tbuckley/cabot-search huggingface dataset:
Integrative analysis of DNA methylation and gene expression reveals hepatocellular carcinoma-specific diagnostic biomarkers
Authors: Jinming Cheng, Dongkai Wei, Yuan Ji, Lingli Chen, Liguang Yang, Guang Li, Leilei Wu, Ting Hou, Lu Xie, Guohui Ding, Hong Li, Yixue Li
Journal: Genome Medicine (2018)

Hepatocellular carcinoma (HCC) is the one of the most common cancers and lethal diseases in the world. DNA methylation alteration is frequently observed in HCC and may play important roles in carcinogenesis and diagnosis.Using the TCGA HCC dataset, we classified HCC patients into different methylation subtypes, identified differentially methylated and expressed genes, and analyzed cis- and trans-regulation of DNA methylation and gene expression. To find potential diagnostic biomarkers for HCC, we screened HCC-specific CpGs by comparing the methylation profiles of 375 samples from HCC patients, 50 normal liver samples, 184 normal blood samples, and 3780 samples from patients with other cancers. A logistic regression model was constructed to distinguish HCC patients from normal controls. Model performance was evaluated using three independent datasets (including 327 HCC samples and 122 normal samples) and ten newly collected biopsies.We identified a group of patients with a CpG island methylator phenotype (CIMP) and found that the overall survival of CIMP patients was poorer than that of non-CIMP patients. Our analyses showed that the cis-regulation of DNA methylation and gene expression was dominated by the negative correlation, while the trans-regulation was more complex. More importantly, we identified six HCC-specific hypermethylated sites as potential diagnostic biomarkers. The combination of six sites achieved ~ 92% sensitivity in predicting HCC, ~ 98% specificity in excluding normal livers, and ~ 98% specificity in excluding other cancers. Compared with previously published methylation markers, our markers are the only ones that can distinguish HCC from other cancers.Overall, our study systematically describes the DNA methylation characteristics of HCC and provides promising biomarkers for the diagnosis of HCC.
Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research
Authors: Jienchi Dorward, Richard Lessells, Paul K Drain, Kogieleum Naidoo, Tulio de Oliveira, Yogan Pillay, Salim S Abdool Karim, Nigel Garrett
Journal: The Lancet HIV (2018)
Corrigendum re “Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma” [Eur Urol 2017;72:747–54]
Authors: Mitchell J. Machiela, Jonathan N. Hofmann, Robert Carreras-Torres, Kevin M. Brown, Mattias Johansson, Zhaoming Wang, Matthieu Foll, Peng Li, Nathaniel Rothman, Sharon A. Savage, Valerie Gaborieau, James D. McKay, Yuanqing Ye, Marc Henrion, Fiona Bruinsma, Susan Jordan, Gianluca Severi, Kristian Hveem, Lars J. Vatten, Tony Fletcher, Kvetoslava Koppova, Susanna C. Larsson, Alicja Wolk, Rosamonde E. Banks, Peter J. Selby, Douglas F. Easton, Paul Pharoah, Gabriella Andreotti, Laura E. Beane Freeman, Stella Koutros, Demetrius Albanes, Satu Mannisto, Stephanie Weinstein, Peter E. Clark, Todd E. Edwards, Loren Lipworth, Susan M. Gapstur, Victoria L. Stevens, Hallie Carol, Matthew L. Freedman, Mark M. Pomerantz, Eunyoung Cho, Peter Kraft, Mark A. Preston, Kathryn M. Wilson, J. Michael Gaziano, Howard S. Sesso, Amanda Black, Neal D. Freedman, Wen-Yi Huang, John G. Anema, Richard J. Kahnoski, Brian R. Lane, Sabrina L. Noyes, David Petillo, Leandro M. Colli, Joshua N. Sampson, Celine Besse, Helene Blanche, Anne Boland, Laurie Burdette, Egor Prokhortchouk, Konstantin G. Skryabin, Meredith Yeager, Mirjana Mijuskovic, Miodrag Ognjanovic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Neonila Szeszenia-Dabrowska, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, H.B(as). Bueno-de-Mesquita, Federico Canzian, Eric J. Duell, Börje Ljungberg, Raviprakash T. Sitaram, Ulrike Peters, Emily White, Garnet L. Anderson, Lisa Johnson, Juhua Luo, Julie Buring, I-Min Lee, Wong-Ho Chow, Lee E. Moore, Christopher Wood, Timothy Eisen, James Larkin, Toni K. Choueiri, G. Mark Lathrop, Bin Tean Teh, Jean-Francois Deleuze, Xifeng Wu, Richard S. Houlston, Paul Brennan, Stephen J. Chanock, Ghislaine Scelo, Mark P. Purdue
Journal: European Urology (2018)
Impact of abemaciclib on the time to subsequent chemotherapy and the time to second disease progression across the MONARCH 2 and 3 studies.
Authors: Sara M. Tolaney, Angelo Di Leo, Antonio Llombart Cussac, Maura N. Dickler, Mario Campone, Hiroji Iwata, Masakazu Toi, Peter A. Kaufman, Valerie AM Andre, Susana Barriga, Matthew P. Goetz, George W. Sledge
Journal: Journal of Clinical Oncology (2018)

1048 Background: Abemaciclib is a selective oral inhibitor of CDK4 & 6 dosed on a twice-daily continuous schedule. Abemaciclib was an effective treatment with a generally tolerable safety profile in combination with fulvestrant (F) (MONARCH 2) and as initial therapy (MONARCH 3) when combined with a nonsteroidal aromatase inhibitor (NSAI) in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. To evaluate the impact of abemaciclib in subsequent treatment, we analyzed time to subsequent chemotherapy (TCT) and time to second disease progression (PFS2). Methods: Enrollment criteria and study designs of MONARCH 2 and 3 were previously reported (Sledge et al., 2017; Goetz et al., 2017). Exploratory analyses were performed to assess TCT and PFS2 using the Kaplan-Meier (KM) method. Hazard ratios (HR) were estimated using a Cox model. TCT was defined as time from randomization (R) to time to first chemotherapy (CT). Since exact progression date on post-therapies was not available, PFS2 was calculated from R to the discontinuation date of next-line (first line of post-discontinuation treatment), or starting date of the second line of post-discontinuation treatment, whichever was earlier. Results: Among randomized patients, 51% and 49% of patients in the MONARCH 2 and 3 trials, respectively, received a post-discontinuation systemic therapy (CT [35%, 26%], endocrine [28%, 38%], targeted agent [18%, 15%], or other [6%, 7%]). Initiation of CT was deferred by adding abemaciclib to F (median: abemaciclib arm, not reached; placebo [P] arm, 26.33 months [m]; HR 0.65, 95% CI 0.50-0.85; p < .01) or NSAI (median: abemaciclib arm, not reached; P arm, 32.52 m; HR 0.54, 95% CI 0.38-0.76; p < .001). KM analyses of PFS2 showed an improvement in the abemaciclib + F vs P + F arms (HR 0.78, 95% CI 0.61-1.00; p < .05) and in the abemaciclib + NSAI vs P + NSAI arms (HR 0.74, 95% CI 0.55-0.99; p < .05). Conclusions: Adding abemaciclib to F or NSAI delayed the start of subsequent chemotherapy, which is a patient-relevant outcome. Overall, the treatment benefit of abemaciclib + F or + NSAI was extended to the next line of the therapy after the initial disease progression. Clinical trial information: NCT02107703, NCT02246621.
Human Enteric α-Defensin 5 Promotes Shigella Infection by Enhancing Bacterial Adhesion and Invasion
Authors: Dan Xu, Chongbing Liao, Bing Zhang, W. David Tolbert, Wangxiao He, Zhijun Dai, Wei Zhang, Weirong Yuan, Marzena Pazgier, Jiankang Liu, Jun Yu, Philippe J. Sansonetti, Charles L. Bevins, Yongping Shao, Wuyuan Lu
Journal: Immunity (2018)
Post-transcriptional regulator Rbm47 elevates IL-10 production and promotes the immunosuppression of B cells
Authors: Yinxiang Wei, Fanghui Zhang, Yu Zhang, Xiaoqian Wang, Chen Xing, Jing Guo, Hui Zhang, Zhimin Suo, Yan Li, Jianli Wang, Renxi Wang, Zhijian Cai
Journal: Cellular and Molecular Immunology (2018)

Regulatory B cells (Bregs) are a functionally defined B cell subset, and IL-10 is crucial for the suppressive functions of Bregs. However, little is known regarding how IL-10 production is regulated in B cells. To explore the mechanisms by which IL-10 is regulated in B cells, we used mRNA microarrays to screen for molecules that are upregulated in IL-10-producing B cells and identified RNA-binding motif protein 47 (Rbm47) as a post-transcriptional regulator. Rbm47 was found to promote IL-10 production in B cells. We found that Rbm47 promotes the stability of IL-10 mRNA by binding to AU-rich elements in the 3′ untranslated region of Il10 mRNA. In addition, we demonstrated that the overexpression of Rbm47 enabled B cells to facilitate Foxp3+ regulator T-cell induction and reduce the severity of DSS-induced ulcerative colitis. Taken together, these results suggest that Rbm47 plays an important role in regulating IL-10 at the post-transcriptional level, thus promoting the regulatory functions of B cells. The findings presented in this study not only increase our understanding of the post-translational regulation of IL-10 in B cells but also identify a novel strategy for the potential application of Bregs.
Management and outcomes of acute respiratory distress syndrome patients with and without comorbid conditions
Authors: E. Azoulay, V. Lemiale, B. Mourvillier, M. Garrouste-Orgeas, C. Schwebel, S. Ruckly, Laurent Argaud, Y. Cohen, B. Souweine, L. Papazian, J. Reignier, G. Marcotte, S. Siami, H. Kallel, M. Darmon, J. F. Timsit, Outcomerea Study Grp
Journal: Intensive Care Medicine (2018)
PARP Inhibitors in Ovarian Cancer: A Trailblazing and Transformative Journey
Authors: Panagiotis A. Konstantinopoulos, Ursula A. Matulonis
Journal: Clinical Cancer Research (2018)

PARP inhibitors have transformed treatment for ovarian cancer, a cancer notable for homologous recombination (HR) deficiencies and aberrant DNA repair, especially in the high-grade serous subtype. PARP inhibitors are now approved for recurrent ovarian cancer as maintenance following response to platinum chemotherapy and BRCA-mutated (BRCAm) cancer treatment. Clin Cancer Res; 24(17); 4062-5. ©2018 AACRSee related article by Ison et al., p. 4066.
Phase II study of cabazitaxel as second-line treatment in patients with HER-2 negative metastatic breast cancer previously treated with taxanes.
Authors: Angelos Koutras, Flora Zagouri, Georgia-Angeliki Koliou, Georgios Lazaridis, Dimitrios Tryfonopoulos, Athanasios Kotsakis, Eleni Res, Nikolaos K. Kentepozidis, Evangelia Razis, Amanda Psyrri, Georgios Koumakis, Haralabos Kalofonos, George Fountzilas, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (2018)

1089 Background: Cabazitaxel is a new taxoid efficient in stabilizing microtubules against depolymerization. Preclinical and limited clinical data indicate that cabazitaxel might be effective in breast cancer patients resistant to first-generation taxanes. Methods: The purpose of the current multicenter phase II trial was to evaluate the activity and safety of cabazitaxel as 2nd-line treatment, given on day 1 of a 21-day cycle, in patients with HER-2 negative metastatic breast cancer (mBC), previously treated with taxanes. Prophylaxis with G-CSF was recommended to all patients. The primary endpoint was the objective response rate (ORR), while secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response (DOR) and the safety profile. Results: Eighty-four patients were enrolled between 2012 and 2016. Among them, 3 patients (3.6%) were ineligible but received at least two cycles of treatment. In total, 499 cycles of cabazitaxel were administered (median 4; range 1-39). Median relative dose intensity was 0.99 (range 0.79-1.49). Seven patients were not evaluated for tumor response. In the 77 patients with evaluable treatment response, the ORR was 24.7% (1 complete and 18 partial responses). The disease-control rate was 58.4%, while the median DOR was 5.6 months (range 0.7-51.3). Within a median follow-up of 32.2 months, the median PFS was 3.7 months (95% CI 2.23-4.36), whereas the median OS was 15.2 months (95% CI 11.21-21.54). Regarding toxicity, grades 3-4 neutropenia and febrile neutropenia were reported in 22.6% and 6.0% of patients, respectively. Two fatal events were reported (1 febrile neutropenia; 1 sepsis) related to study treatment. Most frequent non-hematological events were fatigue, diarrhea, nausea (grade 1-3). There were no unexpected serious AE, and no new safety signal was revealed. Conclusions: This phase II trial suggests that cabazitaxel is active (disease control rate of almost 60%) with a manageable toxicity profile as 2nd-line treatment in taxane-pretreated patients with HER-2 negative mBC. Clinical trial information: NCT01693549.
Evaluation of homologous recombination deficiency (HRD) status with pathological response to carboplatin +/- veliparib in BrighTNess, a randomized phase 3 study in early stage TNBC.
Authors: Melinda L. Telli, Otto Metzger, Kirsten Timms, Brent Evans, Diana Vogel, Helen Wei, Joshua Timothy Jones, Richard J. Wenstrup, Mark D. McKee, Danielle Marie Sullivan, Mathias Fallstrom, David Maag, Peter J Ansell, Joohyuk Sohn, Shou-Tung Chen, Noelia Martinez, Charles E. Geyer, Sibylle Loibl, Mehra Golshan
Journal: Journal of Clinical Oncology (2018)

519 Background: HRD status is significantly associated with a higher rate of response to neoadjuvant platinum-based therapy and improved PFS following adjuvant doxorubicin and cyclophosphamide (AC) in TNBC. We assessed the prognostic and predictive role of the HRD assay for platinum and PARP inhibitor response in BrighTNess. Methods: 634 stage II-III TNBC pts were randomized 2:1:1 to: Arm A: Paclitaxel (T) q wk x 12 + carboplatin (P) (AUC 6) q3 wk x 4 + veliparib (TPV) - > AC q2-3 wk x 4; Arm B: T + P + placebo (TP) - > AC; or Arm C: T + dual placebo (T) - > AC. HRD status was defined as HRD+ (HRD score ≥ 42 or a tumor BRCA1/2 mutation) or HRD- (HRD score < 42 and no tumor BRCA1/2 mutation). An exploratory HRD threshold of ≥ 33 vs < 33 was also assessed. Results: HRD status was available for 438 pts. HRD data by arm for pCR for the 42 and 33 cut-offs are shown. Within each arm using the 42 and 33 cut-offs, respectively, ORs for pCR by HRD status (HRD+/HRD-) were 2.85 (p = 0.0005) and 3.10 (p = 0.004) for Arm A, 1.55 (p = 0.30) and 2.28 (p = 0.10) for Arm B and 2.13 (p = 0.13) and 1.52 (0.48) for Arm C. Comparing between arms using the 42 threshold, ORs for pCR (Arm A/Arm B, Arm A/Arm C, Arm B/Arm C) in the HRD+ group were 1.04, 3.02 and 2.90 and were not statistically significantly different than in the HRD- group (0.57 [p = 0.23], 2.26 [p = 0.60] and 4.0 [p = 0.61]). Similar results were observed with the 33 cut-off. Conclusions: In BrighTNess, higher rates of pCR were observed in HRD+ pts across all treatment arms. However, pts treated with P had higher rates of pCR in both HRD+ and HRD- subsets. The exploratory HRD threshold of 33 appeared to provide greater sensitivity to identify responders with the addition of P + V. Receipt of AC in all pts may have contributed to the lack of interaction observed between HRD status and P +/- V treatment. Clinical trial information: NCT02032277.Arm pCR HRD+ ≥ 42 pCR HRD- < 42 pCR HRD+ ≥ 33 pCR HRD- < 33 TPV-AC (A) n = 213 87/141 (61.7%) 26/72 (36.1%) 93/153 (60.8%) 20/60 (33.3%) TP-AC (B) n = 116 51/84 (60.7%); p = 0.88# 16/32 (50%); p = 0.18# 57/92 (62%); p = 0.89# 10/24 (41.4%); p = 0.61# T-AC (C) n = 109 24/69 (34.8%); p = 0.0003‡ 8/40 (20%); p = 0.08‡ 25/79 (31.6%); p = < 0.0001‡ 7/30 (23.3%); p = 0.46‡ # = for TPV-AC vs TP-AC; ‡ = for TPV-AC vs T-AC
Estimating Surgical Risk for Patients With Severe Comorbidities
Authors: Scott K. Sherman, Elizabeth C. Poli, Muneera R. Kapadia, Kiran K. Turaga
Journal: JAMA Surgery (2018)

This study assesses whether estimates from the new American College of Surgeons Surgical Risk Calculator more closely match residents' estimations of risk and determines outcomes of similar patients in the National Surgical Quality Improvement Project.
Incidence of Diabetes After Cancer Development
Authors: Yul Hwangbo, Danbee Kang, Minwoong Kang, Saemina Kim, Eun Kyung Lee, Young Ae Kim, Yoon Jung Chang, Kui Son Choi, So-Youn Jung, Sang Myung Woo, Jin Seok Ahn, Sung Hoon Sim, Yun Soo Hong, Roberto Pastor-Barriuso, Eliseo Guallar, Eun Sook Lee, Sun-Young Kong, Juhee Cho
Journal: JAMA Oncology (2018)

Diabetes is an established risk factor for developing cancer. A limited body of evidence also suggests that cancer can increase the risk of developing new cases of diabetes, but the evidence is inconclusive.To evaluate whether the development of cancer is associated with increasing risk of subsequent diabetes.This cohort study included a nationally representative sample of the Korean general population observed for up to 10 years (January 1, 2003, to December 31, 2013). A total of 524 089 men and women 20 to 70 years of age without diabetes and with no history of cancer at baseline were included.Incident cancer (time-varying exposure).Incident type 2 diabetes using insurance claim codes.During 3 492 935.6 person-years of follow-up (median follow-up, 7.0 years) in 494 189 individuals (50.0% female; mean [SD] age, 41.8 [12.5] years), 15 130 participants developed cancer and 26 610 participants developed diabetes. After adjustment for age, sex, precancer diabetes risk factors, metabolic factors, and comorbidities, the hazard ratio (HR) for diabetes associated with cancer development was 1.35 (95% CI, 1.26-1.45; P < .001). The excess risk for diabetes was highest in the first 2 years after cancer diagnosis, but it remained elevated throughout follow-up. By cancer type, development of pancreatic (HR, 5.15; 95% CI, 3.32-7.99), kidney (HR, 2.06; 95% CI, 1.34-3.16), liver (HR, 1.95; 95% CI, 1.50-2.54), gallbladder (HR, 1.79; 95% CI, 1.08-2.98), lung (HR, 1.74; 95% CI, 1.34-2.24), blood (HR, 1.61; 95% CI, 1.07-2.43), breast (HR, 1.60; 95% CI, 1.27-2.01), stomach (HR, 1.35; 95% CI, 1.16-1.58), and thyroid cancer (HR, 1.33; 95% CI, 1.12-1.59) was associated with a significantly increased risk of diabetes.In this large Korean cohort, cancer development increased the risk of subsequent diabetes. These data provide evidence that cancer is associated with an increased risk of diabetes in cancer survivors independent of traditional diabetes risk factors. Physicians should remember that patients with cancer develop other clinical problems, such as diabetes, with higher frequency than individuals without cancer, and should consider routine diabetes screening in these patients.
Validation, in silico and in vitro, of a gene-signature based risk score in cutaneous melanoma.
Authors: Georg Brunner, Thomas M. Falk, Beyhan Ertas, Carola Berking, Hans-Joachim Schulze, Norbert Blödorn-Schlicht
Journal: Journal of Clinical Oncology (2017)

9560 Background: Melanoma staging, as defined by the American Joint Committee on Cancer (AJCC), is limited in its ability to predict outcome. We have previously identified and validated a prognostic gene signature expressed in primary cutaneous melanoma and adjacent stroma. The signature comprises seven protective genes (down-regulated with tumor progression) and one risk-associated gene (up-regulated). A signature-based risk score independently predicts patient survival, across AJCC stages IA-IIIC, in formalin-fixed, paraffin-embedded (FFPE) melanomas (training cohort, n = 125; p = 0.0003, hazard ratio 1.85). The score has been validated in 206 melanomas, selected to be significantly mis-prognosticated by AJCC staging regarding patient survival (40.8% mis-prognostication). In this cohort, the score outperforms AJCC staging (p = 0.0005, hazard ratio 1.41 vs. p = n.s.), correcting 34.9% of AJCC-based mis-prognostications. Methods: Here, we report twofold external validation of the risk score, (i) prognostic performance in silico using the SurvExpress web tool (Aguirre-Gamboa et al., 2013), and (ii) technical performance in vitro(Dermatologikum Hamburg; IMGM Munich) . Results: (i) Kaplan Meier analysis and log-rank testing demonstrated that all signature genes combined predicted survival in four different cohorts of metastatic melanoma (from GEO Expression Omnibus or Cancer Genome Atlas; cohorts dichotomized at the median): see table. (ii) The risk score was re-analyzed in melanomas of the training cohort (n=69). The overall concordance of duplicate determinations was 90% (average scores of 1.12 ± 0.14 and 0.97 ± 0.14). Conclusions: In conclusion, we have validated a signature-based FFPE melanoma risk score, complementary to AJCC staging in predicting outcome: (i) Signature genes predicted patient survival in silico(n=449) (ii) The risk score proved to be reproducible and technically robust in vitro. The score improves risk stratification and decision making in melanoma, particularly regarding new adjuvant therapies. [Table: see text]
Author Correction: Impact of remote patient monitoring on clinical outcomes: an updated meta-analysis of randomized controlled trials
Authors: Benjamin Noah, Michelle S. Keller, Sasan Mosadeghi, Libby Stein, Sunny Johl, Sean Delshad, Vartan C. Tashjian, Daniel Lew, James T. Kwan, Alma Jusufagic, Brennan M. R. Spiegel
Journal: npj Digital Medicine (2018)

[This corrects the article DOI: 10.1038/s41746-017-0002-4.].
Multi-organ assessment of compensated cirrhosis patients using quantitative magnetic resonance imaging
Authors: Christopher R. Bradley, Eleanor F. Cox, Robert A. Scott, Martin W. James, Phillip Kaye, Guruprasad P. Aithal, Susan T. Francis, Indra Neil Guha
Journal: Journal of Hepatology (2018)

Advancing liver disease results in deleterious changes in a number of critical organs. The ability to measure structure, blood flow and tissue perfusion within multiple organs in a single scan has implications for determining the balance of benefit vs. harm for therapies. Our aim was to establish the feasibility of magnetic resonance imaging (MRI) to assess changes in Compensated Cirrhosis (CC), and relate this to disease severity and future liver-related outcomes (LROs).A total of 60 patients with CC, 40 healthy volunteers and 7 patients with decompensated cirrhosis were recruited. In a single scan session, MRI measures comprised phase-contrast MRI vessel blood flow, arterial spin labelling tissue perfusion, T1 longitudinal relaxation time, heart rate, cardiac index, and volume assessment of the liver, spleen and kidneys. We explored the association between MRI parameters and disease severity, analysing differences in baseline MRI parameters in the 11 (18%) patients with CC who experienced future LROs.In the liver, compositional changes were reflected by increased T1 in progressive disease (p <0.001) and an increase in liver volume in CC (p = 0.006), with associated progressive reduction in liver (p <0.001) and splenic (p <0.001) perfusion. A significant reduction in renal cortex T1 and increase in cardiac index and superior mesenteric arterial blood flow was seen with increasing disease severity. Baseline liver T1 (p = 0.01), liver perfusion (p <0.01), and renal cortex T1 (p <0.01) were significantly different in patients with CC who subsequently developed negative LROs.MRI enables the contemporaneous assessment of organs in liver cirrhosis in a single scan without the requirement for a contrast agent. MRI parameters of liver T1, renal T1, hepatic and splenic perfusion, and superior mesenteric arterial blood flow were related to the risk of LROs.This study assesses the changes to structure, blood flow and perfusion that occur in the key organs (liver, spleen and kidney) associated with severe liver disease (Compensated Cirrhosis), using magnetic resonance imaging. The magnetic resonance imaging measures which changed with disease severity and were related to negative liver-related clinical outcomes are described.