{"title":"Response to letter from Skouloudi et al","authors":"Kohilan Gananandan, Rajeshwar P. Mookerjee","doi":"10.1111/liv.16107","DOIUrl":"https://doi.org/10.1111/liv.16107","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256660","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":"Reply to Yao et al.","authors":"Yan Zhang, Yanxia Gao, Yi Li","doi":"10.1111/liv.16090","DOIUrl":"https://doi.org/10.1111/liv.16090","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256657","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}
Keqiang Lu, Juanjuan Sui, Wenhui Yu, Yan Chen, Zhiyong Hou, Pengyan Li, Yuli Sun
BackgroundCirrhosis continues to be the most common cause of chronic liver disease‐related deaths globally, which puts significant strain on global health. This report aims to investigate the patterns of cirrhosis in China, the United States, India and worldwide from 1990 to 2019 through an epidemiological analysis of the disease utilizing data from the Global Burden of Disease Study (GBD) 2019 database.MethodsDownload the GBD database's statistics on liver cirrhosis deaths and Disability‐Adjusted Life Years for the years 1990–2019 worldwide as well as for China, the United States and India. Utilize techniques like age–period–cohort interaction, decomposition analysis, study of health inequities, Joinpoint model and Bayesian Average Annual Percentage Change model to process the data.ResultsThe main age group affected by cirrhosis disease, according to the results, is 50–69 years old. According to the Joinpoint model, there has been a negative worldwide Average Annual Percent Change (AAPC) in the burden of cirrhosis between 1990 and 2019. Only the USA's AAPC is positive out of the three nations that were evaluated (albeit its 95% confidence interval spans 0). These are China, India and the United States. Forecasting models indicate that the prevalence of cirrhosis will keep rising in the absence of government action. According to decomposition analysis, the main factors contributing to the rising burden of cirrhosis are population ageing and size, whereas changes in the disease's epidemiology slow the disease's growth. Research on health disparities indicates that, between 1990 and 2019, there was a downward trend in health disparities between various locations.ConclusionHealth organizations across different areas should take aggressive measures to address the worrisome prevalence of cirrhosis.
{"title":"An analysis of the burden of liver cirrhosis: Differences between the global, China, the United States and India","authors":"Keqiang Lu, Juanjuan Sui, Wenhui Yu, Yan Chen, Zhiyong Hou, Pengyan Li, Yuli Sun","doi":"10.1111/liv.16087","DOIUrl":"https://doi.org/10.1111/liv.16087","url":null,"abstract":"BackgroundCirrhosis continues to be the most common cause of chronic liver disease‐related deaths globally, which puts significant strain on global health. This report aims to investigate the patterns of cirrhosis in China, the United States, India and worldwide from 1990 to 2019 through an epidemiological analysis of the disease utilizing data from the Global Burden of Disease Study (GBD) 2019 database.MethodsDownload the GBD database's statistics on liver cirrhosis deaths and Disability‐Adjusted Life Years for the years 1990–2019 worldwide as well as for China, the United States and India. Utilize techniques like age–period–cohort interaction, decomposition analysis, study of health inequities, Joinpoint model and Bayesian Average Annual Percentage Change model to process the data.ResultsThe main age group affected by cirrhosis disease, according to the results, is 50–69 years old. According to the Joinpoint model, there has been a negative worldwide Average Annual Percent Change (AAPC) in the burden of cirrhosis between 1990 and 2019. Only the USA's AAPC is positive out of the three nations that were evaluated (albeit its 95% confidence interval spans 0). These are China, India and the United States. Forecasting models indicate that the prevalence of cirrhosis will keep rising in the absence of government action. According to decomposition analysis, the main factors contributing to the rising burden of cirrhosis are population ageing and size, whereas changes in the disease's epidemiology slow the disease's growth. Research on health disparities indicates that, between 1990 and 2019, there was a downward trend in health disparities between various locations.ConclusionHealth organizations across different areas should take aggressive measures to address the worrisome prevalence of cirrhosis.","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256656","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}
The PNPLA3-rs738409-G variant was the first common variant associated with hepatic fat accumulation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, to date, the clinical translation of this discovery has been minimal because it has not yet been clearly demonstrated where the genetic information may play an independent and additional role in clinical risk prediction. In this mini-review, we will discuss the most relevant evidence regarding the potential integration of the PNPLA3 variant into scores and algorithms for liver disease diagnostics and risk stratification, specifically focusing on MASLD but also extending to liver diseases of other etiologies. The PNPLA3 variant adds little in diagnosing the current state of the disease, whether in terms of presence/absence of metabolic dysfunction-associated steatohepatitis or the stage of fibrosis. While it can play an important role in prediction, allowing for the early definition of risk profiles that enable tailored monitoring and interventions over time, this is most valuable when applied to populations with relatively high pre-test probability of having significant fibrosis based on either non-invasive tests (e.g. Fibrosis-4) or demographics (e.g. diabetes). Indeed, in this context, integrating FIB4 with the PNPLA3 genotype can refine risk stratification, though there is still no evidence that genetic information adds to liver stiffness determined by elastography. Similarly, in patients with known liver cirrhosis, knowing the PNPLA3 genotype can play a role in predicting the risk of hepatocellular carcinoma, while more doubts remain about the risk of decompensation.
{"title":"Integrating PNPLA3 into clinical risk prediction.","authors":"Vincent L Chen, Umberto Vespasiani-Gentilucci","doi":"10.1111/liv.16103","DOIUrl":"https://doi.org/10.1111/liv.16103","url":null,"abstract":"<p><p>The PNPLA3-rs738409-G variant was the first common variant associated with hepatic fat accumulation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, to date, the clinical translation of this discovery has been minimal because it has not yet been clearly demonstrated where the genetic information may play an independent and additional role in clinical risk prediction. In this mini-review, we will discuss the most relevant evidence regarding the potential integration of the PNPLA3 variant into scores and algorithms for liver disease diagnostics and risk stratification, specifically focusing on MASLD but also extending to liver diseases of other etiologies. The PNPLA3 variant adds little in diagnosing the current state of the disease, whether in terms of presence/absence of metabolic dysfunction-associated steatohepatitis or the stage of fibrosis. While it can play an important role in prediction, allowing for the early definition of risk profiles that enable tailored monitoring and interventions over time, this is most valuable when applied to populations with relatively high pre-test probability of having significant fibrosis based on either non-invasive tests (e.g. Fibrosis-4) or demographics (e.g. diabetes). Indeed, in this context, integrating FIB4 with the PNPLA3 genotype can refine risk stratification, though there is still no evidence that genetic information adds to liver stiffness determined by elastography. Similarly, in patients with known liver cirrhosis, knowing the PNPLA3 genotype can play a role in predicting the risk of hepatocellular carcinoma, while more doubts remain about the risk of decompensation.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290417","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}
Yu‐Lian Zhou, Shu‐Tao Pu, Jian‐Bo Xiao, Jun Luo, Li Xue
ObjectiveThis study aims to systematically evaluate the efficacy of probiotics in treating minimum hepatic encephalopathy (MHE).MethodsA systematic search was conducted across three major databases: PubMed, China National Knowledge Infrastructure and Wanfang. The search period spanned from the inception of each database to 9 March 2023. The objective was to identify all randomised controlled trials (RCTs) examining the efficacy of probiotic preparations in treating MHE. The search terms included ‘probiotics’ along with other clinically relevant terms to comprehensively capture all pertinent studies.ResultsA total of 18 RCTs were included. The meta‐analysis showed that probiotic treatment outperformed control groups in reducing blood ammonia levels (standard mean difference [MD] = −2.68, 95% confidence interval [CI]: −3.90 to −1.46, p < .0001), improving the remission rate of MHE (risk ratio [RR] = 2.79, 95% CI: 1.23–6.35, p = .01) and lowering alanine aminotransferase levels (MD = −11.10, 95% CI: −16.17 to −6.03, p < .0001). It also significantly reduced the Model for End‐Stage Liver Disease scores (MD = −2.55, 95% CI: −3.56 to −1.54, p < .00001) and the incidence of MHE (RR = .18, 95% CI: .09–.34, p < .00001).ConclusionOur study demonstrates that probiotics effectively improve blood ammonia levels, liver function and cognitive function in patients with MHE. They significantly enhance the remission rate of MHE and effectively reduce its incidence, providing solid new evidence for treating MHE with probiotics.
{"title":"Meta‐analysis of probiotics efficacy in the treatment of minimum hepatic encephalopathy","authors":"Yu‐Lian Zhou, Shu‐Tao Pu, Jian‐Bo Xiao, Jun Luo, Li Xue","doi":"10.1111/liv.16081","DOIUrl":"https://doi.org/10.1111/liv.16081","url":null,"abstract":"ObjectiveThis study aims to systematically evaluate the efficacy of probiotics in treating minimum hepatic encephalopathy (MHE).MethodsA systematic search was conducted across three major databases: PubMed, China National Knowledge Infrastructure and Wanfang. The search period spanned from the inception of each database to 9 March 2023. The objective was to identify all randomised controlled trials (RCTs) examining the efficacy of probiotic preparations in treating MHE. The search terms included ‘probiotics’ along with other clinically relevant terms to comprehensively capture all pertinent studies.ResultsA total of 18 RCTs were included. The meta‐analysis showed that probiotic treatment outperformed control groups in reducing blood ammonia levels (standard mean difference [MD] = −2.68, 95% confidence interval [CI]: −3.90 to −1.46, <jats:italic>p</jats:italic> < .0001), improving the remission rate of MHE (risk ratio [RR] = 2.79, 95% CI: 1.23–6.35, <jats:italic>p</jats:italic> = .01) and lowering alanine aminotransferase levels (MD = −11.10, 95% CI: −16.17 to −6.03, <jats:italic>p</jats:italic> < .0001). It also significantly reduced the Model for End‐Stage Liver Disease scores (MD = −2.55, 95% CI: −3.56 to −1.54, <jats:italic>p</jats:italic> < .00001) and the incidence of MHE (RR = .18, 95% CI: .09–.34, <jats:italic>p</jats:italic> < .00001).ConclusionOur study demonstrates that probiotics effectively improve blood ammonia levels, liver function and cognitive function in patients with MHE. They significantly enhance the remission rate of MHE and effectively reduce its incidence, providing solid new evidence for treating MHE with probiotics.","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256659","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}
Getahun Molla Kassa,Josephine G Walker,Tesfa Sewunet Alamneh,Melaku Tileku Tamiru,Sandra Bivegete,Aynishet Adane,Wondwossen Amogne,John F Dillon,Peter Vickerman,Emebet Dagne,Elias Ali Yesuf,Matthew Hickman,Clare E French,Aaron G Lim,
BACKGROUND AND AIMSAlthough the evidence is uncertain, existing estimates for hepatitis C virus (HCV) in sub-Saharan Africa (SSA) indicate a high burden. We estimated HCV seroprevalence and viraemic prevalence among the general population in SSA.METHODSWe searched Medline, Embase, Web of Science, APA PsycINFO, and World Health Organization Africa Index Medicus for community-based studies. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool, and heterogeneity using the index of heterogeneity (I2). Two approaches were deployed. First, we used random-effects meta-analysis to pool prevalence. Second, to derive representative estimates, we weighted each country's HCV seroprevalence using 2021 United Nations country population sizes.RESULTSWe synthesized 130 studies. Overall, SSA HCV seroprevalence from the random-effects model was 4.17% (95% confidence interval [CI]: 3.71-4.66, I2 = 99.30%). There were no differences between males (4.31%) and females (4.03%). Seroprevalence was 2.25%, 3.31%, and 16.23% for ages ≤20, 21-64, and ≥65 years, respectively, and was higher in rural (6.63%) versus urban (2.93%). There was indication of decrement overtime from 5.74% to 4.35% to 3.03% in the years 1984-2000, 2001-2014, and 2015-2023, respectively. The weighted overall SSA HCV seroprevalence was estimated to be 2.30% (95% CI: 1.59-3.00) with regional variation: Africa-Southern (.79%), Africa-Central (1.47%), Africa-Eastern (2.71%), and Africa-Western (2.88%). HCV viremia among HCV seropositives was 54.77% (95% CI: 47.80-61.66).CONCLUSIONSHCV seroprevalence in SSA remains high. Populations aged ≥65 years, rural communities, Africa-Western, and some countries in Africa-Central and Africa-Eastern appear disproportionately affected. These results underline the need for governmental commitment to achieve the 2030 global HCV elimination targets.
{"title":"Prevalence, trends, and distribution of hepatitis C virus among the general population in sub-Saharan Africa: A systematic review and meta-analysis.","authors":"Getahun Molla Kassa,Josephine G Walker,Tesfa Sewunet Alamneh,Melaku Tileku Tamiru,Sandra Bivegete,Aynishet Adane,Wondwossen Amogne,John F Dillon,Peter Vickerman,Emebet Dagne,Elias Ali Yesuf,Matthew Hickman,Clare E French,Aaron G Lim,","doi":"10.1111/liv.16102","DOIUrl":"https://doi.org/10.1111/liv.16102","url":null,"abstract":"BACKGROUND AND AIMSAlthough the evidence is uncertain, existing estimates for hepatitis C virus (HCV) in sub-Saharan Africa (SSA) indicate a high burden. We estimated HCV seroprevalence and viraemic prevalence among the general population in SSA.METHODSWe searched Medline, Embase, Web of Science, APA PsycINFO, and World Health Organization Africa Index Medicus for community-based studies. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool, and heterogeneity using the index of heterogeneity (I2). Two approaches were deployed. First, we used random-effects meta-analysis to pool prevalence. Second, to derive representative estimates, we weighted each country's HCV seroprevalence using 2021 United Nations country population sizes.RESULTSWe synthesized 130 studies. Overall, SSA HCV seroprevalence from the random-effects model was 4.17% (95% confidence interval [CI]: 3.71-4.66, I2 = 99.30%). There were no differences between males (4.31%) and females (4.03%). Seroprevalence was 2.25%, 3.31%, and 16.23% for ages ≤20, 21-64, and ≥65 years, respectively, and was higher in rural (6.63%) versus urban (2.93%). There was indication of decrement overtime from 5.74% to 4.35% to 3.03% in the years 1984-2000, 2001-2014, and 2015-2023, respectively. The weighted overall SSA HCV seroprevalence was estimated to be 2.30% (95% CI: 1.59-3.00) with regional variation: Africa-Southern (.79%), Africa-Central (1.47%), Africa-Eastern (2.71%), and Africa-Western (2.88%). HCV viremia among HCV seropositives was 54.77% (95% CI: 47.80-61.66).CONCLUSIONSHCV seroprevalence in SSA remains high. Populations aged ≥65 years, rural communities, Africa-Western, and some countries in Africa-Central and Africa-Eastern appear disproportionately affected. These results underline the need for governmental commitment to achieve the 2030 global HCV elimination targets.","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256658","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}
Anandini Suri, Zidong Zhang, Brent Neuschwander‐Tetri, David A. Lomas, Nina Heyer‐Chauhan, Keith Burling, Rohit Loomba, David A. Brenner, Rosemary Nagy, Andrew Wilson, Danielle Carpenter, Keith Blomenkamp, Jeffrey Teckman
Background and AimsThe course of adults with ZZ alpha‐1‐antitrypsin deficiency (AATD) liver disease is unpredictable. The utility of markers, including liver biopsy, is undefined.MethodsA prospective cohort, including protocol liver biopsies, was enrolled to address these questions.ResultsWe enrolled 96 homozygous ZZ AATD adults prospectively at three US sites with standardized clinical evaluations, and protocol liver biopsies. Fibrosis was scored using Ishak (stages 0–6). Also, 51% of the 96 subjects had Ishak score >1 fibrosis (49% Ishak 0–1, 36% Ishak 2–3 and 15% ≥4). Elevated aspartate aminotransferase (AST) more than alanine aminotransferase (ALT), high body mass index (BMI), obesity, AST platelet ratio index and elevated serum Z alpha 1 antitrypsin (AAT) polymer levels were associated with increased fibrosis. Steatosis did not correlate to fibrosis. Increased fibrosis was associated with increased mutant Z polymer globular inclusions (p = .002) and increased diffuse cytoplasmic Z polymer on biopsy (p = .0029) in a direct relationship. Increased globule Z polymer was associated with increased serum AST (p = .007) and increased periportal inflammation on histopathology (p = .004), but there was no relationship of Z polymer hepatocellular accumulation with ALT, gamma glutamine transferase, inflammation in other parts of the lobule, necrosis or steatosis. Serum Z polymer levels were directly correlated to hepatic Z protein polymer content. Lung function, smoking and alcohol consumption patterns were not associated with fibrosis.ConclusionIn AATD high BMI, obesity and elevated AST are associated with increased fibrosis. Liver biopsy features are correlated to some serum tests. Serum Z AAT polymer levels could be a future biomarker to detect fibrosis early and is directly correlated to liver Z content.
背景和目的ZZ型α-1-抗胰蛋白酶缺乏症（AATD）成人肝病的病程难以预测。为了解决这些问题，我们招募了包括肝活检在内的前瞻性队列。结果我们在美国的三个地点招募了 96 名同种 ZZ AATD 成人，进行了标准化临床评估和肝活检。纤维化采用伊沙克评分法（0-6 级）。此外，96 名受试者中有 51% 患有 Ishak 1 级纤维化（49% Ishak 0-1，36% Ishak 2-3，15% ≥4）。天门冬氨酸氨基转移酶（AST）升高高于丙氨酸氨基转移酶（ALT）升高、高体重指数（BMI）、肥胖、AST血小板比率指数和血清 Zα 1 抗胰蛋白酶（AAT）聚合物水平升高与纤维化程度增加有关。脂肪变性与纤维化无关。纤维化增加与突变 Z 聚合物球状包涵体增加（p = .002）和活检弥散胞质 Z 聚合物增加（p = .0029）有直接关系。球状 Z 聚合物的增加与血清 AST 增加（p = .007）和组织病理学上的肝周炎增加（p = .004）有关，但 Z 聚合物肝细胞积聚与 ALT、γ 谷氨酰胺转移酶、肝小叶其他部位的炎症、坏死或脂肪变性没有关系。血清 Z 聚合物水平与肝脏 Z 蛋白聚合物含量直接相关。结论 在 AATD 中，高体重指数、肥胖和 AST 升高与肝纤维化增加有关。肝活检特征与某些血清检测结果相关。血清 Z AAT 聚合物水平可作为未来早期检测肝纤维化的生物标志物，并与肝 Z 含量直接相关。
{"title":"Fibrosis, biomarkers and liver biopsy in AAT deficiency and relation to liver Z protein polymer accumulation","authors":"Anandini Suri, Zidong Zhang, Brent Neuschwander‐Tetri, David A. Lomas, Nina Heyer‐Chauhan, Keith Burling, Rohit Loomba, David A. Brenner, Rosemary Nagy, Andrew Wilson, Danielle Carpenter, Keith Blomenkamp, Jeffrey Teckman","doi":"10.1111/liv.16094","DOIUrl":"https://doi.org/10.1111/liv.16094","url":null,"abstract":"Background and AimsThe course of adults with ZZ alpha‐1‐antitrypsin deficiency (AATD) liver disease is unpredictable. The utility of markers, including liver biopsy, is undefined.MethodsA prospective cohort, including protocol liver biopsies, was enrolled to address these questions.ResultsWe enrolled 96 homozygous ZZ AATD adults prospectively at three US sites with standardized clinical evaluations, and protocol liver biopsies. Fibrosis was scored using Ishak (stages 0–6). Also, 51% of the 96 subjects had Ishak score >1 fibrosis (49% Ishak 0–1, 36% Ishak 2–3 and 15% ≥4). Elevated aspartate aminotransferase (AST) more than alanine aminotransferase (ALT), high body mass index (BMI), obesity, AST platelet ratio index and elevated serum Z alpha 1 antitrypsin (AAT) polymer levels were associated with increased fibrosis. Steatosis did not correlate to fibrosis. Increased fibrosis was associated with increased mutant Z polymer globular inclusions (<jats:italic>p</jats:italic> = .002) and increased diffuse cytoplasmic Z polymer on biopsy (<jats:italic>p</jats:italic> = .0029) in a direct relationship. Increased globule Z polymer was associated with increased serum AST (<jats:italic>p</jats:italic> = .007) and increased periportal inflammation on histopathology (<jats:italic>p</jats:italic> = .004), but there was no relationship of Z polymer hepatocellular accumulation with ALT, gamma glutamine transferase, inflammation in other parts of the lobule, necrosis or steatosis. Serum Z polymer levels were directly correlated to hepatic Z protein polymer content. Lung function, smoking and alcohol consumption patterns were not associated with fibrosis.ConclusionIn AATD high BMI, obesity and elevated AST are associated with increased fibrosis. Liver biopsy features are correlated to some serum tests. Serum Z AAT polymer levels could be a future biomarker to detect fibrosis early and is directly correlated to liver Z content.","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215423","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}
Alessandro Cherubini, Chiara Rosso, Sara Della Torre
Metabolic dysfunction–associated steatotic liver disease (MASLD, previously termed NAFLD, nonalcoholic fatty liver disease) is a complex multifactorial disease showing generally higher prevalence and severity in men than in women. With respect to women, men are also more prone to develop metabolic dysfunction–associated steatohepatitis, fibrosis and liver‐related complications. Several genetic, hormonal, environmental and lifestyle factors may contribute to sex differences in MASLD development, progression and outcomes. However, after menopause, the sex‐specific prevalence of MASLD shows an opposite trend between men and women, pointing to the relevance of oestrogen signalling in the sexual dimorphism of MASLD. The patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) gene, that encodes a triacylglycerol lipase that plays a crucial role in lipid metabolism, has emerged as a key player in the pathogenesis of MASLD, with the I148M variant being strongly associated with increased liver fat content and disease severity. Recent advances indicate that carrying the PNPLA3 I148M variant can be a risk factor for MASLD especially for women. To elucidate the molecular mechanisms underlying the sex‐specific role of PNPLA3 I148M in the development of MASLD, several in vitro, ex vivo and in vivo models have been developed.
{"title":"Sex‐specific effects of PNPLA3 I148M","authors":"Alessandro Cherubini, Chiara Rosso, Sara Della Torre","doi":"10.1111/liv.16088","DOIUrl":"https://doi.org/10.1111/liv.16088","url":null,"abstract":"Metabolic dysfunction–associated steatotic liver disease (MASLD, previously termed NAFLD, nonalcoholic fatty liver disease) is a complex multifactorial disease showing generally higher prevalence and severity in men than in women. With respect to women, men are also more prone to develop metabolic dysfunction–associated steatohepatitis, fibrosis and liver‐related complications. Several genetic, hormonal, environmental and lifestyle factors may contribute to sex differences in MASLD development, progression and outcomes. However, after menopause, the sex‐specific prevalence of MASLD shows an opposite trend between men and women, pointing to the relevance of oestrogen signalling in the sexual dimorphism of MASLD. The patatin‐like phospholipase domain‐containing protein 3 (<jats:italic>PNPLA3</jats:italic>) gene, that encodes a triacylglycerol lipase that plays a crucial role in lipid metabolism, has emerged as a key player in the pathogenesis of MASLD, with the I148M variant being strongly associated with increased liver fat content and disease severity. Recent advances indicate that carrying the <jats:italic>PNPLA3</jats:italic> I148M variant can be a risk factor for MASLD especially for women. To elucidate the molecular mechanisms underlying the sex‐specific role of <jats:italic>PNPLA3</jats:italic> I148M in the development of MASLD, several in vitro, ex vivo and in vivo models have been developed.","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215422","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}
Alessandro Mantovani, Riccardo Morandin, Veronica Fiorio, Maria Giovanna Lando, Alberto Gaviraghi, Leonardo Motta, Federico Gobbi, Herbert Tilg, Christopher D. Byrne, Giovanni Targher
BackgroundPrevious studies have reported an association between metabolic dysfunction‐associated steatotic liver disease (MASLD) and the risk of serious bacterial infections. However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain. We performed a meta‐analysis of observational studies to quantify the association between MASLD and serious bacterial infections requiring hospital admission.MethodsWe systematically searched PubMed, Scopus, Web of Science and Embase from database inception to 1 April 2024, using predefined keywords to identify studies examining the risk of serious bacterial infections among individuals with and without MASLD. MASLD was diagnosed using liver biopsy, imaging or International Classification of Diseases codes. Meta‐analysis was performed using random‐effects modelling.ResultsWe identified six cross‐sectional and two prospective cohort studies with aggregate data on ~26.6 million individuals. MASLD was significantly associated with higher odds of serious bacterial infections (pooled random‐effects odds ratio 1.93, 95% confidence interval [CI] 1.44–2.58; I2 = 93%). Meta‐analysis of prospective cohort studies showed that MAFLD was associated with an increased risk of developing serious bacterial infections (pooled random‐effects hazard ratio 1.80, 95% CI 1.62–2.0; I2 = 89%). This risk further increased across the severity of MASLD, especially the severity of fibrosis (pooled random‐effects hazard ratio 2.42, 95% CI 1.89–2.29; I2 = 92%). These results remained significant after adjusting for age, sex, obesity, diabetes and other potential confounders. Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias.ConclusionsThis meta‐analysis shows a significant association between MASLD and an increased risk of serious bacterial infections requiring hospital admission.
背景以前的研究报告了代谢功能障碍相关性脂肪性肝病（MASLD）与严重细菌感染风险之间的关系。然而，这种风险的大小以及这种风险是否随 MASLD 的严重程度而变化仍不确定。我们对观察性研究进行了一项荟萃分析，以量化MASLD与需要入院治疗的严重细菌感染之间的关联。方法我们使用预定义的关键词系统地检索了PubMed、Scopus、Web of Science和Embase等数据库，检索时间从数据库建立之初到2024年4月1日，以确定在MASLD患者和非MASLD患者中考察严重细菌感染风险的研究。MASLD通过肝脏活检、影像学检查或国际疾病分类代码进行诊断。结果我们发现了六项横断面研究和两项前瞻性队列研究，共收集了约 2660 万人的数据。MASLD与较高的严重细菌感染几率明显相关（汇总随机效应几率比 1.93，95% 置信区间 [CI] 1.44-2.58；I2 = 93%）。前瞻性队列研究的 Meta 分析表明，MAFLD 与发生严重细菌感染的风险增加有关（汇总随机效应危险比 1.80，95% 置信区间 [CI] 1.62-2.0；I2 = 89%）。这一风险随着MASLD的严重程度，尤其是纤维化的严重程度而进一步增加（汇总随机效应危险比2.42，95% CI 1.89-2.29；I2 = 92%）。在对年龄、性别、肥胖、糖尿病和其他潜在混杂因素进行调整后，这些结果仍具有显著性。敏感性分析并未改变这些结果。结论这项荟萃分析表明，MASLD 与需要入院治疗的严重细菌感染风险增加之间存在显著关联。
{"title":"Association between MASLD and increased risk of serious bacterial infections requiring hospital admission: A meta‐analysis","authors":"Alessandro Mantovani, Riccardo Morandin, Veronica Fiorio, Maria Giovanna Lando, Alberto Gaviraghi, Leonardo Motta, Federico Gobbi, Herbert Tilg, Christopher D. Byrne, Giovanni Targher","doi":"10.1111/liv.16101","DOIUrl":"https://doi.org/10.1111/liv.16101","url":null,"abstract":"BackgroundPrevious studies have reported an association between metabolic dysfunction‐associated steatotic liver disease (MASLD) and the risk of serious bacterial infections. However, the magnitude of the risk and whether this risk varies with the severity of MASLD remains uncertain. We performed a meta‐analysis of observational studies to quantify the association between MASLD and serious bacterial infections requiring hospital admission.MethodsWe systematically searched PubMed, Scopus, Web of Science and Embase from database inception to 1 April 2024, using predefined keywords to identify studies examining the risk of serious bacterial infections among individuals with and without MASLD. MASLD was diagnosed using liver biopsy, imaging or International Classification of Diseases codes. Meta‐analysis was performed using random‐effects modelling.ResultsWe identified six cross‐sectional and two prospective cohort studies with aggregate data on ~26.6 million individuals. MASLD was significantly associated with higher odds of serious bacterial infections (pooled random‐effects odds ratio 1.93, 95% confidence interval [CI] 1.44–2.58; <jats:italic>I</jats:italic><jats:sup><jats:italic>2</jats:italic></jats:sup> = 93%). Meta‐analysis of prospective cohort studies showed that MAFLD was associated with an increased risk of developing serious bacterial infections (pooled random‐effects hazard ratio 1.80, 95% CI 1.62–2.0; <jats:italic>I</jats:italic><jats:sup><jats:italic>2</jats:italic></jats:sup> = 89%). This risk further increased across the severity of MASLD, especially the severity of fibrosis (pooled random‐effects hazard ratio 2.42, 95% CI 1.89–2.29; <jats:italic>I</jats:italic><jats:sup><jats:italic>2</jats:italic></jats:sup> = 92%). These results remained significant after adjusting for age, sex, obesity, diabetes and other potential confounders. Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias.ConclusionsThis meta‐analysis shows a significant association between MASLD and an increased risk of serious bacterial infections requiring hospital admission.","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215424","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}
Esli Medina‐Morales, Mohamed Ismail, Ritik M. Goyal, Ana Marenco‐Flores, Behnam Saberi, Zachary Fricker, Alan Bonder, Hirsh D. Trivedi
Background and AimsMetabolic dysfunction‐associated steatotic liver disease (MASLD), in the context of autoimmune hepatitis (AIH) among liver transplantation (LT) candidates or recipients remains poorly understood. This study compares waitlist and post‐LT outcomes in patients with MASLD/AIH to MASLD and AIH alone.MethodsUsing the united network organ sharing database (2002–2022), we compared waitlist outcomes and post‐LT survival among patients with MASLD/AIH (n = 282), AIH (n = 5812), and MASLD (n = 33 331). Competing risk, Kaplan Meier estimates and Cox proportional hazard analyses were performed.ResultsMASLD/AIH group had the highest rates of encephalopathy and ascites, and highest MELD scores. MASLD/AIH patients had higher transplantation incidence (adjusted subdistribution hazard ratio [aSHR] 1.64, 95% CI 1.44–1.85; p < .001) and lower waitlist removal risk (aSHR .30, 95% CI .20–.44; p < .001) compared to MASLD alone. One‐year post‐LT survival favoured MASLD compared to AIH (patient: 92% vs. 91%, p < .001; graft: 89% vs. 88%, p < .001) and MASLD/AIH (patient: 92% vs. 90%, p = .008; graft: 89% vs. 88%, p = .023). Recipients with MASLD/AIH showed no significant difference in survival at 10‐year post‐LT compared to MASLD (patient: 63% vs. 61%, p = .68; graft 60% vs. 59%, p = .83) and AIH (patient: 63% vs. 70%, p = .07; graft: 60% vs. 64%, p = .42).ConclusionsOur study showed that MASLD/AIH patients demonstrate higher LT incidence and lower dropout rates. Long‐term post‐LT outcomes did not significantly differ between groups. Further prospective multicenter studies are needed to validate these findings.
{"title":"Waitlist and transplant outcomes in patients with metabolic dysfunction‐associated steatotic liver disease and autoimmune hepatitis","authors":"Esli Medina‐Morales, Mohamed Ismail, Ritik M. Goyal, Ana Marenco‐Flores, Behnam Saberi, Zachary Fricker, Alan Bonder, Hirsh D. Trivedi","doi":"10.1111/liv.16100","DOIUrl":"https://doi.org/10.1111/liv.16100","url":null,"abstract":"Background and AimsMetabolic dysfunction‐associated steatotic liver disease (MASLD), in the context of autoimmune hepatitis (AIH) among liver transplantation (LT) candidates or recipients remains poorly understood. This study compares waitlist and post‐LT outcomes in patients with MASLD/AIH to MASLD and AIH alone.MethodsUsing the united network organ sharing database (2002–2022), we compared waitlist outcomes and post‐LT survival among patients with MASLD/AIH (<jats:italic>n</jats:italic> = 282), AIH (<jats:italic>n</jats:italic> = 5812), and MASLD (<jats:italic>n</jats:italic> = 33 331). Competing risk, Kaplan Meier estimates and Cox proportional hazard analyses were performed.ResultsMASLD/AIH group had the highest rates of encephalopathy and ascites, and highest MELD scores. MASLD/AIH patients had higher transplantation incidence (adjusted subdistribution hazard ratio [aSHR] 1.64, 95% CI 1.44–1.85; <jats:italic>p</jats:italic> < .001) and lower waitlist removal risk (aSHR .30, 95% CI .20–.44; <jats:italic>p</jats:italic> < .001) compared to MASLD alone. One‐year post‐LT survival favoured MASLD compared to AIH (patient: 92% vs. 91%, <jats:italic>p</jats:italic> < .001; graft: 89% vs. 88%, <jats:italic>p</jats:italic> < .001) and MASLD/AIH (patient: 92% vs. 90%, <jats:italic>p</jats:italic> = .008; graft: 89% vs. 88%, <jats:italic>p</jats:italic> = .023). Recipients with MASLD/AIH showed no significant difference in survival at 10‐year post‐LT compared to MASLD (patient: 63% vs. 61%, <jats:italic>p</jats:italic> = .68; graft 60% vs. 59%, <jats:italic>p</jats:italic> = .83) and AIH (patient: 63% vs. 70%, <jats:italic>p</jats:italic> = .07; graft: 60% vs. 64%, <jats:italic>p</jats:italic> = .42).ConclusionsOur study showed that MASLD/AIH patients demonstrate higher LT incidence and lower dropout rates. Long‐term post‐LT outcomes did not significantly differ between groups. Further prospective multicenter studies are needed to validate these findings.","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215290","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：