Circulating tumor cells (CTC) have shown promise in predicting the outcomes of adjuvant treatments for several malignancies. The clinical significance of CTC in predicting the efficacy of tyrosine kinase inhibitor (TKI) administration in patients with hepatocellular carcinoma (HCC) was unclear.
Methods
A total of 429 patients who underwent liver transplantation for HCC had provided 335 preoperative and 373 postoperative blood samples that could be used for CTC detection (pre-CTC and post-CTC). The association of the pre-CTC and post-CTC findings with the efficacy of TKI administration was assessed. Additionally, CTC surveillance was performed in 27 patients during TKI administration.
Results
Patients with detectable post-CTC, instead of pre-CTC, showed a significantly longer time to recurrence when receiving a TKI after liver transplantation for HCC (hazard ratio 0.57; P = 0.042). Whereas patients without detectable post-CTC did not benefit from the TKI administration (P = 0.270). Furthermore, we also found that patients who persistently harbored CTC during TKI administration showed significantly higher early recurrence rates (≤1 year; 40% vs. 5.9%, P < 0.001) and a shorter time to recurrence (HR 7.03; P < 0.001) than those whose CTC status switched from positive to negative. In addition, longitudinal CTC monitoring demonstrated that CTC tended to reflect drug resistance during TKI administration.
Conclusions
The postoperative CTC level could predict the efficacy of TKI treatment for HCC patients after liver transplantation. Dynamic monitoring for CTC during treatment could sensitively reflect the response to the TKI, the development of drug resistance, and foresee tumor recurrence.
{"title":"Postoperative circulating tumor cells predict the benefits of tyrosine kinase inhibitor for hepatocellular carcinoma after transplantation","authors":"De-Zhen Guo, Shi-Yu Zhang, Man Yang, Yang Xu, Peng-Xiang Wang, Wei Guo, Xiao-Wu Huang, Jia Fan, Jian Zhou, Xin-Rong Yang, Jian-Wen Cheng","doi":"10.1111/hepr.14154","DOIUrl":"https://doi.org/10.1111/hepr.14154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Circulating tumor cells (CTC) have shown promise in predicting the outcomes of adjuvant treatments for several malignancies. The clinical significance of CTC in predicting the efficacy of tyrosine kinase inhibitor (TKI) administration in patients with hepatocellular carcinoma (HCC) was unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 429 patients who underwent liver transplantation for HCC had provided 335 preoperative and 373 postoperative blood samples that could be used for CTC detection (pre-CTC and post-CTC). The association of the pre-CTC and post-CTC findings with the efficacy of TKI administration was assessed. Additionally, CTC surveillance was performed in 27 patients during TKI administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with detectable post-CTC, instead of pre-CTC, showed a significantly longer time to recurrence when receiving a TKI after liver transplantation for HCC (hazard ratio 0.57; <i>P</i> = 0.042). Whereas patients without detectable post-CTC did not benefit from the TKI administration (<i>P</i> = 0.270). Furthermore, we also found that patients who persistently harbored CTC during TKI administration showed significantly higher early recurrence rates (≤1 year; 40% vs. 5.9%, <i>P</i> < 0.001) and a shorter time to recurrence (HR 7.03; <i>P</i> < 0.001) than those whose CTC status switched from positive to negative. In addition, longitudinal CTC monitoring demonstrated that CTC tended to reflect drug resistance during TKI administration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The postoperative CTC level could predict the efficacy of TKI treatment for HCC patients after liver transplantation. Dynamic monitoring for CTC during treatment could sensitively reflect the response to the TKI, the development of drug resistance, and foresee tumor recurrence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"588-599"},"PeriodicalIF":3.9,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762169","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}
Atezolizumab plus bevacizumab is an established first-line treatment for unresectable hepatocellular carcinoma (HCC). Our previous research identified CD8+ tumor-infiltrating lymphocytes (TILs) as a potential biomarker for predicting patient response to this therapy. However, not all HCC patients with CD8+ TILs respond favorably to atezolizumab and bevacizumab. Moreover, elevated serum C-reactive protein (CRP) levels have been associated with poor outcomes in patients treated with immune checkpoint inhibitors across various cancer types. The aim of this study was to determine whether CD8+ TIL numbers combined with serum CRP levels could collectively predict the response to atezolizumab and bevacizumab better than CD8+ TIL numbers alone.
Methods
A total of 46 HCC patients who provided liver biopsy samples were included. CD8+ TIL numbers in liver tissue were measured using immunohistochemistry.
Results
A group of 13 patients (28.3%) with high CD8+ TIL numbers and low (≤0.54 mg/dl) serum CRP levels demonstrated the highest treatment response rate. Furthermore, this group had a significantly longer median overall survival and progression-free survival than the remaining 33 patients. Multivariate analysis revealed that high CD8+ TIL numbers with low CRP levels (HR 0.264; p = 0.037) and Child–Pugh class A (HR 0.277; p = 0.009) were associated with improved overall survival.
Conclusions
These findings suggest that the combination of CD8+ TIL numbers and serum CRP levels may serve as a useful biomarker for predicting the efficacy of atezolizumab plus bevacizumab in HCC patients.
目的 阿特珠单抗联合贝伐单抗是治疗不可切除肝细胞癌（HCC）的成熟一线疗法。我们之前的研究发现，CD8+肿瘤浸润淋巴细胞（TILs）是预测患者对该疗法反应的潜在生物标志物。然而，并非所有具有 CD8+ TILs 的 HCC 患者都能对阿特珠单抗和贝伐珠单抗产生良好反应。此外，血清C反应蛋白（CRP）水平升高与接受免疫检查点抑制剂治疗的各种癌症患者的不良预后有关。本研究旨在确定 CD8+ TIL 数量与血清 CRP 水平相结合是否比单独的 CD8+ TIL 数量更能预测对阿特珠单抗和贝伐珠单抗的反应。 方法 共纳入 46 名提供肝活检样本的 HCC 患者。采用免疫组化方法测量肝组织中的 CD8+ TIL 数量。 结果 CD8+ TIL 数量高且血清 CRP 水平低（≤0.54 mg/dl）的 13 例患者（28.3%）的治疗反应率最高。此外，这组患者的中位总生存期和无进展生存期明显长于其余33名患者。多变量分析显示，CD8+ TIL 数量高、CRP 水平低（HR 0.264；p = 0.037）和 Child-Pugh 分级 A（HR 0.277；p = 0.009）与总生存期的改善相关。 结论 这些研究结果表明，CD8+ TIL 数量和血清 CRP 水平的组合可作为预测阿特珠单抗加贝伐单抗对 HCC 患者疗效的有用生物标志物。
{"title":"Tumor-infiltrating CD8+ T-cell numbers and serum C-reactive protein levels as a prognostic biomarker in hepatocellular carcinoma patients receiving atezolizumab plus bevacizumab","authors":"Akifumi Kuwano, Masayoshi Yada, Kosuke Tanaka, Junro Takahira, Hideo Suzuki, Yoshihiro Ohishi, Kenta Motomura","doi":"10.1111/hepr.14157","DOIUrl":"https://doi.org/10.1111/hepr.14157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Atezolizumab plus bevacizumab is an established first-line treatment for unresectable hepatocellular carcinoma (HCC). Our previous research identified CD8<sup>+</sup> tumor-infiltrating lymphocytes (TILs) as a potential biomarker for predicting patient response to this therapy. However, not all HCC patients with CD8<sup>+</sup> TILs respond favorably to atezolizumab and bevacizumab. Moreover, elevated serum C-reactive protein (CRP) levels have been associated with poor outcomes in patients treated with immune checkpoint inhibitors across various cancer types. The aim of this study was to determine whether CD8<sup>+</sup> TIL numbers combined with serum CRP levels could collectively predict the response to atezolizumab and bevacizumab better than CD8<sup>+</sup> TIL numbers alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 46 HCC patients who provided liver biopsy samples were included. CD8<sup>+</sup> TIL numbers in liver tissue were measured using immunohistochemistry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A group of 13 patients (28.3%) with high CD8<sup>+</sup> TIL numbers and low (≤0.54 mg/dl) serum CRP levels demonstrated the highest treatment response rate. Furthermore, this group had a significantly longer median overall survival and progression-free survival than the remaining 33 patients. Multivariate analysis revealed that high CD8<sup>+</sup> TIL numbers with low CRP levels (HR 0.264; <i>p</i> = 0.037) and Child–Pugh class A (HR 0.277; <i>p</i> = 0.009) were associated with improved overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings suggest that the combination of CD8<sup>+</sup> TIL numbers and serum CRP levels may serve as a useful biomarker for predicting the efficacy of atezolizumab plus bevacizumab in HCC patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"600-610"},"PeriodicalIF":3.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762037","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":"Expression patterns of hepatic Mac2-BP in the liver microenvironment","authors":"Tomoko Tadokoro","doi":"10.1111/hepr.14159","DOIUrl":"https://doi.org/10.1111/hepr.14159","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 2","pages":"166-167"},"PeriodicalIF":3.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111169","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":"Recent advances in systemic therapies for unresectable hepatocellular carcinoma and their impact on clinical outcomes","authors":"Kyoko Oura","doi":"10.1111/hepr.14158","DOIUrl":"https://doi.org/10.1111/hepr.14158","url":null,"abstract":"","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 2","pages":"163-165"},"PeriodicalIF":3.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143111171","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}
While the Fatty Liver Index (FLI) has been the most prominent among interpretable predictors for steatotic liver disease (SLD), we aimed to prepare a novel diagnostic/prognostic index better than FLI for SLD using a non-black-box and modified parsimonious machine learning method.
Methods
We included individuals who participated in an annual health checkup in Tokyo, Japan, between January 2008 and December 2018. In the training set (randomly selected 80% of the sample), we developed a novel interpretable model, Steatotic Liver Index (SLI), using a modified method of least absolute shrinkage and selection operator regression focusing on parsimony and interpretability using as few variables as FLI, and confirming its superiority to FLI using the test set (the remaining 20%). The predictive performance of the constructed index was assessed for the diagnosis, development, and remission of SLD.
Results
Among ultrasound data of 92 968 participants at the first health checkup, 20 380 (21.9%) had SLD. Using a modified method of least absolute shrinkage and selection operator regression, SLI was constructed with four variables: body mass index, waist circumference, alanine aminotransferase, and triglycerides. The C-statistic of SLI for SLD diagnosis was superior to that of FLI (0.909 vs. 0.892, p < 0.001). In participants without SLD, SLI was more accurate than FLI in predicting SLD development, whereas among those with SLD, SLI showed better accuracy in predicting SLD remission compared with FLI.
Conclusions
We developed SLI, a novel interpretable and parsimonious index for diagnosing SLD, which demonstrates superior predictive capability compared with FLI. Further studies are necessary to validate the diagnostic ability outside Japan.
{"title":"Steatotic liver index: An interpretable predictor of steatotic liver disease using machine learning with an enhanced shrinkage method","authors":"Akira Okada, Koji Oba, Takeshi Kimura, Yasuhiro Hagiwara, Sachiko Ono, Kayo Ikeda Kurakawa, Nobuaki Michihata, Toshimasa Yamauchi, Masaomi Nangaku, Yutaka Matsuyama, Takashi Kadowaki, Satoko Yamaguchi","doi":"10.1111/hepr.14156","DOIUrl":"https://doi.org/10.1111/hepr.14156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>While the Fatty Liver Index (FLI) has been the most prominent among interpretable predictors for steatotic liver disease (SLD), we aimed to prepare a novel diagnostic/prognostic index better than FLI for SLD using a non-black-box and modified parsimonious machine learning method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included individuals who participated in an annual health checkup in Tokyo, Japan, between January 2008 and December 2018. In the training set (randomly selected 80% of the sample), we developed a novel interpretable model, Steatotic Liver Index (SLI), using a modified method of least absolute shrinkage and selection operator regression focusing on parsimony and interpretability using as few variables as FLI, and confirming its superiority to FLI using the test set (the remaining 20%). The predictive performance of the constructed index was assessed for the diagnosis, development, and remission of SLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among ultrasound data of 92 968 participants at the first health checkup, 20 380 (21.9%) had SLD. Using a modified method of least absolute shrinkage and selection operator regression, SLI was constructed with four variables: body mass index, waist circumference, alanine aminotransferase, and triglycerides. The C-statistic of SLI for SLD diagnosis was superior to that of FLI (0.909 vs. 0.892, <i>p</i> < 0.001). In participants without SLD, SLI was more accurate than FLI in predicting SLD development, whereas among those with SLD, SLI showed better accuracy in predicting SLD remission compared with FLI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We developed SLI, a novel interpretable and parsimonious index for diagnosing SLD, which demonstrates superior predictive capability compared with FLI. Further studies are necessary to validate the diagnostic ability outside Japan.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"527-546"},"PeriodicalIF":3.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14156","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762351","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}
Fariha Hasan, Avneet Singh, Alexander Garcia, Syeda Hafsa Qadri, Hina Sattar, Rimmel Ali, Hassam Ali, Tommy Nguyen, Babu P. Mohan, Krysta Contino
Aim
Metabolic dysfunction-associated steatotic liver disease (MASLD) can lead to increased morbidity and mortality. Diets high in refined carbohydrates and saturated fats elevate MASLD risk. The Dietary Approaches to Stop Hypertension (DASH) diet has shown metabolic benefits. This meta-analysis evaluates the impact of the DASH diet on MASLD progression.
Methods
A systematic search from 2016 to 2023 across PubMed, Embase, Web of Science, and Cochrane databases was conducted to identify studies reporting on the role of the DASH diet in MASLD. Standard meta-analysis methods were employed using a random-effects model. Heterogeneity was assessed by I2 statistics.
Results
We identified five randomized controlled trials meeting inclusion criteria, involving 280 participants (140 in the DASH group and 140 in the control group). Mean ages were approximately 41 years, and the proportions of women were similar between groups. Compared with controls, the DASH diet group had a significantly reduced risk of grade 0 and 1 liver fibrosis (RR 1.21, 95% CI 1.04–1.41, p = 0.01). They also showed lower levels of aspartate aminotransferase (MD −4.81, 95% CI −6.98 to −2.64, p < 0.0001), alanine aminotransferase (MD −10.31, 95% CI −13.82 to −6.80, p < 0.00001), body mass index (MD −0.74, 95% CI −1.45 to −0.03, p = 0.04), and cholesterol-to-high-density lipoprotein ratio (MD −0.40, 95% CI −0.68 to −0.11, p = 0.006). No significant differences were found for weight, waist and hip circumference, total cholesterol, low-density lipoprotein, or high-density lipoprotein levels. Heterogeneity was low for most outcomes (I2 = 0%).
Conclusion
Based on our meta-analysis of five randomized controlled trials, the DASH diet may reduce MASLD progression. These findings suggest it could be an effective dietary intervention for MASLD management.
{"title":"Evaluating the impact of the Dietary Approaches to Stop Hypertension diet versus a calorie-restricted diet on metabolic dysfunction-associated steatotic liver disease: A meta-analysis of randomized controlled trials","authors":"Fariha Hasan, Avneet Singh, Alexander Garcia, Syeda Hafsa Qadri, Hina Sattar, Rimmel Ali, Hassam Ali, Tommy Nguyen, Babu P. Mohan, Krysta Contino","doi":"10.1111/hepr.14155","DOIUrl":"https://doi.org/10.1111/hepr.14155","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) can lead to increased morbidity and mortality. Diets high in refined carbohydrates and saturated fats elevate MASLD risk. The Dietary Approaches to Stop Hypertension (DASH) diet has shown metabolic benefits. This meta-analysis evaluates the impact of the DASH diet on MASLD progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic search from 2016 to 2023 across PubMed, Embase, Web of Science, and Cochrane databases was conducted to identify studies reporting on the role of the DASH diet in MASLD. Standard meta-analysis methods were employed using a random-effects model. Heterogeneity was assessed by <i>I</i><sup>2</sup> statistics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified five randomized controlled trials meeting inclusion criteria, involving 280 participants (140 in the DASH group and 140 in the control group). Mean ages were approximately 41 years, and the proportions of women were similar between groups. Compared with controls, the DASH diet group had a significantly reduced risk of grade 0 and 1 liver fibrosis (RR 1.21, 95% CI 1.04–1.41, <i>p</i> = 0.01). They also showed lower levels of aspartate aminotransferase (MD −4.81, 95% CI −6.98 to −2.64, <i>p</i> < 0.0001), alanine aminotransferase (MD −10.31, 95% CI −13.82 to −6.80, <i>p</i> < 0.00001), body mass index (MD −0.74, 95% CI −1.45 to −0.03, <i>p</i> = 0.04), and cholesterol-to-high-density lipoprotein ratio (MD −0.40, 95% CI −0.68 to −0.11, <i>p</i> = 0.006). No significant differences were found for weight, waist and hip circumference, total cholesterol, low-density lipoprotein, or high-density lipoprotein levels. Heterogeneity was low for most outcomes (<i>I</i><sup>2</sup> = 0%).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Based on our meta-analysis of five randomized controlled trials, the DASH diet may reduce MASLD progression. These findings suggest it could be an effective dietary intervention for MASLD management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"515-526"},"PeriodicalIF":3.9,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762175","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}
Mimi Kim, Eileen L. Yoon, Huiyul Park, Takanori Ito, Masatoshi Ishigami, Ae Jung Jo, Chul-Min Lee, Bo-Kyeong Kang, Hye-Lin Kim, Taeang Arai, Masanori Atsukawa, Miwa Kawanaka, Hidenori Toyoda, Ming-Lung Yu, Dae Won Jun, Mindie H. Nguyen
Aim
Screening for liver fibrosis holds significant importance in patients with type 2 diabetes mellitus (T2DM) due to their elevated risk of advanced hepatic fibrosis. However, it is recognized that the diagnostic performance of the Fibrosis-4 (FIB-4) index is relatively low in T2DM patients. Our study aims to explore the potential and limitations of utilizing FIB-4 as a screening tool in patients with T2DM.
Methods
A retrospective biopsy cohort of 1906 patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease from South Korea, Japan, and Taiwan. Diagnostic performance according to T2DM was again compared after propensity score matching on age, sex, and body mass index.
Results
Patients with T2DM were significantly older than those without. The area under the receiver operating characteristic curve (AUROC) of FIB-4 for ruling out advanced fibrosis in non-T2DM patients was significantly higher than that of T2DM (0.821 vs. 0.761, p = 0.044). However, the AUROCs of FIB-4 according to the same age groups showed no significant difference between patients with T2DM and without (all p > 0.05). In the middle-aged group, the sensitivity of FIB-4 for ruling out advanced hepatic fibrosis was 77.1% for T2DM and did not differ with that of non-T2DM patients (73.0%) (p = 0.093). After propensity score matching of age, there was no statistically significant difference in the AUROCs of the T2DM and non-T2DM groups (0.860 vs. 0.761, p = 0.142).
Conclusion
Although the diagnostic performance of FIB-4 was found to be suboptimal in patients with T2DM, its limited use in individuals under 65 years of age with T2DM still holds value as a screening tool.
{"title":"Limited use of FIB-4 index in patients under 65 years of age with type 2 diabetes mellitus","authors":"Mimi Kim, Eileen L. Yoon, Huiyul Park, Takanori Ito, Masatoshi Ishigami, Ae Jung Jo, Chul-Min Lee, Bo-Kyeong Kang, Hye-Lin Kim, Taeang Arai, Masanori Atsukawa, Miwa Kawanaka, Hidenori Toyoda, Ming-Lung Yu, Dae Won Jun, Mindie H. Nguyen","doi":"10.1111/hepr.14152","DOIUrl":"https://doi.org/10.1111/hepr.14152","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Screening for liver fibrosis holds significant importance in patients with type 2 diabetes mellitus (T2DM) due to their elevated risk of advanced hepatic fibrosis. However, it is recognized that the diagnostic performance of the Fibrosis-4 (FIB-4) index is relatively low in T2DM patients. Our study aims to explore the potential and limitations of utilizing FIB-4 as a screening tool in patients with T2DM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective biopsy cohort of 1906 patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease from South Korea, Japan, and Taiwan. Diagnostic performance according to T2DM was again compared after propensity score matching on age, sex, and body mass index.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients with T2DM were significantly older than those without. The area under the receiver operating characteristic curve (AUROC) of FIB-4 for ruling out advanced fibrosis in non-T2DM patients was significantly higher than that of T2DM (0.821 vs. 0.761, <i>p</i> = 0.044). However, the AUROCs of FIB-4 according to the same age groups showed no significant difference between patients with T2DM and without (all <i>p</i> > 0.05). In the middle-aged group, the sensitivity of FIB-4 for ruling out advanced hepatic fibrosis was 77.1% for T2DM and did not differ with that of non-T2DM patients (73.0%) (<i>p</i> = 0.093). After propensity score matching of age, there was no statistically significant difference in the AUROCs of the T2DM and non-T2DM groups (0.860 vs. 0.761, <i>p</i> = 0.142).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although the diagnostic performance of FIB-4 was found to be suboptimal in patients with T2DM, its limited use in individuals under 65 years of age with T2DM still holds value as a screening tool.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"505-514"},"PeriodicalIF":3.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762341","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}
Hepatolithiasis is prevalent in East Asian countries and not common in Western countries. In recent years, because of the increased number of immigrants from East Asia in Western countries, hepatolithiasis has gradually become a global problem. Although current surgical interventions for hepatolithiasis boast a high rate of stone clearance, the persistent challenges of the disease's refractory nature and high recurrence rate continue to complicate its treatment. Therefore, understanding its underlying pathogenesis is meaningful for effective treatment. In this review, we discuss the common risk factors: infection, cholangitis, environmental factors and diet habits, abnormal bile components, anatomical abnormalities, and bile stasis, and summarize the relevant mechanisms.
{"title":"Hepatolithiasis pathogenesis update","authors":"Wei Lu, Zhi-Yuan Li, Zhi-Ming Yang, Jing-Cheng Hao","doi":"10.1111/hepr.14153","DOIUrl":"https://doi.org/10.1111/hepr.14153","url":null,"abstract":"<p>Hepatolithiasis is prevalent in East Asian countries and not common in Western countries. In recent years, because of the increased number of immigrants from East Asia in Western countries, hepatolithiasis has gradually become a global problem. Although current surgical interventions for hepatolithiasis boast a high rate of stone clearance, the persistent challenges of the disease's refractory nature and high recurrence rate continue to complicate its treatment. Therefore, understanding its underlying pathogenesis is meaningful for effective treatment. In this review, we discuss the common risk factors: infection, cholangitis, environmental factors and diet habits, abnormal bile components, anatomical abnormalities, and bile stasis, and summarize the relevant mechanisms.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 2","pages":"168-180"},"PeriodicalIF":3.9,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143115898","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}
Durvalumab plus tremelimumab (Dur/Tre) is a first-line systemic treatment option for unresectable hepatocellular carcinoma (uHCC). However, the management of severe immune-mediated adverse events (imAEs) is challenging. Therefore, we investigated the relationship between severe imAEs and antitumor responses in patients with uHCC treated with Dur/Tre.
Methods
We included 157 patients with uHCC treated with Dur/Tre in this multicenter, retrospective study and analyzed the relationship between progression-free survival (PFS)/antitumor response and severe imAEs requiring high-dose corticosteroid treatment.
Results
Thirty-two patients (20.4%) developed severe imAEs, including enterocolitis/diarrhea (n = 10), liver injury (n = 9), interstitial lung disease (n = 5), rashes (n = 4), cytokine-release syndrome/fever (n = 2), pancreatitis (n = 2), and others (n = 4) (median follow-up period, 6.8 months). Infliximab was administered in six patients with steroid-refractory enterocolitis. Although the objective response rate (ORR) and disease control rate (DCR) were significantly higher with first-line therapy than with later-line therapy (p = 0.026), the frequency of severe imAEs was not significantly different (p = 0.221). The ORR and DCR in patients with and without severe imAEs were 15.6% and 17.6% and 65.6% and 47.2%, respectively, with no significant differences. Five patients with severe imAEs, including rashes and liver injury, showed objective responses (partial response + complete response). Among patients who achieved an objective response, the PFS at 10 months was good (100% and 70.3% with and without high-dose corticosteroids, respectively).
Conclusions
Severe imAEs of Dur/Tre treatment requiring high-dose corticosteroid treatment did not affect antitumor efficacy, which differed depending on the type of imAEs. Therefore, appropriately managing imAEs is essential to guide sequential treatment.
{"title":"Antitumor effects and immune-mediated adverse events of durvalumab plus tremelimumab treatment for unresectable hepatocellular carcinoma","authors":"Takanori Ito, Shigeo Shimose, Joji Tani, Tetsu Tomonari, Issei Saeki, Yasuto Takeuchi, Takeshi Hatanaka, Kyo Sasaki, Satoru Kakizaki, Yuki Kanayama, Naoki Yoshioka, Takehito Naito, Mamiko Takeuchi, Tetsuya Yasunaka, Masahiro Sakata, Hideki Iwamoto, Satoshi Itano, Tomotake Shirono, Norikazu Tanabe, Takafumi Yamamoto, Atsushi Naganuma, Sohji Nishina, Motoyuki Otsuka, Taro Takami, Tetsuji Takayama, Takumi Kawaguchi, Hiroki Kawashima, Hepatology InVestigator Experts in Japan (HIVE-J) Study Group","doi":"10.1111/hepr.14151","DOIUrl":"https://doi.org/10.1111/hepr.14151","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Durvalumab plus tremelimumab (Dur/Tre) is a first-line systemic treatment option for unresectable hepatocellular carcinoma (uHCC). However, the management of severe immune-mediated adverse events (imAEs) is challenging. Therefore, we investigated the relationship between severe imAEs and antitumor responses in patients with uHCC treated with Dur/Tre.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 157 patients with uHCC treated with Dur/Tre in this multicenter, retrospective study and analyzed the relationship between progression-free survival (PFS)/antitumor response and severe imAEs requiring high-dose corticosteroid treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-two patients (20.4%) developed severe imAEs, including enterocolitis/diarrhea (<i>n</i> = 10), liver injury (<i>n</i> = 9), interstitial lung disease (<i>n</i> = 5), rashes (<i>n</i> = 4), cytokine-release syndrome/fever (<i>n</i> = 2), pancreatitis (<i>n</i> = 2), and others (<i>n</i> = 4) (median follow-up period, 6.8 months). Infliximab was administered in six patients with steroid-refractory enterocolitis. Although the objective response rate (ORR) and disease control rate (DCR) were significantly higher with first-line therapy than with later-line therapy (<i>p</i> = 0.026), the frequency of severe imAEs was not significantly different (<i>p</i> = 0.221). The ORR and DCR in patients with and without severe imAEs were 15.6% and 17.6% and 65.6% and 47.2%, respectively, with no significant differences. Five patients with severe imAEs, including rashes and liver injury, showed objective responses (partial response + complete response). Among patients who achieved an objective response, the PFS at 10 months was good (100% and 70.3% with and without high-dose corticosteroids, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Severe imAEs of Dur/Tre treatment requiring high-dose corticosteroid treatment did not affect antitumor efficacy, which differed depending on the type of imAEs. Therefore, appropriately managing imAEs is essential to guide sequential treatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 4","pages":"577-587"},"PeriodicalIF":3.9,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14151","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143761985","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}
Asumi Yamazaki, Yuka Takachi, Hirokazu Takahashi, Nagisa Hara, Yuji Ogawa, Hideyuki Hyogo, Masahiro Koseki, Mariko Hayakawa, Atsushi Nakajima, Michihiro Iwaki, Makoto Fujii, Takayuki Ishida, Yoshihiro Kamada, Japan Study Group of NAFLD (JSG-NAFLD)
Aim
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), including its severe subtype, metabolic dysfunction-associated steatohepatitis (MASH), is increasing worldwide. This condition is a major health concern as MASH can progress to cirrhosis and hepatocellular carcinoma. With no specific medications available, lifestyle modifications, particularly dietary and exercise interventions, are crucial for managing MASLD. This study aimed to analyze the color characteristics of meals consumed by MASLD patients, seeking insights for dietary modifications.
Methods
We quantitatively analyzed the chromaticity, hue, and chroma of photographs of patients' meals and compared these statistical measures with those of nutritionally balanced meals recommended by dietitians. We also examined associations between the color characteristics of patients' meals, their clinical data, and dietary nutrients.
Results
Patients' meals exhibited significantly lower variances in chromaticity (a∗ and b∗) and lower average chroma compared to nutritionally balanced meals. Specifically, the overall mean of variance of a∗ for patients' meals was 151.1, compared to 340.5 for nutritionally balanced meals. The overall mean of average chroma for patients' meals was 24.54, whereas that for nutritionally balanced meals was 34.47. Additionally, patients' dietary patterns were found to be potentially linked not only to nutritional deficiencies but also to the prognosis and progression of hepatic fibrosis and MASLD severity.
Conclusions
This study reveals reduced color vibrancy and diversity in the diets of MASLD patients, suggesting potential dietary modifications to improve nutritional habits and clinical management for MASLD patients.
{"title":"Quantitative color analysis of the diets of patients with metabolic dysfunction-associated steatotic liver disease: Comparative study with nutritionally balanced diets","authors":"Asumi Yamazaki, Yuka Takachi, Hirokazu Takahashi, Nagisa Hara, Yuji Ogawa, Hideyuki Hyogo, Masahiro Koseki, Mariko Hayakawa, Atsushi Nakajima, Michihiro Iwaki, Makoto Fujii, Takayuki Ishida, Yoshihiro Kamada, Japan Study Group of NAFLD (JSG-NAFLD)","doi":"10.1111/hepr.14138","DOIUrl":"https://doi.org/10.1111/hepr.14138","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), including its severe subtype, metabolic dysfunction-associated steatohepatitis (MASH), is increasing worldwide. This condition is a major health concern as MASH can progress to cirrhosis and hepatocellular carcinoma. With no specific medications available, lifestyle modifications, particularly dietary and exercise interventions, are crucial for managing MASLD. This study aimed to analyze the color characteristics of meals consumed by MASLD patients, seeking insights for dietary modifications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We quantitatively analyzed the chromaticity, hue, and chroma of photographs of patients' meals and compared these statistical measures with those of nutritionally balanced meals recommended by dietitians. We also examined associations between the color characteristics of patients' meals, their clinical data, and dietary nutrients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients' meals exhibited significantly lower variances in chromaticity (<i>a</i><sup>∗</sup> and <i>b</i><sup>∗</sup>) and lower average chroma compared to nutritionally balanced meals. Specifically, the overall mean of variance of <i>a</i><sup>∗</sup> for patients' meals was 151.1, compared to 340.5 for nutritionally balanced meals. The overall mean of average chroma for patients' meals was 24.54, whereas that for nutritionally balanced meals was 34.47. Additionally, patients' dietary patterns were found to be potentially linked not only to nutritional deficiencies but also to the prognosis and progression of hepatic fibrosis and MASLD severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study reveals reduced color vibrancy and diversity in the diets of MASLD patients, suggesting potential dietary modifications to improve nutritional habits and clinical management for MASLD patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":"55 3","pages":"398-409"},"PeriodicalIF":3.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/hepr.14138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612353","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}
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