Yasaman Vali, Anne-Marieke van Dijk, Jenny Lee, Jerome Boursier, Vlad Ratziu, Carla Yunis, Jörn M. Schattenberg, Luca Valenti, Manuel Romero Gomez, Detlef Schuppan, Salvatore Petta, Mike Allison, Mark L. Hartman, Kimmo Porthan, Jean-Francois Dufour, Elisabetta Bugianesi, Amalia Gastadelli, Zoltan Derdak, Celine Fournier-Poizat, Elizabeth Shumbayawonda, Michael Kalutkiewicz, Hannele Yki-Jarvinen, Mattias Ekstedt, Andreas Geier, Aldo Trylesinski, Sven Francque, Clifford Brass, Michael Pavlides, Adriaan G. Holleboom, Max Nieuwdorp, Quentin M. Anstee, Patrick M. Bossuyt, the LITMUS investigators
Background and Aims
The performance of non-invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) status or liver enzymes.
Methods
Data from 586 adult LITMUS Metacohort participants with histologically characterised MASLD were included. The diagnostic performance of the Fibrosis-4 Index (FIB-4), enhanced liver fibrosis (ELF) and vibration-controlled transient elastography liver stiffness measurement (VCTE LSM) was evaluated. Performance was expressed as the area under the receiver operating characteristics curve (AUC). Thresholds for detecting advanced fibrosis (≥F3) were calculated for each NIT for fixed (high) sensitivity, specificity and predictive values.
Results
Differences in AUC between all subgroups were small and statistically not significant, indicating comparable performance in detecting ≥F3, irrespective of these clinical factors. However, different thresholds were needed to achieve the same level of accuracy with each test. For example, for a fixed sensitivity and specificity, the thresholds for all three NITs were higher in patients with T2DM. Effects for sex, age and liver enzymes were less pronounced.
Conclusions
Performance of the selected NITs in detecting advanced liver fibrosis does not vary substantially with clinical characteristics. However, different thresholds have to be selected to achieve the same sensitivity, specificity and predictive values in the respective subgroups. Large prospective studies are called for to study NIT accuracy considering multiple patient characteristics.
{"title":"Precision in Liver Diagnosis: Varied Accuracy Across Subgroups and the Need for Variable Thresholds in Diagnosis of MASLD","authors":"Yasaman Vali, Anne-Marieke van Dijk, Jenny Lee, Jerome Boursier, Vlad Ratziu, Carla Yunis, Jörn M. Schattenberg, Luca Valenti, Manuel Romero Gomez, Detlef Schuppan, Salvatore Petta, Mike Allison, Mark L. Hartman, Kimmo Porthan, Jean-Francois Dufour, Elisabetta Bugianesi, Amalia Gastadelli, Zoltan Derdak, Celine Fournier-Poizat, Elizabeth Shumbayawonda, Michael Kalutkiewicz, Hannele Yki-Jarvinen, Mattias Ekstedt, Andreas Geier, Aldo Trylesinski, Sven Francque, Clifford Brass, Michael Pavlides, Adriaan G. Holleboom, Max Nieuwdorp, Quentin M. Anstee, Patrick M. Bossuyt, the LITMUS investigators","doi":"10.1111/liv.16240","DOIUrl":"10.1111/liv.16240","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The performance of non-invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) status or liver enzymes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from 586 adult LITMUS Metacohort participants with histologically characterised MASLD were included. The diagnostic performance of the Fibrosis-4 Index (FIB-4), enhanced liver fibrosis (ELF) and vibration-controlled transient elastography liver stiffness measurement (VCTE LSM) was evaluated. Performance was expressed as the area under the receiver operating characteristics curve (AUC). Thresholds for detecting advanced fibrosis (≥F3) were calculated for each NIT for fixed (high) sensitivity, specificity and predictive values.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Differences in AUC between all subgroups were small and statistically not significant, indicating comparable performance in detecting ≥F3, irrespective of these clinical factors. However, different thresholds were needed to achieve the same level of accuracy with each test. For example, for a fixed sensitivity and specificity, the thresholds for all three NITs were higher in patients with T2DM. Effects for sex, age and liver enzymes were less pronounced.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Performance of the selected NITs in detecting advanced liver fibrosis does not vary substantially with clinical characteristics. However, different thresholds have to be selected to achieve the same sensitivity, specificity and predictive values in the respective subgroups. Large prospective studies are called for to study NIT accuracy considering multiple patient characteristics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa Sandmann, Valerie Ohlendorf, Alena Ehrenbauer, Birgit Bremer, Anke R. M. Kraft, Markus Cornberg, Katja Deterding, Heiner Wedemeyer, Benjamin Maasoumy
Background and Aims
Chronic hepatitis D virus (HDV) infection can cause severe liver disease. With new treatment options available, it is important to identify patients at risk for liver-related complications. We aimed to investigate kinetics and predictive values of novel virological and immunological markers in the natural course of chronic HDV infection.
Methods
HBcrAg, HBV RNA and quantitative anti-HBc were analysed in samples from HDV-infected patients at three consecutive time points. Results were linked to clinical outcome by univariable and multivariable analyses. Primary endpoint was the composite endpoint of any liver-related event.
Results
Samples from 190 individual patients were analysed with a median clinical follow-up time of 2.69 (IQR 1.13–6.51) years. The majority of patients had cirrhosis (98/190, 52%), and the primary endpoint occurred in 33% (62/190). In univariable analysis, age, cirrhosis, lower quantitative anti-HBc, higher ratio of HBcrAg/anti-HBc and detectable HDV RNA were associated with the primary endpoint. In multivariable analysis, only the presence of liver cirrhosis (HR 7.74, p < 0.001) and age (1.06, p < 0.001) remained independently associated with the primary endpoint. Kinetics of virological parameters during follow-up were similar between the groups. Quantitative anti-HBc was significantly lower in patients with liver cirrhosis (687 (IQR 188–3388) IU/ml vs. 309 (IQR 82–924) IU/ml, p < 0.0004), and lower levels were independently associated with the development of the primary endpoint (HR 1.0, p = 0.014).
Conclusion
In chronic HDV infection, neither baseline values nor kinetics of HBV RNA, HBcrAg and anti-HBc were independently associated with clinical outcome, while stage of liver disease and age were predictors of liver-related events.
{"title":"Value and Kinetics of Virological Markers in the Natural Course of Chronic Hepatitis D Virus Infection","authors":"Lisa Sandmann, Valerie Ohlendorf, Alena Ehrenbauer, Birgit Bremer, Anke R. M. Kraft, Markus Cornberg, Katja Deterding, Heiner Wedemeyer, Benjamin Maasoumy","doi":"10.1111/liv.70003","DOIUrl":"10.1111/liv.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Chronic hepatitis D virus (HDV) infection can cause severe liver disease. With new treatment options available, it is important to identify patients at risk for liver-related complications. We aimed to investigate kinetics and predictive values of novel virological and immunological markers in the natural course of chronic HDV infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>HBcrAg, HBV RNA and quantitative anti-HBc were analysed in samples from HDV-infected patients at three consecutive time points. Results were linked to clinical outcome by univariable and multivariable analyses. Primary endpoint was the composite endpoint of any liver-related event.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Samples from 190 individual patients were analysed with a median clinical follow-up time of 2.69 (IQR 1.13–6.51) years. The majority of patients had cirrhosis (98/190, 52%), and the primary endpoint occurred in 33% (62/190). In univariable analysis, age, cirrhosis, lower quantitative anti-HBc, higher ratio of HBcrAg/anti-HBc and detectable HDV RNA were associated with the primary endpoint. In multivariable analysis, only the presence of liver cirrhosis (HR 7.74, <i>p</i> < 0.001) and age (1.06, p < 0.001) remained independently associated with the primary endpoint. Kinetics of virological parameters during follow-up were similar between the groups. Quantitative anti-HBc was significantly lower in patients with liver cirrhosis (687 (IQR 188–3388) IU/ml vs. 309 (IQR 82–924) IU/ml, <i>p</i> < 0.0004), and lower levels were independently associated with the development of the primary endpoint (HR 1.0, <i>p</i> = 0.014).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In chronic HDV infection, neither baseline values nor kinetics of HBV RNA, HBcrAg and anti-HBc were independently associated with clinical outcome, while stage of liver disease and age were predictors of liver-related events.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Imante Lasyte, Linnea Widman, Annika Bergquist, Hannes Hagström
Background/Aims
Epidemiological data on mortality in autoimmune liver diseases (AILDs) are scarce. We examined all-cause and cancer-related mortality in individuals with AILD from Sweden.
Methods
We identified 9654 individuals with AILD (3342 with autoimmune hepatitis (AIH), 3751 with primary biliary cholangitis (PBC), and 2561 with primary sclerosing cholangitis (PSC)) using national Swedish registries between 2001 and 2020. These were matched with 80 685 comparators from the general population at a ratio of 1:10 on age, sex, year of diagnosis and municipality. Rates of outcomes were estimated using Cox regression models, adjusted for matching factors and cardiovascular disease, diabetes, inflammatory bowel disease, chronic obstructive pulmonary disease, and education.
Results
Individuals with AILD had higher mortality than comparators (adjusted hazard ratio (aHR) = 2.3, 95% CI = 2.2–2.4) and higher rates of cancer-related death (aHR = 2.1, 95% CI = 1.9–2.3). The presence of liver cirrhosis in AILD was related to even higher mortality, with aHR 5.8 (95% CI = 5.1–6.6). Both males and females with AILD had increased mortality (males aHR = 2.6, 95% CI = 2.4–3.0, and females aHR = 2.2, 95% CI = 2.1–2.3). The mortality was higher in individuals aged 18–50 years (aHR = 4.6, 95% CI = 3.6–5.8), than in individuals above 50 years (aHR = 2.2, 95% CI = 2.1–2.3). Overall mortality rates and cancer-related death were particularly high in individuals with PSC compared to their matched comparators, with aHR = 4.1 (95% CI = 3.2–5.2) and aHR = 6.4 (95% CI = 4.0–10.3), respectively.
Conclusions
Patients with AILDs have increased rates of overall and cancer-related mortality compared to matched comparators, and relative risks are highest in cirrhosis, younger age and PSC.
背景/目的：关于自身免疫性肝病（AILDs）死亡率的流行病学数据很少。我们研究了瑞典AILD患者的全因死亡率和癌症相关死亡率。方法：我们在2001年至2020年期间通过瑞典国家登记处确定了9654例AILD患者（3342例自身免疫性肝炎（AIH）， 3751例原发性胆道炎（PBC）， 2561例原发性硬化性胆管炎（PSC））。按年龄、性别、诊断年份和所在城市按1:10的比例与普通人群中的80685名比较者进行匹配。使用Cox回归模型估计结局率，并根据心血管疾病、糖尿病、炎症性肠病、慢性阻塞性肺病和教育等匹配因素进行调整。结果：与比较组相比，AILD患者的死亡率更高（校正危险比(aHR) = 2.3, 95% CI = 2.2-2.4），癌症相关死亡率更高（aHR = 2.1, 95% CI = 1.9-2.3）。肝硬化的存在与更高的死亡率相关，aHR为5.8 （95% CI = 5.1-6.6）。患有AILD的男性和女性死亡率均增加（男性aHR = 2.6, 95% CI = 2.4-3.0，女性aHR = 2.2, 95% CI = 2.1-2.3）。18-50岁人群的死亡率（aHR = 4.6, 95% CI = 3.6-5.8）高于50岁以上人群（aHR = 2.2, 95% CI = 2.1-2.3）。与匹配的比较组相比，PSC患者的总死亡率和癌症相关死亡率特别高，aHR分别为4.1 （95% CI = 3.2-5.2）和6.4 （95% CI = 4.0-10.3）。结论：与匹配的比较者相比，aild患者的总体死亡率和癌症相关死亡率增加，肝硬化、年轻和PSC患者的相对风险最高。
{"title":"Mortality in Autoimmune Liver Disease in Sweden: A Population-Based Cohort Study of 9,654 Patients","authors":"Imante Lasyte, Linnea Widman, Annika Bergquist, Hannes Hagström","doi":"10.1111/liv.70007","DOIUrl":"10.1111/liv.70007","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Aims</h3>\u0000 \u0000 <p>Epidemiological data on mortality in autoimmune liver diseases (AILDs) are scarce. We examined all-cause and cancer-related mortality in individuals with AILD from Sweden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified 9654 individuals with AILD (3342 with autoimmune hepatitis (AIH), 3751 with primary biliary cholangitis (PBC), and 2561 with primary sclerosing cholangitis (PSC)) using national Swedish registries between 2001 and 2020. These were matched with 80 685 comparators from the general population at a ratio of 1:10 on age, sex, year of diagnosis and municipality. Rates of outcomes were estimated using Cox regression models, adjusted for matching factors and cardiovascular disease, diabetes, inflammatory bowel disease, chronic obstructive pulmonary disease, and education.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Individuals with AILD had higher mortality than comparators (adjusted hazard ratio (aHR) = 2.3, 95% CI = 2.2–2.4) and higher rates of cancer-related death (aHR = 2.1, 95% CI = 1.9–2.3). The presence of liver cirrhosis in AILD was related to even higher mortality, with aHR 5.8 (95% CI = 5.1–6.6). Both males and females with AILD had increased mortality (males aHR = 2.6, 95% CI = 2.4–3.0, and females aHR = 2.2, 95% CI = 2.1–2.3). The mortality was higher in individuals aged 18–50 years (aHR = 4.6, 95% CI = 3.6–5.8), than in individuals above 50 years (aHR = 2.2, 95% CI = 2.1–2.3). Overall mortality rates and cancer-related death were particularly high in individuals with PSC compared to their matched comparators, with aHR = 4.1 (95% CI = 3.2–5.2) and aHR = 6.4 (95% CI = 4.0–10.3), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Patients with AILDs have increased rates of overall and cancer-related mortality compared to matched comparators, and relative risks are highest in cirrhosis, younger age and PSC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of hepatocellular carcinoma (HCC). In this study, we combine metabolomic and gene expression analysis to compare HCC tissues with non-tumoural tissues (NTT).
Methods
A non-targeted metabolomic strategy LC–MS was applied to 52 pairs of human MASLD-HCC and NTT separated into 2 groups according to fibrosis severity F0F1-F2 versus F3F4. The expression of genes related to de Novo lipogenesis (DNL) and fatty acid oxidation (FAO) has been analysed by quantitative RT-PCR and/or interrogation of RNA-seq datasets in 259 pairs of tissues (MASLD-HCC vs. VIRUS-HCC).
Results
Metabolomic analysis revealed that acylcarnitines were the main discriminating metabolites according to fibrosis severity when we compared MASLD-HCC-F0F1-F2 versus NTT and MASLD-HCC-F3F4 versus NTT. Based on these metabolomic data, the analysis of a panel of 15 selected genes related to DNL and FAO indicated that there is no difference between the 2 groups of MASLD-HCC. In contrast the same comparative gene analysis according to the aetiology of HCC: MASLD-HCC versus VIRUS-HCC showed that both aetiologies shared the same upregulation of genes involved in DNL. However, five genes involved in FAO (HADHA, CRAT, CPT1, CPT2 and PPARA) are upregulated exclusively in MASLD-HCC. This result indicates that FAO and DNL pathways are simultaneously activated in MASLD-HCC in contrast to VIRUS-HCC.
Conclusions
These results suggest that, the involvement of adaptive metabolic pathways is different depending on the aetiology of HCC. Moreover, the dogma that simultaneous activation of FAO and DNL is incompatible in cancer would not apply to MASLD-HCC.
背景和目的：代谢功能障碍相关的脂肪变性肝病（MASLD）是肝细胞癌（HCC）最常见的病因。在这项研究中，我们结合代谢组学和基因表达分析来比较HCC组织和非肿瘤组织（NTT）。方法：采用非靶向代谢组学策略LC-MS对52对人MASLD-HCC和NTT按纤维化严重程度分为F0F1-F2和F3F4两组。通过定量RT-PCR和/或对259对组织（MASLD-HCC vs. VIRUS-HCC）的RNA-seq数据集分析了与从头脂肪生成（DNL）和脂肪酸氧化（FAO）相关的基因表达。结果：代谢组学分析显示，当我们比较MASLD-HCC-F0F1-F2与NTT、MASLD-HCC-F3F4与NTT时，酰基肉碱是区分纤维化严重程度的主要代谢物。基于这些代谢组学数据，对15个与DNL和FAO相关的基因进行分析表明，两组MASLD-HCC之间没有差异。相反，根据HCC的病因进行相同的基因比较分析：MASLD-HCC与病毒-HCC显示，这两种病因都有相同的DNL相关基因上调。然而，参与FAO的5个基因（HADHA、CRAT、CPT1、CPT2和PPARA）在MASLD-HCC中只表达上调。这一结果表明，与病毒型hcc相比，MASLD-HCC中FAO和DNL通路同时被激活。结论：这些结果表明，适应性代谢途径的参与是不同的，取决于HCC的病因。此外，在癌症中同时激活FAO和DNL不相容的教条不适用于MASLD-HCC。
{"title":"Simultaneous Activation of Beta-Oxidation and De Novo Lipogenesis in MASLD-HCC: A New Paradigm","authors":"Fatima Dahboul, Jihan Sun, Benjamin Buchard, Natali Abeywickrama-Samarakoon, Estelle Pujos-Guillot, Stéphanie Durand, Mélanie Petera, Delphine Centeno, Francesca Guerrieri, Massimiliano Cocca, Massimo Levrero, Adrien Rossary, Delphine Weil, Vincent Di Martino, Aicha Demidem, Armando Abergel","doi":"10.1111/liv.70006","DOIUrl":"10.1111/liv.70006","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of hepatocellular carcinoma (HCC). In this study, we combine metabolomic and gene expression analysis to compare HCC tissues with non-tumoural tissues (NTT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A non-targeted metabolomic strategy LC–MS was applied to 52 pairs of human MASLD-HCC and NTT separated into 2 groups according to fibrosis severity F0F1-F2 versus F3F4. The expression of genes related to de Novo lipogenesis (DNL) and fatty acid oxidation (FAO) has been analysed by quantitative RT-PCR and/or interrogation of RNA-seq datasets in 259 pairs of tissues (MASLD-HCC vs. VIRUS-HCC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Metabolomic analysis revealed that acylcarnitines were the main discriminating metabolites according to fibrosis severity when we compared MASLD-HCC-F0F1-F2 versus NTT and MASLD-HCC-F3F4 versus NTT. Based on these metabolomic data, the analysis of a panel of 15 selected genes related to DNL and FAO indicated that there is no difference between the 2 groups of MASLD-HCC. In contrast the same comparative gene analysis according to the aetiology of HCC: MASLD-HCC versus VIRUS-HCC showed that both aetiologies shared the same upregulation of genes involved in DNL. However, five genes involved in FAO (HADHA, CRAT, CPT1, CPT2 and PPARA) are upregulated exclusively in MASLD-HCC. This result indicates that FAO and DNL pathways are simultaneously activated in MASLD-HCC in contrast to VIRUS-HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results suggest that, the involvement of adaptive metabolic pathways is different depending on the aetiology of HCC. Moreover, the dogma that simultaneous activation of FAO and DNL is incompatible in cancer would not apply to MASLD-HCC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qi Chen, Shu Huang, Jieyu Peng, Ping Wang, Xiaomin Shi, Rui Luo, Huan Xu, Wei Zhang, Lei Shi, Yan Peng, Fangfang Yuan, Xiaowei Tang
Aim
This research was aimed to uncover the hepatitis B virus (HBV) and hepatitis C virus (HCV) related diseases burden in Asia over the past 3 decades, estimating from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.
Methods
Age-standardised rates, case numbers of prevalence, disability-adjusted life-years (DALYs), incidence and deaths with 95% uncertainty intervals (UI) for HBV/HCV-related diseases from 1990 to 2019 were derived from GBD 2019 database, with the estimated annual percentage changes (EAPCs) calculated. Our analysis also encompassed the association between the Sociodemographic Index (SDI) and the burden of HBV/HCV-related diseases, future disease burden predictions in six selected countries and various risk factors.
Result
A general downward trend in the age-standardised rates of death, disability-adjusted life years (DALYs), prevalence and incidence for both HBV and HCV-related diseases was observed in Asia during the past 30 years. Despite overall declining trends, some analysed diseases experienced an increase. Compared with females, the disease burden was greater in the male population and peaked in the age of 50–54 for both sexes. It is significant for the HBV-related and HCV-related diseases burden in Afghanistan, Cambodia, Mongolia and Pakistan. Drug use and smoking were prominent contributors to HCV and HBV-related diseases. There was a negative relationship between the burden of HCV and HBV-related diseases and SDI.
Conclusion
Although decreases were observed in Asia, the HBV- and HCV-associated diseases burden remained high, highlighting that imperative measures for prevention and treatment should be taken by governments in Asia.
{"title":"The Burden of Hepatitis B and C in Asia, 1990–2019: An Update Analysis From the Global Burden of Disease Study 2019","authors":"Qi Chen, Shu Huang, Jieyu Peng, Ping Wang, Xiaomin Shi, Rui Luo, Huan Xu, Wei Zhang, Lei Shi, Yan Peng, Fangfang Yuan, Xiaowei Tang","doi":"10.1111/liv.70004","DOIUrl":"10.1111/liv.70004","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This research was aimed to uncover the hepatitis B virus (HBV) and hepatitis C virus (HCV) related diseases burden in Asia over the past 3 decades, estimating from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Age-standardised rates, case numbers of prevalence, disability-adjusted life-years (DALYs), incidence and deaths with 95% uncertainty intervals (UI) for HBV/HCV-related diseases from 1990 to 2019 were derived from GBD 2019 database, with the estimated annual percentage changes (EAPCs) calculated. Our analysis also encompassed the association between the Sociodemographic Index (SDI) and the burden of HBV/HCV-related diseases, future disease burden predictions in six selected countries and various risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>A general downward trend in the age-standardised rates of death, disability-adjusted life years (DALYs), prevalence and incidence for both HBV and HCV-related diseases was observed in Asia during the past 30 years. Despite overall declining trends, some analysed diseases experienced an increase. Compared with females, the disease burden was greater in the male population and peaked in the age of 50–54 for both sexes. It is significant for the HBV-related and HCV-related diseases burden in Afghanistan, Cambodia, Mongolia and Pakistan. Drug use and smoking were prominent contributors to HCV and HBV-related diseases. There was a negative relationship between the burden of HCV and HBV-related diseases and SDI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although decreases were observed in Asia, the HBV- and HCV-associated diseases burden remained high, highlighting that imperative measures for prevention and treatment should be taken by governments in Asia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cyriac Abby Philips, Arif Hussain Theruvath, Rizwan Ahamed, Philip Augustine
{"title":"G-CSF for Severe Alcohol-Associated Hepatitis-'That Which Can Be Asserted Without Evidence, Can Be Dismissed Without Evidence'.","authors":"Cyriac Abby Philips, Arif Hussain Theruvath, Rizwan Ahamed, Philip Augustine","doi":"10.1111/liv.16183","DOIUrl":"https://doi.org/10.1111/liv.16183","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gabriele Mocciaro, Amy L. George, Michael Allison, Mattia Frontini, Isabel Huang-Doran, Frank Reiman, Fiona Gribble, Julian L. Griffin, Antonio Vidal-Puig, Vian Azzu, Richard Kay, Michele Vacca
Background
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of histological conditions ranging from simple steatosis to fibrosing steatohepatitis, and is a risk factor for cardiovascular diseases (CVD). While oxidised apolipoproteins A and B have been linked to obesity and CVD, the association between other oxidised apolipoproteins and MASLD is yet to be established. To fill this gap, we characterised the circulating serum peptidome of patients with MASLD.
Methods
We studied the serum of 87 biopsy-confirmed MASLD patients and 20 age- and sex-matched control (CTRL) subjects. We first employed an untargeted LC-MS/MS peptidomics approach (9 CTRL, 32 MASLD) to identify key hits differentially modulated, and subsequently validated the most relevant findings through targeted peptidomics in an enlarged study population (87 MASLD and 20 CTRL).
Results
Untargeted serum peptidomics identified several oxidised apolipoprotein peptide fragments, including ApoE and ApoC-III, significantly upregulated in MASLD compared to CTRL. Specifically focusing on the oxidative status of intact ApoC-III, studied through its major glycoforms (ApoC-III0, ApoC-IIIi and ApoC-IIIii), we observed a marked reduction in non-oxidised forms of these circulating peptides alongside substantially increased levels of their oxidised proteoforms in MASLD versus controls (but not within the disease stages). Oxidised ApoE and ApoC-III peptide fragments were also significantly correlated with obesity, insulin resistance, dyslipidaemia and transaminases, suggesting a potential link between circulating apolipoprotein oxidation and systemic/hepatic metabolic dysfunction.
Conclusion
Our data reveals a previously unreported oxidised apolipoprotein profile associated with MASLD. The functional and clinical implications of these findings warrant further mechanistic investigation.
{"title":"Oxidised Apolipoprotein Peptidome Characterises Metabolic Dysfunction-Associated Steatotic Liver Disease","authors":"Gabriele Mocciaro, Amy L. George, Michael Allison, Mattia Frontini, Isabel Huang-Doran, Frank Reiman, Fiona Gribble, Julian L. Griffin, Antonio Vidal-Puig, Vian Azzu, Richard Kay, Michele Vacca","doi":"10.1111/liv.16200","DOIUrl":"10.1111/liv.16200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of histological conditions ranging from simple steatosis to fibrosing steatohepatitis, and is a risk factor for cardiovascular diseases (CVD). While oxidised apolipoproteins A and B have been linked to obesity and CVD, the association between other oxidised apolipoproteins and MASLD is yet to be established. To fill this gap, we characterised the circulating serum peptidome of patients with MASLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We studied the serum of 87 biopsy-confirmed MASLD patients and 20 age- and sex-matched control (CTRL) subjects. We first employed an untargeted LC-MS/MS peptidomics approach (9 CTRL, 32 MASLD) to identify key hits differentially modulated, and subsequently validated the most relevant findings through targeted peptidomics in an enlarged study population (87 MASLD and 20 CTRL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Untargeted serum peptidomics identified several oxidised apolipoprotein peptide fragments, including ApoE and ApoC-III, significantly upregulated in MASLD compared to CTRL. Specifically focusing on the oxidative status of intact ApoC-III, studied through its major glycoforms (ApoC-III<sub>0</sub>, ApoC-III<sub>i</sub> and ApoC-III<sub>ii</sub>), we observed a marked reduction in non-oxidised forms of these circulating peptides alongside substantially increased levels of their oxidised proteoforms in MASLD versus controls (but not within the disease stages). Oxidised ApoE and ApoC-III peptide fragments were also significantly correlated with obesity, insulin resistance, dyslipidaemia and transaminases, suggesting a potential link between circulating apolipoprotein oxidation and systemic/hepatic metabolic dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data reveals a previously unreported oxidised apolipoprotein profile associated with MASLD. The functional and clinical implications of these findings warrant further mechanistic investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hanyun Wang, Mingxiao Guo, Fengtao Cui, Mengdi Li, Xianan Zhang, Wei Gao, Xingqiang Fang, Li Chen, Ye Xin, Yucheng Sun, Piye Niu, Junxiang Ma
Background
Metabolic associated fatty liver disease (MAFLD), previously defined as non-alcoholic fatty liver disease (NAFLD), has been shown to be closely related to many environmental pollutants. Lately, we found methyl tert-butyl ether (MTBE), a new environmental pollutant, could increase NAFLD risk in American adults, which still needs more population epidemiological studies to verify, and its pathogenic mechanism is not yet clear.
Methods
We conducted a cross-sectional study among petrol station workers, diagnosed their MAFLD according to internationally recognised diagnostic criteria, assessed the potential association of MTBE exposure with MAFLD risk, and explored the miR-18a-5p/PXR/SREBP2 pathway as possible pathogenic mechanisms in male Wistar rats and HepaRG cells treated with MTBE.
Results
Blood MTBE levels were found to be significantly correlated with an increased risk of MAFLD, and MAFLD risk increased by 24.3% for every 0.1 μg/L increase in blood MTBE. Consistently, we found that MTBE exposure could induce MAFLD in rats and HepaRG cells, and activate pregnane X receptor (PXR) by inhibiting miR-18a-5p to upregulate the expression of sterol regulatory element-binding protein 2 (SREBP2) and its nuclear translocation, thereby upregulating the expression of its downstream target genes.
Conclusions
Our study demonstrated that MTBE exposure might be a significant risk factor for MAFLD, and MTBE could promote liver cholesterol synthesis and lipid deposition by activating the miRNA-18a-5p/PXR/SREBP2 pathway.
{"title":"miR-18a-5p/PXR/SREBP2 Was Involved in MAFLD Associated With Methyl Tert-Butyl Ether Among Petrol Station Workers","authors":"Hanyun Wang, Mingxiao Guo, Fengtao Cui, Mengdi Li, Xianan Zhang, Wei Gao, Xingqiang Fang, Li Chen, Ye Xin, Yucheng Sun, Piye Niu, Junxiang Ma","doi":"10.1111/liv.16246","DOIUrl":"10.1111/liv.16246","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic associated fatty liver disease (MAFLD), previously defined as non-alcoholic fatty liver disease (NAFLD), has been shown to be closely related to many environmental pollutants. Lately, we found methyl tert-butyl ether (MTBE), a new environmental pollutant, could increase NAFLD risk in American adults, which still needs more population epidemiological studies to verify, and its pathogenic mechanism is not yet clear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a cross-sectional study among petrol station workers, diagnosed their MAFLD according to internationally recognised diagnostic criteria, assessed the potential association of MTBE exposure with MAFLD risk, and explored the miR-18a-5p/PXR/SREBP2 pathway as possible pathogenic mechanisms in male Wistar rats and HepaRG cells treated with MTBE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Blood MTBE levels were found to be significantly correlated with an increased risk of MAFLD, and MAFLD risk increased by 24.3% for every 0.1 μg/L increase in blood MTBE. Consistently, we found that MTBE exposure could induce MAFLD in rats and HepaRG cells, and activate pregnane X receptor (PXR) by inhibiting miR-18a-5p to upregulate the expression of sterol regulatory element-binding protein 2 (SREBP2) and its nuclear translocation, thereby upregulating the expression of its downstream target genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our study demonstrated that MTBE exposure might be a significant risk factor for MAFLD, and MTBE could promote liver cholesterol synthesis and lipid deposition by activating the miRNA-18a-5p/PXR/SREBP2 pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to the Potential and Challenges of Autophagy in the Treatment of Liver Fibrosis","authors":"Li-Shuang Hou, Bang-Le Zhang","doi":"10.1111/liv.16238","DOIUrl":"10.1111/liv.16238","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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