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Tsai FP, Su TH, Huang SC, Tseng TC, Hsu SJ, Liao SH, Hong CM, Liu CH, Yang HC, Liu CJ, Chen PJ, Kao JH. Outcomes of radiofrequency ablation for hepatocellular carcinoma with concurrent steatotic liver disease. Cancer 2025; 131:e35541. [PMID: 39238423 DOI: 10.1002/cncr.35541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 07/28/2024] [Accepted: 08/05/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND Steatotic liver disease (SLD) is an emerging liver disease that has been associated with an increased risk for hepatocellular carcinoma (HCC). The impact of concurrent SLD on the prognosis of HCC remains unknown. This study investigates how concurrent SLD affects the outcomes of patients with HCC undergoing curative radiofrequency ablation (RFA) therapy. METHODS A retrospective analysis of patients with early-stage HCC receiving curative RFA at a tertiary medical center was conducted. Laboratory data and HCC characteristics were recorded and analyzed by a Cox proportional hazards regression model to predict recurrence and all-cause mortality after RFA. RESULTS A total of 598 patients with HCC were included between 2005 and 2015, with 139 and 459 classified in SLD and non-SLD groups, respectively. The SLD group exhibited a significantly better liver reserve and a lower cumulative incidence of HCC recurrence and liver-related and all-cause mortality after a median follow-up of 51 months. After adjusting for metabolic dysfunction, liver reserve, and HCC characteristics, the presence of SLD reduced all-cause mortality (adjusted hazard ratio [aHR], 0.67; 95% confidence interval [CI], 0.45-0.996; p = .048), which was supported by inverse probability weighting analysis (aHR, 0.65; 95% CI, 0.42-1.00; p = .049). Poor liver functional reserve (high albumin-bilirubin grades) increased all-cause mortality dose dependently. Barcelona Clinic Liver Cancer staging and a higher Fibrosis-4 index were predictors for HCC recurrence, whereas SLD was not. CONCLUSIONS Among patients with HCC undergoing curative RFA, those with concurrent SLD had a lower risk of all-cause mortality compared to those with poor liver functional reserve. PLAIN LANGUAGE SUMMARY The present research demonstrated that patients with both liver cancer and steatotic liver disease who received curative radiofrequency ablation for liver cancer survived longer compared to those without steatotic liver disease. Maintaining good liver function is an important prognostic factor for survival.
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Affiliation(s)
- Feng-Pai Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu County, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Sih-Han Liao
- National Taiwan University Cancer Center, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Shin H, Hur MH, Song BG, Park SY, Kim GA, Choi G, Nam JY, Kim MA, Park Y, Ko Y, Park J, Lee HA, Chung SW, Choi NR, Park MK, Lee YB, Sinn DH, Kim SU, Kim HY, Kim JM, Park SJ, Lee HC, Lee DH, Chung JW, Kim YJ, Yoon JH, Lee JH. AI model using CT-based imaging biomarkers to predict hepatocellular carcinoma in patients with chronic hepatitis B. J Hepatol 2024:S0168-8278(24)02784-3. [PMID: 39710148 DOI: 10.1016/j.jhep.2024.12.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 11/12/2024] [Accepted: 12/07/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND & AIMS Various hepatocellular carcinoma (HCC) prediction models have been proposed for patients with chronic hepatitis B (CHB) using clinical variables. We aimed to develop an artificial intelligence (AI)-based HCC prediction model by incorporating imaging biomarkers derived from abdominal computed tomography (CT) images along with clinical variables. METHODS An AI prediction model employing a gradient-boosting machine algorithm was developed utilizing imaging biomarkers extracted by DeepFore, a deep learning-based CT auto-segmentation software. The derivation cohort (n = 5,585) was randomly divided into the training and internal validation sets at a 3:1 ratio. The external validation cohort included 2,883 patients. Six imaging biomarkers (i.e. abdominal visceral fat-total fat volume ratio, total fat-trunk volume ratio, spleen volume, liver volume, liver-spleen Hounsfield unit ratio, and muscle Hounsfield unit) and eight clinical variables were selected as the main variables of our model, PLAN-B-DF. RESULTS In the internal validation set (median follow-up duration = 7.4 years), PLAN-B-DF demonstrated an excellent predictive performance with a c-index of 0.91 and good calibration function (p = 0.78 by the Hosmer-Lemeshow test). In the external validation cohort (median follow-up duration = 4.6 years), PLAN-B-DF showed a significantly better discrimination function compared to previous models, including PLAN-B, PAGE-B, modified PAGE-B, and CU-HCC (c-index, 0.89 vs. 0.65-0.78; all p <0.001), and maintained a good calibration function (p = 0.42 by the Hosmer-Lemeshow test). When patients were classified into four groups according to the risk probability calculated by PLAN-B-DF, the 10-year cumulative HCC incidence was 0.0%, 0.4%, 16.0%, and 46.2% in the minimal-, low-, intermediate-, and high-risk groups, respectively. CONCLUSION This AI prediction model, integrating deep learning-based auto-segmentation of CT images, offers improved performance in predicting HCC risk among patients with CHB compared to previous models. IMPACT AND IMPLICATIONS The novel predictive model PLAN-B-DF, employing an automated computed tomography segmentation algorithm, significantly improves predictive accuracy and risk stratification for hepatocellular carcinoma in patients with chronic hepatitis B (CHB). Using a gradient-boosting algorithm and computed tomography metrics, such as visceral fat volume and myosteatosis, PLAN-B-DF outperforms previous models based solely on clinical and demographic data. This model not only shows a higher c-index compared to previous models, but also effectively classifies patients with CHB into different risk groups. This model uses machine learning to analyze the complex relationships among various risk factors contributing to hepatocellular carcinoma occurrence, thereby enabling more personalized surveillance for patients with CHB.
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Affiliation(s)
- Hyunjae Shin
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Gyeonggi-do, Korea
| | - Moon Haeng Hur
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Byeong Geun Song
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Gi-Ae Kim
- Divisions of Gastroenterology and Hepatology, Department of Internal Medicine, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Gwanghyeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Gyeonggi-do, Korea
| | | | - Minseok Albert Kim
- Department of Internal Medicine, ABC Hospital, Hwaseong, Gyeonggi-do, Korea
| | - Youngsu Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Yunmi Ko
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeayeon Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, College of Medicine, Chung-Ang University, Seoul, Korea
| | - Sung Won Chung
- Division of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Na Ryung Choi
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Min Kyung Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Gyeonggi-do, Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | | | - Sang Joon Park
- AI Center, MedicalIP. Co. Ltd., Seoul, Korea; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Hyung-Chul Lee
- Department of Anesthesiology, Seoul National University College of Medicine, Seoul, Korea
| | - Dong Ho Lee
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Wook Chung
- Department of Radiology, Seoul National University College of Medicine, Seoul, Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea; Inocras Inc., San Diego, CA, USA.
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Lu Y, Zhao YC, Liu K, Bever A, Zhou Z, Wang K, Fang Z, Polychronidis G, Liu Y, Tao L, Dickerman BA, Giovannucci EL, Song M. A validated estimate of visceral adipose tissue volume in relation to cancer risk. J Natl Cancer Inst 2024; 116:1942-1951. [PMID: 39150790 DOI: 10.1093/jnci/djae193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/17/2024] [Accepted: 08/12/2024] [Indexed: 08/18/2024] Open
Abstract
BACKGROUND Despite the recognized role of visceral adipose tissue in carcinogenesis, its independent association with cancer risk beyond traditional obesity measures remains unknown because of limited availability of imaging data. METHODS We developed an estimation equation for visceral adipose tissue volume using elastic net regression based on demographic and anthropometric data in a subcohort of participants in the UK Biobank (UKB; n = 23 148) with abdominal magnetic resonance imaging scans. This equation was externally validated in 2713 participants from the 2017-2018 National Health and Nutrition Examination Survey according to sex, age, and race groups. We then applied the equation to the overall UKB cohort of 461 665 participants to evaluate the prospective association between estimated visceral adipose tissue and cancer risk using Cox proportional hazards models. We also calculated the population attributable risk of cancer associated with estimated visceral adipose tissue and body mass index (BMI). RESULTS Estimated visceral adipose tissue showed a high correlation with measured visceral adipose tissue in internal and external validations (r = 0.81-0.86). During a median 12-year follow-up in the UKB, we documented 37 397 incident cancer cases; estimated visceral adipose tissue was statistically significantly associated with elevated risk of obesity-related and individual cancers, independent of BMI and waist circumference. Population attributable risk for total cancer associated with high (quartiles 2-4 vs 1) estimated visceral adipose tissue (9.0% for men, 11.6% for women) was higher than high BMI (quartiles 2-4 vs 1 = 5.0% for men, 8.2% for women). CONCLUSIONS Estimated visceral adipose tissue showed robust performance in UKB and National Health and Nutrition Examination Survey and was associated with cancer risk independent of BMI and waist circumference. This study provides a potential clinical tool for visceral adipose tissue estimation and underscores that visceral adipose tissue can be an important target for cancer prevention.
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Affiliation(s)
- Yujia Lu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Yu Chen Zhao
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Kuangyu Liu
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Alaina Bever
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA, USA
| | - Ziyi Zhou
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- School of Health and Wellbeing, University of Glasgow, Glasgow, UK
| | - Kai Wang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Zhe Fang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Yuchen Liu
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Liyuan Tao
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China
| | - Barbra A Dickerman
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Gastroenterology, Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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Vogel L, Güttler M, Theinert KB, Snedec T, Reichelt K, Pietsch F, Schären-Bannert M, Rachidi F, Dobeleit G, Fuhrmann H, Spilke J, Edlich F, Starke A. A potential gateway to understanding liver disease development: peripartum lipid fluctuations in dairy cows. Front Cell Dev Biol 2024; 12:1370717. [PMID: 39659522 PMCID: PMC11628505 DOI: 10.3389/fcell.2024.1370717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 11/04/2024] [Indexed: 12/12/2024] Open
Abstract
Current lifestyles are leading to a worldwide increase in metabolic liver diseases that favor the development of liver disease. Changes in hepatocytes are caused by altered lipid concentrations, oxidative stress or toxicity by individual lipids. The complexity of the underlying processes and differences of the pathology to proposed rodent models makes the development of an effective targeted therapy difficult. The lipid mobilization that occurs in dairy cows in the postpartum period could be a natural model for the metabolic stress commonly observed in the development of liver diseases. We therefore used gas chromatography and histopathological staining techniques to analyze lipid patterns in diparous and multiparous cows during the peripartum period. The most striking change in lipid composition is the homogenous increase in palmitoleic acid (C16:1n7) content in all cows around the time of calving, with multiparous cows exhibiting consistently higher C16:1n7 levels by the end of the study. Elevated C16:1n7 levels have a potential key role in the development of non-alcoholic steatohepatitis (NASH) and tumorigenesis in the liver. Changes in C16:1n7, therefore, support the idea that lipid mobilization in dairy cows could serve as model for various liver diseases, such as nonalcoholic fatty liver disease (NAFLD) or NASH development.
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Affiliation(s)
- Laura Vogel
- Clinic for Ruminants and Swine, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Markus Güttler
- Institute of Biochemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Kirsten B. Theinert
- Clinic for Ruminants and Swine, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Teja Snedec
- Clinic for Ruminants and Swine, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Kristin Reichelt
- Institute of Biochemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Fabian Pietsch
- Clinic for Ruminants and Swine, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Melanie Schären-Bannert
- Clinic for Ruminants and Swine, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Fanny Rachidi
- Clinic for Ruminants and Swine, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Gabriele Dobeleit
- Institute of Biochemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Herbert Fuhrmann
- Institute of Biochemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Joachim Spilke
- Biometrics and Informatics in Agriculture Group, Institute of Agriculture and Nutrition, Martin-Luther-University, Halle, Germany
| | - Frank Edlich
- Institute of Biochemistry, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
| | - Alexander Starke
- Clinic for Ruminants and Swine, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany
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Anbarasu CR, Williams-Perez S, Camp ER, Erstad DJ. Surgical Implications for Nonalcoholic Steatohepatitis-Related Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:2773. [PMID: 39199546 PMCID: PMC11352989 DOI: 10.3390/cancers16162773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 07/27/2024] [Accepted: 07/31/2024] [Indexed: 09/01/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer that arises in a background of chronic hepatic injury. Metabolic syndrome-associated fatty liver disease (MAFLD) and its severe form, nonalcoholic steatohepatitis (NASH), are increasingly common mechanisms for new HCC cases. NASH-HCC patients are frequently obese and medically complex, posing challenges for clinical management. In this review, we discuss NASH-specific challenges and the associated implications, including benefits of minimally invasive operative approaches in obese patients; the value of y90 as a locoregional therapy; and the roles of weight loss and immunotherapy in disease management. The relevant literature was identified through queries of PubMed, Google Scholar, and clinicaltrials.gov. Provider understanding of clinical nuances specific to NASH-HCC can improve treatment strategy and patient outcomes.
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Affiliation(s)
| | | | - Ernest R. Camp
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
- Department of Surgery, Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA
| | - Derek J. Erstad
- Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
- Department of Surgery, Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA
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Greco F, Piccolo CL, D’Andrea V, Scardapane A, Beomonte Zobel B, Mallio CA. Fat Matters: Exploring Cancer Risk through the Lens of Computed Tomography and Visceral Adiposity. J Clin Med 2024; 13:453. [PMID: 38256587 PMCID: PMC10817009 DOI: 10.3390/jcm13020453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 01/08/2024] [Accepted: 01/12/2024] [Indexed: 01/24/2024] Open
Abstract
Obesity is an established risk factor for cancer. However, conventional measures like body mass index lack precision in assessing specific tissue quantities, particularly of the two primary abdominal fat compartments, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Computed tomography (CT) stands as the gold standard for precisely quantifying diverse tissue types. VAT, distinguished by heightened hormonal and metabolic activity, plays a pivotal role in obesity-related tumor development. Excessive VAT is linked to aberrant secretion of adipokines, proinflammatory cytokines, and growth factors, fostering the carcinogenesis of obesity-related tumors. Accurate quantification of abdominal fat compartments is crucial for understanding VAT as an oncological risk factor. The purpose of the present research is to elucidate the role of CT, performed for staging purposes, in assessing VAT (quantity and distribution) as a critical factor in the oncogenesis of obesity-related tumors. In the field of precision medicine, this work takes on considerable importance, as quantifying VAT in oncological patients becomes fundamental in understanding the influence of VAT on cancer development-the potential "phenotypic expression" of excessive VAT accumulation. Previous studies analyzed in this research showed that VAT is a risk factor for clear cell renal cell carcinoma, non-clear cell renal cell carcinoma, prostate cancer, and hepatocarcinoma recurrence. Further studies will need to quantify VAT in other oncological diseases with specific mutations or gene expressions, in order to investigate the relationship of VAT with tumor genomics.
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Affiliation(s)
- Federico Greco
- Department of Radiology, Cittadella della Salute Azienda Sanitaria Locale di Lecce, Piazza Filippo Bottazzi 2, 73100 Lecce, Italy
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
| | - Claudia Lucia Piccolo
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Valerio D’Andrea
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Arnaldo Scardapane
- Dipartimento Interdisciplinare di Medicina, Sezione di Diagnostica per Immagini, Università degli Studi di Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124 Bari, Italy;
| | - Bruno Beomonte Zobel
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
| | - Carlo Augusto Mallio
- Research Unit of Radiology, Department of Medicine and Surgery, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Roma, Italy; (C.L.P.); (B.B.Z.); (C.A.M.)
- Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo 200, 00128 Roma, Italy
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Mao XC, Shi S, Yan LJ, Wang HC, Ding ZN, Liu H, Pan GQ, Zhang X, Han CL, Tian BW, Wang DX, Tan SY, Dong ZR, Yan YC, Li T. A model based on adipose and muscle-related indicators evaluated by CT images for predicting microvascular invasion in HCC patients. Biomark Res 2023; 11:87. [PMID: 37794517 PMCID: PMC10548702 DOI: 10.1186/s40364-023-00527-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 09/20/2023] [Indexed: 10/06/2023] Open
Abstract
BACKGROUND AND AIM The presence of microvascular invasion (MVI) will impair the surgical outcome of hepatocellular carcinoma (HCC). Adipose and muscle tissues have been confirmed to be associated with the prognosis of HCC. We aimed to develop and validate a nomogram based on adipose and muscle related-variables for preoperative prediction of MVI in HCC. METHODS One hundred fifty-eight HCC patients from institution A (training cohort) and 53 HCC patients from institution B (validation cohort) were included, all of whom underwent preoperative CT scan and curative resection with confirmed pathological diagnoses. Least absolute shrinkage and selection operator (LASSO) logistic regression was applied to data dimensionality reduction and screening. Nomogram was constructed based on the independent variables, and evaluated by external validation, calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA). RESULTS Histopathologically identified MVI was found in 101 of 211 patients (47.9%). The preoperative imaging and clinical variables associated with MVI were visceral adipose tissue (VAT) density, intramuscular adipose tissue index (IMATI), skeletal muscle (SM) area, age, tumor size and cirrhosis. Incorporating these 6 factors, the nomogram achieved good concordance index of 0.79 (95%CI: 0.72-0.86) and 0.75 (95%CI: 0.62-0.89) in training and validation cohorts, respectively. In addition, calibration curve exhibited good consistency between predicted and actual MVI probabilities. ROC curve and DCA of the nomogram showed superior performance than that of models only depended on clinical or imaging variables. Based on the nomogram score, patients were divided into high (> 273.8) and low (< = 273.8) risk of MVI presence groups. For patients with high MVI risk, wide-margin resection or anatomical resection could significantly improve the 2-year recurrence free survival. CONCLUSION By combining 6 preoperative independently predictive factors of MVI, a nomogram was constructed. This model provides an optimal preoperative estimation of MVI risk in HCC patients, and may help to stratify high-risk individuals and optimize clinical decision making.
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Affiliation(s)
- Xin-Cheng Mao
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Shuo Shi
- Department of Radiology, Qilu Hospital, Shandong University, Jinan, China
| | - Lun-Jie Yan
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Han-Chao Wang
- Institute for Financial Studies, Shandong University, Jinan, 250100, China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Guo-Qiang Pan
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Xiao Zhang
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Cheng-Long Han
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Bao-Wen Tian
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Si-Yu Tan
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Yu-Chuan Yan
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China
| | - Tao Li
- Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, China.
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Ha NB, Fan B, Shui AM, Huang CY, Brandman D, Lai JC. CT-quantified sarcopenic visceral obesity is associated with poor transplant waitlist mortality in patients with cirrhosis. Liver Transpl 2023; 29:476-484. [PMID: 36735830 PMCID: PMC10193893 DOI: 10.1097/lvt.0000000000000010] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 10/25/2022] [Indexed: 02/05/2023]
Abstract
Sarcopenic obesity is associated with higher rates of morbidity and mortality than seen with either sarcopenia or obesity alone. We aimed to define sarcopenic visceral obesity (SVO) using CT-quantified skeletal muscle index and visceral-to-subcutaneous adipose tissue ratio and to examine its association with waitlist mortality in patients with cirrhosis. Included were 326 adults with cirrhosis awaiting liver transplantation in the ambulatory setting with available abdominal CT within 6 months from enrollment between February 2015 and January 2018. SVO was defined as patients with sarcopenia (skeletal muscle index <50 cm 2 /m 2 in men and <39 cm 2 /m 2 in women) and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥1.21 in men and ≥0.48 in women). The percentage who met criteria for sarcopenia, visceral obesity, and SVO were 44%, 29%, and 13%, respectively. Cumulative incidence of waitlist mortality was higher in patients with SVO compared to patients with sarcopenia without visceral obesity or visceral obesity without sarcopenia at 12 months (40% vs. 21% vs. 12%) (overall logrank p =0.003). In univariable Cox regression, SVO was associated with waitlist mortality (HR: 3.42, 95% CI: 1.58-7.39), which remained significant after adjusting for age, sex, diabetes, ascites, encephalopathy, MELDNa, liver frailty index, and different body compositions (HR: 2.64, 95% CI: 1.11-6.30). SVO was associated with increase waitlist mortality in patients with cirrhosis in the ambulatory setting awaiting liver transplantation. Concurrent loss of skeletal muscle and gain of adipose tissue seen in SVO quantified by CT may be a useful and objective measurement to identify patients at risk for suboptimal pretransplant outcomes.
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Affiliation(s)
- Nghiem B. Ha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Bo Fan
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Amy M. Shui
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - Chiung-Yu Huang
- Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
| | - Danielle Brandman
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA, USA
- Liver Center, University of California, San Francisco, CA, USA
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9
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Kono M, Shatila M, Xu G, Lu Y, Mathew A, Mohajir W, Varatharajalu K, Qiao W, Thomas AS, Wang Y. Obesity Measured via Body Mass Index May Be Associated with Increased Incidence but Not Worse Outcomes of Immune-Mediated Diarrhea and Colitis. Cancers (Basel) 2023; 15:2329. [PMID: 37190257 PMCID: PMC10136922 DOI: 10.3390/cancers15082329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 04/07/2023] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
Obesity defined by high body mass index (BMI) has traditionally been associated with gastrointestinal inflammatory processes but has recently been correlated with better survival in patients receiving immune checkpoint inhibitors (ICI). We sought to investigate the association between BMI and immune-mediated diarrhea and colitis (IMDC) outcomes and whether BMI reflects body fat content on abdominal imaging. This retrospective, single-center study included cancer patients with ICI exposure who developed IMDC and had BMI and abdominal computed tomography (CT) obtained within 30 days before initiating ICI from April 2011 to December 2019. BMI was categorized as <25, ≥25 but <30, and ≥30. Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA: VFA+SFA), and visceral to subcutaneous fat (V/S) ratio were obtained from CT at the umbilical level. Our sample comprised 202 patients; 127 patients (62.9%) received CTLA-4 monotherapy or a combination, and 75 (37.1%) received PD-1/PD-L1 monotherapy. Higher BMIs ≥ 30 were associated with a higher incidence of IMDC than BMIs ≤ 25 (11.4% vs. 7.9%, respectively; p = 0.029). Higher grades of colitis (grade 3-4) correlated with lower BMI (p = 0.03). BMI level was not associated with other IMDC characteristics or did not influence overall survival (p = 0.83). BMI is strongly correlated with VFA, SFA, and TFA (p < 0.0001). Higher BMI at ICI initiation was linked to a higher incidence of IMDC but did not appear to affect outcomes. BMI strongly correlated with body fat parameters measured by abdominal imaging, suggesting its reliability as an obesity index.
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Affiliation(s)
- Miho Kono
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Malek Shatila
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Guofan Xu
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yang Lu
- Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Antony Mathew
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Wasay Mohajir
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Krishnavathana Varatharajalu
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Wei Qiao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Anusha S. Thomas
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yinghong Wang
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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10
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Wu ZQ, Cheng J, Xiao XX, Zhang HR, Wang J, Peng J, Liu C, Cai P, Li XM. Preoperative prediction of early recurrence of HBV-related hepatocellular carcinoma (≤5 cm) by visceral adipose tissue index. Front Surg 2023; 9:985168. [PMID: 36684155 PMCID: PMC9852492 DOI: 10.3389/fsurg.2022.985168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 11/04/2022] [Indexed: 01/09/2023] Open
Abstract
Background This study aimed to investigate whether visceral adipose tissue index (VATI) is a significant risk factor for the early recurrence (ER) of HBV-related hepatocellular carcinoma (HCC) (≤5 cm) after hepatectomy. Methods The recruited cohort patients who were positive for hepatitis B virus, presented with surgically confirmed HCC (≤5 cm) from Army Medical University (internal training cohort: n = 192) and Chongqing Medical University (external validation group: n = 46). We measured VATI, subcutaneous adipose tissue index (SATI) via computed tomography (CT). ER was defined as recurrence within 2 years after hepatectomy. The impact of parameters on outcome after hepatectomy for HCC was analyzed. Results Univariate analysis showed that alpha-fetoprotein levels (p = 0.044), body mass index (BMI) (p < 0.001), SATI (p < 0.001), and VATI (p < 0.001) were significantly different between ER and non-ER groups in internal training cohort. Multivariate analysis identified VATI as an independent risk factor for ER (odds ratio = 1.07, 95% confidence interval: 1.047-1.094, p < 0.001), with a AUC of 0.802, based on the cut-off value of VATI, which was divided into high risk (≥37.45 cm2/m2) and low risk (<37.45 cm2/m2) groups. The prognosis of low risk group was significantly higher than that of high risk group (p < 0.001). The AUC value of VATI in external validation group was 0.854. Conclusion VATI was an independent risk factor for the ER, and higher VATI was closely related to poor outcomes after hepatectomy for HBV-related HCC (≤5 cm).
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Affiliation(s)
- Zong-qian Wu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jie Cheng
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xi-xi Xiao
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Hua-rong Zhang
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Jian Wang
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Juan Peng
- Department of Radiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Chen Liu
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Ping Cai
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China,Correspondence: Ping Cai Xiao-ming Li
| | - Xiao-ming Li
- Department of Radiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China,Correspondence: Ping Cai Xiao-ming Li
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11
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Shah PA, Patil R, Harrison SA. NAFLD-related hepatocellular carcinoma: The growing challenge. Hepatology 2023; 77:323-338. [PMID: 35478412 PMCID: PMC9970023 DOI: 10.1002/hep.32542] [Citation(s) in RCA: 99] [Impact Index Per Article: 49.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 02/15/2022] [Accepted: 02/17/2022] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality and morbidity worldwide. With the obesity pandemic, NAFLD-related HCC is contributing to the burden of disease exponentially. Genetic predisposition and clinical risk factors for NAFLD-related HCC have been identified. Cirrhosis is a well-known and major risk factor for NAFLD-related HCC. However, the occurrence of NAFLD-related HCC in patients without cirrhosis is increasingly recognized and poses a significant challenge regarding cancer surveillance. It is of paramount importance to develop optimal risk stratification scores and models to identify subsets of the population at high risk so they can be enrolled in surveillance programs. In this review, we will discuss the risks and prediction models for NAFLD-related HCC.
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Affiliation(s)
- Pir Ahmad Shah
- Department of Internal Medicine, University of Texas Health Science Center, San Antonio, Texas, USA
| | - Rashmee Patil
- South Texas Research Institute, Edinburg, Texas, USA
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12
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Lacotte S, Slits F, Moeckli B, Peloso A, Koenig S, Tihy M, El Hajji S, Gex Q, Rubbia-Brandt L, Toso C. Anti-CD122 antibody restores specific CD8 + T cell response in nonalcoholic steatohepatitis and prevents hepatocellular carcinoma growth. Oncoimmunology 2023; 12:2184991. [PMID: 36891258 PMCID: PMC9988345 DOI: 10.1080/2162402x.2023.2184991] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023] Open
Abstract
Nonalcoholic steatohepatitis (NASH) can lead to hepatocellular carcinoma (HCC). Although immunotherapy is used as first-line treatment for advanced HCC, the impact of NASH on anticancer immunity is only partially characterized. We assessed the tumor-specific T cell immune response in the context of NASH. In a mouse model of NASH, we observed an expansion of the CD44+CXCR6+PD-1+CD8+ T cells in the liver. After intra-hepatic injection of RIL-175-LV-OVA-GFP HCC cells, NASH mice had a higher percentage of peripheral OVA-specific CD8+ T cells than control mice, but these cells did not prevent HCC growth. In the tumor, the expression of PD-1 on OVA-specific CD44+CXCR6+CD8+ cells was higher in NASH mice suggesting lowered immune activity. Treating mice with an anti-CD122 antibody, which reduced the number of CXCR6+PD-1+ cells, we restored OVA-specific CD8 activity, and reduced HCC growth compared to untreated NASH mice. Human dataset confirmed that NASH-affected livers, NASH tissues adjacent to HCC and HCC in patients with NASH exhibited gene expression patterns supporting mouse observations. Our findings demonstrate the immune system fails to prevent HCC growth in NASH, primarily linked to a higher representation of CD44+CXCR6+PD-1+CD8+ T cells. Treatment with an anti-CD122 antibody reduces the number of these cells and prevents HCC growth.
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Affiliation(s)
- Stéphanie Lacotte
- Transplantation and Hepatology Laboratory, Department of Surgery, University of Geneva, Geneva, Switzerland
| | - Florence Slits
- Transplantation and Hepatology Laboratory, Department of Surgery, University of Geneva, Geneva, Switzerland
| | - Beat Moeckli
- Transplantation and Hepatology Laboratory, Department of Surgery, University of Geneva, Geneva, Switzerland.,Division of Abdominal Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Andrea Peloso
- Transplantation and Hepatology Laboratory, Department of Surgery, University of Geneva, Geneva, Switzerland.,Division of Abdominal Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Stéphane Koenig
- Department of Physiology, University of Geneva, Geneva, Switzerland
| | - Matthieu Tihy
- Division of Clinical Pathology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Sofia El Hajji
- Transplantation and Hepatology Laboratory, Department of Surgery, University of Geneva, Geneva, Switzerland
| | - Quentin Gex
- Transplantation and Hepatology Laboratory, Department of Surgery, University of Geneva, Geneva, Switzerland
| | - Laura Rubbia-Brandt
- Division of Clinical Pathology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
| | - Christian Toso
- Transplantation and Hepatology Laboratory, Department of Surgery, University of Geneva, Geneva, Switzerland.,Division of Abdominal Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland
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13
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Yokoyama K, Takamura M, Watanabe J, Nakamura A, Sato Y, Sekine A, Terai S. The Visceral-to-subcutaneous Adipose Tissue Area Ratio Is Associated with Retreatment in Chronic Pancreatitis Patients with Pancreatolithiasis after Extracorporeal Shock Wave Lithotripsy. Intern Med 2022; 61:3633-3639. [PMID: 35650122 PMCID: PMC9841102 DOI: 10.2169/internalmedicine.9038-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Objective Extracorporeal shock wave lithotripsy (ESWL) has been used to treat pancreatolithiasis in patients with chronic pancreatitis (CP), but the high recurrence rate remains challenging. We therefore evaluated the association between body composition parameters and the prediction of retreatment after ESWL. Methods This study retrospectively evaluated 42 patients with CP who had been treated with ESWL between 2008 and 2019 in a single center. Body composition parameters were measured on pretreatment computed tomography images. Patients who underwent repeat ESWL were classified as the retreatment group. Results There were 13 (31.0%) and 29 (69.0%) patients in the retreatment and non-retreatment groups, respectively. The visceral-to-subcutaneous adipose tissue area ratio (VSR) of the retreatment group was significantly lower than that of the non-retreatment group (p=0.016). When divided by the median VSR, 10 of the 20 patients with a VSR of <0.85 underwent retreatment, whereas 3 of the 22 patients with a VSR of ≥0.85 underwent retreatment (p=0.019). According to a multivariate analysis, the VSR (p=0.010) and age (p=0.037) were independent factors associated with retreatment after ESWL. Conclusion This study showed that the VSR can predict the retreatment of patients with CP after ESWL.
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Affiliation(s)
- Kunihiko Yokoyama
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Science, Japan
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Science, Japan
- Department of Gastroenterology, JA Niigata Kouseiren Nagaoka Chuo General Hospital, Japan
| | - Jun Watanabe
- Department of Internal Medicine, Niigata Prefectural Yoshida Hospital, Japan
| | - Atsuo Nakamura
- Department of Internal Medicine, Niigata Prefectural Yoshida Hospital, Japan
| | - Yuichi Sato
- Department of Gastroenterology, JA Niigata Kouseiren Nagaoka Chuo General Hospital, Japan
| | - Atsuo Sekine
- Department of Internal Medicine, Niigata Prefectural Yoshida Hospital, Japan
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Science, Japan
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14
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Radu P, Ebadi M, Montano-Loza AJ, Dufour JF. What Is the Role of Body Composition Assessment in HCC Management? Cancers (Basel) 2022; 14:5290. [PMID: 36358709 PMCID: PMC9656561 DOI: 10.3390/cancers14215290] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Revised: 10/23/2022] [Accepted: 10/24/2022] [Indexed: 10/06/2023] Open
Abstract
In the last decade, body composition (BC) assessment has emerged as an innovative tool that can offer valuable data concerning nutritional status in addition to the information provided by the classical parameters (i.e., body mass index, albumin). Furthermore, published data have revealed that different types of body composition are associated with different outcomes. For example, abnormalities of skeletal muscle, a common finding in cirrhotic and oncologic patients, are associated with poor outcome (i.e., high morbidity and high mortality). The disposition (visceral/subcutaneous adipose tissue) and radiodensity of adipose tissue proved to also be determinant factors for HCC outcome. Despite all the advantages, BC assessment is not part of the standard pre-therapeutic workup. The main reasons are the high heterogeneity of data, the paucity of prospective studies, the lack of a standard assessment method, and the interpopulation variation of BC. This paper aims to review the available evidence regarding the role of BC as a prognostic tool in the HCC population undergoing various therapies.
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Affiliation(s)
- Pompilia Radu
- Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, 3008 Bern, Switzerland
| | - Maryam Ebadi
- Division of Gastroenterology & Liver Unit, University of Alberta, Edmonton, AB T6G 2X8, Canada
| | - Aldo J. Montano-Loza
- Division of Gastroenterology & Liver Unit, University of Alberta, Edmonton, AB T6G 2X8, Canada
| | - Jean Francois Dufour
- Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, 3008 Bern, Switzerland
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15
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Cheng E, Kirley J, Cespedes Feliciano EM, Caan BJ. Adiposity and cancer survival: a systematic review and meta-analysis. Cancer Causes Control 2022; 33:1219-1246. [PMID: 35971021 PMCID: PMC10101770 DOI: 10.1007/s10552-022-01613-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Accepted: 07/07/2022] [Indexed: 10/28/2022]
Abstract
PURPOSE The increasing availability of clinical imaging tests (especially CT and MRI) that directly quantify adipose tissue has led to a rapid increase in studies examining the relationship of visceral, subcutaneous, and overall adiposity to cancer survival. To summarize this emerging body of literature, we conducted a systematic review and meta-analysis of imaging-measured as well as anthropometric proxies for adipose tissue distribution and cancer survival across a wide range of cancer types. METHODS Using keywords related to adiposity, cancer, and survival, we conducted a systematic search of the literature in PubMed and MEDLINE, Embase, and Web of Science Core Collection databases from database inception to 30 June 2021. We used a random-effect method to calculate pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) within each cancer type and tested for heterogeneity using Cochran's Q test and the I2 test. RESULTS We included 203 records for this review, of which 128 records were utilized for quantitative analysis among 10 cancer types: breast, colorectal, gastroesophageal, head and neck, hepatocellular carcinoma, lung, ovarian, pancreatic, prostate, and renal cancer. We found that imaging-measured visceral, subcutaneous, and total adiposity were not significantly associated with increased risk of overall mortality, death from primary cancer, or cancer progression among patients diagnosed with these 10 cancer types; however, we found significant or high heterogeneity for many cancer types. For example, heterogeneity was similarly high when the pooled HRs (95% CI) for overall mortality associated with visceral adiposity were essentially null as in 1.03 (0.55, 1.92; I2 = 58%) for breast, 0.99 (0.81, 1.21; I2 = 71%) for colorectal, versus when they demonstrated a potential increased risk 1.17 (0.85, 1.60; I2 = 78%) for hepatocellular carcinoma and 1.62 (0.90, 2.95; I2 = 84%) for renal cancer. CONCLUSION Greater adiposity at diagnosis (directly measured by imaging) is not associated with worse survival among cancer survivors. However, heterogeneity and other potential limitations were noted across studies, suggesting differences in study design and adiposity measurement approaches, making interpretation of meta-analyses challenging. Future work to standardize imaging measurements and data analyses will strengthen research on the role of adiposity in cancer survival.
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Affiliation(s)
- En Cheng
- Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA
| | - Jocelyn Kirley
- Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA
| | | | - Bette J Caan
- Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA, 94612, USA.
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16
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Ueno M, Takeda H, Takai A, Seno H. Risk factors and diagnostic biomarkers for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: Current evidence and future perspectives. World J Gastroenterol 2022; 28:3410-3421. [PMID: 36158261 PMCID: PMC9346451 DOI: 10.3748/wjg.v28.i27.3410] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/24/2022] [Accepted: 06/16/2022] [Indexed: 02/06/2023] Open
Abstract
High rates of excessive calorie intake diets and sedentary lifestyles have led to a global increase in nonalcoholic fatty liver disease (NAFLD). As a result, this condition has recently become one of the leading causes of hepatocellular carcinoma (HCC). Furthermore, the incidence of NAFLD-associated HCC (NAFLD-HCC) is expected to increase in the near future. Advanced liver fibrosis is the most common risk factor for NAFLD-HCC. However, up to 50% of NAFLD-HCC cases develop without underlying liver cirrhosis. Epidemiological studies have revealed many other risk factors for this condition; including diabetes, other metabolic traits, obesity, old age, male sex, Hispanic ethnicity, mild alcohol intake, and elevated liver enzymes. Specific gene variants, such as single-nucleotide polymorphisms of patatin-like phospholipase domain 3, transmembrane 6 superfamily member 2, and membrane-bound O-acyl-transferase domain-containing 7, are also associated with an increased risk of HCC in patients with NAFLD. This clinical and genetic information should be interpreted together for accurate risk prediction. Alpha-fetoprotein (AFP) is the only biomarker currently recommended for HCC screening. However, it is not sufficiently sensitive in addressing this diagnostic challenge. The GALAD score can be calculated based on sex, age, lectin-bound AFP, AFP, and des-carboxyprothrombin and is reported to show better diagnostic performance for HCC. In addition, emerging studies on genetic and epigenetic biomarkers have also yielded promising diagnostic potential. However, further research is needed to establish an effective surveillance program for the early diagnosis of NAFLD-HCC.
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Affiliation(s)
- Masayuki Ueno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan
| | - Haruhiko Takeda
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan
| | - Atsushi Takai
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 6068507, Japan
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17
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Ha NB, Cho S, Mohamad Y, Kent D, Jun G, Wong R, Swarnakar V, Lin S, Maher JJ, Lai JC. Visceral Adipose Tissue Inflammation and Radiographic Visceral-to-Subcutaneous Adipose Tissue Ratio in Patients with Cirrhosis. Dig Dis Sci 2022; 67:3436-3444. [PMID: 34136974 PMCID: PMC8815298 DOI: 10.1007/s10620-021-07099-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 06/07/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Accumulation of visceral adipose tissue is associated with hepatic inflammation and fibrosis, suggestive of its metabolic and inflammatory properties. We aimed to examine the histologic findings of visceral and subcutaneous adipose tissue and to associate these findings with clinical and radiologic characteristics in patients with cirrhosis. METHODS Included were 55 adults with cirrhosis who underwent liver transplantation from 3/2017-12/2018 and had an abdominal computed tomography (CT) scan within 6 months prior to transplant. Visceral-to-subcutaneous adipose tissue ratio (VSR) was calculated using visceral (VATI) and subcutaneous adipose tissue index (SATI) quantified by CT at the L3-vertebral level and normalized for height (cm2/m2). VAT (greater omentum), SAT (abdominal wall), and skeletal muscle (rectus abdominis) biopsies were collected at transplant. RESULTS Majority of patients had VAT inflammation (71%); only one patient (2%) had SAT inflammation. Patients with VAT inflammation had similar median VATI (42 vs 41 cm2/m2), lower median SATI (64 vs 97 cm2/m2), and higher median VSR (0.63 vs 0.37, p = 0.002) than patients without inflammation. In univariable logistic regression, VSR was associated with VAT inflammation (OR 1.47, 95%CI 1.11-1.96); this association remained significant even after adjusting for age, sex, BMI, HCC, or MELD-Na on bivariable analyses. CONCLUSION In patients with cirrhosis undergoing liver transplantation, histologic VAT inflammation was common, but SAT inflammation was not. Increased VSR was independently associated with VAT inflammation. Given the emerging data demonstrating the prognostic value of VSR, our findings support the value of CT-quantified VSR as a prognostic marker for adverse outcomes in the liver transplant setting.
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Affiliation(s)
- Nghiem B. Ha
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA
| | - Soo‑Jin Cho
- Department of Pathology, University of California, San Francisco, CA, USA
| | - Yara Mohamad
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Dorothea Kent
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA
| | - Grace Jun
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Randi Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA
| | - Vivek Swarnakar
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Shezhang Lin
- 3D Lab, Center for Intelligent Imaging, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA
| | - Jacquelyn J. Maher
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA,Liver Center, University of California, San Francisco, CA, USA
| | - Jennifer C. Lai
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0538, San Francisco, CA 94143, USA,Liver Center, University of California, San Francisco, CA, USA
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Ahmad MI, Khan MU, Kodali S, Shetty A, Bell SM, Victor D. Hepatocellular Carcinoma Due to Nonalcoholic Fatty Liver Disease: Current Concepts and Future Challenges. J Hepatocell Carcinoma 2022; 9:477-496. [PMID: 35673598 PMCID: PMC9167599 DOI: 10.2147/jhc.s344559] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 05/14/2022] [Indexed: 12/24/2022] Open
Abstract
Obesity has been labeled as the global pandemic of the 21st century, resulting from a sedentary lifestyle and caloric excess. Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic steatosis, is strongly associated with obesity and metabolic syndrome and is estimated to be present in one-quarter of the world population, making it the most common cause of the chronic liver disease (CLD). NAFLD spectrum varies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The burden of NAFLD has been predicted to increase in the coming decades resulting in increased rates of decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths. In the current review, we describe the pathophysiology of NAFLD and NASH, risk factors associated with disease progression, related complications, and mortality. Later, we have discussed the changing epidemiology of HCC, with NAFLD emerging as the most common cause of CLD and HCC. We have also addressed the risk factors of HCC development in the NAFLD population (including demographic, metabolic, genetic, dietary, and lifestyle factors), presentation of NAFLD-associated HCC, its prognosis, and the issue of HCC development in non-cirrhotic NAFLD. Lastly, the problems related to HCC screening in the NAFLD population, the remaining challenges, and future directions, especially the need to identify the high-risk individuals, will be discussed. We will conclude the review by summarizing the clinical evidence for treating fibrosis and preventing HCC in those at risk with NAFLD-associated HCC.
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Affiliation(s)
- Muhammad Imran Ahmad
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital Houston, Houston, TX, USA
| | - Muhammad Umair Khan
- Department of Gastroenterology and Hepatology, Hamad Medical Corporation, Doha, Qatar
- ECPE- Executive and Continuing Professional Education, Harvard T.H Chan School of Public Health, Boston, MA, 02115-5810, USA
| | - Sudha Kodali
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital Houston, Houston, TX, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
| | - Akshay Shetty
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital Houston, Houston, TX, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
| | - S Michelle Bell
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
| | - David Victor
- Lynda K and David M Underwood Center for Digestive Disorders, Division of Gastroenterology and Hepatology, Houston Methodist Hospital Houston, Houston, TX, USA
- Sherrie and Alan Conover Center for Liver Disease and Transplantation, Houston Methodist Hospital, Houston, TX, USA
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Non-alcoholic fatty liver disease: a multi-system disease influenced by ageing and sex, and affected by adipose tissue and intestinal function. Proc Nutr Soc 2022; 81:146-161. [DOI: 10.1017/s0029665121003815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
In recent years, a wealth of factors are associated with increased risk of developing non-alcoholic fatty liver disease (NAFLD) and NAFLD is now thought to increase the risk of multiple extra-hepatic diseases. The aim of this review is first to focus on the role of ageing and sex as key, poorly understood risk factors in the development and progression of NAFLD. Secondly, we aim to discuss the roles of white adipose tissue (WAT) and intestinal dysfunction, as producers of extra-hepatic factors known to further contribute to the pathogenesis of NAFLD. Finally, we aim to summarise the role of NAFLD as a multi-system disease affecting other organ systems beyond the liver. Both increased age and male sex increase the risk of NAFLD and this may be partly driven by alterations in the distribution and function of WAT. Similarly, changes in gut microbiota composition and intestinal function with ageing and chronic overnutrition are likely to contribute to the development of NAFLD both directly (i.e. by affecting hepatic function) and indirectly via exacerbating WAT dysfunction. Consequently, the presence of NAFLD significantly increases the risk of various extra-hepatic diseases including CVD, type 2 diabetes mellitus, chronic kidney disease and certain extra-hepatic cancers. Thus changes in WAT and intestinal function with ageing and chronic overnutrition contribute to the development of NAFLD – a multi-system disease that subsequently contributes to the development of other chronic cardiometabolic diseases.
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20
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Magnetic resonance elastography and proton density fat fraction predict adverse outcomes in hepatocellular carcinoma. Hepatol Int 2022; 16:371-380. [DOI: 10.1007/s12072-022-10305-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Accepted: 01/25/2022] [Indexed: 01/27/2023]
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Muhimpundu S, Conway RBN, Warren Andersen S, Lipworth L, Steinwandel MD, Blot WJ, Shu XO, Sudenga SL. Racial Differences in Hepatocellular Carcinoma Incidence and Risk Factors among a Low Socioeconomic Population. Cancers (Basel) 2021; 13:cancers13153710. [PMID: 34359611 PMCID: PMC8345125 DOI: 10.3390/cancers13153710] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 07/13/2021] [Accepted: 07/20/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Liver cancer incidence in the United States is higher among African Americans compared to White Americans. The determinants of racial disparities in liver cancer incidence are not clear. Using data from White and African Americans from low socioeconomic backgrounds, we compared the prevalence of known liver cancer risk factors by race and assessed factors associated with liver cancer incidence. Understanding liver cancer risk differences can assist prevention strategies that target people at high risk, potentially based on risk factors that differ by race. Abstract The purpose of this study was to examine differences in risk factors associated with hepatocellular carcinoma (HCC) among White and African Americans from low socioeconomic backgrounds in the Southern Community Cohort Study (SCCS). The SCCS is a prospective cohort study with participants from the southeastern US. HCC incidence rates were calculated. Multivariable Cox regression was used to calculate HCC-adjusted hazard ratios (aHR) associated with known baseline HCC risk factors for White and African Americans, separately. There were 294 incident HCC. The incidence rate ratio for HCC was higher (IRR = 1.4, 95%CI: 1.1–1.9) in African Americans compared to White Americans. White Americans saw a stronger association between self-reported hepatitis C virus (aHR = 19.24, 95%CI: 10.58–35.00) and diabetes (aHR = 3.55, 95%CI: 1.96–6.43) for the development of HCC compared to African Americans (aHR = 7.73, 95%CI: 5.71–10.47 and aHR = 1.48, 95%CI: 1.06–2.06, respectively) even though the prevalence of these risk factors was similar between races. Smoking (aHR = 2.91, 95%CI: 1.87–4.52) and heavy alcohol consumption (aHR = 1.59, 95%CI: 1.19–2.11) were significantly associated with HCC risk among African Americans only. In this large prospective cohort, we observed racial differences in HCC incidence and risk factors associated with HCC among White and African Americans.
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Affiliation(s)
- Sylvie Muhimpundu
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (S.M.); (L.L.); (W.J.B.); (X.-O.S.)
| | - Rebecca Baqiyyah N. Conway
- School of Community and Rural Health, University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA;
- American Academy of Epidemiology, Inc., Tyler, TX 75701, USA
| | - Shaneda Warren Andersen
- Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA;
- Cancer Prevention and Control, University of Wisconsin Carbone Cancer Center, Madison, WI 53706, USA
| | - Loren Lipworth
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (S.M.); (L.L.); (W.J.B.); (X.-O.S.)
| | | | - William J. Blot
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (S.M.); (L.L.); (W.J.B.); (X.-O.S.)
- International Epidemiology Institute, Rockville, MD 20850, USA;
| | - Xiao-Ou Shu
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (S.M.); (L.L.); (W.J.B.); (X.-O.S.)
| | - Staci L. Sudenga
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; (S.M.); (L.L.); (W.J.B.); (X.-O.S.)
- Correspondence:
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22
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Kondo T, Miyakawa N, Kitano S, Watanabe T, Goto R, Suico MA, Sato M, Takaki Y, Sakaguchi M, Igata M, Kawashima J, Motoshima H, Matsumura T, Kai H, Araki E. Activation of heat shock response improves biomarkers of NAFLD in patients with metabolic diseases. Endocr Connect 2021; 10:521-533. [PMID: 33883285 PMCID: PMC8183630 DOI: 10.1530/ec-21-0084] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 04/21/2021] [Indexed: 11/11/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities but is deteriorated by chronic metabolic insults. Heat shock (HS) with an appropriate mild electrical stimulation (MES) activates HSR and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (two times/week, n = 10), patients with metabolic syndrome (four times/week, n = 40), and patients with T2DM (n = 100; four times/week (n = 40) and two, four, seven times/week (n = 20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.
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Affiliation(s)
- Tatsuya Kondo
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Chuo-Ward, Kumamoto, Japan
- Correspondence should be addressed to T Kondo:
| | - Nobukazu Miyakawa
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Sayaka Kitano
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Chuo-Ward, Kumamoto, Japan
| | - Takuro Watanabe
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Rieko Goto
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Mary Ann Suico
- Department of Molecular Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Miki Sato
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Yuki Takaki
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Masaji Sakaguchi
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Motoyuki Igata
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Chuo-Ward, Kumamoto, Japan
| | - Junji Kawashima
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Hiroyuki Motoshima
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Takeshi Matsumura
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Hirofumi Kai
- Department of Molecular Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
| | - Eiichi Araki
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Chuo-Ward, Kumamoto, Japan
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Heo JW, Kim SE, Sung MK. Sex Differences in the Incidence of Obesity-Related Gastrointestinal Cancer. Int J Mol Sci 2021; 22:ijms22031253. [PMID: 33513939 PMCID: PMC7865604 DOI: 10.3390/ijms22031253] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 01/20/2021] [Accepted: 01/23/2021] [Indexed: 01/04/2023] Open
Abstract
Cancer is the second leading cause of death worldwide, with 9.6 million people estimated to have died of cancer in 2018. Excess body fat deposition is a risk factor for many types of cancer. Men and women exhibit differences in body fat distribution and energy homeostasis regulation. This systematic review aimed to understand why sex disparities in obesity are associated with sex differences in the incidence of gastrointestinal cancers. Cancers of the esophagus, liver, and colon are representative gastrointestinal cancers, and obesity is a convincing risk factor for their development. Numerous epidemiological studies have found sex differences in the incidence of esophageal, liver, and colorectal cancers. We suggest that these sexual disparities are partly explained by the availability of estrogens and other genetic factors regulating inflammation, cell growth, and apoptosis. Sex differences in gut microbiota composition may contribute to differences in the incidence and phenotype of colorectal cancer. To establish successful practices in personalized nutrition and medicine, one should be aware of the sex differences in the pathophysiology and associated mechanisms of cancer development.
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Affiliation(s)
| | - Sung-Eun Kim
- Correspondence: (S.-E.K.); (M.-K.S.); Tel.: +82-2-2077-7722 (S.-E.K.); +82-2-710-9395 (M.-K.S.)
| | - Mi-Kyung Sung
- Correspondence: (S.-E.K.); (M.-K.S.); Tel.: +82-2-2077-7722 (S.-E.K.); +82-2-710-9395 (M.-K.S.)
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Plaz Torres MC, Bodini G, Furnari M, Marabotto E, Zentilin P, Strazzabosco M, Giannini EG. Surveillance for Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease: Universal or Selective? Cancers (Basel) 2020; 12:E1422. [PMID: 32486355 PMCID: PMC7352281 DOI: 10.3390/cancers12061422] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 05/22/2020] [Accepted: 05/24/2020] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC), the most frequent primary liver cancer, is the sixth most common cancer, the fourth leading cause of cancer-related deaths worldwide, and accounts globally for about 800,000 deaths/year. Early detection of HCC is of pivotal importance as it is associated with improved survival and the ability to apply curative treatments. Chronic liver diseases, and in particular cirrhosis, are the main risk factors for HCC, but the etiology of liver disease is rapidly changing due to improvements in the prevention and treatment of HBV (Hepatitis B virus) and HCV (Hepatitis C virus) infections and to the rising incidence of the metabolic syndrome, of which non-alcoholic fatty liver (NAFLD) is a manifestation. NAFLD is now a recognized and rapidly increasing cause of cirrhosis and HCC. Indeed, the most recent guidelines for NAFLD management recommend screening for HCC in patients with established cirrhosis. Screening in NAFLD patients without cirrhosis is not recommended; however, the prevalence of HCC in this group of NAFLD patients has been reported to be as high as 38%, a proportion significantly higher than the one observed in the general population and in non-cirrhotic subjects with other causes of liver disease. Unfortunately, solid data regarding the risk stratification of patients with non-cirrhotic NAFLD who might best benefit from HCC surveillance are scarce, and specific recommendations in this field are urgently needed due to the increasing NAFLD epidemic, at least in Western countries. To further complicate matters, liver ultrasonography, which represents the current standard for HCC surveillance, has a decreased diagnostic accuracy in patients with NAFLD, and therefore disease-specific surveillance tools will be required for the early identification of HCC in this population. In this review, we summarize the most recent evidence on the epidemiology and risk factors for HCC in patients with NAFLD, with and without cirrhosis, and the evidence supporting surveillance for early HCC detection in these patients, reviewing the potential limitations of currently recommended surveillance strategies, and assessing data on the accuracy of potential new screening tools. At this stage it is difficult to propose general recommendations, and best clinical judgement should be exercised, based on the profile of risk factors specific to each patient.
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Affiliation(s)
- Maria Corina Plaz Torres
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Manuele Furnari
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Patrizia Zentilin
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
| | - Mario Strazzabosco
- Liver Center and Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA;
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, IRCCS-Ospedale Policlinico San Martino, 16132 Genoa, Italy; (M.C.P.T.); (G.B.); (M.F.); (E.M.); (P.Z.)
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25
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Lipid Metabolism in Development and Progression of Hepatocellular Carcinoma. Cancers (Basel) 2020; 12:cancers12061419. [PMID: 32486341 PMCID: PMC7352397 DOI: 10.3390/cancers12061419] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 05/19/2020] [Accepted: 05/27/2020] [Indexed: 12/11/2022] Open
Abstract
: Metabolic reprogramming is critically involved in the development and progression of cancer. In particular, lipid metabolism has been investigated as a source of energy, micro-environmental adaptation, and cell signalling in neoplastic cells. However, the specific role of lipid metabolism dysregulation in hepatocellular carcinoma (HCC) has not been widely described yet. Alterations in fatty acid synthesis, β-oxidation, and cellular lipidic composition contribute to initiation and progression of HCC. The aim of this review is to elucidate the mechanisms by which lipid metabolism is involved in hepatocarcinogenesis and tumour adaptation to different conditions, focusing on the transcriptional aberrations with new insights in lipidomics and lipid zonation. This will help detect new putative therapeutic approaches in the second most frequent cause of cancer-related death.
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26
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Kus T, Cinkir HY, Aktas G, Abali H. Recurrence pattern in the presence of hepatosteatosis in breast cancer: does it facilitate liver metastasis? Future Oncol 2020; 16:1257-1267. [PMID: 32356676 DOI: 10.2217/fon-2019-0634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: We aimed to investigate the impact of hepatosteatosis (HS) severity on the recurrence pattern of breast cancer and to clarify whether HS causes affinity to recurrence with liver metastasis. Materials & methods: The median follow-up was 80.0 (4-217) months and the mean age was 47.9 ± 11.3 years. Among all, 181 (39.9%) patients were diagnosed with grades 2 and 3 HS. Of total, 158 (34.8%) patients have experienced recurrence. Results: While higher degree of HS was more common in patients presented with liver recurrence (odds ratio; 95% CI: 2.50; 1.27-4.92; p = 0.007), it was lesser in those with other metastatic sites (all were >0.05). Liver-recurrence-free survival was significantly worse in the group with higher degree of HS (hazard ratio; 95% CI: 2.46; 1.4-4.3; p = 0.002) together with younger age (hazard ratio; 95% CI: 2.44; 1.4-4.3; p = 0.002) in multivariate analysis. Conclusion: HS might have produced an affinity for liver metastasis in common types of breast cancer patients in remission independent from metabolic disorders or clinicopathologic features.
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Affiliation(s)
- Tulay Kus
- Department of Medical Oncology, Adıyaman University, Training & Research Hospital, TR 02040, Adıyaman, Turkey
| | - Havva Yesil Cinkir
- Department of Medical Oncology, School of Medicine, Gaziantep University, TR 27310, Gaziantep, Turkey
| | - Gokmen Aktas
- Department of Medical Oncology, School of Medicine, Kahramanmaras Sütçü İmam University, TR 46100, Kahramanmaraş, Turkey
| | - Huseyin Abali
- Department of Medical Oncology, School of Medicine, Acıbadem Mehmet Ali Aydınlar University, Adana, Turkey
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Liu X, Ju W, Huo C, Zhang S, Wang X, Huang K. Overweight and Obesity as Independent Factors for Increased Risk of Hepatocellular Cancer-Related Mortality: A Meta-Analysis. J Am Coll Nutr 2020; 40:287-293. [PMID: 32281914 DOI: 10.1080/07315724.2020.1751007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Obesity is related to the amplified risk of developing hepatocellular cancer, but its outcome on hepatocellular cancer-related mortality remains uncertain. Hence, the present study aimed to perform a meta-analysis study to evaluate the relationship between weight and hepatocellular cancer-related deaths. Through a systematic literature search up to December 2019, 7 observational studies with 2,349,834 subjects, 4834 hepatocellular cancer-related deaths were identified reporting relationships between body mass index (BMI), and hepatocellular cancer-related mortality. Odd ratio (OR) with 95% confidence intervals (CIs) was calculated comparing obese, BML > 30kg/m2, and overweight, BMI, 25-29.9 kg/m2 to subjects with normal BMI using the dichotomous method with a random-effect model. In obese subjects, males (OR, 1.84; 95% CI, 1.25-2.70) and females (OR, 1.26; 95% CI, 1.11-1.44), had higher hepatocellular cancer-related mortality compared to normal BMI subjects. However, overweight males (OR, 1.12; 95% CI, 0.98-1.28) and overweight females (OR, 1.06; 95% CI, 0.95-1.18), did not have such risk with moderate heterogeneity. The extent of increased mortality was higher in obese males compared to obese females. The impact of obesity on hepatocellular cancer-related mortality was observed in all populations with less extant in the black population. Based on this meta-analysis, obesity may have an independent relationship with up to the 1.84-fold risk of hepatocellular cancer-related mortality. This relationship was more pronounced in males than in females. Key teaching pointsBeing overweight is related to the amplified risk of developing hepatocellular cancer.Obesity's affect on hepatocellular cancer-related mortality remains uncertain.Based on this meta-analysis, obesity may have an independent relationship with up to the 1.84-fold risk of hepatocellular cancer-related mortality.This relationship was more pronounced in males than in females.
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Affiliation(s)
- Xiaoyu Liu
- Department of Oncology, Dezhou People's Hospital, Dezhou, Shandong Province, China
| | - Wenhui Ju
- Department of rehabilitation medicine, Dezhou People's Hospital, Dezhou, Shandong Province, China
| | - Chuanhong Huo
- Department of Infectious Disease, Dezhou people's Hospital, Dezhou, Shandong Province, China
| | - Shuhong Zhang
- Department of Oncology, Dezhou People's Hospital, Dezhou, Shandong Province, China
| | - Xingang Wang
- Nursing Department, Dezhou People's Hospital, Dezhou, Shandong Province, China
| | - Kai Huang
- Department of Oncology, Dezhou People's Hospital, Dezhou, Shandong Province, China
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28
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Tan Y, Jin Y, Wu X, Ren Z. PSMD1 and PSMD2 regulate HepG2 cell proliferation and apoptosis via modulating cellular lipid droplet metabolism. BMC Mol Biol 2019; 20:24. [PMID: 31703613 PMCID: PMC6842266 DOI: 10.1186/s12867-019-0141-z] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 10/29/2019] [Indexed: 01/18/2023] Open
Abstract
Background Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC). The lipid-rich environment enhances the proliferation and metastasis abilities of tumor cells. Previous studies showed the effect of the ubiquitin–proteasome system (UPS) on tumor cell proliferation. However, the underlying mechanism of UPS in regulating the proliferation of lipid-rich tumor cells is not totally clear. Results Here, we identify two proteasome 26S subunits, non-ATPase 1 and 2 (PSMD1 and PSMD2), which regulate HepG2 cells proliferation via modulating cellular lipid metabolism. Briefly, the knockdown of PSMD1 and/or PSMD2 decreases the formation of cellular lipid droplets, the provider of the energy and membrane components for tumor cell proliferation. Mechanically, PSMD1 and PSMD2 regulate the expression of genes related to de novo lipid synthesis via p38-JNK and AKT signaling. Moreover, the high expression of PSMD1 and PSMD2 is significantly correlated with poor prognosis of HCC. Conclusion We demonstrate that PSMD1 and PSMD2 promote the proliferation of HepG2 cells via facilitating cellular lipid droplet accumulation. This study provides a potential therapeutic strategy for the treatment of lipid-rich tumors.
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Affiliation(s)
- Yanjie Tan
- Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture & Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China
| | - Yi Jin
- Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture & Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China
| | - Xiang Wu
- Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture & Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China
| | - Zhuqing Ren
- Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture & Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China. .,Bio-Medical Center of Huazhong Agricultural University, Wuhan, 430070, Hubei, People's Republic of China.
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Young S, Sanghvi T, Rubin N, Hall D, Roller L, Charaf Y, Golzarian J. Transarterial Chemoembolization of Hepatocellular Carcinoma: Propensity Score Matching Study Comparing Survival and Complications in Patients with Nonalcoholic Steatohepatitis Versus Other Causes Cirrhosis. Cardiovasc Intervent Radiol 2019; 43:65-75. [PMID: 31686136 DOI: 10.1007/s00270-019-02363-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 10/21/2019] [Indexed: 01/06/2023]
Abstract
PURPOSE To evaluate the oncologic outcomes and complication profile in nonalcoholic steatohepatitis (NASH)-induced cirrhosis leading to hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). MATERIALS AND METHODS Two hundred and twenty patients who underwent treatment of 353 HCCs were retrospectively reviewed, including 30 NASH patients who received TACE for 46 HCCs. Patient charts were evaluated for time to progression (TTP), complications and overall survival (OS). The group was split into NASH and non-NASH cohorts for comparison and additional analyses were done using propensity score matching (PSM). RESULTS Patients in the NASH cohort presented with significantly larger lesions (4.9 ± 5.8 cm vs 3.1 ± 2.4 cm, p = 0.05). There was no significant difference in TTP overall [Median NASH 396 days (95% CI 308-526 days) vs non-NASH cohort 307 days (95% CI 272-364), p = 0.25) or after PSM [259 days non-NASH (95% CI 215-490) vs 396 days NASH (95% CI (349-not reached), p = 0.43]. There was a non-significant increased OS in the non-NASH [median 1078 days (95% CI 668-1594)] as compared to the NASH cohort [median 706 days (95% CI 314-not reached)] (p = 0.08) which decreased following PSM [853 days (95% CI 526-1511) non-NASH vs 706 days (95% CI 314-not reached) NASH, p = 0.48]. The number of complications did not differ significantly between the two groups (p = 0.23). CONCLUSION The oncologic outcomes and complication profile of TACE for HCC induced by NASH cirrhosis appear to be similar to that of other etiologies of cirrhosis. NASH patients presented with larger tumors emphasizing the need for early surveillance.
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Affiliation(s)
- Shamar Young
- Department of Radiology, Division of Interventional Radiology, University of Minnesota, 420 Delaware St SE MMC 292, Minneapolis, MN, 55455, USA.
| | - Tina Sanghvi
- VA Department of Radiology, Minneapolis VA Health Care System, 1 Veterans Dr, Minneapolis, MN, 55417, USA
| | - Nathan Rubin
- Department of Radiology, Division of Interventional Radiology, University of Minnesota, 420 Delaware St SE MMC 292, Minneapolis, MN, 55455, USA
| | - Damian Hall
- Department of Radiology, Division of Interventional Radiology, University of Minnesota, 420 Delaware St SE MMC 292, Minneapolis, MN, 55455, USA
| | - Luke Roller
- Department of Radiology, Division of Interventional Radiology, University of Minnesota, 420 Delaware St SE MMC 292, Minneapolis, MN, 55455, USA
| | - Yassine Charaf
- Department of Radiology, Division of Interventional Radiology, University of Minnesota, 420 Delaware St SE MMC 292, Minneapolis, MN, 55455, USA
| | - Jafar Golzarian
- Department of Radiology, Division of Interventional Radiology, University of Minnesota, 420 Delaware St SE MMC 292, Minneapolis, MN, 55455, USA
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30
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Tan Y, Jin Y, Wang Q, Huang J, Wu X, Ren Z. Perilipin 5 Protects against Cellular Oxidative Stress by Enhancing Mitochondrial Function in HepG2 Cells. Cells 2019; 8:cells8101241. [PMID: 31614673 PMCID: PMC6830103 DOI: 10.3390/cells8101241] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 09/29/2019] [Accepted: 10/08/2019] [Indexed: 12/20/2022] Open
Abstract
: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Reactive oxygen species (ROS), as potent oxidants in cells, have been shown to promote the development of NAFLD. Previous studies reported that for ROS-induced cellular oxidative stress, promoting lipid droplet (LD) accumulation is associated with the cellular antioxidation process. However, the regulatory role of LDs in relieving cellular oxidative stress is poorly understood. Here, we showed that Perilipin 5 (PLIN5), a key LD protein related to mitochondria-LD contact, reduced ROS levels and improved mitochondrial function in HepG2 cells. Both mRNA and protein levels of PLIN5 were significantly increased in cells with hydrogen peroxide or lipopolysaccharide (LPS) treatment (p < 0.05). Additionally, the overexpression of PLIN5 promoted LD formation and mitochondria-LD contact, reduced cellular ROS levels and up-regulated mitochondrial function-related genes such as COX and CS. Knockdown PLIN5, meanwhile, showed opposite effects. Furthermore, we identified that cellular oxidative stress up-regulated PLIN5 expression via the JNK-p38-ATF pathway. This study shows that the up-regulation of PLIN5 is a kind of survival strategy for cells in response to stress. PLIN5 can be a potential therapeutic target in NAFLD.
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Affiliation(s)
- Yanjie Tan
- Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
| | - Yi Jin
- Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
| | - Qian Wang
- Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
| | - Jin Huang
- Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
| | - Xiang Wu
- Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
| | - Zhuqing Ren
- Key Laboratory of Agriculture Animal Genetics, Breeding and Reproduction of the Ministry of Education, College of Animal Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
- The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
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31
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Pocha C, Xie C. Hepatocellular carcinoma in alcoholic and non-alcoholic fatty liver disease-one of a kind or two different enemies? Transl Gastroenterol Hepatol 2019; 4:72. [PMID: 31728429 DOI: 10.21037/tgh.2019.09.01] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 08/22/2019] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular cancer (HCC) is a cancer with an overall poor prognosis and an alarming globally rising incidence. While viral etiology of chronic liver disease and HCC is down-trending, alcohol and excess calorie intake have emerged as major culprits. Alcohol related liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) share similar pathogenetic mechanism of hepatic injury and in promoting development of HCC; yet some genetic and epigenetic features are distinct and may promise clinical utility. Population based intervention are urgently needed to reduce alcohol use and improve metabolic factors such as obesity and diabetes. The goal is to identify at-risk patients, to link these patients to care and to provide effective management of chronic liver disease and HCC. This review focuses on the epidemiology, pathophysiology including genetic and epigenetic altercation as well as clinical aspects of ALD and NAFLD associated HCC.
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Affiliation(s)
- Christine Pocha
- Avera McKennnan Hospital and University Medical Center, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.,Department of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USA
| | - Chencheng Xie
- Avera McKennnan Hospital and University Medical Center, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, USA.,Department of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA, USA
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32
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Kim SS, Kim JH, Jeong WK, Lee J, Kim YK, Choi D, Lee WJ. Semiautomatic software for measurement of abdominal muscle and adipose areas using computed tomography: A STROBE-compliant article. Medicine (Baltimore) 2019; 98:e15867. [PMID: 31145342 PMCID: PMC6708812 DOI: 10.1097/md.0000000000015867] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The aim of the study was to introduce our in-house software to measure the muscle and adipose area on axial computed tomography (CT) scans and to compare with various quantification methods.Our institutional review board approved this retrospective study and informed consent was waived. We developed in-house software to identify body composition analysis on CT scan, which semiautomatically operates 3 image processing steps. Abdominal images were obtained using multidetector row CT (MDCT). Two radiologists analyzed the same cross-sectional areas of subcutaneous fat, muscle, and visceral fat using the following techniques: manual measurements, Aquarius, ImageJ, and our newly developed software. We calculated an intraclass correlation coefficient (ICC) for comparison of muscle and fat areas quantified by various measurement methods using a 2-way random model. Interobserver agreement between the radiologists was also evaluated.Agreements in the measurement of subcutaneous fat and muscle areas were excellent among the methods (ICC = 0.962 and 0.897, respectively), and that of the visceral fat area was good (ICC = 0.822). In the subgroup analysis, ICC of the visceral fat area in the female group and in subjects with ascites was slightly lower than the other group (ICC = 0.742 and 0.787, respectively). The correlation coefficients between our software and other methods were relatively high (r = 0.854-0.996). Additionally, ICCs between both observers of our program for quantification of subcutaneous fat, muscle, and visceral fat areas were 0.999, 0.980, and 0.999, respectively.In conclusion, our method showed be reliable in quantifying muscle and adipose tissue using cross-sectional areas of MDCT with high reproducibility.
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Affiliation(s)
- Seung Soo Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
- Department of Radiology, Soonchunhyang University College of Medicine, Cheonan Hospital, Chungcheongnam-do
| | - Jae-Hun Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
| | - Woo Kyoung Jeong
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
| | - Jisun Lee
- Department of Radiology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju-si, Korea
| | - Young Kon Kim
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
| | - Dongil Choi
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
| | - Won Jae Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul
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Homeostatic Model Assessment of Insulin Resistance for Predicting the Recurrence of Hepatocellular Carcinoma after Curative Treatment. Int J Mol Sci 2019; 20:ijms20030605. [PMID: 30704150 PMCID: PMC6387449 DOI: 10.3390/ijms20030605] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Revised: 01/18/2019] [Accepted: 01/29/2019] [Indexed: 02/07/2023] Open
Abstract
Diabetes mellitus (DM) is a risk factor for hepatocellular carcinoma (HCC). The purpose of this study was to investigate the impact of the disorder of glucose metabolism on the recurrence of HCC after curative treatment. Two hundred and eleven patients with HCC who received curative treatment in our hospital from 2006 to 2017 were enrolled in this study. Recurrence-free survival was estimated using the Kaplan–Meier method, and the differences between the groups partitioned by the presence or absence of DM and the values of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), fasting immunoreactive insulin (FIRI), and homeostasis model assessment-insulin resistance (HOMA-IR) were evaluated using the log-rank test. There were no significant differences in the recurrence-free survival rate between the patients with and without DM (p = 0.144), higher and lower levels of HbA1c (≥6.5 and <6.5%, respectively; p = 0.509), FPG (≥126 and <126 mg/dL, respectively; p = 0.143), and FIRI (≥10 and <10 μU/mL, respectively; p = 0.248). However, the higher HOMA-IR group (≥2.3) had HCC recurrence significantly earlier than the lower HOMA-IR group (<2.3, p = 0.013). Moreover, there was a significant difference between the higher and lower HOMA-IR groups without DM (p = 0.009), and there was no significant difference between those groups with DM (p = 0.759). A higher HOMA-IR level, particularly in non-diabetic patients, was a significant predictor for HCC recurrence after curative treatment.
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Komatsu G, Nonomura T, Sasaki M, Ishida Y, Arai S, Miyazaki T. AIM-deficient mouse fed a high-trans fat, high-cholesterol diet: a new animal model for nonalcoholic fatty liver disease. Exp Anim 2018; 68:147-158. [PMID: 30487357 PMCID: PMC6511520 DOI: 10.1538/expanim.18-0108] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Owing to changes in lifestyle, nonalcoholic fatty liver disease (NAFLD) is becoming a
common form of chronic liver injury. NAFLD comprises a wide variety of disease stages,
from simple steatosis to nonalcoholic steatohepatitis, which is a risk factor for the
development of hepatocellular carcinoma (HCC). Because animal models for NAFLD are needed
to investigate the precise pathogenesis, we aimed to establish a new mouse model employing
mice deficient for apoptosis inhibitor of macrophage (AIM−/−),
which exhibit accelerated lipid storage in the liver and high susceptibility to developing
HCC in response to a high-fat diet (HFD). AIM−/− mice were fed
the D09100301 diet, which contains 40 kcal% fat (trans fat 30 kcal%), high cholesterol
(2%), and 40 kcal% carbohydrates (20 kcal% fructose), and then features of obesity and
NAFLD including steatosis, inflammation, fibrosis, and HCC development were analyzed.
Although a comparable grade of liver steatosis was promoted in
AIM−/− mice by the D09100301 diet and the standard HFD (60
kcal% largely lard fat), significantly less lipid storage in visceral fat was observed
when the mice were fed the D09100301 diet. Accelerated liver inflammation was promoted by
the D09100301 diet compared with the HFD, but interestingly, HCC development was decreased
in mice fed the D09100301 diet. Our findings suggest that
AIM−/− mice fed the D09100301 diet exhibited a phenotype
that resembled nonobese NAFLD patients and thus could be an appropriate tool to study the
pathophysiology by which obesity increases the risk of HCC.
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Affiliation(s)
- Ginga Komatsu
- Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Toru Nonomura
- Research Division Pharmacology Group, New Drug Research Center Inc., 452-1 Toiso, Eniwa-shi, Hokkaido 061-1405, Japan
| | - Mai Sasaki
- Research Division Pathology Group, New Drug Research Center Inc., 452-1 Toiso, Eniwa-shi, Hokkaido 061-1405, Japan
| | - Yuki Ishida
- Research Division Pharmacology Group, New Drug Research Center Inc., 452-1 Toiso, Eniwa-shi, Hokkaido 061-1405, Japan
| | - Satoko Arai
- Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
| | - Toru Miyazaki
- Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.,AMED-CREST, Japan Agency for Medical Research and Development, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.,Max Planck-The University of Tokyo Center for Integrative Inflammology, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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35
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Nakagawa H, Hayata Y, Kawamura S, Yamada T, Fujiwara N, Koike K. Lipid Metabolic Reprogramming in Hepatocellular Carcinoma. Cancers (Basel) 2018; 10:cancers10110447. [PMID: 30445800 PMCID: PMC6265967 DOI: 10.3390/cancers10110447] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 11/10/2018] [Accepted: 11/13/2018] [Indexed: 12/23/2022] Open
Abstract
Metabolic reprogramming for adaptation to the local environment has been recognized as a hallmark of cancer. Although alterations in fatty acid (FA) metabolism in cancer cells have received less attention compared to other metabolic alterations such as glucose or glutamine metabolism, recent studies have uncovered the importance of lipid metabolic reprogramming in carcinogenesis. Obesity and nonalcoholic steatohepatitis (NASH) are well-known risk factors of hepatocellular carcinoma (HCC), and individuals with these conditions exhibit an increased intake of dietary FAs accompanied by enhanced lipolysis of visceral adipose tissue due to insulin resistance, resulting in enormous exogenous FA supplies to hepatocytes via the portal vein and lymph vessels. This “lipid-rich condition” is highly characteristic of obesity- and NASH-driven HCC. Although the way in which HCC cells adapt to such a condition and exploit it to aid their progression is not understood, we recently obtained new insights into this mechanism through lipid metabolic reprogramming. In addition, accumulating evidence supports the importance of lipid metabolic reprogramming in various situations of hepatocarcinogenesis. Thus, in this review, we discuss the latest findings regarding the role of FA metabolism pathways in hepatocarcinogenesis, focusing on obesity- and NASH-driven lipid metabolic reprogramming.
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Affiliation(s)
- Hayato Nakagawa
- Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
| | - Yuki Hayata
- Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
| | - Satoshi Kawamura
- Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
| | - Tomoharu Yamada
- Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
| | - Naoto Fujiwara
- Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
| | - Kazuhiko Koike
- Department of Gastroenterology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
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Zhang Y, Wang JP, Wang XL, Tian H, Gao TT, Tang LM, Tian F, Wang JW, Zheng HJ, Zhang L, Gao XJ, Li GL, Wang XY. Computed tomography-quantified body composition predicts short-term outcomes after gastrectomy in gastric cancer. ACTA ACUST UNITED AC 2018; 25:e411-e422. [PMID: 30464692 DOI: 10.3747/co.25.4014] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Malnutrition is a common and critical problem that influences outcome in cancer patients. Body composition reflects a patient's metabolic profile and physiologic reserves, which might be the true determinant of prognosis. In the present study, which aimed to identify valuable new prognostic indicators, we investigated the association between computed tomography-quantified body composition and short-term outcomes after gastrectomy for gastric cancer. Methods Skeletal muscle index, mean muscle attenuation, and ratio of visceral-to-subcutaneous adipose tissue area (vsr) were calculated from preoperative computed tomography images. Low skeletal muscle index, low mean muscle attenuation, and high vsr were respectively termed "sarcopenia," "myosteatosis," and "visceral obesity." The association of body composition with postoperative complications and serum markers of nutrition and inflammation after radical gastrectomy were analyzed. Results The overall complication rate was significantly higher in the sarcopenia (62.5% vs. 27.3%, p = 0.001) and myosteatosis groups (38.2% vs. 4%, p = 0.002). Patients with visceral obesity had a higher incidence of inflammatory complications (20.3% vs. 6.5%, p = 0.01). Multivariate logistic regression analysis demonstrated that sarcopenia (p = 0.013), myosteatosis (p = 0.017), and low serum retinol-binding protein (p = 0.019) were independent risk factors for overall complications. Compared with control subjects, patients with sarcopenia had lower postoperative levels of serum retinol-binding protein (p = 0.007), and patients with visceral obesity had higher levels of C-reactive protein (p = 0.026). Conclusions Sarcopenia, myosteatosis, and visceral obesity were significantly associated with increased rates of postoperative complications and affected the postoperative nutrition and inflammation status of patients with gastric cancer.
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Affiliation(s)
- Y Zhang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C.,Department of Cardiothoracic Surgery, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, P.R.C
| | - J P Wang
- Jinling Clinical Medical College of Nanjing Medical University, Nanjing, P.R.C.,Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C
| | - X L Wang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C
| | - H Tian
- Department of General Surgery, Jinling Hospital Affiliated to Southern Medical University, Nanjing, P.R.C
| | - T T Gao
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C
| | - L M Tang
- Changzhou No. 2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou School of Clinical Medicine of Nanjing Medical University, Changzhou, P.R.C
| | - F Tian
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C
| | - J W Wang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C
| | - H J Zheng
- Intensive Care Unit, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, P.R.C
| | - L Zhang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C
| | - X J Gao
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C
| | - G L Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C
| | - X Y Wang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R.C
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Kobayashi T, Kawai H, Nakano O, Abe S, Kamimura H, Sakamaki A, Kamimura K, Tsuchiya A, Takamura M, Yamagiwa S, Terai S. Prognostic value of subcutaneous adipose tissue volume in hepatocellular carcinoma treated with transcatheter intra-arterial therapy. Cancer Manag Res 2018; 10:2231-2239. [PMID: 30100754 PMCID: PMC6065564 DOI: 10.2147/cmar.s167417] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Prognosis of patients with hepatocellular carcinoma (HCC) who undergo transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, is affected by many clinical factors including liver function and tumor progression. However, the effect of body composition such as skeletal muscle and visceral and subcutaneous adipose tissues (VAT and SAT, respectively) on the prognosis of these patients remains unclear. We investigated the prognostic value of body composition in HCC patients treated with transcatheter intra-arterial therapies. Patients and methods This study retrospectively evaluated 100 HCC patients treated with transcatheter intra-arterial therapies between 2005 and 2015. Areas of skeletal muscle, VAT, and SAT were measured on computed tomography images at third lumbar vertebra level and normalized by the height squared to calculate the skeletal muscle index, VAT index, and SAT index (SATI). The visceral to subcutaneous adipose tissue area ratio was also calculated. Overall survival (OS) was compared between high- and low-index groups for each body composition. Furthermore, prognostic significance was assessed by univariate and multivariate analyses using Cox proportional hazards models. Results Among the body composition indexes, only SATI could significantly differentiate OS (p=0.012). Multivariate analysis showed that SATI (low- vs. high-SATI: HR, 2.065; 95% CI, 1.187–3.593; p=0.010), serum albumin (<3.5 vs. ≥3.5 g/dL; HR, 2.007; 95% CI, 1.037–3.886; p=0.039), serum alpha-fetoprotein (<20 vs. ≥20 ng/mL; HR, 0.311; 95% CI, 0.179–0.540; p<0.001), and Modified Response Evaluation Criteria in Solid Tumors assessment (complete response+partial response+stable disease vs. progressive disease; HR, 0.392; 95% CI, 0.221–0.696; p=0.001) were indicated as independent prognostic factors for OS. Conclusion High SAT volume is associated with better survival outcomes in HCC patients treated with transcatheter intra-arterial therapies. Elucidation of the mechanisms regulating SAT volume may offer a new therapeutic strategy for these patients.
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Affiliation(s)
- Takamasa Kobayashi
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Hirokazu Kawai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Oki Nakano
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Satoshi Abe
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Hiroteru Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Akira Sakamaki
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Kenya Kamimura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Atsunori Tsuchiya
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Masaaki Takamura
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Satoshi Yamagiwa
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
| | - Shuji Terai
- Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan,
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38
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Kwon OS, Kim JH, Kim JH. [The Development of Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018. [PMID: 28637103 DOI: 10.4166/kjg.2017.69.6.348] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). NAFLD-related HCCs (NAFLD-HCCs) have the following clinical features: high body mass index, deranged lipid profiles, diabetes mellitus, hypertension, and metabolic syndrome. Among them, obesity, diabetes mellitus, and high Fe contents in the liver are risk factors of developing HCC in patients with NAFLD. Inflammatory cytokines, adipokines, insulin like growth factor-I, and lipotoxicity are intermingled and may cross react with each other to develop HCC. Because there is no guideline for early detection of HCC in patients with NAFLD, NAFLD-HCCs tend to be greater in size and in advanced stages when detected compared with hepatitis virus-related HCCs. Therefore, there is an urgent need of a surveillance program for the early detection of HCC. Treatment of NAFLD-HCCs is not different from other causes-related HCCs. However, patients with NAFLD-HCCs have cardiovascular disease and other metabolic problems, which may complicate treatment.
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Affiliation(s)
- Oh Sang Kwon
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Joon Hwan Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Ju Hyun Kim
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
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39
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Montano-Loza AJ, Mazurak VC, Ebadi M, Meza-Junco J, Sawyer MB, Baracos VE, Kneteman N. Visceral adiposity increases risk for hepatocellular carcinoma in male patients with cirrhosis and recurrence after liver transplant. Hepatology 2018; 67:914-923. [PMID: 29023899 DOI: 10.1002/hep.29578] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 08/30/2017] [Accepted: 10/03/2017] [Indexed: 12/21/2022]
Abstract
UNLABELLED Visceral adipose tissue (VAT) is a metabolically active organ, associated with higher risk of malignancies. We evaluated whether VAT is associated with the risk of hepatocellular carcinoma (HCC) in patients presenting with cirrhosis as well as HCC recurrence after liver transplantation (LT). Patients with cirrhosis (n = 678; 457 male) who were assessed for LT (289 with HCC) were evaluated for body composition analysis. Patients who underwent LT (n = 247, 168 male) were subsequently evaluated for body composition, and 96 of these patients (78 male) had HCC. VAT, subcutaneous adipose tissues, and total adipose tissues were quantified by computed tomography at the level of the third lumbar vertebra and reported as indexes (cross-sectional area normalized for height [square centimeters per square meter]). At the time of LT assessment, the VAT index (VATI) was higher in male patients with HCC compared to non-HCC patients (75 ± 3 versus 60 ± 3 cm2 /m2 , P = 0.001). The VATI, subcutaneous adipose tissue index, and total adipose tissue index were higher in male patients with HCC compared to non-HCC patients. By multivariate analysis, male patients with VATI ≥65 cm2 /m2 had a higher risk of HCC (hazard ratio, 1.90; 95% confidence interval, 1.31-2.76; P = 0.001). In male patients with HCC who underwent LT, a VATI ≥65 cm2 /m2 adjusted for Milan criteria was independently associated with higher risk of HCC recurrence (hazard ratio, 5.34; 95% confidence interval, 1.19-23.97; P = 0.03). CONCLUSION High VATI is an independent risk factor for HCC in male patients with cirrhosis and for recurrence of HCC after LT. (Hepatology 2018;67:914-923).
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Affiliation(s)
- Aldo J Montano-Loza
- Division of Gastroenterology & Liver Unit, University of Alberta Hospital, Edmonton, Alberta, Canada
| | - Vera C Mazurak
- Division of Human Nutrition, University of Alberta, Edmonton, Alberta, Canada
| | - Maryam Ebadi
- Division of Human Nutrition, University of Alberta, Edmonton, Alberta, Canada
| | - Judith Meza-Junco
- Department of Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Michael B Sawyer
- Department of Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Vickie E Baracos
- Department of Oncology, Cross Cancer Institute, Edmonton, Alberta, Canada
| | - Norman Kneteman
- Division of Transplantation, Department of Surgery, University of Alberta, Edmonton, Canada
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40
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Increased visceral fat volume raises the risk for recurrence of hepatocellular carcinoma after curative treatment. Oncotarget 2018; 9:14058-14067. [PMID: 29581826 PMCID: PMC5865652 DOI: 10.18632/oncotarget.24500] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2017] [Accepted: 02/10/2018] [Indexed: 12/15/2022] Open
Abstract
Obesity is a risk factor for the development of hepatocellular carcinoma (HCC). This study aimed to assess the influence of visceral fat on the recurrence of HCC after curative treatment. In 207 curative cases of HCC, the cross-sectional areas of visceral and subcutaneous fat mass on the computed tomographic image at the fourth lumbar vertebra were normalized by the square of the height to obtain the visceral fat mass index (VFMI) and the subcutaneous fat mass index (SFMI), respectively. Whether VFMI and SFMI contributed to recurrence of HCC and overall survival was analyzed using a Cox proportional hazards model. Increased VFMI was significantly associated with recurrence of HCC (P = 0.006), whereas SFMI was not (P = 0.502). When the patients were divided based on the optimal cut off value for VFMI (47.2 cm2/m2), obtained from maximally selected rank statistics to best predict the risk for recurrence, the higher VFMI group (n = 79) had more probability of recurrence than the lower VFMI group (n = 128) (log rank test, P = 0.002). There were significant differences in body mass index (P < .0001), SFMI (P < .0001), L3 skeletal muscle index (P < .0001), platelet count (P = 0.003), hemoglobin A1c (P < .0001), triglycerides (P = 0.004), serum leptin (P = 0.043), and underlying liver disease (P < .0001) between the groups. Neither VFMI (P = 0.689) nor SFMI (P = 0.117) significantly contributed to overall survival. VFMI, which is involved in obesity and its related metabolic disorders such as diabetes, hyperlipidemia, and adipokine imbalance, is an extremely promising indicator that can predict the risk of recurrence of HCC after curative treatment.
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41
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Emerging metabolic risk factors in hepatocellular carcinoma and their influence on the liver microenvironment. Biochim Biophys Acta Mol Basis Dis 2018; 1864:607-617. [PMID: 29197664 DOI: 10.1016/j.bbadis.2017.11.026] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2017] [Revised: 11/14/2017] [Accepted: 11/28/2017] [Indexed: 12/14/2022]
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42
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McDonald AM, Fiveash JB, Kirkland RS, Cardan RA, Jacob R, Kim RY, Dobelbower MC, Yang ES. Subcutaneous adipose tissue characteristics and the risk of biochemical recurrence in men with high-risk prostate cancer. Urol Oncol 2017; 35:663.e15-663.e21. [DOI: 10.1016/j.urolonc.2017.07.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 05/08/2017] [Accepted: 07/11/2017] [Indexed: 10/19/2022]
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43
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Klein S, Dufour JF. Nonalcoholic fatty liver disease and hepatocellular carcinoma. Hepat Oncol 2017; 4:83-98. [PMID: 30191057 DOI: 10.2217/hep-2017-0013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 08/22/2017] [Indexed: 02/07/2023] Open
Abstract
Hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease is becoming more common globally. The incidence of HCC due to nonalcoholic steatohepatitis in comparison to other etiologies is increasing. This is due to the pandemic of obesity and diabetes mellitus, two important risk factors for HCC. HCC arising in this context occurs in about 40% of the cases in a liver which is not yet cirrhotic. This has implications regarding the population which should be enrolled in an HCC surveillance program and regarding the treatment options. Surgery is more frequently contemplated in patients with HCC and no cirrhosis. However, patients with nonalcoholic steatohepatitis-induced HCC have frequent co-morbidities which have to be taken into account when developing a management strategy. Interestingly, these patients are frequently on medications which have been suggested to decrease the risk to develop HCC.
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Affiliation(s)
- Stephanie Klein
- Department of Clinical Research, Hepatology, University of Bern, Bern, Switzerland.,University Clinic for Visceral Surgery & Medicine, Inselspital Bern, Bern, Switzerland.,Department of Clinical Research, Hepatology, University of Bern, Bern, Switzerland.,University Clinic for Visceral Surgery & Medicine, Inselspital Bern, Bern, Switzerland
| | - Jean-François Dufour
- Department of Clinical Research, Hepatology, University of Bern, Bern, Switzerland.,University Clinic for Visceral Surgery & Medicine, Inselspital Bern, Bern, Switzerland.,Department of Clinical Research, Hepatology, University of Bern, Bern, Switzerland.,University Clinic for Visceral Surgery & Medicine, Inselspital Bern, Bern, Switzerland
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44
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Aberle D, Charles H, Hodak S, O'Neill D, Oklu R, Deipolyi AR. Optimizing care for the obese patient in interventional radiology. Diagn Interv Radiol 2017; 23:156-162. [PMID: 28082253 DOI: 10.5152/dir.2016.16230] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
With the rising epidemic of obesity, interventional radiologists are treating increasing numbers of obese patients, as comorbidities associated with obesity preclude more invasive treatments. These patients are at heightened risk of vascular and oncologic disease, both of which often require interventional radiology care. Obese patients pose unique challenges in imaging, technical feasibility, and periprocedural monitoring. This review describes the technical and clinical challenges posed by this population, with proposed methods to mitigate these challenges and optimize care.
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Affiliation(s)
- Dwight Aberle
- Vascular and Interventional Radiology, NYU Langone Medical Center, New York, NY, USA.
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45
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Labenz C, Prenosil V, Koch S, Huber Y, Marquardt JU, Schattenberg JM, Galle PR, Weinmann A, Wörns MA. Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib. Dig Dis 2017; 36:78-88. [PMID: 28675895 DOI: 10.1159/000477578] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2017] [Accepted: 05/15/2017] [Indexed: 02/02/2023]
Abstract
BACKGROUND/AIM Individual components of the metabolic syndrome (MS) such as obesity or diabetes mellitus impair the prognosis of patients with hepatocellular carcinoma (HCC) following curative treatment approaches or transarterial therapies. The aim of this retrospective study was to assess the impact of these factors on the overall survival (OS) of patients with advanced HCC treated with sorafenib. METHODS Univariate and multivariate analyses were performed to assess the impact of individual components of the MS on the OS of 152 consecutive patients with advanced HCC treated with sorafenib. RESULTS The presence of overweight/obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and of the MS itself did not impair the median OS. Multivariate analysis showed that Eastern Cooperative Oncology Group Performance Status ≥1 (hazards ratio [HR] 2.03), presence of macrovascular invasion (HR 1.71), Child-Pugh score B/C (HR 2.19), tumor grading G3 (HR 2.17), no prior HCC treatment (HR 2.34), and the presence of 2 or more out of 5 individual components of the MS (HR 0.65) were independent prognostic factors regarding the median OS. CONCLUSIONS Our investigations do not confirm a negative prognostic role of individual components of the MS or the MS itself for patients with advanced HCC treated with sorafenib.
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Affiliation(s)
- Christian Labenz
- Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
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46
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Abstract
There is great geographical variation in the distribution of hepatocellular carcinoma (HCC), with the majority of all cases worldwide found in the Asia–Pacific region, where HCC is one of the leading public health problems. Since the “Toward Revision of the Asian Pacific Association for the Study of the Liver (APASL) HCC Guidelines” meeting held at the 25th annual conference of the APASL in Tokyo, the newest guidelines for the treatment of HCC published by the APASL has been discussed. This latest guidelines recommend evidence-based management of HCC and are considered suitable for universal use in the Asia–Pacific region, which has a diversity of medical environments.
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47
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Sakitani K, Enooku K, Kubo H, Tanaka A, Arai H, Kawazu S, Koike K. Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan. J Int Med Res 2017; 45:1208-1220. [PMID: 28553763 PMCID: PMC5536430 DOI: 10.1177/0300060517707672] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2016] [Accepted: 04/10/2017] [Indexed: 12/17/2022] Open
Abstract
Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females.
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Affiliation(s)
- Kosuke Sakitani
- The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kenichiro Enooku
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hirokazu Kubo
- The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
| | - Akifumi Tanaka
- The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
| | - Hisakatsu Arai
- The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
| | - Shoji Kawazu
- The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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48
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Krishna SG, Hussan H, Cruz-Monserrate Z, Conteh LF, Mumtaz K, Conwell DL. A review of the impact of obesity on common gastrointestinal malignancies. ACTA ACUST UNITED AC 2017; 4. [PMID: 28819564 PMCID: PMC5557628 DOI: 10.15761/icst.1000223] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Obesity is a global pandemic and is a well-recognized risk factor for various gastrointestinal diseases. The prevalence of obesity is increasing across all age groups. There is an emergent need for focused guidelines aimed at reducing the incidence, prevalence, and associated risks of obesity. The impact of obesity on gastrointestinal cancers being multifactorial adversely influences the associated risk, disease course, prognosis, and overall survival. We have summarized the current literature highlighting the association between obesity and common gastrointestinal cancers, with specific focus on esophageal adenocarcinoma, colon cancer, hepatocellular cancer, cholangiocarcinoma, and pancreatic malignancies.
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Affiliation(s)
- Somashekar G Krishna
- Sections of Pancreatic Disorders and Advanced Endoscopy, Division of Gastroenterology, Hepatology and Nutrition, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, USA
| | - Hisham Hussan
- Sections of Intestinal Neoplasia and Hereditary Polyposis, and Obesity and Bariatric Endoscopy, Division of Gastroenterology, Hepatology and Nutrition, Comprehensive Cancer Center, The Ohio State University, USA
| | - Zobeida Cruz-Monserrate
- Section of Molecular and Cellular Biology, Division of Gastroenterology, Hepatology and Nutrition, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, USA
| | - Lanla F Conteh
- Section of Hepatology & Comprehensive Transplant Center, Division of Gastroenterology, Hepatology and Nutrition, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, USA
| | - Khalid Mumtaz
- Section of Hepatology & Comprehensive Transplant Center, Division of Gastroenterology, Hepatology and Nutrition, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, USA
| | - Darwin L Conwell
- Section of Pancreatic Disorders, Division of Gastroenterology, Hepatology and Nutrition, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, USA
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49
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Abstract
The prevalence of overweight (body mass index [BMI], 25 to 29.9 kg/m2) and obesity (BMI ≥ 30 kg/m2) have increased dramatically in the United States. Because increasing BMI is associated with the development of multiple different cancer types, including most GI cancers, providers will frequently encounter patients with GI cancer who are overweight or obese. Mounting evidence associates overweight and/or obesity with worsened prognosis in multiple GI cancers, including esophageal, gastric, hepatocellular, pancreatic, and colorectal. However, these data are observational and may be subject to bias and/or confounding. Furthermore, in some cancer types, the associations between BMI and outcomes is not linear, where overweight and class I obese patients may have an improvement in outcome. This report provides a brief highlight of existing studies that have linked overweight and/or obesity to prognosis in GI cancer; provides recommendations on best management practices; and discusses limitations, controversies, and future directions in this rapidly evolving area. There are multiple areas of promise that warrant continued investigation: What are the comparative contributions of energy balance, including weight, dietary patterns, and physical activity on cancer prognosis? What are the specific physiologic pathways that mediate the relationship between energy balance and prognosis? What is the relationship between low muscle mass (sarcopenia) or sarcopenic obesity and cancer prognosis? Are there subsets of patients for whom purposefully altering energy balance would be deleterious to prognosis? This area is rich with opportunities to understand how states of energy (im)balance can be favorably altered to promote healthy survivorship.
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Affiliation(s)
- Justin C. Brown
- Justin C. Brown, University of Pennsylvania, Philadelphia, PA; and Jeffrey A. Meyerhardt, Dana-Farber Cancer Institute, Boston, MA
| | - Jeffrey A. Meyerhardt
- Justin C. Brown, University of Pennsylvania, Philadelphia, PA; and Jeffrey A. Meyerhardt, Dana-Farber Cancer Institute, Boston, MA
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50
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Lee J, Yoo SH, Sohn W, Kim HW, Choi YS, Won JH, Heo JY, Park SJ, Park YM. Obesity and hepatocellular carcinoma in patients receiving entecavir for chronic hepatitis B. Clin Mol Hepatol 2016; 22:339-349. [PMID: 27729627 PMCID: PMC5066372 DOI: 10.3350/cmh.2016.0021] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 06/13/2016] [Accepted: 06/29/2016] [Indexed: 12/11/2022] Open
Abstract
Background/Aims This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. Methods This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). Results The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm2 (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m2 (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm2 (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602). Conclusion HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.
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Affiliation(s)
- Jaemin Lee
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Sun Hong Yoo
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Won Sohn
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Hyung Woo Kim
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Yong Sun Choi
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Jung Ho Won
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Jin Young Heo
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Sang Jong Park
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Young Min Park
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
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