Liver International最新文献

{"title":"MASLD and CMRFs: Combination or Separation? An Open Exploration From the Perspective of All-Cause Mortality","authors":"Zheng Li, Ting Luo, Dan Zheng, Zhiping Li, Dan Cao, Yue Hu","doi":"10.1111/liv.70212","DOIUrl":"https://doi.org/10.1111/liv.70212","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519946","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":"Exploring Genetic and Clinical Implications of Methylprednisolone-Induced Liver Injury","authors":"Dongdong Feng, Huicong Zhang","doi":"10.1111/liv.70203","DOIUrl":"https://doi.org/10.1111/liv.70203","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514942","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":"Commentary on ‘Rationalising Hepatocellular Carcinoma Screening in Chronic Hepatitis B: Evaluation of Predictive Scores in an Australian Cohort’","authors":"Jiawei Hu, Jiale Wu, Zhikang Ying","doi":"10.1111/liv.70211","DOIUrl":"https://doi.org/10.1111/liv.70211","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515000","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 ‘Methodological Considerations and Future Directions in Cardiac Geometry Assessment for Cirrhotic Cardiomyopathy’","authors":"Yiheng Zhou, Bo Yuan, Xiaoyang Liao, Yu Jia","doi":"10.1111/liv.70204","DOIUrl":"https://doi.org/10.1111/liv.70204","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514943","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: Alcohol Cessation as a Multidisciplinary Imperative in Liver Cancer Survivorship: Clinical and Psychosocial Considerations","authors":"Thi Tra Bui, Jin-Kyoung Oh","doi":"10.1111/liv.70205","DOIUrl":"https://doi.org/10.1111/liv.70205","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 8","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503112","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":"Hospitalisations With Cryoglobulin-Related Diseases in Spain Over 25 Years","authors":"Mario Martín-Portugués,&nbsp;Jorge Esteban-Sampedro,&nbsp;Carmen de Mendoza,&nbsp;Guillermo Ruiz-Irastorza,&nbsp;Ana Royuela,&nbsp;Alfonso Ortega-de la Puente,&nbsp;Marina de la Cruz-Echeandía,&nbsp;Xiomara Patricia Blanco-Valencia,&nbsp;Vicente Soriano,&nbsp;Víctor Moreno-Torres","doi":"10.1111/liv.70195","DOIUrl":"https://doi.org/10.1111/liv.70195","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The epidemiology of cryoglobulinemia in Spain has likely changed following the widespread adoption of direct-acting antivirals (DAAs) since 2015 for the treatment of hepatitis C virus (HCV) infection, the principal cause of mixed cryoglobulinemia (MC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>All hospital admissions of patients with cryoglobulinemic disease at the National Registry of Hospital Discharges were retrospectively examined in Spain from 1997 to 2022. The following primary conditions associated with cryoglobulinemia were considered: chronic viral infections, haematological diseases (HD), and autoimmune diseases (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 16 929 admissions for patients with cryoglobulinemic disease were recorded during the study period. Hospitalisation rates for patients with cryoglobulinemia steadily increased from 1997 to 2015 (from 10.8 to 17.9 admissions per 1 million habitants, APC = +2.1), and decreased from 2018 to 2022 (from 15.7 to 11 admissions per 1 million habitants, APC = −7) (<i>p</i> &lt; 0.001 for all). The drastic changes in HCV prevalence rates determined this shift (26.3% in 1997, 52.7% in 2016 and 27.9% in 2022, <i>p</i> &lt; 0.001). The proportion of patients with cryoglobulinemia associated with hepatitis B virus (HBV), paraproteinemias, non-Hodgkin lymphoma, systemic lupus erythematosus, primary Sjögren syndrome and rheumatoid arthritis steadily increased during the study period as cause of hospitalisation in patients with cryoglobulinemia (from 1997 to 2022, <i>p</i> &lt; 0.001), while human immunodeficiency virus infection remained fairly stable since 2005.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The introduction of DAA as treatment for HCV has resulted in a significant reduction in hospitalisations due to cryoglobulinemia in Spain. As a result, cases due to HBV, hematologic and autoimmune diseases have emerged as conditions of growing importance associated with cryoglobulinemia hospitalisations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492790","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}

{"title":"Extrahepatic Replication and Genomic Signatures of the Hepatitis E Virus in the Kidney","authors":"Avista Wahid,&nbsp;Nele Meyer,&nbsp;Christine Wundes,&nbsp;Lucas Hüffner,&nbsp;Saskia Janshoff,&nbsp;Nicola Frericks,&nbsp;Martina Friesland,&nbsp;Katja Dinkelborg,&nbsp;Elmira Aliabadi,&nbsp;Fenja Laue,&nbsp;Markus Cornberg,&nbsp;Benjamin Maasoumy,&nbsp;Birgit Bremer,&nbsp;Sven Pischke,&nbsp;Tobias Müller,&nbsp;Julian Zur Schulze Wiesch,&nbsp;Julia Benckert,&nbsp;Rainer G. Ulrich,&nbsp;Svenja Hardtke,&nbsp;Petra Dörge,&nbsp;Florian Vondran,&nbsp;Ansgar Lohse,&nbsp;Michael Peter Manns,&nbsp;Daniel Todt,&nbsp;Heiner Wedemeyer,&nbsp;Thomas Pietschmann,&nbsp;Eike Steinmann,&nbsp;André Gömer,&nbsp;Patrick Behrendt","doi":"10.1111/liv.70183","DOIUrl":"https://doi.org/10.1111/liv.70183","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The hepatitis E virus (HEV; species <i>Paslahepevirus balayani</i>) is a common human pathogenic and zoonotic virus that can cause both acute fulminant and chronic hepatitis. Despite its reputation as a hepatotropic virus, HEV infection is also associated with a number of extrahepatic diseases, including kidney disorders. However, the extent to which HEV replicates in kidney cells remains unclear. The present study aims to investigate the capacity of HEV to propagate in kidney cells in vitro and to assess whether HEV displays mutational signatures that correlate with compartmentalisation in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We use HEV cell culture models to study the replication cycle and the effect of antivirals in human kidney cell lines and primary cells. In addition, we identified patients with chronic HEV infection (<i>n</i> = 9) from which we then sequenced the viral RNA of urine, stools and plasma to analyse the viral sequence composition, to assess intra-host diversity and compartmentalisation (<i>n</i> = 2).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A wide range of human kidney cell lines as well as primary cells supports viral entry, replication and propagation of HEV in vitro. Interestingly, the broad-spectrum antiviral ribavirin was less effective in inhibiting HEV replication in some kidney cells. Sequencing of HEV RNA-directed RNA polymerase coding region from plasma, stool and urine and subsequent phylogenetic analysis revealed diversification of HEV into tissue-specific viral subpopulations. In particular, the viruses derived from urine were found to be distinct from those derived from plasma and stool.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In conclusion, kidney cells support the propagation of HEV in vitro and exhibit reduced sensitivity to antiviral treatment. Furthermore, HEV patient-derived sequences demonstrated compartmentalisation into distinct clusters that correlated with sample source. Collectively, these data indicate the potential for extrahepatic replication of HEV, which may result in clinically significant disease or serve as a reservoir for patient relapse.</p>\u0000 \u0000 <p><b>Trial Registration:</b> HepNet-SofE study (NCT03282474)</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492791","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}

{"title":"Amelioration of Liver Fibrosis via In Situ Hepatic Stellate Cell Conversion Through Co-Inhibition of TGF-β and GSK-3 Signalling","authors":"Xiang-Jie Zhu,&nbsp;Zhi Zhong,&nbsp;Jiang-Chuan Du,&nbsp;Jiu-Yu Zhang,&nbsp;Xu Zhang,&nbsp;Xiu-Liang Cui,&nbsp;Ling-Ting Guan,&nbsp;Yan-Yu Hu,&nbsp;Can Chen,&nbsp;Han Wang,&nbsp;Xiang-Yu Wu,&nbsp;Wei-Jia Zhang,&nbsp;Pei-Lin Zhang,&nbsp;Hong-Yang Wang","doi":"10.1111/liv.70187","DOIUrl":"https://doi.org/10.1111/liv.70187","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Liver fibrosis, a progressive condition driven by chronic liver injury and excessive scar tissue formation, can lead to cirrhosis, a life-threatening disease. Activation of hepatic stellate cells (HSCs) is central to fibrosis progression, yet current therapies fail to halt or reverse this process. This study evaluated a combination therapy targeting HSCs to ameliorate fibrosis and promote liver repair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A small molecule cocktail, SBCH (SB431542, a TGF-β inhibitor, and CHIR99021, a GSK-3 inhibitor), was tested in three fibrosis models: CCl₄-induced, bile duct ligation (BDL) and non-alcoholic steatohepatitis (NASH) with diethylnitrosamine (DEN). Therapeutic effects were assessed using phenotypic analyses, in vivo tracing and single-cell RNA sequencing to uncover mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SBCH significantly reduced fibrosis in all models by inhibiting HSC activation and fibrogenic activity. The suppression of PI3K/Akt pathway and EMT cascade contribute to the fibrosis-ameliorating effect of SBCH treatment. Furthermore, in vivo tracing and single-cell RNA sequencing revealed that SBCH induced the conversion of activated HSCs into hepatocyte-like cells (ciHeps), which integrated into liver tissue, repaired liver damage and restored liver integrity and function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SBCH mitigates liver fibrosis through multifaceted mechanisms, including the inhibition of HSC activation, suppression of fibrogenic activity and regulation of key signalling pathways such as PI3K/Akt and EMT. In addition, SBCH induces the trans-differentiation of activated HSCs into hepatocyte-like cells (ciHeps), effectively reducing pathogenic HSCs while increasing functional ciHeps. This dual-target approach not only facilitates liver tissue repair but also restores liver function, offering a promising therapeutic strategy for liver fibrosis and cirrhosis, with potential applications in conditions arising from various aetiologies of liver injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492976","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}

{"title":"Impact of Socio-Economic, Behavioural and Clinical Factors on Liver Disease Progression in Individuals With HIV and Hepatitis B","authors":"Clémence Ramier,&nbsp;Anders Boyd,&nbsp;Colette Smit,&nbsp;Rosan van Zoest,&nbsp;Mark A. A. Claassen,&nbsp;Katalin Pogány,&nbsp;Dirk Posthouwer,&nbsp;Theodora E. M. S. de Vries-Sluijs,&nbsp;Patrizia Carrieri,&nbsp;Marc Van der Valk","doi":"10.1111/liv.70191","DOIUrl":"https://doi.org/10.1111/liv.70191","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Little is known about the contribution of sociodemographic and behavioural factors to developing liver disease in individuals with an HIV and chronic hepatitis B virus (HBV) co-infection. We aimed to quantify the impact of these factors on incident liver disease in individuals with HIV/HBV receiving care in the Netherlands.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from the Dutch observational ATHENA cohort combined with Statistics Netherlands. We included all hepatitis B surface antigen-positive individuals with HIV in care from 2008–2022. Severe liver disease (i.e., significant fibrosis (≥F2), cirrhosis, hepatocellular carcinoma, liver transplantation) was defined by physician diagnosis or a transient elastography result &gt; 7 kPa. Determinants of incident liver disease were assessed using Cox proportional hazard models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the 1319 individuals included (12,277 person-years (PY); 93.3% HIV-RNA &lt; 200 copies/ml), the incidence rate of severe liver disease was 0.59 per 100 PY [95% confidence interval (CI) = 0.47–0.75]. After adjustment for age and time since HBV diagnosis, tobacco smoking, HCV coinfection and body mass index &gt; 25 kg/m² increased the risk of liver disease [adjusted hazards ratio (aHR) = 2.33, 95% CI = 1.38–3.94; aHR = 4.00, 95% CI = 2.18–7.33, aHR = 1.75, 95% CI = 1.05–2.92, respectively]. Conversely, men who have sex with men (vs. other transmission routes, aHR = 0.54, 95% CI = 0.32–0.90), and individuals living in an urbanised municipality (aHR = 0.50, 95% CI = 0.30–0.85) had a reduced risk of liver disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Liver disease progression in people living with HIV/HBV appears to be linked to psychosocial/behavioural factors. More effective screening/management of coinfection and metabolic syndrome, as well as strategies for smoking cessation, should be included in clinical follow-up.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.70191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492974","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}

{"title":"A Multifaceted Approach Leads to Improved Linkage to HCV Therapy: A Multicenter Randomised Controlled Trial","authors":"Peng Xu,&nbsp;Dandan Yang,&nbsp;Yan Guo,&nbsp;Jiejun Yu,&nbsp;Wanyue Zhang,&nbsp;Xiaobin Zhang,&nbsp;Chuanwu Sun,&nbsp;Xingyun Chen,&nbsp;Peidong Zhang,&nbsp;Zhongfu Liu,&nbsp;Jian Li","doi":"10.1111/liv.70200","DOIUrl":"https://doi.org/10.1111/liv.70200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>Hepatitis C virus (HCV) treatment rate was low in China. We aimed to evaluate a four-support approach in linking previous HCV RNA-positive patients to antiviral treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a randomised controlled trial (ChiCTR2200060858, https://www.chictr.org.cn) and selected HCV RNA-positive participants from previous HCV antibody/RNA-positive patients, and assigned them into intervention or control arm. The control arm received routine care, whereas intervention arm received additional four-support intervention, including simplified treatment delivery, minimal examinations, insurance assistance, and social supports. The primary outcome was proportion of treatment initiation. The secondary outcomes included sustained virologic response (SVR) rates, time-to-treatment initiation, treatment completion, and treatment willingness. Adverse events were recorded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Among 394 participants, 199 and 195 were in the four-support and control arms, respectively. The four-support arm had significant higher proportions of treatment initiation than control arm at 1 and 2 months (35.68% vs. 13.85% and 47.24% vs. 17.44%, respectively, <i>p</i> &lt; 0.05). SVR was confirmed in 74.47% of four-support arm compared with 61.76% of control arm (adjusted odds ratio [aOR] 2.06). Patients in four-support arm had a shorter time-to-treatment initiation (adjusted hazard ratio [aHR] 3.10) and more frequent treatment completion (aOR 4.13) than control arm. The cumulative probability of treatment initiation at 1 and 2 months had a significant difference between two arms. Only one adverse event occurred in four-support arm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The four-support intervention could improve both antiviral treatment initiation and SVR in HCV RNA-positive patients with a previous HCV antibody/RNA-positive result and could be applied in these patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":"45 7","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492792","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}