Hepatology最新文献

{"title":"Discovery of a MET-driven monogenic cause of steatotic liver disease","authors":"Filippo Pinto e Vairo, Michael T. Zimmermann, Jessica Wagenknecht, Salomão Doria Jorge, Shulan Tian, Robert A. Vierkant, Anthony C. Luehrs, Thiago Milech de Assunção, Angela Mathison, Paldeep S. Atwal, Yang Cao, Alina M. Allen, Eric W. Klee, Raul Urrutia, Konstantinos N. Lazaridis","doi":"10.1097/hep.0000000000001249","DOIUrl":"https://doi.org/10.1097/hep.0000000000001249","url":null,"abstract":"Background &amp; Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects about a third of adults worldwide and is projected soon to be the leading cause of cirrhosis. It occurs when fat accumulates in hepatocytes and can progress to metabolic dysfunction-associated steatohepatitis (MASH), liver cirrhosis, and hepatocellular carcinoma. MASLD pathogenesis is believed to involve a combination of genetic and environmental risk factors. Single nucleotide polymorphisms have been implicated but non-syndromic monogenic causes are lacking. Methods: We identified a novel genetic variant in a familial case of MASH and performed deep variant functional analysis including protein modeling, dynamics, and cell-based assays to assess molecular mechanisms of dysfunction and altered cellular signaling. We analyzed exome sequencing data of 3,904 individuals with steatotic liver disease (SLD) to identify additional cases and establish the link between specific gene variants and SLD diagnosis. Results: We discovered and functionally validated the NM_000245.4:c.3505A&gt;T; p.(Ile1169Phe) variant in the <jats:italic toggle=\"yes\">MET</jats:italic> (mesenchymal epithelial transition) kinase domain as a monogenic cause of SLD. Subsequently, we detected additional ultra-rare, previously un-interpreted, and likely deleterious variants in <jats:italic toggle=\"yes\">MET</jats:italic> from screening sequencing data. Among individuals with confirmed SLD based on electronic record review, 1.1% (45/3,904) had rare predicted deleterious <jats:italic toggle=\"yes\">MET</jats:italic> variants. Eight of 45 (17.7%) individuals had predicted deleterious variants in the <jats:italic toggle=\"yes\">MET</jats:italic> kinase domain confirmed to be functionally like the familial case variant. Conclusions: We report the first germline non-malignant rare <jats:italic toggle=\"yes\">MET</jats:italic>-driven disease, a monogenic form of SLD.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"22 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term starvation boosts anti-PD-L1 therapy by reshaping tumor-associated macrophages in hepatocellular carcinoma","authors":"Kun Cheng, Ning Cai, Xing Yang, Danfeng Li, Zhu Jinghan, Hui Yuan Yang, Sha Liu, Deng Ning, Huifang Liang, Jianping Zhao, Zhanguo Zhang, Wanguang Zhang","doi":"10.1097/hep.0000000000001244","DOIUrl":"https://doi.org/10.1097/hep.0000000000001244","url":null,"abstract":"Background and Aims: Immune checkpoint inhibitors (ICIs) have revolutionized systemic hepatocellular carcinoma (HCC) treatment. Nevertheless, numerous patients are refractory to ICIs therapy. It is currently unknown whether diet therapies such as short-term starvation (STS) combined with ICIs can be used to treat HCC. This study aimed to investigate whether STS could sensitize HCC tumors to immunotherapy. Approach and Results: STS was found to attenuate tumor progression by inducing tumor-associated macrophages (TAMs) to switch to an antitumoral phenotype, enhancing phagocytosis of tumor cells, and stimulating subsequent anti-tumor immunity of CD8<jats:sup>+</jats:sup> T cells as demonstrated in three HCC mouse models, NCG mice, and Rag2-KO mice. Furthermore, STS combined with anti-PD1/L1 suppressed tumor progression, while the efficacy of anti-programmed cell death 1 ligand 1 (PD-L1) was improved when combined with STS. Mechanistically, TAM-derived exosomal PD-L1 (exoPD-L1) impairs the efficacy of anti-PD-1/L1. STS attenuates exoPD-L1 secretion from TAM by regulating the fructose diphosphatase 1 (FBP1) /Akt/Rab27a axis. Modulating FBP1/Akt/Rab27a axis potentiates the anti-PD-L1 response using two liposomal delivery systems and macrophage adoptive transfer. Conclusions: This study describes the immunomodulatory effects of STS and provides a rationale for its application as an adjuvant in HCC immunotherapy.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"12 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes and care for spontaneous bacterial peritonitis: A national cohort study","authors":"Marina Serper, Helen Tang, Siqi Zhang, Alexadra McCullough, David E. Kaplan, Tamar H. Taddei, Nadim Mahmud","doi":"10.1097/hep.0000000000001251","DOIUrl":"https://doi.org/10.1097/hep.0000000000001251","url":null,"abstract":"Background &amp; Aims: SBP leads to high rates acute kidney injury (AKI) -hepatorenal syndrome and mortality. Population-based studies on contemporary SBP epidemiology are needed to inform care. In a large, national cohort of patients diagnosed with SBP and confirmed by ascitic fluid criteria, we characterized ascitic fluid characteristics, in-hospital and 12-month mortality, AKI, and recurrent SBP. Approach &amp; Results: We investigated how individual and bundled quality measures for SBP associated with outcomes after multi-level adjustment for health-system, patient clinical factors and quality measures. Individual and bundled quality metrics were inpatient antibiotics within 48 hours, intravenous albumin, repeat paracentesis within 48 hours, recognition of SBP, and prophylactic antibiotics upon discharge. Among 4,330 patients with newly diagnosed SBP, in-hospital mortality was 15.5% and 12-month mortality was 56.6%. The incidence of Stage 1 AKI was 26.6%, 15.7% for Stage 2, and 22.8% for Stage 3. The cumulative incidence of recurrent SBP was 10.3%. Guideline-recommended albumin was the only individual metric associated with reduced in-hospital mortality (HR 0.73, 95%CI 0.59 - 0.91). Receipt of a higher number of metrics from the SBP bundle was associated with progressively lower 12-month post-discharge mortality: patients who received 3, 4, and 5 SBP bundle components had 20%, 38%, and 56% lower hazard of mortality, respectively, relative to those receiving 2 or fewer (all <jats:italic toggle=\"yes\">p</jats:italic>&lt;0.001). The SBP bundle was associated with lower incidence of Stage 3 versus Stage 0-2 AKI (OR 0.66, 95%CI 0.51-0.86). Conclusion: Prospective implementation of evidence-based SBP bundles may improve care outcomes and mortality in SBP.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"7 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and predictors of cirrhosis and portal hypertension in the united states","authors":"Zobair M. Younossi, Leyla de Avila, Andrei Racila, Fatema Nader, James Paik, Linda Henry, Maria Stepanova","doi":"10.1097/hep.0000000000001243","DOIUrl":"https://doi.org/10.1097/hep.0000000000001243","url":null,"abstract":"Background and aim: There is paucity of data about the prevalence of cirrhosis and portal hypertension in the US general population. Methods: We used National Health and Nutrition Examination Surveys (NHANES 2017-2020) to estimate the prevalence of cirrhosis and clinically significant (CS)-portal hypertension in alcoholic liver disease (ALD), MetALD, viral hepatitis (VH) to include chronic hepatitis B (CHB) and chronic hepatitis C (CHC), and metabolic dysfunction-associated steatotic liver disease (MASLD). Cirrhosis was evaluated using liver stiffness measurement (LSM) by transient elastography or FIB-4 score; CS-portal hypertension was defined via LSM and platelet count or the use of non-selective beta-blockers in the presence of cirrhosis. Results: The prevalence of CLD etiologies was ALD 0.85%, MetALD 3.38%, CHB 0.23%, CHC 0.73%, ALD+VH 0.16%, MASLD 33.05%. In general population, the prevalence of ALD-cirrhosis was 0.08%, MetALD-cirrhosis 0.19%, CHB-cirrhosis 0.01%, CHC-cirrhosis 0.10%, MASLD-cirrhosis 1.27%, ALD+VH-cirrhosis 0.08%, and other cirrhosis 0.87%. The prevalence of CS-portal hypertension in CLD was: 1.31% in MetALD, 1.60% in CHB, 4.73% in CHC, 2.00% in MASLD, and 0.35% in controls, to yield the population prevalence of 0.98%. In multivariate analysis, excessive alcohol use, CHC, male sex, obesity, type 2 diabetes, and hypertension were independently associated with an increased risk of cirrhosis (all <jats:italic toggle=\"yes\">P</jats:italic>&lt;0.05). Predictors of having CS-portal hypertension in CLD included CHC, obesity, and type 2 diabetes (all <jats:italic toggle=\"yes\">P</jats:italic>&lt;0.05). Conclusions: The prevalence of cirrhosis in the U.S. is 2.6% while the prevalence of CS-portal hypertension is 0.98%. Individuals with MASLD comprise the majority of U.S. residents with cirrhosis.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"20 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticosteroids in severe alcohol-associated hepatitis? Not so fast: A systematic review of randomized controlled trials","authors":"Michael A. Shi, Prisca Pungwe, Lauren LM. Comer, Maya Balakrishnan, Tzu-Hao Lee, George Cholankeril, Kavish R. Patidar, Avegail G. Flores, Vijay H. Shah, Ramon Bataller, Sumeet K. Asrani, Juan P. Arab, Fasiha Kanwal, Ruben Hernaez","doi":"10.1097/hep.0000000000001237","DOIUrl":"https://doi.org/10.1097/hep.0000000000001237","url":null,"abstract":"Background: Severe alcohol-associated hepatitis (AH) is rising in incidence with a high mortality burden. While corticosteroids are recommended for eligible patients with severe AH, no guidance exists for the timing of steroid initiation, tapering regimens, and surveillance of adverse events. Objective: We aim to systematically review these variables and provide evidence-based recommendations for the inpatient and outpatient management of severe AH. Design: We performed a literature search from inception to 5/30/2024 to include clinical trials published in full form and assessed the quality of evidence using the Cochrane Risk of Bias tool. Data were collected on the timing of initiation, rate, and complications following steroid therapy, and taper regimens in the setting of severe AH. Results: Of 28 studies that fulfilled our inclusion criteria, median time from admission to steroid initiation was 6.5 days. The most common steroid dosing regimen was prednisolone 40 mg daily for 28 days. Twenty-five studies containing 3,196 subjects reported adverse events, with exactly 50% in the steroid arm and the other half in the comparison arm. Infections, gastrointestinal bleeds, and renal impairment were the most frequently reported adverse events. Most infections occurred within the first month of the study. A two-week steroid taper was the most frequently reported regimen. Conclusion: We recommend taking up to a week to systematically and thoroughly evaluate patients before initiating steroids, and vigilant monitoring in the first month of treatment. We also recommend the lowest possible steroid exposure with a two-week steroid taper and close outpatient follow-up.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"25 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Intrahepatic immunoglobulin a complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of hepatocellular carcinoma_reply","authors":"Deok Hwa Seo, Pil Soo Sung","doi":"10.1097/hep.0000000000001253","DOIUrl":"https://doi.org/10.1097/hep.0000000000001253","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"9 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TIGIT-expression on natural killer cell subsets is an early indicator of alleviating liver inflammation following bulevirtide treatment in chronic hepatitis D.","authors":"Po-Chun Chen, Katja Deterding, Sophie Anna Engelskircher, Kerstin Port, Lisa Sandmann, Athira Chakkadath, Tijana Ristic, Qingyu Wu, Birgit Bremer, Anke R M Kraft, Markus Cornberg, Albert Heim, Helenie Kefalakes, Niklas K Björkström, Norman Woller, Heiner Wedemeyer","doi":"10.1097/HEP.0000000000001238","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001238","url":null,"abstract":"<p><strong>Background aims: </strong>Bulevirtide (BLV) is a novel and the only approved treatment option for patients with chronic hepatitis D (CHD). BLV alleviates liver inflammation already early during treatment when only minor HDV RNA changes are observed. We hypothesized that BLV-treatment may influence immune cells in CHD patients and performed a high-resolution analysis of natural killer (NK) cells before and during BLV-therapy.</p><p><strong>Methods: </strong>BLV-treated CHD patients (n=20) from a single-center cohort were longitudinally analyzed for clinical, molecular, and virological parameters. Peripheral blood mononuclear cells (PBMCs) were studied at baseline (BL), therapy weeks 3 (TW3) and 48 (TW48) by spectral flow cytometry. Healthy donors (HD), chronic hepatitis C (CHC) patients after direct-acting antivirals (DAA)-treatment and patients with chronic hepatitis B (CHB) were used as controls.</p><p><strong>Results: </strong>Overall NK cell frequencies remained stable during BLV-treatment. However, biochemical responders (BR) showed distinct NK cell immunophenotypic features before and during therapy. TIGIT-expression increased on CD56dim and CD56bright NK cells during the course of BLV-treatment and inversely correlated with alanine aminotransferase (ALT) levels in CHD but not CHC or CHB patients. High frequencies of TIGIT- CD57+ CD56dim NK cells at BL and low levels during therapy were indicative of a biochemical response.</p><p><strong>Conclusions: </strong>We here suggest that lacking the expression of the immune checkpoint inhibitor TIGIT on NK cell subtypes may be a hallmark of liver inflammation in HDV infection. BLV-therapy is associated with a reappearance of TIGIT on these cells, which may be one mechanism of why liver enzymes rapidly improve during therapy.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of glycogen synthase kinase 3alpha/beta as a host factor required for hepatitis B virus transcription using high-throughput screening.","authors":"Hironori Nishitsuji, Yui Naito, Yuuna Murakami, Masaya Sugiyama, Masashi Mizokami, Ikuo Shoji, Takayuki Murata, Kunitada Shimotohno","doi":"10.1097/HEP.0000000000001239","DOIUrl":"https://doi.org/10.1097/HEP.0000000000001239","url":null,"abstract":"<p><strong>Background aims: </strong>Hepatitis B virus (HBV) leads to severe liver diseases, such as cirrhosis and hepatocellular carcinoma. Identification of host factors that regulate HBV replication can provide new therapeutic targets. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) as an HBV entry receptor has enabled the establishment of hepatic cell lines for analyzing HBV infection and propagation. Using this new system, studies aimed at identifying host factors that regulate HBV propagation have increased.</p><p><strong>Approach results: </strong>We established an HBV-based-reporter gene expression system that mimics HBV replication from transcription to virus egress. Using this approach, we screened 1,827 Food and Drug Administration-approved compounds and identified glycogen synthase kinase 3 (GSK3)alpha/beta inhibitors, including AZD1080, CHIR-98014, CHIR-98021, BIO, and AZD2858, as anti-HBV compounds. These compounds suppressed hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg) production in HBV-infected human primary hepatocytes. Proteome analysis revealed that GSK3alpha/beta phosphorylated forkhead box K1/2 (FOXK1/2)s. A double-knockout of FOXK1/2 in HBV-infected HepG2-NTCP cells reduced HBeAg and HBsAg production. The rescue of FOXK2 expression, but not FOXK1 expression, in FOXK1/2-double-knockout cells restored HBeAg and HBsAg production. Importantly, phosphorylation of FOXK2 at Ser 424 is required for GSK3alpha/beta-mediated HBeAg and HBsAg production. We observed the binding of FOXK2 to HBV DNA in HepG2-NTCP cells.</p><p><strong>Conclusions: </strong>Our recombinant HBV-based screening system enables the discovery of new targets. Using our approach, we identified GSK3 inhibitors as potential anti-HBV agents.</p>","PeriodicalId":177,"journal":{"name":"Hepatology","volume":" ","pages":""},"PeriodicalIF":12.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PSC and colitis: A complex relationship","authors":"Ludwig J. Horst, Jan Kempski, Martine Walmsley, Samuel Huber, Christoph Schramm","doi":"10.1097/hep.0000000000001236","DOIUrl":"https://doi.org/10.1097/hep.0000000000001236","url":null,"abstract":"Primary sclerosing cholangitis is one of the most challenging conditions in hepatology, and due to our limited understanding of its pathogenesis, no causal therapies are currently available. While it was long assumed that a minority of people with IBD also develop PSC, which is sometimes labeled an extraintestinal manifestation of IBD, the clinical phenotype, genetic and intestinal microbiota associations strongly argue for PSC-IBD being a distinct form of IBD, existing alongside ulcerative colitis and Crohn’s disease. In fact, the liver itself could contribute to intestinal pathology, clinically overt in 60 – 80 % of patients. Recent studies suggested that on a molecular level, almost all people with PSC have underlying colitis. The extent to which the liver and gut influence each other clinically and in terms of disease progression has not yet been conclusively revealed. However, while it seemed intuitive that the two diseases have a negative influence on each other, evidence suggests that sclerosing cholangitis can also be protective for the gut and that colitis can in certain settings ameliorate liver pathology. This underscores the complex pathophysiological relationships, where factors such as genetic predisposition, changes in the intestinal microbiota, altered bile acid metabolism, and immune cell migration are among the suspected contributors. PSC is an emerging disease with a significant impact on health-related quality of life of affected people. With this review, we aim to summarize the current knowledge on the gut-liver axis in PSC-IBD, provide new perspectives on risk stratification and treatment and identify gaps in our current knowledge. Our understanding of this complex relationship will therefore help to design clinical trials and shape the future therapy of PSC-IBD.","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"17 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143020361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the immune landscape of IDH1-mutant cholangiocarcinoma: Pathways to new therapies","authors":"Binbin Li, Sumera I. Ilyas","doi":"10.1097/hep.0000000000001241","DOIUrl":"https://doi.org/10.1097/hep.0000000000001241","url":null,"abstract":"","PeriodicalId":177,"journal":{"name":"Hepatology","volume":"32 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}