3 (mean ± SD), ranging from 0 to 24 per facility. Of these, the majority included hepatologists and oncologists, whose numbers were 3.3 ± 2.4 (mean ± SD) (range, 0–11) and 0.8 ± 1.0 (0–3), respectively. Gastroenterologists and internal medicine specialists participated in the treatment at some facilities.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The survey results revealed that physicians administered ICI therapy for an average of 20 HCC cases per institution, with more than 17 types of irAEs reported. The most common irAEs were hepatic dysfunction, followed by thyroid dysfunction, skin disorders, interstitial pneumonia, and renal dysfunction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"547-555"},"PeriodicalIF":3.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768553","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":"Clinical benefits of partial splenic embolization for cancer patients","authors":"Toru Beppu,&nbsp;Toshiro Masuda,&nbsp;Katsunori Imai,&nbsp;Hiromitsu Hayashi","doi":"10.1111/hepr.14142","DOIUrl":"10.1111/hepr.14142","url":null,"abstract":"<p>Partial splenic embolization (PSE) has developed as an alternative to surgical splenectomy, mainly to improve hypersplenism and esophagogastric varices in cirrhotic patients. We proposed the novel concept that splenic infarction volume, rather than the splenic infarction ratio, is essential for patients receiving PSE. A splenic infarction volume between 388 and 540 mL is suitable for a sufficient increase in platelet count and less severe PSE-related complications. When restricted to patients with massive splenomegaly &gt;700 mL, the noninfarcted volume of the spleen plays an important role in increasing platelet counts. Based on the splenic volume concept, PSE or laparoscopic splenectomy should be selected. Partial splenic embolization is effective for cancer patients with hypersplenism. Hypersplenism can occur due to portal vein congestion by thrombosis or tumor thrombosis, and hepatic sinusoidal obstruction syndrome after oxaliplatin-including chemotherapy other than liver cirrhosis. Therefore, PSE has been emphasized as a pretreatment intervention for invasive treatments for cancer patients and is applied synchronously with systemic chemotherapy or chemoembolization for patients with liver malignancies. It was reported that additional PSE on chemoembolization can prolong progression-free survival for patients with hepatocellular carcinoma. Moreover, PSE can improve liver function and fibrosis, promote liver regeneration, and activate host immunity. Partial splenic embolization can result in thrombocytosis (&lt;200 × 10⁹/L), but this platelet count is unlikely to promote cancer progression. Partial splenic embolization can improve hypersplenism caused by various factors related to the patient's comorbidity and cancer treatment. Our splenic volume concept helps identify appropriate treatment procedures. A proper understanding of PSE and its dissemination is strongly required.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 1","pages":"4-11"},"PeriodicalIF":3.9,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754931","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":"Developing a feasible classification model for surgical hepatocellular carcinoma: More questions than answers","authors":"Teh-Ia Huo,&nbsp;Shu-Yein Ho","doi":"10.1111/hepr.14140","DOIUrl":"10.1111/hepr.14140","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"622-623"},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750810","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":"Aspartate aminotransferase-to-platelet ratio index outperforms Fibrosis-4 in 2843 Korean patients with metabolic dysfunction-associated steatotic liver disease","authors":"Se Young Jang,&nbsp;Ki Tae Yoon,&nbsp;Young Youn Cho,&nbsp;Hoon Gil Jo,&nbsp;Yang Hyun Baek,&nbsp;Sang Yi Moon,&nbsp;Ae Jeong Jo,&nbsp;Young-Oh Kweon,&nbsp;Soo Young Park,&nbsp;Yu Rim Lee,&nbsp;Dae Won Jun,&nbsp;Won Young Tak","doi":"10.1111/hepr.14143","DOIUrl":"10.1111/hepr.14143","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The definition of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration-controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and serum Mac-2-binding protein glycosylation isomer were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis ≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis ≥F3, and 0.890, 0.884, and 0.889 for fibrosis ≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB-4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis ≥F2, 0.788, 0.814, and 0.79 for fibrosis ≥F3, and 0.846, 0.859, and 0.856 for fibrosis ≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64 years for fibrosis ≥F4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age-stratified analyses. Further research is needed to establish standardized cut-off values and enhance the clinical utility of these markers in managing liver fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"479-491"},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750803","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 diagnostic criteria for mild-to-advanced stages of Fontan-associated liver disease: A nationwide epidemiological survey in Japan","authors":"Tomomi Kogiso,&nbsp;Daisuke Tokuhara,&nbsp;Satoko Ohfuji,&nbsp;Atsushi Tanaka,&nbsp;Tatsuya Kanto","doi":"10.1111/hepr.14141","DOIUrl":"10.1111/hepr.14141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Fontan-associated liver disease (FALD) is a complication after Fontan surgery, and a common cause of liver tumors and cirrhosis. However, no diagnostic criteria for FALD have been established, leading to an underestimation of its prevalence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a national survey to elucidate the characteristics of FALD by collecting data from high-volume centers managing patients who had undergone the Fontan surgery in Japan. In total, 1168 patients were enrolled in the study. First, we examined typical liver findings on ultrasonography after the Fontan surgery. Next, we proposed diagnostic criteria for FALD and advanced FALD based on blood tests, imaging, liver tumors, and pathological examinations. We investigated the sensitivity of histologically diagnosed FALD and advanced FALD based on criteria for blood or imaging tests.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hepatomegaly, hepatic venous dilatation, caudate lobe enlargement, splenomegaly, liver atrophy, ascites, hepatocellular carcinoma, and hepatic tumors other than hepatocellular carcinoma were observed in 37.7%, 29.9%, 18.4%, 33.2%, 3.2%, 6.0%, 0.85%, and 10.0% of patients, respectively. Typical ultrasound findings of FALD included hepatomegaly, hepatic vein dilatation, and splenomegaly, reflecting liver congestion. With the progression of fibrosis, caudate lobe enlargement and splenomegaly became more prominent. Based on these findings, we proposed diagnostic criteria for FALD. Using these criteria, FALD was diagnosed in 1014 (86.8%) of the patients, and all patients with a pathological diagnosis of FALD were successfully identified. Eight patients were found to have pathological cirrhosis, and all were diagnosed with advanced FALD using our criteria based on blood tests or imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our diagnostic criteria facilitate detection of FALD or advanced FALD after the Fontan surgery. The accuracy of these criteria should be further evaluated.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"611-621"},"PeriodicalIF":3.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142727914","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":"Association of proteinuria with improved prognosis in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab, and the predictive role of serum vascular endothelial growth factor D levels: A multicenter retrospective study","authors":"Zijian Yang,&nbsp;Goki Suda,&nbsp;Takuya Sho,&nbsp;Osamu Maehara,&nbsp;Masatsugu Ohara,&nbsp;Tomoka Yoda,&nbsp;Qingjie Fu,&nbsp;Takashi Sasaki,&nbsp;Risako Kohya,&nbsp;Sonoe Yoshida,&nbsp;Shunichi Hosoda,&nbsp;Takashi Kitagataya,&nbsp;Naoki Kawagishi,&nbsp;Masato Nakai,&nbsp;Mitsuteru Natsuizaka,&nbsp;Koji Ogawa,&nbsp;Shunsuke Ohnishi,&nbsp;Yoshiya Yamamoto,&nbsp;Masaru Baba,&nbsp;Ren Yamada,&nbsp;Tomoe Kobayashi,&nbsp;Minhu Chen,&nbsp;Naoya Sakamoto,&nbsp;for the NORTE Study Group","doi":"10.1111/hepr.14139","DOIUrl":"10.1111/hepr.14139","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Atezolizumab/bevacizumab is a first-line therapy for unresectable hepatocellular carcinoma (HCC). Among several adverse events, grade ≥2 proteinuria is considered a significant adverse event that may cause bevacizumab interruption. Studies have shown that proteinuria might predict improved prognosis, although data are scarce and the association remains controversial, and the mechanisms and predictive factors remain unclear. We aimed to clarify these.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this multicenter retrospective study, we screened patients with HCC treated with atezolizumab/bevacizumab. The prognostic impact of grade ≥2 proteinuria was examined in patients with proper clinical data and preserved serum for growth factor analysis. For biomarker analysis predicting proteinuria, baseline serum vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D levels were analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study included 75 patients, and 32 (42.7%) experienced grade ≥2 proteinuria. No significant differences were observed between those with or without proteinuria, except for aspartate transaminase and alanine transaminase levels. Time-dependent Cox proportional hazards analysis revealed that grade ≥2 proteinuria was significantly associated with better prognosis (hazard ratio 0.221; 95% confidence interval 0.082–0.592; <i>p</i> = 0.003). In biomarker analysis, low baseline serum VEGF-C and VEGF-D levels were significantly associated with proteinuria, and multivariate analysis demonstrated that baseline serum VEGF-D level was significantly associated with grade ≥2 proteinuria (hazard ratio 0.101; 95% confidence interval 0.029–0.357; <i>p</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Grade ≥2 proteinuria in patients with unresectable HCC treated with atezolizumab/bevacizumab indicates a better prognosis, and baseline serum VEGF-D levels can help predict its occurrence. These findings can help in managing adverse events and prognosis in advanced HCC treated with atezolizumab/bevacizumab.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 3","pages":"433-443"},"PeriodicalIF":3.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710024","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 durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma in immunotherapy era clinical practice","authors":"Atsushi Hiraoka,&nbsp;Toshifumi Tada,&nbsp;Masashi Hirooka,&nbsp;Kazuya Kariyama,&nbsp;Joji Tani,&nbsp;Masanori Atsukawa,&nbsp;Koichi Takaguchi,&nbsp;Ei Itobayashi,&nbsp;Shinya Fukunishi,&nbsp;Kunihiko Tsuji,&nbsp;Toru Ishikawa,&nbsp;Kazuto Tajiri,&nbsp;Hideko Ohama,&nbsp;Hidenori Toyoda,&nbsp;Chikara Ogawa,&nbsp;Takashi Nishimura,&nbsp;Takeshi Hatanaka,&nbsp;Satoru Kakizaki,&nbsp;Kazuhito Kawata,&nbsp;Atsushi Naganuma,&nbsp;Hisashi Kosaka,&nbsp;Tomomitsu Matono,&nbsp;Hidekatsu Kuroda,&nbsp;Yutaka Yata,&nbsp;Hiroki Nishikawa,&nbsp;Michitaka Imai,&nbsp;Tomoko Aoki,&nbsp;Hironori Ochi,&nbsp;Fujimasa Tada,&nbsp;Shinichiro Nakamura,&nbsp;Yoshiko Nakamura,&nbsp;Kazuhiro Nouso,&nbsp;Asahiro Morishita,&nbsp;Norio Itokawa,&nbsp;Tomomi Okubo,&nbsp;Taeang Arai,&nbsp;Akemi Tsutsui,&nbsp;Takuya Nagano,&nbsp;Kazunari Tanaka,&nbsp;Hironori Tanaka,&nbsp;Yuichi Koshiyama,&nbsp;Yuki Kanayama,&nbsp;Hidenao Noritake,&nbsp;Hirayuki Enomoto,&nbsp;Masaki Kaibori,&nbsp;Yoichi Hiasa,&nbsp;Masatoshi Kudo,&nbsp;Takashi Kumada,&nbsp;RELPEC Group and HCC 48 Group","doi":"10.1111/hepr.14136","DOIUrl":"10.1111/hepr.14136","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Since the development of tremelimumab plus durvalumab (Dur/Tre) for unresectable hepatocellular carcinoma (uHCC), it has been used as not only an initial but also later line treatment in clinical practice. This study aimed to elucidate clinical prognostic factors for progression-free survival (PFS) in Dur/Tre treatment cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Enrolled were 183 uHCC patients treated with Dur/Tre from 2023 to May 2024 (median age, 74 years; male patients, 152; Child–Pugh class A:B, 150:33; Barcelona Clinic Liver Cancer stage B:C, 59:124; initial line use, 64). Clinical factors with prognostic influence on PFS in these patients were retrospectively evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The median observation period was 7.2 months (interquartile range, 3.2–10.4). History of atezolizumab plus bevacizumab (Atz/Bev) treatment was the only significant prognostic factor for PFS at introduction of Dur/Tre in multivariate analysis (hazard ratio 2.040, <i>p</i> = 0.028) (median PFS: without vs. with = 5.6 vs. 2.7 months, <i>p</i> &lt; 0.001). Although immune-mediated adverse events (imAE) occurrence was only significant in univariate analysis, when objective response and disease control rates were examined according to imAE positivity (any grade) at the time of analysis, those were noted in 14.4% and 39.2%, respectively, of patients without imAE, while in patients with imAE (any grade), they were noted in 18.2% and 56.1%, respectively (<i>p</i> = 0.523 and <i>p</i> = 0.038, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>History of Atz/Bev treatment may be an independent clinical factor for poor PFS at Dur/Tre introduction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 3","pages":"444-453"},"PeriodicalIF":3.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619102","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":"Refining the predictive utility of aspartate aminotransferase to platelet ratio index in nonalcoholic fatty liver disease patients with COVID-19","authors":"Kengo Matsumoto,&nbsp;Tsutomu Nishida","doi":"10.1111/hepr.14137","DOIUrl":"10.1111/hepr.14137","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 3","pages":"465-467"},"PeriodicalIF":3.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604402","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}