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Busso C, Nault JC, Layese R, Demory A, Blaise L, Nkontchou G, Grando V, Nahon P, Ganne-Carrié N. Prolonged survival in women with hepatocellular carcinoma: A French observational study. Clin Res Hepatol Gastroenterol 2024; 48:102498. [PMID: 39549996 DOI: 10.1016/j.clinre.2024.102498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 11/04/2024] [Accepted: 11/14/2024] [Indexed: 11/18/2024]
Abstract
BACKGROUND AND AIM Less than 25 % of hepatocellular carcinoma (HCC) occurs in women, in whom prognosis could be better. Due to the lack of date in Europe, this study aims to assess survival of patients with HCC according sex in a tertiary French liver center. PATIENTS AND METHODS Every patient diagnosed with a first diagnosis of HCC presented at our weekly multidisciplinary tumor board between 2013 and 2017 were included. Baseline characteristics of patients and tumors were compared according sex using the Mann-Whitney test for Continuous variables and the Fisher or Chi-square test for dichotomous variables. Survival analyses according sex were conducted using the Kaplan-Meier method, the log-rank test, Cox models and a propensity score. RESULTS 694 patients were included, of whom 130 (18.7 %) were women. Among them, 587 (86 %) had cirrhosis, mainly compensated (Child A 62.7 %), and related to alcohol (48.7 %), HCV (27.2 %), and/or metabolic-associated fatty liver disease (25.8 %). HCC was unifocal in 54 % of cases, with a mean main nodule size of 37 mm. Curative treatment was administered in 45.4 % of cases (percutaneous ablation 93 %). Compared to men, women diagnosed with HCC were older (73 vs. 65 years, p < 0.001), were more frequently HCV-infected (40 % vs. 24 %, p = 0.0003) and presented more often with a solitary HCC (63 % vs. 52 %, p = 0.020). After a median follow-up of 57 months, overall survival was significantly longer in women both in multivariate analysis (aHR 1.39 (CI95 %: 1.07-1.81) p=0.014) and using a propensity score (HR 1.51 (1.13-2.02, p=0.005)). CONCLUSION Despite being diagnosed at an older age, women with HCC exhibit significant better overall survival.
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Affiliation(s)
- Cécilia Busso
- AP-HP, Service d'Hépatologie, Hôpital Avicenne, Bobigny, France
| | - Jean-Charles Nault
- AP-HP, Service d'Hépatologie, Hôpital Avicenne, Bobigny, France; Sorbonne Paris Nord, UFR SMBH, Bobigny, France; Cordeliers research center, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, F-75006 Paris, France
| | - Richard Layese
- Université Paris Est Creteil, INSERM, IMRB, F-94010 Creteil, France; AP-HP, Département de Santé Publique, Unité de Recherche Clinique (URC Mondor), Hôpital Henri Mondor, Créteil, France
| | - Alix Demory
- AP-HP, Service d'Hépatologie, Hôpital Avicenne, Bobigny, France
| | - Lorraine Blaise
- AP-HP, Service d'Hépatologie, Hôpital Avicenne, Bobigny, France
| | | | | | - Pierre Nahon
- AP-HP, Service d'Hépatologie, Hôpital Avicenne, Bobigny, France; Sorbonne Paris Nord, UFR SMBH, Bobigny, France; Cordeliers research center, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, F-75006 Paris, France
| | - Nathalie Ganne-Carrié
- AP-HP, Service d'Hépatologie, Hôpital Avicenne, Bobigny, France; Sorbonne Paris Nord, UFR SMBH, Bobigny, France; Cordeliers research center, Sorbonne Université, Inserm, Université de Paris, team « Functional Genomics of Solid Tumors », Equipe labellisée Ligue Nationale Contre le Cancer, Labex OncoImmunology, F-75006 Paris, France.
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Kim D, Manikat R, Wijarnpreecha K, Cholankeril G, Ahmed A. Burden of mortality from hepatocellular carcinoma and biliary tract cancers by race and ethnicity and sex in US, 2018-2023. Clin Mol Hepatol 2024; 30:756-770. [PMID: 38910110 PMCID: PMC11540356 DOI: 10.3350/cmh.2024.0318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 06/20/2024] [Accepted: 06/20/2024] [Indexed: 06/25/2024] Open
Abstract
BACKGROUNDS/AIMS The trends in mortality of hepatocellular carcinoma (HCC) and biliary tract cancers stratified by sex and race/ethnicity in the US continue to evolve. We estimated the sex- and race/ethnicity-based trends in HCC and biliary tract cancers-related mortality in US adults with a focus on disease burden. METHODS We performed a population-based analysis using the US national mortality records from 2018 to 2023. We identified HCC and biliary tract cancer using appropriate ICD-10 codes. Temporal trends in mortality were calculated by joinpoint analysis with annual percentage change (APC). RESULTS Annual age-standardized mortality from HCC decreased steadily with an APC of -1.4% (95% confidence interval [CI]: -2.0% to -0.7%). While there was a linear increase in intrahepatic cholangiocarcinoma-related mortality (APC: 3.1%, 95% CI: 1.2-4.9%) and ampulla of Vater cancer-related mortality (APC: 4.1%, 95% CI: 0.5-7.9%), gallbladder cancer-related mortality decreased (APC: -1.9%, 95% CI: -3.8% to -0.0%). Decreasing trends in mortality from HCC were noted in males, not females. HCC-related mortality decreased more steeply in racial and ethnic minority individuals compared with non-Hispanic White individuals. Racial and ethnic differences in trends in mortality for biliary tract cancers depended on the malignancy's anatomical site. CONCLUSION While the annual mortality for HCC and gallbladder cancer demonstrated declining trends, ICC- and AVC-related mortality continued to increase from 2018 to 2023. Although racial and ethnic minority individuals in the US experienced disproportionately higher HCC and biliary tract cancer, recent declines in HCC may be primarily due to declines among racial and ethnic minority individuals and males.
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Affiliation(s)
- Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Richie Manikat
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
| | - Karn Wijarnpreecha
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Phoenix, AZ, USA
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Banner University Medical Center, Phoenix, AZ, USA
| | - George Cholankeril
- Liver Center, Division of Abdominal Transplantation, Michael E DeBakey Department of General Surgery, Baylor College of Medicine, Houston, TX, USA
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Aijaz Ahmed
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA
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Flavin B. Nonalcoholic steatohepatitis/metabolic dysfunction-associated steatohepatitis emerging market: Preparing managed care for early intervention, equitable access, and integrating the patient perspective. J Manag Care Spec Pharm 2024; 30:S1-S13. [PMID: 39213163 PMCID: PMC11365455 DOI: 10.18553/jmcp.2024.30.9-a.s1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
Nonalcoholic steatohepatitis (NASH)/metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of liver disease that can lead to significant morbidity and mortality primarily due to hepatic complications including fibrosis, cirrhosis, hepatocellular carcinoma, and liver failure, as well as cardiovascular disease. As the development of NASH/MASH is closely linked to cardiometabolic risk factors such as obesity and type 2 diabetes mellitus, its prevalence is increasing along with the prevalence of those conditions. Identifying at-risk patients or those early in the disease process is essential to optimizing care and may prevent future complications. Current treatment options include disease-modifying interventions, off-label use of US Food and Drug Administration (FDA)-approved medications for comorbid conditions, and resmetirom, the recently first-ever FDA-approved medication specifically for use in NASH/MASH. There is also considerable continued activity in related drug development research with several other potential emerging treatments. With the increasing prevalence of NASH/MASH and emerging treatments, it is important for managed care organizations (MCOs) to be prepared to assist in patient care and implement equitable treatment management. Understanding patient perspectives and their experience with NASH/MASH provides insights for MCOs such as the need for education of both health care providers and patients to encourage early diagnosis and for enhancing access to individualized care including resources and support. Additionally, MCOs can consider potential management strategies for new and emerging treatments.
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Yin J, Liu G, Zhang Y, Zhou Y, Pan Y, Zhang Q, Yu R, Gao S. Gender differences in gliomas: From epidemiological trends to changes at the hormonal and molecular levels. Cancer Lett 2024; 598:217114. [PMID: 38992488 DOI: 10.1016/j.canlet.2024.217114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 06/28/2024] [Accepted: 07/08/2024] [Indexed: 07/13/2024]
Abstract
Gender plays a crucial role in the occurrence and development of cancer, as well as in the metabolism of nutrients and energy. Men and women display significant differences in the incidence, prognosis, and treatment response across various types of cancer, including certain sex-specific tumors. It has been observed that male glioma patients have a higher incidence and worse prognosis than female patients, but there is currently a limited systematic evaluation of sex differences in gliomas. The purpose of this study is to provide an overview of the association between fluctuations in sex hormone levels and changes in their receptor expression with the incidence, progression, treatment, and prognosis of gliomas. Estrogen may have a protective effect on glioma patients, while exposure to androgens increases the risk of glioma. We also discussed the specific genetic and molecular differences between genders in terms of the malignant nature and prognosis of gliomas. Factors such as TP53, MGMT methylation status may play a crucial role. Therefore, it is essential to consider the gender of patients while treating glioma, particularly the differences at the hormonal and molecular levels. This approach can help in the adoption of an individualized treatment strategy.
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Affiliation(s)
- Jiale Yin
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, China; Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China
| | - Gai Liu
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, China; Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China
| | - Yue Zhang
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, China; Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China
| | - Yu Zhou
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, China; Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China
| | - Yuchun Pan
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, China; Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China
| | - Qiaoshan Zhang
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, China; Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China
| | - Rutong Yu
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, China; Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China
| | - Shangfeng Gao
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221002, China; Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221002, China.
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Toniutto P, Shalaby S, Mameli L, Morisco F, Gambato M, Cossiga V, Guarino M, Marra F, Brunetto MR, Burra P, Villa E. Role of sex in liver tumor occurrence and clinical outcomes: A comprehensive review. Hepatology 2024; 79:1141-1157. [PMID: 37013373 DOI: 10.1097/hep.0000000000000277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 12/06/2022] [Indexed: 04/05/2023]
Abstract
Clinical research on sex-based differences in the manifestations, pathophysiology, and prevalence of several diseases, including those affecting the liver, has expanded considerably in recent years. Increasing evidence suggests that liver diseases develop, progress, and respond to treatment differently depending on the sex. These observations support the concept that the liver is a sexually dimorphic organ in which estrogen and androgen receptors are present, which results in disparities between men and women in liver gene expression patterns, immune responses, and the progression of liver damage, including the propensity to develop liver malignancies. Sex hormones play protective or deleterious roles depending on the patient's sex, the severity of the underlying disease, and the nature of precipitating factors. Moreover, obesity, alcohol consumption, and active smoking, as well as social determinants of liver diseases leading to sex-related inequalities, may interact strongly with hormone-related mechanisms of liver damage. Drug-induced liver injury, viral hepatitis, and metabolic liver diseases are influenced by the status of sex hormones. Available data on the roles of sex hormones and gender differences in liver tumor occurrence and clinical outcomes are conflicting. Here, we critically review the main gender-based differences in the molecular mechanisms associated with liver carcinogenesis and the prevalence, prognosis, and treatment of primary and metastatic liver tumors.
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Affiliation(s)
- Pierluigi Toniutto
- Hepatology and Liver Transplantation Unit, Azienda Sanitaria Universitaria Integrata, Department of Medical Area, University of Udine, Udine, Italy
| | - Sarah Shalaby
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Laura Mameli
- Liver and Pancreas Transplant Center, Azienda Ospedaliera Brotzu Piazzale Ricchi 1, Cagliari, Italy
| | - Filomena Morisco
- Department of Clinical Medicine and Surgery, Departmental Program "Diseases of the Liver and Biliary System," University of Naples "Federico II," Napoli, Italy
| | - Martina Gambato
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Valentina Cossiga
- Department of Clinical Medicine and Surgery, Departmental Program "Diseases of the Liver and Biliary System," University of Naples "Federico II," Napoli, Italy
| | - Maria Guarino
- Department of Clinical Medicine and Surgery, Departmental Program "Diseases of the Liver and Biliary System," University of Naples "Federico II," Napoli, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | | | - Patrizia Burra
- Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Erica Villa
- Gastroenterology Department, University of Modena and Reggio Emilia, Modena, Italy
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Ali H, Vikash F, Moond V, Khalid F, Jamil AR, Dahiya DS, Sohail AH, Gangwani MK, Patel P, Satapathy SK. Global trends in hepatitis C-related hepatocellular carcinoma mortality: A public database analysis (1999-2019). World J Virol 2024; 13:89469. [PMID: 38616850 PMCID: PMC11008397 DOI: 10.5501/wjv.v13.i1.89469] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/19/2023] [Accepted: 01/18/2024] [Indexed: 03/11/2024] Open
Abstract
BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma (HCC). However, there are marked variations in the incidence and mortality rates of HCC across different geographical regions. With the advent of new widely available treatment modalities, such as direct-acting antivirals, it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C. Furthermore, gender disparities in HCC mortality related to Hepatitis C are a crucial, yet underexplored aspect that adds to the disease's global impact. While some studies shed light on gender-specific trends, there is a lack of comprehensive data on global and regional mortality rates, particularly those highlighting gender disparities. This gap in knowledge hinders the development of targeted interventions and resource allocation strategies. AIM To understand the global and regional trends in Hepatitis C-related HCC mortality rates from 1990 to 2019, along with gender disparities. METHODS We utilized the Global Burden of Disease database, a comprehensive repository for global health metrics to age-standardized mortality rates due to Hepatitis C-related HCC from 1999 to 2019. Rates were evaluated per 100000 population and assessed by World Bank-defined regions. Temporal trends were determined using Joinpoint software and the Average Annual Percent Change (AAPC) method, and results were reported with 95% confidence intervals (CI). RESULTS From 1990 to 2019, overall, there was a significant decline in HCC-related mortality rates with an AAPC of -0.80% (95%CI: -0.83 to -0.77). Females demonstrated a marked decrease in mortality with an AAPC of -1.06% (95%CI: -1.09 to -1.03), whereas the male cohort had a lower AAPC of -0.52% (95%CI: -0.55 to -0.48). Regionally, East Asia and the Pacific demonstrated a significant decline with an AAPC of -2.05% (95%CI: -2.10 to -2.00), whereas Europe and Central Asia observed an uptrend with an AAPC of 0.72% (95%CI: 0.69 to 0.74). Latin America and the Caribbean also showed an uptrend with an AAPC of 0.06% (95%CI: 0.02 to 0.11). In the Middle East and North Africa, the AAPC was non-significant at 0.02% (95%CI: -0.09 to 0.12). North America, in contrast, displayed a significant upward trend with an AAPC of 2.63% (95%CI: 2.57 to 2.67). South Asia (AAPC -0.22%, 95%CI: -0.26 to -0.16) and Sub-Saharan Africa (AAPC -0.14%, 95%CI: -0.15 to -0.12) trends significantly declined over the study period. CONCLUSION Our study reports disparities in Hepatitis C-related HCC mortality between 1999 to 2019, both regionally and between genders. While East Asia and the Pacific regions showed a promising decline in mortality, North America has experienced a concerning rise in mortality. These regional variations highlight the need for healthcare policymakers and practitioners to tailor public health strategies and interventions. The data serves as a call to action, particularly for regions where mortality rates are not improving, emphasizing the necessity for a nuanced, region-specific approach to combat the global challenge of HCC secondary to Hepatitis C.
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Affiliation(s)
- Hassam Ali
- Department of Internal Medicine/Gastroenterology, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Fnu Vikash
- Department of Internal Medicine, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY 10461, United States
| | - Vishali Moond
- Department of Internal Medicine, Saint Peter's University Hospital/Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Fatima Khalid
- Department of Internal Medicine, Quaid-e-Azam Medical College, Bahawalpur 63100, Punjab, Pakistan
| | - Abdur Rehman Jamil
- Department of Internal Medicine, Samaritan Medical Centre, Watertown, MA 13601, United States
| | - Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, United States
| | - Amir Humza Sohail
- Department of Surgery, New York University Winthrop Hospital, New York, Mineloa, NY 11501, United States
| | - Manesh Kumar Gangwani
- Department of Internal Medicine, The University of Toledo, Toledo, OH 43606, United States
| | - Pratik Patel
- Department of Gastroenterology, Mather Hospital/Hofstra University Zucker School of Medicine, NY 11777, United States
| | - Sanjaya K Satapathy
- Division of Hepatology, Department of Medicine, North Shore University Hospital, Manhasset, NY 11030, United States
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Huo RR, Pan LX, Wu PS, Liang XM, You XM, Ma L, Zhong JH. Prognostic value of aspartate aminotransferase/alanine aminotransferase ratio in hepatocellular carcinoma after hepatectomy. BJS Open 2024; 8:zrad155. [PMID: 38242573 PMCID: PMC10798825 DOI: 10.1093/bjsopen/zrad155] [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: 07/12/2023] [Revised: 10/30/2023] [Accepted: 11/19/2023] [Indexed: 01/21/2024] Open
Abstract
BACKGROUND The prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators. METHODS This retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed. RESULTS Among the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival). CONCLUSION The AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.
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Affiliation(s)
- Rong-Rui Huo
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Li-Xin Pan
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Pei-Sheng Wu
- Hepatobiliary Surgery Department, The First People’s Hospital of Qinzhou, Qinzhou, China
| | - Xiu-Mei Liang
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xue-Mei You
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumour (Guangxi Medical University), Ministry of Education, Nanning, China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumour (Guangxi Medical University), Nanning, China
| | - Liang Ma
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumour (Guangxi Medical University), Ministry of Education, Nanning, China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumour (Guangxi Medical University), Nanning, China
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Kumar A, Acharya SK, Singh SP, Duseja A, Madan K, Shukla A, Arora A, Anand AC, Bahl A, Soin AS, Sirohi B, Dutta D, Jothimani D, Panda D, Saini G, Varghese J, Kumar K, Premkumar M, Panigrahi MK, Wadhawan M, Sahu MK, Rela M, Kalra N, Rao PN, Puri P, Bhangui P, Kar P, Shah SR, Baijal SS, Shalimar, Paul SB, Gamanagatti S, Gupta S, Taneja S, Saraswat VA, Chawla YK. 2023 Update of Indian National Association for Study of the Liver Consensus on Management of Intermediate and Advanced Hepatocellular Carcinoma: The Puri III Recommendations. J Clin Exp Hepatol 2024; 14:101269. [PMID: 38107186 PMCID: PMC10724697 DOI: 10.1016/j.jceh.2023.08.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 08/12/2023] [Indexed: 12/19/2023] Open
Abstract
Hepatocellular carcinoma (HCC) presents significant treatment challenges despite considerable advancements in its management. The Indian National Association for the Study of the Liver (INASL) first published its guidelines to aid healthcare professionals in the diagnosis and treatment of HCC in 2014. These guidelines were subsequently updated in 2019. However, INASL has recognized the need to revise its guidelines in 2023 due to recent rapid advancements in the diagnosis and management of HCC, particularly for intermediate and advanced stages. The aim is to provide healthcare professionals with evidence-based recommendations tailored to the Indian context. To accomplish this, a task force was formed, and a two-day round table discussion was held in Puri, Odisha. During this event, experts in their respective fields deliberated and finalized consensus statements to develop these updated guidelines. The 2023 INASL guidelines offer a comprehensive framework for the diagnosis, staging, and management of intermediate and advanced HCC in India. They represent a significant step forward in standardizing clinical practices nationwide, with the primary objective of ensuring that patients with HCC receive the best possible care based on the latest evidence. The guidelines cover various topics related to intermediate and advanced HCC, including biomarkers of aggressive behavior, staging, treatment options, and follow-up care.
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Affiliation(s)
- Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Kaushal Madan
- Clinical Hepatology, Max Hospitals, Saket, New Delhi, India
| | - Akash Shukla
- Department of Gastroenterology, Seth GSMC & KEM Hospital, Mumbai, 400022, India
| | - Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India
| | - Anil C. Anand
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| | - Ankur Bahl
- Department of Medical Oncology, Fortis Memorial Research Institute, Sector - 44, Opp. HUDA City Center, Gurugram, 122002, India
| | - Arvinder S. Soin
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Bhawna Sirohi
- Medical Oncology, BALCO Medical Centre, Raipur Chattisgarh, 493661, India
| | - Debnarayan Dutta
- Radiation Oncology, Amrita Institute of Medical Sciences, Ponekkara, AIMS (P.O.), Kochi, 682041, India
| | - Dinesh Jothimani
- Department of Hepatology, Dr. Rela Institute & Medical Centre, #7, CLC Works Road, Chromepet, Chennai, 600044, India
| | - Dipanjan Panda
- Department of Medical Oncology, Apollo Cancer Centre, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110076, India
| | - Gagan Saini
- Radiation Oncology, Max Institute of Cancer Care, Max Super-Speciality Hospital, W-3, Ashok Marg, near Radisson Blu Hotel, Sector-1, Vaishali, Ghaziabad, 201012, India
| | - Joy Varghese
- Department of Hepatology & Transplant Hepatology, Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600100, India
| | - Karan Kumar
- Department of HPB Sciences and Liver Transplantation, Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur, 302022, Rajasthan, India
| | - Madhumita Premkumar
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Manas K. Panigrahi
- Department of Gastroenterology, All India Institute of Medical Sciences, Bhubaneswar, 751019, Odisha, India
| | - Manav Wadhawan
- Liver & Digestive Diseases Institute, Institute of Liver & Digestive Diseases, BLK Max Hospital, Delhi, 110 005, India
| | - Manoj K. Sahu
- Department of Medical Gastroenterology, IMS & SUM Hospital, K8 Kalinga Nagar, Shampur, Bhubaneswar, Odisha 751 003, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, #7, CLC Works Road, Chromepet, Chennai, 600044, India
| | - Naveen Kalra
- Department of Radio Diagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Padaki N. Rao
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, No. 6-3-661, Punjagutta Road, Somajiguda, Hyderabad, Telangana, 500 082, India
| | - Pankaj Puri
- Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Heart Institute & Research Centre, Okhla Road, New Delhi, 110025, India
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta The Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Premashis Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
| | - Samir R. Shah
- Department of Hepatology and Liver Intensive Care, Institute of Liver Disease, HPB Surgery and Transplant Global Hospitals, Dr E Borges Road, Parel, Mumbai, 400012, India
| | - Sanjay S. Baijal
- Diagnostic and Interventional Radiology, Medanta The Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Shashi B. Paul
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Shivanand Gamanagatti
- Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Heart Institute & Research Centre, Okhla Road, New Delhi, 110025, India
| | - Subash Gupta
- Centre for Liver & Biliary Sciences, Liver Transplant and Biliary Sciences, Robotic Surgery, Max Super Speciality Hospital, No. 1, 2, Press Enclave Road, Mandir Marg, Saket Institutional Area, Saket, New Delhi, Delhi, 110017, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Vivek A. Saraswat
- Department of Gastroenterology and Hepatology, Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur, 302022, Rajasthan, India
| | - Yogesh K. Chawla
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
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9
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Joo SK, Kim W. Sex/Gender Differences in Liver Diseases. SEX/GENDER-SPECIFIC MEDICINE IN CLINICAL AREAS 2024:209-217. [DOI: 10.1007/978-981-97-0130-8_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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10
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Motta BM, Masarone M, Torre P, Persico M. From Non-Alcoholic Steatohepatitis (NASH) to Hepatocellular Carcinoma (HCC): Epidemiology, Incidence, Predictions, Risk Factors, and Prevention. Cancers (Basel) 2023; 15:5458. [PMID: 38001718 PMCID: PMC10670704 DOI: 10.3390/cancers15225458] [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: 10/12/2023] [Revised: 11/07/2023] [Accepted: 11/15/2023] [Indexed: 11/26/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% over the next 10 years. There is growing epidemiological evidence that NAFLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD. In this review, NAFLD/NASH-associated HCC will be described, including its epidemiology, risk factors promoting hepatocarcinogenesis, and management of HCC in patients with obesity and associated metabolic comorbidities, including preventive strategies and therapeutic approaches to address this growing problem.
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Affiliation(s)
| | | | | | - Marcello Persico
- Department of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of Salerno, 84081 Baronissi, Italy; (B.M.M.); (M.M.); (P.T.)
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11
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Engel BJ, Paolillo V, Uddin MN, Gonzales KA, McGinnis KM, Sutton MN, Patnana M, Grindel BJ, Gores GJ, Piwnica-Worms D, Beretta L, Pisaneschi F, Gammon ST, Millward SW. Gender Differences in a Mouse Model of Hepatocellular Carcinoma Revealed Using Multi-Modal Imaging. Cancers (Basel) 2023; 15:3787. [PMID: 37568603 PMCID: PMC10417617 DOI: 10.3390/cancers15153787] [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: 05/12/2023] [Revised: 07/14/2023] [Accepted: 07/18/2023] [Indexed: 08/13/2023] Open
Abstract
The worldwide incidence of hepatocellular carcinoma (HCC) continues to rise, in part due to poor diet, limited exercise, and alcohol abuse. Numerous studies have suggested that the loss or mutation of PTEN plays a critical role in HCC tumorigenesis through the activation of the PI3K/Akt signaling axis. The homozygous knockout of PTEN in the livers of mice results in the accumulation of fat (steatosis), inflammation, fibrosis, and eventually progression to HCC. This phenotype bears a striking similarity to non-alcoholic steatohepatitis (NASH) which is thought to occupy an intermediate stage between non-alcoholic fatty liver disease (NAFLD), fibrosis, and HCC. The molecular and physiological phenotypes that manifest during the transition to HCC suggest that molecular imaging could provide a non-invasive screening platform to identify the hallmarks of HCC initiation prior to the presentation of clinical disease. We have carried out longitudinal imaging studies on the liver-specific PTEN knockout mouse model using CT, MRI, and multi-tracer PET to interrogate liver size, steatosis, inflammation, and apoptosis. In male PTEN knockout mice, significant steatosis was observed as early as 3 months using both magnetic resonance spectroscopy (MRS) and computed tomography (CT). Enhanced uptake of the apoptosis tracer 18F-TBD was also observed in the livers of male PTEN homozygous knockout mice between 3 and 4 months of age relative to heterozygous knockout controls. Liver uptake of the inflammation tracer [18F]4FN remained relatively low and constant over 7 months in male PTEN homozygous knockout mice, suggesting the suppression of high-energy ROS/RNS with PTEN deletion relative to heterozygous males where the [18F]4FN liver uptake was elevated at early and late time points. All male PTEN homozygous mice developed HCC lesions by month 10. In contrast to the male cohort, only 20% (2 out of 10) of female PTEN homozygous knockout mice developed HCC lesions by month 10. Steatosis was significantly less pronounced in the female PTEN homozygous knockout mice relative to males and could not accurately predict the eventual occurrence of HCC. As with the males, the [18F]4FN uptake in female PTEN homozygous knockout mice was low and constant throughout the time course. The liver uptake of 18F-TBD at 3 and 4.5 months was higher in the two female PTEN knockout mice that would eventually develop HCC and was the most predictive imaging biomarker for HCC in the female cohort. These studies demonstrate the diagnostic and prognostic role of multi-modal imaging in HCC mouse models and provide compelling evidence that disease progression in the PTEN knockout model is highly dependent on gender.
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Affiliation(s)
- Brian J. Engel
- Department of Cancer Systems Imaging, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Vincenzo Paolillo
- Cyclotron Radiochemistry Facility, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Md. Nasir Uddin
- Department of Cancer Systems Imaging, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Kristyn A. Gonzales
- Department of Molecular and Cellular Oncology, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Kathryn M. McGinnis
- Department of Molecular and Cellular Oncology, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Margie N. Sutton
- Department of Cancer Systems Imaging, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Madhavi Patnana
- Department of Abdominal Imaging, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Brian J. Grindel
- Department of Cancer Systems Imaging, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | | | - David Piwnica-Worms
- Department of Cancer Systems Imaging, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Laura Beretta
- Department of Molecular and Cellular Oncology, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Federica Pisaneschi
- Department of Cancer Systems Imaging, UT MD Anderson Cancer Center, Houston, TX 77030, USA
- Center for Translational Cancer Research, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM) at the University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Seth T. Gammon
- Department of Cancer Systems Imaging, UT MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Steven W. Millward
- Department of Cancer Systems Imaging, UT MD Anderson Cancer Center, Houston, TX 77030, USA
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12
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Fa A, Danos DM, Maniscalco L, Yi Y, Wu XC, Maluccio MA, Chu QD, Lyons JM. Is There Really a Difference in Outcomes between Men and Women with Hepatocellular Cancer? Cancers (Basel) 2023; 15:cancers15112892. [PMID: 37296854 DOI: 10.3390/cancers15112892] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Revised: 05/08/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a male-dominated disease. Currently, gender differences remain incompletely defined. Data from the state tumor registry were used to investigate differences in demographics, comorbidities, treatment patterns, and cancer-specific survival (HSS) among HCC patients according to gender. Additional analyses were performed to evaluate racial differences among women with HCC. 2627 patients with HCC were included; 498 (19%) were women. Women were mostly white (58%) or African American (39%)-only 3.8% were of another or unknown race. Women were older (65.1 vs. 61.3 years), more obese (33.7% vs. 24.2%), and diagnosed at an earlier stage (31.7% vs. 28.4%) than men. Women had a lower incidence of liver associated comorbidities (36.1% vs. 43%), and more often underwent liver-directed surgery (LDS; 27.5% vs. 22%). When controlling for LDS, no survival differences were observed between genders. African American women had similar HSS rates compared to white women (HR 1.14 (0.91,1.41), p = 0.239) despite having different residential and treatment geographical distributions. African American race and age >65 were predictive for worse HSS in men, but not in women. Overall, women with HCC undergo more treatment options-likely because of the earlier stage of the cancer and/or less severe underlying liver disease. However, when controlling for similar stages and treatments, HCC treatment outcomes were similar between men and women. African American race did not appear to influence outcomes among women with HCC as it did in men.
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Affiliation(s)
- Andrea Fa
- School of Medicine, LSU Health Sciences Center-New Orleans, New Orleans, LA 70112, USA
| | - Denise M Danos
- School of Public Health, LSU Health Science Center-New Orleans, New Orleans, LA 70112, USA
| | - Lauren Maniscalco
- Louisiana Tumor Registry, School of Public Health, LSU Health Science Center-New Orleans, New Orleans, LA 70112, USA
| | - Yong Yi
- Louisiana Tumor Registry, School of Public Health, LSU Health Science Center-New Orleans, New Orleans, LA 70112, USA
| | - Xiao-Cheng Wu
- Louisiana Tumor Registry, School of Public Health, LSU Health Science Center-New Orleans, New Orleans, LA 70112, USA
| | - Mary A Maluccio
- School of Medicine, LSU Health Sciences Center-New Orleans, New Orleans, LA 70112, USA
| | - Quyen D Chu
- Orlando Health Cancer Institute, Orlando, FL 32806, USA
| | - John M Lyons
- School of Medicine, LSU Health Sciences Center-New Orleans, New Orleans, LA 70112, USA
- Our Lady of the Lake Regional Medical Center, Baton Rouge, LA 70808, USA
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13
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Liou W, Tan TJ, Chen K, Goh GB, Chang JP, Tan C. Gender survival differences in hepatocellular carcinoma: Is it all due to adherence to surveillance? A study of 1716 patients over three decades. JGH Open 2023; 7:377-386. [PMID: 37265931 PMCID: PMC10230112 DOI: 10.1002/jgh3.12910] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 03/25/2023] [Accepted: 04/17/2023] [Indexed: 06/03/2023]
Abstract
Background and Aims Hepatocellular carcinoma (HCC) is one of the commonest causes of cancer-related death worldwide. Whether gender is an independent factor for HCC survival is debatable. We studied the influence of gender on the clinical characteristics of HCC and on survival. Methods The study cohort comprised patients with HCC seen in our department from 1988 to 2021. Clinical data were prospectively collected. We studied and compared demography, HCC characteristics, and survival between females and males. Survival analysis was censored on October 31, 2015. Results There were 1716 HCC patients. 343 (20.0%) were females. Females were significantly older at diagnosis (median 69 vs 62 years, P < 0.001). More females were diagnosed via regular HCC surveillance (37.9% vs 29.6%, P = 0.003). Hence, as expected, females had less-advanced HCC at diagnosis with smaller median tumor diameter (30 vs 39.5 mm, P = 0.038), lower frequency of portal vein tumor thrombus (19.4% vs 33.4%, P < 0.001), less distant metastases (7.7% vs 11%, P = 0.043), and earlier Barcelona Clinic Liver Cancer (BCLC) stages (0/A, 39.7% vs 28.4%, P < 0.001). On multivariable analysis, HCC diagnosis via surveillance but not female gender was an independent predictor of improved HCC survival. Conclusions In this large cohort of multi-ethnic Asian patients, females with HCC were significantly more adherent to surveillance and hence presented with less advanced HCC with correspondingly better overall survival than males. The gender difference in survival is likely due to females having better adherence to HCC surveillance. Surveillance to diagnose early-stage HCC remains crucial in improving outcomes.
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Affiliation(s)
- Wei‐Lun Liou
- Department of Gastroenterology and HepatologySingapore General HospitalSingaporeSingapore
| | - Terence J‐Y. Tan
- Department of Gastroenterology and HepatologySingapore General HospitalSingaporeSingapore
| | - Kaina Chen
- Department of Gastroenterology and HepatologySingapore General HospitalSingaporeSingapore
| | - George B‐B. Goh
- Department of Gastroenterology and HepatologySingapore General HospitalSingaporeSingapore
| | - Jason P‐E. Chang
- Department of Gastroenterology and HepatologySingapore General HospitalSingaporeSingapore
| | - Chee‐Kiat Tan
- Department of Gastroenterology and HepatologySingapore General HospitalSingaporeSingapore
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14
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Gheorghe EC, Nicolau C, Kamal A, Udristoiu A, Gruionu L, Saftoiu A. Artificial Intelligence (AI)-Enhanced Ultrasound Techniques Used in Non-Alcoholic Fatty Liver Disease: Are They Ready for Prime Time? APPLIED SCIENCES 2023; 13:5080. [DOI: 10.3390/app13085080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease, affecting approximately 2 billion individuals worldwide with a spectrum that can range from simple steatosis to cirrhosis. Typically, the diagnosis of NAFLD is based on imaging studies, but the gold standard remains liver biopsies. Hence, the use of artificial intelligence (AI) in this field, which has recently undergone rapid development in various aspects of medicine, has the potential to accurately diagnose NAFLD and steatohepatitis (NASH). This paper provides an overview of the latest research that employs AI for the diagnosis and staging of NAFLD, as well as applications for future developments in this field.
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Affiliation(s)
- Elena Codruta Gheorghe
- Department of Family Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
| | - Carmen Nicolau
- Lotus Image Medical Center, ActaMedica SRL Târgu Mureș, 540084 Târgu Mureș, Romania
| | - Adina Kamal
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
| | - Anca Udristoiu
- Faculty of Automation, Computers and Electronics, University of Craiova, 200776 Craiova, Romania
| | - Lucian Gruionu
- Faculty of Mechanics, University of Craiova, 200512 Craiova, Romania
| | - Adrian Saftoiu
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania
- Department of Gastroenterology, Ponderas Academic Hospital, 014142 Bucharest, Romania
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15
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Kaplan A, Wahid N, Fortune BE, Verna E, Halazun K, Samstein B, Brown RS, Rosenblatt R. Black patients and women have reduced access to liver transplantation for alcohol-associated liver disease. Liver Transpl 2023; 29:259-267. [PMID: 37160081 DOI: 10.1002/lt.26544] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 06/13/2022] [Accepted: 06/14/2022] [Indexed: 12/13/2022]
Abstract
Although sex and racial disparities for liver transplantation (LT) are known, it is unclear if disparities exist for patients with alcohol-associated liver disease (ALD). We aimed to compare sex and racial/ethnic differences in mortality, LT listing, and LT rates in patients with and without ALD. We analyzed patients who were listed for LT and/or died of end-stage liver disease (ESLD) between 2014 and 2018 using the United Network for Organ Sharing Standard Transplant Analysis and Research and Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research databases, respectively. Patients with ALD were compared with non-ALD patients. Our primary outcome was the ratio of listings for LT to deaths from ESLD-listing-to-death ratio (LDR)-a previously derived metric to assess access to the waiting list. Differences between sex and race/ethnicity were analyzed with chi-square tests and multivariable linear regression. There were 65,588 deaths and 16,133 listings for ALD compared with 75,020 deaths and 40,194 listings for non-ALD. LDR was lower for ALD (0.25 vs. 0.54; p < 0.001). Black patients had the lowest LDR in both ALD and non-ALD (0.13 and 0.39 for Black patients vs. 0.26 and 0.54 for White patients; p < 0.001). Women with ALD had a lower LDR (0.21 vs. 0.26; p < 0.001), whereas women without ALD had higher LDR than men (0.69 vs. 0.47; p < 0.001). There were significant negative interactions between women and ALD in LDR and the transplant-to-death ratio. Multivariable analysis and a sensitivity analysis, with more liberal definitions of ALD and non-ALD, confirmed these findings. Patients with ALD have lower access to LT. Among those with ALD, female and Black patients have the lowest access. New initiatives are needed to eliminate these inequities.
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Affiliation(s)
- Alyson Kaplan
- Division of Gastroenterology and Hepatology , Weill Cornell Medicine , New York , New York , USA
| | - Nabeel Wahid
- Division of Gastroenterology and Hepatology , Weill Cornell Medicine , New York , New York , USA
| | - Brett E Fortune
- Division of Gastroenterology and Hepatology , Weill Cornell Medicine , New York , New York , USA.,Center for Liver Disease and Transplantation , New York , New York , USA
| | - Elizabeth Verna
- Division of Digestive and Liver Disease , Columbia University Irving Medical Center , New York , New York , USA
| | - Karim Halazun
- Center for Liver Disease and Transplantation , New York , New York , USA.,Liver Transplant and Hepatobiliary Surgery , Weill Cornell Medical College , New York , New York , USA
| | - Benjamin Samstein
- Center for Liver Disease and Transplantation , New York , New York , USA.,Liver Transplant and Hepatobiliary Surgery , Weill Cornell Medical College , New York , New York , USA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology , Weill Cornell Medicine , New York , New York , USA.,Center for Liver Disease and Transplantation , New York , New York , USA
| | - Russell Rosenblatt
- Division of Gastroenterology and Hepatology , Weill Cornell Medicine , New York , New York , USA.,Center for Liver Disease and Transplantation , New York , New York , USA
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16
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Chauhan M, Zhang T, Thuluvath PJ. Gender Differences in Liver Transplantation Outcomes in Polycystic Liver Disease. Dig Dis Sci 2022; 67:3445-3454. [PMID: 34191186 DOI: 10.1007/s10620-021-07125-9] [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: 03/08/2021] [Accepted: 06/16/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND In this study, our objective was to determine gender differences in the outcomes of patients with PLD undergoing liver (LT) or liver/kidney transplantation (SLK). METHODS We analyzed the UNOS datasets of all adults who had transplanted for PLD between 1988 and 2018. RESULTS During the study period, 663 LT/SLK (51% LT only and 49% SLK) were done for PLD patients and of these 500 (75%) were in women. Women were younger (52.8 vs. 56.7 years, p < 0.001), had lower MELD at transplant (16.6 vs. 19.4, p < 0.001), had higher serum albumin (3.7 vs. 3.5, p < 0.001), and had a lower CTP class (p < 0.008). During the follow-up, 18% (n = 89) women and 29% (n = 47) men died (p = 0.002). Kaplan-Meier (KM) survival estimates showed similar survival rate for patients who had LT and SLK (p = 0.459), but survival rate was significantly higher for women compared to men (p < 0.001). Multivariable analysis showed that female gender (aHR 0.54, 95% CI 0.33-0.90) was associated with a lower mortality. Moreover, Karnofsky Performance Status was excellent for 70% of women and 55% of men (p = 0.03) after LT. Women had better survival whether they received liver or SLK. The era of transplant, whether they were transplanted with MELD exception points or whether they were on dialysis at the time of transplant, did not have an effect on the gender differences in outcomes. CONCLUSIONS Women had 46% lower risk of mortality after adjusting for other covariates compared to men after LT/SLK for PLD.
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Affiliation(s)
- Mahak Chauhan
- Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, MD, USA
| | - Talan Zhang
- Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, MD, USA
| | - Paul J Thuluvath
- Institute of Digestive Health and Liver Diseases, Mercy Medical Center, Baltimore, MD, USA. .,Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
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17
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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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18
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Brown R, Goulder P, Matthews PC. Sexual Dimorphism in Chronic Hepatitis B Virus (HBV) Infection: Evidence to Inform Elimination Efforts. Wellcome Open Res 2022; 7:32. [PMID: 36212217 PMCID: PMC9520633 DOI: 10.12688/wellcomeopenres.17601.3] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/29/2022] [Indexed: 11/20/2022] Open
Abstract
Sexual dimorphism in infectious diseases refers to the different infection susceptibilities and outcomes between males and females, and has been described for many pathogens, including hepatitis B virus (HBV). HBV is a substantial global health problem, with close to 300 million people chronically infected, and accounting for a million deaths each year, with an urgent need for enhanced interventions to support progress towards elimination goals. Sexual dimorphism has a strong influence in HBV infection, with males more likely to be exposed, to develop chronic infection, and to suffer from complications including cirrhosis and hepatocellular carcinoma (HCC) compared to females. Different outcomes are driven by differential immune responses, sexual dimorphism of the liver, and androgen response elements in the HBV genome. The impact of sex may also vary with age, with changes at puberty and influences of menarche, pregnancy and menopause in females. In addition, gender has complex influences on education, beliefs, behaviour and access to / engagement with healthcare services, which may contribute to differences in diagnosis and treatment. Interplay between these complex factors, alongside other attributes of host, virus and the environment, accounts for different outcomes of infection. However, gaps remain in our understanding of sexual dimorphism in HBV, and little effort has previously been made to harness this knowledge for translational gains. In this review, we assimilate human and animal data to consider the mechanism, outcomes and impact of sexual dimorphism, and consider how these insights can be used to inform advances in surveillance, treatment and prevention for HBV infection.
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Affiliation(s)
- Robin Brown
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
| | - Philip Goulder
- Department of Paediatrics, University of Oxford, Oxford, Oxon, OX1 3SY, UK
| | - Philippa C. Matthews
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
- The Francis Crick Institute, London, London, NW1 1AT, UK
- Division of Infection and Immunity, University College London, London, WC1E 6BT, UK
- Department of Infectious Diseases, University College London Hospital, London, NW1 2BU, UK
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19
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Brown R, Goulder P, Matthews PC. Sexual Dimorphism in Chronic Hepatitis B Virus (HBV) Infection: Evidence to Inform Elimination Efforts. Wellcome Open Res 2022; 7:32. [PMID: 36212217 PMCID: PMC9520633 DOI: 10.12688/wellcomeopenres.17601.2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/19/2022] [Indexed: 08/27/2024] Open
Abstract
Sexual dimorphism in infectious diseases refers to the different infection susceptibilities and outcomes between males and females, and has been described for many pathogens, including hepatitis B virus (HBV). HBV is a substantial global health problem, with close to 300 million people chronically infected, and accounting for a million deaths each year, with an urgent need for enhanced interventions to support progress towards elimination goals. Sexual dimorphism has a strong influence in HBV infection, with males more likely to be exposed, to develop chronic infection, and to suffer from complications including cirrhosis and hepatocellular carcinoma (HCC) compared to females. Different outcomes are driven by differential immune responses, sexual dimorphism of the liver, and androgen response elements in the HBV genome. The impact of sex may also vary with age, with changes at puberty and influences of menarche, pregnancy and menopause in females. In addition, gender has complex influences on education, beliefs, behaviour and access to / engagement with healthcare services, which may contribute to differences in diagnosis and treatment. Interplay between these complex factors, alongside other attributes of host, virus and the environment, accounts for different outcomes of infection. However, gaps remain in our understanding of sexual dimorphism in HBV, and little effort has previously been made to harness this knowledge for translational gains. In this review, we assimilate human and animal data to consider the mechanism, outcomes and impact of sexual dimorphism, and consider how these insights can be used to inform advances in surveillance, treatment and prevention for HBV infection.
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Affiliation(s)
- Robin Brown
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
| | - Philip Goulder
- Department of Paediatrics, University of Oxford, Oxford, Oxon, OX1 3SY, UK
| | - Philippa C. Matthews
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
- The Francis Crick Institute, London, London, NW1 1AT, UK
- Division of Infection and Immunity, University College London, London, WC1E 6BT, UK
- Department of Infectious Diseases, University College London Hospital, London, NW1 2BU, UK
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20
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Brown R, Goulder P, Matthews PC. Sexual Dimorphism in Chronic Hepatitis B Virus (HBV) Infection: Evidence to Inform Elimination Efforts. Wellcome Open Res 2022; 7:32. [PMID: 36212217 PMCID: PMC9520633 DOI: 10.12688/wellcomeopenres.17601.1] [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] [Accepted: 01/20/2022] [Indexed: 09/06/2024] Open
Abstract
Sexual dimorphism in infectious diseases refers to the different infection susceptibilities and outcomes between males and females, and has been described for many pathogens, including hepatitis B virus (HBV) infection. HBV is a substantial global health problem, with close to 300 million people infected, and accounting for a million deaths each year, with an urgent need for enhanced interventions to support progress towards elimination goals. Sexual dimorphism has a strong influence in HBV infection, with males more likely to be exposed, to develop chronic infection, and to suffer from complications including cirrhosis and hepatocellular carcinoma (HCC) compared to females. Different outcomes are driven by differential immune responses, sexual dimorphism of the liver, and androgen response elements in the HBV genome. The impact of sex may also vary with age, with changes at puberty and influences of menarche, pregnancy and menopause in females. In addition, gender has complex influences on education, beliefs, behaviour and access to / engagement with healthcare services, which may contribute to differences in diagnosis and treatment. Interplay between these complex factors, alongside other attributes of host, virus and the environment, accounts for different outcomes of infection. However, gaps remain in our understanding of sexual dimorphism in HBV, and little effort has previously been made to harness this knowledge for translational gains. In this review, we assimilate human and animal data to consider the mechanism, outcomes and impact of sexual dimorphism, considering how these insights can be used to inform advances in surveillance, treatment and prevention for HBV infection.
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Affiliation(s)
- Robin Brown
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
| | - Philip Goulder
- Department of Paediatrics, University of Oxford, Oxford, Oxon, OX1 3SY, UK
| | - Philippa C. Matthews
- Harris Manchester College, University of Oxford, Oxford, Oxon, OX1 3TD, UK
- The Francis Crick Institute, London, London, NW1 1AT, UK
- Division of Infection and Immunity, University College London, London, WC1E 6BT, UK
- Department of Infectious Diseases, University College London Hospital, London, NW1 2BU, UK
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21
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Chrysavgis L, Giannakodimos I, Diamantopoulou P, Cholongitas E. Non-alcoholic fatty liver disease and hepatocellular carcinoma: Clinical challenges of an intriguing link. World J Gastroenterol 2022; 28:310-331. [PMID: 35110952 PMCID: PMC8771615 DOI: 10.3748/wjg.v28.i3.310] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 10/19/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common liver disorder worldwide mainly attributed to the epidemic spread of obesity and type 2 diabetes mellitus. Although it is considered a benign disease, NAFLD can progress to non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). Most data regarding the epidemiology of NAFLD-related HCC are derived from cohort and population studies and show that its incidence is increasing as well as it is likely to emerge as the leading indication for liver transplantation, especially in the Western World. Although cirrhosis constitutes the main risk factor for HCC development, in patients with NAFLD, HCC can arise in the absence of cirrhosis, indicating specific carcinogenic molecular pathways. Since NAFLD as an underlying liver disease for HCC is often underdiagnosed due to lack of sufficient surveillance in this population, NAFLD-HCC patients are at advanced HCC stage at the time of diagnosis making the management of those patients clinically challenging and affecting their prognostic outcomes. In this current review, we summarize the latest literature on the epidemiology, other than liver cirrhosis-pathogenesis, risk factors and prognosis of NAFLD-HCC patients. Finally, we emphasize the prevention of the development of NAFLD-associated HCC and we provide some insight into the open questions and issues regarding the appropriate surveillance policies for those patients.
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Affiliation(s)
- Lampros Chrysavgis
- Department of Experimental Physiology, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Ilias Giannakodimos
- First Department of Internal Medicine, "Laiko" General Hospital of Athens, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Panagiota Diamantopoulou
- First Department of Internal Medicine, "Laiko" General Hospital of Athens, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, "Laiko" General Hospital of Athens, National and Kapodistrian University of Athens, Athens 11527, Greece
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22
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Kim W. Hepatocellular Carcinoma. SEX/GENDER-SPECIFIC MEDICINE IN THE GASTROINTESTINAL DISEASES 2022:229-234. [DOI: 10.1007/978-981-19-0120-1_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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23
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Mathur K, Mazhar A, Patel M, Dakhoul L, Burney H, Liu H, Nephew L, Chalasani N, deLemos A, Gawrieh S. Changing Trends of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the Era of Directly-Acting Antiviral Agents. Clin Transl Gastroenterol 2021; 12:e00420. [PMID: 34730559 PMCID: PMC8568358 DOI: 10.14309/ctg.0000000000000420] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/22/2021] [Indexed: 02/08/2023] Open
Abstract
INTRODUCTION The impact of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) on burden of cirrhotic and noncirrhotic hepatocellular carcinoma (HCC) has not been examined. We assessed recent trends in liver disease etiologies of HCC and proportion of noncirrhotic HCC since DAAs introduction. METHODS Clinical characteristics including presence or absence of underlying cirrhosis were collected from 2,623 patients diagnosed with HCC between 2009 and 2019 at 2 large US centers. Logistic regression was performed to investigate the annual trends of HCC due to different liver diseases and proportions of noncirrhotic cases. RESULTS In the DAA era (2014-2019), annual decline in HCV-HCC (odds ratio [OR] = 0.93, 95% confidence interval [CI] 0.88-0.99, P = 0.019), without change in trends of other liver diseases-related HCC, was observed. Annual increase in noncirrhotic HCC (OR 1.13, 95% CI 1.03-1.23, P = 0.009) and decline in cirrhotic HCC (OR 0.89, 95% CI 0.81-0.97, P = 0.009) along with similar trends for HCV-HCC-increase in noncirrhotic cases (OR 1.35, 95% CI 1.08-1.69, P = 0.009) and decrease in cirrhotic cases (OR 0.92, 95% CI 0.86-0.98, P = 0.012)-were observed during the DAA era. Compared with the pre-DAA era, HCC resection rate increased (10.7% vs 14.0%, P = 0.013) whereas liver transplantation rate decreased (15.1% vs 12.0%, P = 0.023) in the DAA era. DISCUSSION Since introduction of DAAs, proportions of cirrhotic HCC have decreased, whereas proportions of noncirrhotic HCC have increased. These new trends were associated with change in utilization of liver resection and transplantation for HCC. The impact of changing patterns of DAA use on these trends will require further study.
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Affiliation(s)
- Karan Mathur
- Division of Gastroenterology & Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA;
| | - Areej Mazhar
- Department of Medicine, Atrium Health, Charlotte, North Carolina, USA;
| | - Milin Patel
- Department of Medicine, Atrium Health, Charlotte, North Carolina, USA;
| | - Lara Dakhoul
- Department of Gastroenterology & Hepatology, Roudebush VA Medical Center, Indianapolis, Indiana, USA;
| | - Heather Burney
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.
| | - Hao Liu
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.
| | - Lauren Nephew
- Division of Gastroenterology & Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA;
| | - Naga Chalasani
- Division of Gastroenterology & Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA;
| | - Andrew deLemos
- Department of Medicine, Atrium Health, Charlotte, North Carolina, USA;
| | - Samer Gawrieh
- Division of Gastroenterology & Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA;
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24
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Talens M, Tumas N, Lazarus JV, Benach J, Pericàs JM. What Do We Know about Inequalities in NAFLD Distribution and Outcomes? A Scoping Review. J Clin Med 2021; 10:5019. [PMID: 34768539 PMCID: PMC8584385 DOI: 10.3390/jcm10215019] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 10/17/2021] [Accepted: 10/25/2021] [Indexed: 02/06/2023] Open
Abstract
With prevalence high and rising given the close relationship with obesity and diabetes mellitus, non-alcoholic fatty liver disease (NAFLD) is progressively becoming the most common chronic liver condition worldwide. However, little is known about the health inequalities in NAFLD distribution and outcomes. This review aims to analyze health inequalities in NAFLD distribution globally and to assess the health disparities in NAFLD-related outcomes. We conducted a scoping review of global health inequalities in NAFLD distribution and outcomes according to gender/sex, ethnicity/race, and socioeconomic position from PubMed's inception to May 2021. Ultimately, 20 articles were included in the review, most (75%) of them carried out in the United States. Males were found to have a higher NAFLD prevalence (three articles), while available evidence suggests that women have an overall higher burden of advanced liver disease and complications (four articles), whereas they are less likely to be liver-transplanted once cirrhosis develops (one article). In the US, the Hispanic population had the highest NAFLD prevalence and poorer outcomes (seven articles), whereas Whites had fewer complications than other ethnicities (two articles). Patients with low socioeconomic status had higher NAFLD prevalence (four articles) and a higher likelihood of progression and complications (five articles). In conclusion, globally there is a lack of studies analyzing NAFLD prevalence and outcomes according to various axes of inequality through joint intersectional appraisals, and most studies included in our review were based on the US population. Available evidence suggests that NAFLD distribution and outcomes show large inequalities by social group. Further research on this issue is warranted.
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Affiliation(s)
- Mar Talens
- Research Group on Health Inequalities, Environment, and Employment Conditions, Department of Social and Political Science, Pompeu Fabra University, 08005 Barcelona, Spain; (M.T.); (N.T.); (J.B.)
| | - Natalia Tumas
- Research Group on Health Inequalities, Environment, and Employment Conditions, Department of Social and Political Science, Pompeu Fabra University, 08005 Barcelona, Spain; (M.T.); (N.T.); (J.B.)
- Public Policy Center (UPF-BSM), Johns Hopkins University-Pompeu Fabra University, 08005 Barcelona, Spain
- Centro de Investigaciones y Estudios sobre Cultura y Sociedad, Consejo Nacional de Investigaciones Científicas y Técnicas y Universidad Nacional de Córdoba, Córdoba 5016, Argentina
| | - Jeffrey V. Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain;
| | - Joan Benach
- Research Group on Health Inequalities, Environment, and Employment Conditions, Department of Social and Political Science, Pompeu Fabra University, 08005 Barcelona, Spain; (M.T.); (N.T.); (J.B.)
- Public Policy Center (UPF-BSM), Johns Hopkins University-Pompeu Fabra University, 08005 Barcelona, Spain
- Transdisciplinary Research Group on Socioecological Transitions (GinTrans2), Universidad Autónoma de Madrid, 28049 Madrid, Spain
| | - Juan M. Pericàs
- Research Group on Health Inequalities, Environment, and Employment Conditions, Department of Social and Political Science, Pompeu Fabra University, 08005 Barcelona, Spain; (M.T.); (N.T.); (J.B.)
- Public Policy Center (UPF-BSM), Johns Hopkins University-Pompeu Fabra University, 08005 Barcelona, Spain
- Liver Unit, Internal Medicine Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute for Research, 08035 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029 Madrid, Spain
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25
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Burra P, Bizzaro D, Gonta A, Shalaby S, Gambato M, Morelli MC, Trapani S, Floreani A, Marra F, Brunetto MR, Taliani G, Villa E. Clinical impact of sexual dimorphism in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Liver Int 2021; 41:1713-1733. [PMID: 33982400 DOI: 10.1111/liv.14943] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 05/05/2021] [Accepted: 05/06/2021] [Indexed: 12/11/2022]
Abstract
NAFLD/NASH is a sex-dimorphic disease, with a general higher prevalence in men. Women are at reduced risk of NAFLD compared to men in fertile age, whereas after menopause women have a comparable prevalence of NAFLD as men. Indeed, sexual category, sex hormones and gender habits interact with numerous NAFLD factors including cytokines, stress and environmental factors and alter the risk profiles and phenotypes of NAFLD. In the present review, we summarized the last findings about the influence of sex on epidemiology, pathogenesis, progression in cirrhosis, indication for liver transplantation and alternative therapies, including lifestyle modification and pharmacological strategies. We are confident that an appropriate consideration of sex, age, hormonal status and sociocultural gender differences will lead to a better understanding of sex differences in NAFLD risk, therapeutic targets and treatment responses and will aid in achieving sex-specific personalized therapies.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Debora Bizzaro
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Anna Gonta
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Sarah Shalaby
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy
| | | | - Silvia Trapani
- Italian National Transplant Center, Italian National Institute of Health, Rome, Italy
| | - Annarosa Floreani
- University of Padova, Padua, Italy.,IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Fabio Marra
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Maurizia Rossana Brunetto
- Hepatology and Liver Physiopathology Laboratory and Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Gloria Taliani
- Infectious Diseases Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Erica Villa
- Gastroenterology Unit, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, Italy
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Ratana-Amornpin S, Vilaichone RK, Miftahussurur M, Aumpan N, Kaewkarnjanarat K, Nun-Anan P, Chonprasertsuk S, Siramolpiwat S, Bhanthumkomol P, Pornthisarn B, Uchida T, Mahachai V. Clinical Features and Overall Survival of Females with Hepatocellular Carcinoma: A Retrospective Study and Review of the Literature in the Association of Southeast Asian Nations. Int J Womens Health 2021; 13:717-725. [PMID: 34326670 PMCID: PMC8314927 DOI: 10.2147/ijwh.s311419] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 06/23/2021] [Indexed: 12/24/2022] Open
Abstract
Introduction Hepatocellular carcinoma (HCC) causes more than 200,000 women deaths annually. This study aimed to investigate the clinical features, provide prognostic factors for female patients with HCC, and performed a literature review on them in the Association of Southeast Asian Nations (ASEAN). Materials and Methods We conducted a retrospective cohort study of female patients with HCC at Thammasat University Hospital, Thailand between January 2009 and January 2019. Furthermore, important aspects of female patients with HCC in the ASEAN published in PubMed and Scopus up to October 2020 were extensively reviewed. Results A total of 187 female patients with HCC were included (mean age 65.7±11.9 years). Elderly females were diagnosed with HCC at a more advanced stage than younger individuals (37.0% vs 23.2%, p=0.049, OR 1.94, 95% CI 1.00-3.78) and the younger group had a significantly higher overall 2-year survival rate than the elderly group (65.0% vs 45.5%, p=0.03, OR 2.23, 95% CI 1.09-4.57). Abdominal pain (HR 9.89, 95% CI 2.85-34.38, p<0.001), ascites at presentation (HR 2.77, 95% CI 1.11-6.92, p=0.03), ruptured hepatoma (HR 14.68, 95% CI 12.60-83.09, p=0.002), advanced-stage HCC (HR 9.74, 95% CI 1.89-50.26; p=0.007), and serum hypoalbuminemia (HR 4.67, 95% CI 1.62-13.50, p=0.004) were significantly associated with poor survival rate. From the ASEAN, a total of 543 females HCC patients from 6 studies were extensively reviewed. Chronic hepatitis B infection was among the pre-existing liver disease leading to HCC in ASEAN. HCC in females of the ASEAN occurred most often at an advanced age and had a grave prognosis. Conclusion HCC affects a large number of females, especially in Thailand and the ASEAN, is diagnosed at an advanced stage and had a grave prognosis. Abdominal pain, ascites, ruptured HCC, advanced-stage HCC, and serum hypoalbuminemia are associated with poor prognosis. Early detection of HCC and prompt treatment in patients at risk could result in better survival outcomes.
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Affiliation(s)
- Sarita Ratana-Amornpin
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand
| | - Ratha-Korn Vilaichone
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand.,Department of Medicine, Chulabhorn International College of Medicine (CICM) at Thammasat University, Pathumthani, Thailand.,Gastroentero-Hepatology Section, Internal Medicine Department, Universitas Airlangga, Surabaya, Indonesia
| | - Muhammad Miftahussurur
- Gastroentero-Hepatology Section, Internal Medicine Department, Universitas Airlangga, Surabaya, Indonesia
| | - Natsuda Aumpan
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand
| | - Kittipong Kaewkarnjanarat
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand
| | - Pongjarat Nun-Anan
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand
| | - Soonthorn Chonprasertsuk
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand
| | - Sith Siramolpiwat
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand.,Department of Medicine, Chulabhorn International College of Medicine (CICM) at Thammasat University, Pathumthani, Thailand
| | - Patommatat Bhanthumkomol
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand
| | - Bubpha Pornthisarn
- Center of Excellence in Digestive Diseases and Gastroenterology Unit, Department of Medicine, Thammasat University Hospital, Pathumthani, Thailand
| | - Tomohisa Uchida
- Department of Molecular Pathology, Oita University Faculty of Medicine, Yufu, Japan
| | - Varocha Mahachai
- Department of Medicine, Chulabhorn International College of Medicine (CICM) at Thammasat University, Pathumthani, Thailand.,Gastrointestinal and Liver Center, Bangkok Medical Center, Bangkok, Thailand
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27
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Guo A, Pomenti S, Wattacheril J. Health Disparities in Screening, Diagnosis, and Treatment of Hepatocellular Carcinoma. Clin Liver Dis (Hoboken) 2021; 17:353-358. [PMID: 34136141 PMCID: PMC8177833 DOI: 10.1002/cld.1057] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 10/03/2020] [Accepted: 10/11/2020] [Indexed: 02/04/2023] Open
Affiliation(s)
- Averill Guo
- Department of MedicineColumbia University Irving Medical Center
| | - Sydney Pomenti
- Department of MedicineColumbia University Irving Medical Center
| | - Julia Wattacheril
- Division of Digestive and Liver DiseasesCenter for Liver Disease and TransplantationNew York Presbyterian Hospital
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28
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Zhang HY, Liang HX, Wu SH, Jiang HQ, Wang Q, Yu ZJ. Overexpressed Tumor Suppressor Exosomal miR-15a-5p in Cancer Cells Inhibits PD1 Expression in CD8+T Cells and Suppresses the Hepatocellular Carcinoma Progression. Front Oncol 2021; 11:622263. [PMID: 33816255 PMCID: PMC8018596 DOI: 10.3389/fonc.2021.622263] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 02/01/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common primary liver tumor, and the main reason is the unclear pathogenesis of HCC, which leads to a high fatality rate of HCC. Therefore, it is of great clinical significance to explore the molecular mechanism of HCC and find a targeted therapeutic approach from the molecular level. MATERIALS AND METHODS MicroRNA-15a-5p (miR-15a-5p) expression level was measured by bioinformatics and qRT-PCR. Luciferase assay and RIP assays were used to verify the relationship between programmed cell death protein 1 (PD1) PD 1 with miR-15a-5p. Exosomes were identified using TEM, Zetasizer Nano ZS, and western blot. Edu, Transwell, and scratch assay were performed to explore the role of miR-15a-5p or exo-miR-15a-5p on HepG2 cells progression. RESULTS MicroRNA-15a-5p (miR-15a-5p) was decreased in HCC tissues and cell lines, which indicated a poor prognosis. Overexpression of miR-15a-5p inhibited viability, proliferation, migration and invasion of HepG2 cells. Then, we isolated exosomes from cancer cells, and found that miR-15a-5p was packaged into exosomes from cancer cells. Furthermore, exo-miR-15a-5p was secreted into CD8+ T cells, then directly inhibited PD1 expression via targeted binding. Then, we co-cultured CD8+ T cells transfected with PD1 with HepG2 transfected with miR-15a-5p, PD1 remitted the inhibitory role of miR-15a-5p on HCC progression. CONCLUSION Together, present study revealed exo-miR-15a-5p from cancer cells inhibited PD1 expression in CD8+ T cells, which suppressed the development of HCC.
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Affiliation(s)
| | | | | | | | | | - Zu-Jiang Yu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Response to Braillon. Am J Gastroenterol 2021; 116:617-618. [PMID: 33538421 DOI: 10.14309/ajg.0000000000001180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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The Current View of Nonalcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma. Cancers (Basel) 2021; 13:cancers13030516. [PMID: 33572797 PMCID: PMC7866271 DOI: 10.3390/cancers13030516] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/19/2021] [Accepted: 01/26/2021] [Indexed: 02/08/2023] Open
Abstract
Simple Summary The incidence of nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) is increasing. However, an effective screening or surveillance method is not established. Recently, the NAFLD/nonalcoholic steatohepatitis (NASH) guidelines of Japan were revised to incorporate new strategies and evidence for the management and surveillance of NAFLD/NASH. Advanced fibrosis and lifestyle-related and metabolic comorbidities, especially obesity and diabetes mellitus, are associated with HCC development. At the first screening, serum markers of hepatic fibrosis (hyaluronic acid, type IV collagen 7S, and mac-2 binding protein), or the fibrosis (FIB)-4 index or the nonalcoholic fatty liver disease fibrosis score (NFS), or a platelet count should be evaluated. When liver fibrosis is indicated, consultation with a gastroenterology specialist should be considered for the second screening. The risk of HCC should be stratified using the FIB-4 index or the NFS. Liver stiffness should be measured using vibration-controlled transient elastography in those at intermediate or high risk. Blood tests and imaging should be performed every 6–12 months in patients with advanced fibrosis for HCC surveillance. We review here what is known about NAFLD-HCC and provide perspectives for future research. Abstract Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and can develop into hepatocellular carcinoma (HCC). The incidence of NAFLD-related HCC, which is accompanied by life-threatening complications, is increasing. Advanced fibrosis and lifestyle-related and metabolic comorbidities, especially obesity and diabetes mellitus, are associated with HCC development. However, HCC is also observed in the non-cirrhotic liver. Often, diagnosis is delayed until the tumor is relatively large and the disease is advanced; an effective screening or surveillance method is urgently required. Recently, the NAFLD/nonalcoholic steatohepatitis (NASH) guidelines of Japan were revised to incorporate new strategies and evidence for the management and surveillance of NAFLD/NASH. Fibrosis must be tested for noninvasively, and the risk of carcinogenesis must be stratified. The treatment of lifestyle-related diseases is expected to reduce the incidence of NAFLD and prevent liver carcinogenesis.
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