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1
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Wang J, Qiu K, Zhou S, Gan Y, Jiang K, Wang D, Wang H. Risk factors for hepatocellular carcinoma: an umbrella review of systematic review and meta-analysis. Ann Med 2025; 57:2455539. [PMID: 39834076 PMCID: PMC11753015 DOI: 10.1080/07853890.2025.2455539] [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: 10/21/2024] [Revised: 01/09/2025] [Accepted: 01/10/2025] [Indexed: 01/22/2025] Open
Abstract
BACKGROUND Numerous meta-analyses have identified various risk factors for hepatocellular carcinoma (HCC), prompting a comprehensive study to synthesize evidence quality and strength. METHODS This umbrella review of meta-analyses was conducted throughout PubMed, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews. Evidence strength was evaluated according to the evidence categories criteria. RESULTS We identified 101 risk factors throughout 175 meta-analyses. 31 risk factors were classified as evidence levels of class I, II, or III. HBV and HCV infections increase HCC risk by 12.5-fold and 11.2-fold, respectively. These risks are moderated by antiviral treatments and virological responses but are exacerbated by higher HBsAg levels, anti-HBc positivity, and co-infection. Smoking, obesity, non-alcoholic fatty liver disease, diabetes, low platelet, elevated liver enzymes and liver fluke infection increase HCC risk, while coffee consumption, a healthy diet, and bariatric surgery lower it. Medications like metformin, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), aspirin, statins, and selective serotonin reuptake inhibitors reduce HCC risk, while acid suppressive agents, particularly proton pump inhibitors, elevate it. Blood type O reduces the risk of HCC, while male gender and older age increase the risk. CONCLUSIONS HBV and HCV are major HCC risk factors, with risk mitigation through antiviral treatments. Lifestyle habits such as smoking and alcohol use significantly increase HCC risk, highlighting the importance of cessation. Certain drugs like aspirin, statins, GLP-1 RAs, and metformin may reduce HCC occurrence, but further research is needed to confirm these effects.
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Affiliation(s)
- Jie Wang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Kaijie Qiu
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Songsheng Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Yichao Gan
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Keting Jiang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Donghuan Wang
- Operations Department, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
| | - Haibiao Wang
- Department of Hepatobiliary and Pancreatic Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China
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2
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Tuo JY, Shen QM, Li ZY, Yang DN, Zou YX, Tan YT, Li HL, Xiang YB. Adherence to dietary guidelines and liver cancer risk: Results from two prospective cohort studies. Clin Nutr ESPEN 2025; 67:599-611. [PMID: 40187735 DOI: 10.1016/j.clnesp.2025.03.173] [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: 01/25/2025] [Revised: 03/20/2025] [Accepted: 03/24/2025] [Indexed: 04/07/2025]
Abstract
BACKGROUND AND AIMS Although dietary factors have been extensively investigated as potential risk factors for liver cancer, the evidence is inconclusive. Our study systematically assessed the associations between ten dietary guidelines compliance scores and liver cancer risk among adult people, and found out the dietary patterns for liver cancer prevention. METHODS Participants of 59,844 men and 72,680 women, aged 40-74 years and living in urban Shanghai, were included in two prospective cohort studies conducted between 2002-2006 and 1996-2000, respectively. Dietary intakes were assessed during baseline in-person interviews using validated food-frequency questionnaires, and dietary guideline compliance scores were calculated by adjusting for total energy intake and adapting existing dietary recommendations. Hazards ratios (HRs) with 95 % confidence intervals (CIs) were evaluated by both tertile categories and per standard deviation (SD) increment using Cox proportional hazard regression models to assess the associations between ten dietary guideline compliance scores and liver cancer risk. RESULTS In the two cohorts, 431 male and 256 female incident liver cancer cases were identified during a mean follow-up of 11.90 and 17.44 years, respectively. There were no statistically significant associations between these ten dietary guidelines and male liver cancer risk (P > 0.05). In contrast, only the modified reversed Empirical Dietary Inflammation Pattern (rEDIP) tended to be associated with the low risk of female liver cancer (HR T3 vs. T1 = 0.67, 95 % CI: 0.48-0.92, Ptrend = 0.016, HR per SD = 0.94, 95 % CI: 0.85-1.03). The inverse associations appeared stronger between rEDIP and liver cancer risk at younger ages (<55 years) in women (HR per SD = 0.91, 95 % CI: 0.84-0.99) compared to the older women (≥55 years). There were suggestive but non-significant inverse associations between the modified Diabetes Risk Reduction Diet (mDRRD) (men: HR per SD = 0.92, 95 % CI: 0.84-1.02; women: HR per SD = 0.97, 95 % CI: 0.84-1.02) and the modified World Cancer Research Fund/American Institute for Cancer Research (mWCRF/AICR) (men: HR per SD = 0.93, 95 % CI: 0.84-1.02; women: HR per SD = 0.91, 95 % CI: 0.80-1.03) and liver cancer incidence. The associations of mDRRD (HR per SD = 0.82, 95 % CI: 0.75-0.98) and mWCRF/AICR (HR per SD = 0.83, 95 % CI: 0.74-0.99) on liver cancer risk were significant in men who ever smoked. CONCLUSIONS Our findings confirm that greater adherence to some healthy dietary patterns (i.e. rEDIP, mDRRD and mWCRF/AICR) is inversely associated with liver cancer risk, especially in certain populations. Future studies are required to confirm these findings and elucidate potential mechanisms.
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Affiliation(s)
- Jia-Yi Tuo
- State Key Laboratory of Systems Medicine for Cancer & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, PR China
| | - Qiu-Ming Shen
- State Key Laboratory of Systems Medicine for Cancer & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
| | - Zhuo-Ying Li
- State Key Laboratory of Systems Medicine for Cancer & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
| | - Dan-Ni Yang
- State Key Laboratory of Systems Medicine for Cancer & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, PR China
| | - Yi-Xin Zou
- State Key Laboratory of Systems Medicine for Cancer & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; School of Public Health, Fudan University, Shanghai, PR China
| | - Yu-Ting Tan
- State Key Laboratory of Systems Medicine for Cancer & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
| | - Hong-Lan Li
- State Key Laboratory of Systems Medicine for Cancer & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
| | - Yong-Bing Xiang
- State Key Laboratory of Systems Medicine for Cancer & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China; School of Public Health, Shanghai Jiaotong University School of Medicine, Shanghai, PR China; School of Public Health, Fudan University, Shanghai, PR China.
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3
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Argenziano ME, Kim MN, Montori M, Di Bucchianico A, Balducci D, Ahn SH, Svegliati Baroni G. Epidemiology, pathophysiology and clinical aspects of Hepatocellular Carcinoma in MAFLD patients. Hepatol Int 2024; 18:922-940. [PMID: 39012579 DOI: 10.1007/s12072-024-10692-4] [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: 02/03/2024] [Accepted: 04/24/2024] [Indexed: 07/17/2024]
Abstract
Hepatocellular carcinoma (HCC) is undergoing a transformative shift, with metabolic-associated fatty liver disease (MAFLD) emerging as a dominant etiology. Diagnostic criteria for MAFLD involve hepatic steatosis and metabolic dysregulation. Globally, MAFLD prevalence stands at 38.77%, significantly linked to the escalating rates of obesity. Epidemiological data indicate a dynamic shift in the major etiologies of hepatocellular carcinoma (HCC), transitioning from viral to metabolic liver diseases. Besides the degree of liver fibrosis, several modifiable lifestyle risk factors, such as type 2 diabetes, obesity, alcohol use, smoking, and HBV, HCV infection contribute to the pathogenesis of HCC. Moreover gut microbiota and genetic variants may contribute to HCC development.The pathophysiological link between MAFLD and HCC involves metabolic dysregulation, impairing glucose and lipid metabolism, inflammation and oxidative stress. Silent presentation poses challenges in early MAFLD-HCC diagnosis. Imaging, biopsy, and AI-assisted techniques aid diagnosis, while HCC surveillance in non-cirrhotic MAFLD patients remains debated.ITA.LI.CA. group proposes a survival-based algorithm for treatment based on Barcelona clinic liver cancer (BCLC) algorithm. Liver resection, transplantation, ablation, and locoregional therapies are applied based on the disease stage. Systemic treatments is promising, with initial immunotherapy results indicating a less favorable response in MAFLD-related HCC.Adopting lifestyle interventions and chemopreventive measures with medications, including aspirin, metformin, and statins, constitute promising approaches for the primary prevention of HCC.Prognosis is influenced by multiple factors, with MAFLD-HCC associated with prolonged survival. Emerging diagnostic biomarkers and epigenomic markers, show promising results for early HCC detection in the MAFLD population.
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Affiliation(s)
- Maria Eva Argenziano
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
- Faculty of Medicine and Health Sciences, University of Ghent, Ghent, Belgium
| | - Mi Na Kim
- Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Michele Montori
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
| | - Alessandro Di Bucchianico
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
| | - Daniele Balducci
- Clinic of Gastroenterology, Hepatology, and Emergency Digestive Endoscopy, Università Politecnica Delle Marche, 60126,, Ancona, Italy
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
| | - Gianluca Svegliati Baroni
- Liver Disease and Transplant Unit, Obesity Center, Azienda Ospedaliero-Universitaria Delle Marche, Polytechnic University of Marche, Ancona, Italy
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4
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Gedallovich SM, Kwo PY. Reply to correspondence on "Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy". Clin Mol Hepatol 2024; 30:1050-1052. [PMID: 38993076 PMCID: PMC11540377 DOI: 10.3350/cmh.2024.0546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 07/11/2024] [Indexed: 07/13/2024] Open
Affiliation(s)
- Seren M. Gedallovich
- Division of Gastroenterology and Hepatology, Stanford University Medical School, Stanford, CA, USA
| | - Paul Y. Kwo
- Division of Gastroenterology and Hepatology, Stanford University Medical School, Stanford, CA, USA
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5
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Singal AG, Llovet JM, Yarchoan M, Mehta N, Heimbach JK, Dawson LA, Jou JH, Kulik LM, Agopian VG, Marrero JA, Mendiratta-Lala M, Brown DB, Rilling WS, Goyal L, Wei AC, Taddei TH. AASLD Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma. Hepatology 2023; 78:1922-1965. [PMID: 37199193 PMCID: PMC10663390 DOI: 10.1097/hep.0000000000000466] [Citation(s) in RCA: 597] [Impact Index Per Article: 298.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2023] [Accepted: 05/01/2023] [Indexed: 05/19/2023]
Affiliation(s)
- Amit G. Singal
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Josep M. Llovet
- Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA
- Translational Research in Hepatic Oncology, Liver Unit, August Pi i Sunyer Biomedical Research Institute, Hospital Clinic, University of Barcelona, Catalonia, Spain
- Institució Catalana de Recerca i Estudis Avançats, Barcelona, Catalonia, Spain
| | - Mark Yarchoan
- Department of Medical Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA
| | - Neil Mehta
- University of California, San Francisco, San Francisco, California, USA
| | | | - Laura A. Dawson
- Radiation Medicine Program/University Health Network, Department of Radiation Oncology, University of Toronto, Toronto, Canada
| | - Janice H. Jou
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon, USA
| | - Laura M. Kulik
- Northwestern Medical Faculty Foundation, Chicago, Illinois, USA
| | - Vatche G. Agopian
- The Dumont–University of California, Los Angeles, Transplant Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA
| | - Jorge A. Marrero
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Mishal Mendiratta-Lala
- Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan, USA
| | - Daniel B. Brown
- Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - William S. Rilling
- Division of Interventional Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
| | - Lipika Goyal
- Department of Medicine, Stanford School of Medicine, Palo Alto, California, USA
| | - Alice C. Wei
- Memorial Sloan Kettering Cancer Center, New York City, New York, USA
| | - Tamar H. Taddei
- Department of Medicine (Digestive Diseases), Yale School of Medicine, New Haven, CT, USA
- Veterans Affairs Connecticut Healthcare System, West Haven, CT, USA
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6
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Cernea S, Onișor D. Screening and interventions to prevent nonalcoholic fatty liver disease/nonalcoholic steatohepatitis-associated hepatocellular carcinoma. World J Gastroenterol 2023; 29:286-309. [PMID: 36687124 PMCID: PMC9846941 DOI: 10.3748/wjg.v29.i2.286] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 11/06/2022] [Accepted: 12/21/2022] [Indexed: 01/06/2023] Open
Abstract
Liver cancer is the sixth most commonly diagnosed cancer worldwide, with hepatocellular carcinoma (HCC) comprising most cases. Besides hepatitis B and C viral infections, heavy alcohol use, and nonalcoholic steatohepatitis (NASH)-associated advanced fibrosis/cirrhosis, several other risk factors for HCC have been identified (i.e. old age, obesity, insulin resistance, type 2 diabetes). These might in fact partially explain the occurrence of HCC in non-cirrhotic patients without viral infection. HCC surveillance through effective screening programs is still an unmet need for many nonalcoholic fatty liver disease (NAFLD) patients, and identification of pre-cirrhotic individuals who progress to HCC represents a substantial challenge in clinical practice at the moment. Patients with NASH-cirrhosis should undergo systematic HCC surveillance, while this might be considered in patients with advanced fibrosis based on individual risk assessment. In this context, interventions that potentially prevent NAFLD/ NASH-associated HCC are needed. This paper provided an overview of evidence related to lifestyle changes (i.e. weight loss, physical exercise, adherence to healthy dietary patterns, intake of certain dietary components, etc.) and pharmacological interventions that might play a protective role by targeting the underlying causative factors and pathogenetic mechanisms. However, well-designed prospective studies specifically dedicated to NAFLD/NASH patients are still needed to clarify the relationship with HCC risk.
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Affiliation(s)
- Simona Cernea
- Department M3/Internal Medicine I, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureş 540139, Romania
- Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş 540136, Romania
| | - Danusia Onișor
- Department ME2/Internal Medicine VII, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, Târgu Mureş 540139, Romania
- Gastroenterology Department, Mureș County Clinical Hospital, Târgu Mureș 540072, Romania
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Kubota N, Fujiwara N, Hoshida Y. Liver cancer risk-predictive molecular biomarkers specific to clinico-epidemiological contexts. Adv Cancer Res 2022; 156:1-37. [PMID: 35961696 PMCID: PMC7616039 DOI: 10.1016/bs.acr.2022.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
Hepatocellular carcinoma (HCC) risk prediction is increasingly important because of the low annual HCC incidence in patients with the rapidly emerging non-alcoholic fatty liver disease or cured HCV infection. To date, numerous clinical HCC risk biomarkers and scores have been reported in literature. However, heterogeneity in clinico-epidemiological context, e.g., liver disease etiology, patient race/ethnicity, regional environmental exposure, and lifestyle-related factors, obscure their real clinical utility and applicability. Proper characterization of these factors will help refine HCC risk prediction according to certain clinical context/scenarios and contribute to improved early HCC detection. Molecular factors underlying the clinical heterogeneity encompass various features in host genetics, hepatic and systemic molecular dysregulations, and cross-organ interactions, which may serve as clinical-context-specific biomarkers and/or therapeutic targets. Toward the goal to enable individual-risk-based HCC screening by incorporating the HCC risk biomarkers/scores, their assessment in patient with well-defined clinical context/scenario is critical to gauge their real value and to maximize benefit of the tailored patient management for substantial improvement of the poor HCC prognosis.
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Affiliation(s)
- Naoto Kubota
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | - Naoto Fujiwara
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States; Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yujin Hoshida
- Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States.
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Statins Reduce Hepatocellular Carcinoma Risk in Patients with Chronic Kidney Disease and End-Stage Renal Disease: A 17-Year Longitudinal Study. Cancers (Basel) 2022; 14:cancers14030825. [PMID: 35159093 PMCID: PMC8834435 DOI: 10.3390/cancers14030825] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 01/29/2022] [Accepted: 02/04/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Statins are medicines used to treat patients with high lipid levels (hyperlipidemia). Studies have reported that patients undergoing statin therapy are at reduced risk of developing liver cancer. In this study, we compared the risk of developing liver cancer among hyperlipidemic patients with and without statin therapy in three patient groups classified by renal function: normal renal function (NRF) group, chronic kidney disease (CKD) not requiring dialysis, and dialysis-dependent end stage of real disease (ESRD). Our results showed that the risk of developing liver cancer increased progressively from NRF group to CKD and ESRD groups, but was lower for patients receiving statins treatment than non-treated patients. We also found that the statin therapy effectiveness was better in patients taking hydrophilic statins than in those taking lipophilic statins, and in patients taking statin-ezetimibe combination than in those taking statin alone, particularly in the NRF group. Ezetimibe is also an effective option of treating hyperlipidemia. Abstract Hepatocellular carcinoma (HCC) is the most common cancer in end-stage renal disease (ESRD) patients in Taiwan. Whether statin therapy associated with the HCC risk in hyperlipidemic patients with chronic kidney disease (CKD) and ESRD is unclear. Using population-based insurance claim data from Taiwan, we identified from hyperlipidemic patients taking statins or not (677,364 versus 867,707) in 1999–2015. Among them, three pairs of propensity score matched statin and non-statin cohorts were established by renal function: 413,867 pairs with normal renal function (NRF), 46,851 pairs with CKD and 6372 pairs with ESRD. Incidence rates of HCC were compared, by the end of 2016, between statin and non-statin cohorts, between hydrophilic statins (HS) and lipophilic statins (LS) users, and between statin-ezetimibe combination therapy (SECT) and statin monotherapy (SM) users. The HCC incidence increased progressively from NRF to CKD and ESRD groups, was lower in the statin cohort than in the non-statin cohort, with the differences of incidence per 10,000 person-years increased from (7.77 vs. 21.4) in NRF group to (15.8 vs. 37.1) in CKD group to (19.1 vs. 47.8) in ESRD group. The incidence increased with age, but the Cox method estimated hazard ratios showed a greater statin effectiveness in older patients. Among statin users, the HCC incidence was lower in HS users than in LS users, and lower in SECT users than in SM users, but the difference was significant only in the NRF group. Hyperlipidemic patients with CKD and ESRD receiving statins are at reduced HCC risks; the treatment effectiveness is superior for HS users than for LS users, and for SECT users than for SM users, but not significant.
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9
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Zhang X, Guan L, Tian H, Zeng Z, Chen J, Huang D, Sun J, Guo J, Cui H, Li Y. Risk Factors and Prevention of Viral Hepatitis-Related Hepatocellular Carcinoma. Front Oncol 2021; 11:686962. [PMID: 34568017 PMCID: PMC8458967 DOI: 10.3389/fonc.2021.686962] [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: 03/28/2021] [Accepted: 08/20/2021] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common cancer in the world, and its incidence is increasing yearly. Hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection are important causes of HCC. Liver cirrhosis, age, sex, smoking and drinking, and metabolic risk factors will increase the risk of cancer in HBV/HCV patients. And viral load, APRI, FIB-4, and liver stiffness can all predict the risk of HCC in patients with viral infection. In addition, effective prevention strategies are essential in reducing the risk of HCC. The prevention of HCC involves mainly tertiary prevention strategies, while the primary prevention is based on standardized vaccine injections to prevent the occurrence of HBV/HCV. Eliminating the route of transmission and vaccination will lead to a decrease in the incidence of HCC. Secondary prevention involves effective antiviral treatment of HBV/HCV to prevent the disease from progressing to HCC, and tertiary prevention is actively treating HCC to prevent its recurrence.
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Affiliation(s)
- Xinhe Zhang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Lin Guan
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Haoyu Tian
- The 3rd Clinical Department of China Medical University, Shenyang, China
| | - Zilu Zeng
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jiayu Chen
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Die Huang
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Ji Sun
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jiaqi Guo
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Huipeng Cui
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Yiling Li
- Gastroenterology Department, The First Affiliated Hospital of China Medical University, Shenyang, China
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10
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Hsu YC, Tseng CH, Huang YT, Yang HI. Application of Risk Scores for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B: Current Status and Future Perspective. Semin Liver Dis 2021; 41:285-297. [PMID: 34161993 DOI: 10.1055/s-0041-1730924] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Accurate risk prediction for hepatocellular carcinoma (HCC) among patients with chronic hepatitis B (CHB) may guide treatment strategies including initiation of antiviral therapy and also inform implementation of HCC surveillance. There have been 26 risk scores developed to predict HCC in CHB patients with (n = 14) or without (n = 12) receiving antiviral treatment; all of them invariably include age in the scoring formula. Virological biomarkers of replicative activities (i.e., hepatitis B virus DNA level or hepatitis B envelope antigen status) are frequently included in the scores derived from patients with untreated CHB, whereas measurements that gauge severity of liver fibrosis and/or reserve of hepatic function (i.e., cirrhosis diagnosis, liver stiffness measurement, platelet count, or albumin) are essential components in the scores developed from treated patients. External validation is a prerequisite for clinical application but not yet performed for all scores. For the future, higher predictive accuracy may be achieved with machine learning based on more comprehensive data.
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Affiliation(s)
- Yao-Chun Hsu
- Center for Liver Diseases, E-Da Hospital, Kaohsiung, Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.,Department of Medicine, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.,Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan
| | - Cheng-Hao Tseng
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.,Division of Gastroenterology and Hepatology, E-Da Cancer Hospital, Kaohsiung, Taiwan
| | - Yen-Tsung Huang
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.,Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan
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11
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Liao M, Wang C, Zhang B, Jiang Q, Liu J, Liao J. Distinguishing Hepatocellular Carcinoma From Hepatic Inflammatory Pseudotumor Using a Nomogram Based on Contrast-Enhanced Ultrasound. Front Oncol 2021; 11:737099. [PMID: 34692513 PMCID: PMC8529164 DOI: 10.3389/fonc.2021.737099] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 09/14/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) and hepatic iflammatory pseudotumor (IPT) share similar symptoms and imaging features, which makes it challenging to distinguish from each other in clinical practice. This study aims to develop a predictive model based on contrast-enhanced ultrasound (CEUS) and clinical features to discriminate HCC from IPT. METHODS Sixty-two IPT and 146 HCC patients were enrolled in this study, where pathological diagnosis served as the reference standard for diagnosis. Clinical and ultrasound imaging data including CEUS features: enhancement degree during arterial phase, portal phase and delayed phase, enhancement pattern, early washout within 60 s, feeding artery, peritumoral vessels, peritumoral enhancement, and margin of nonenhanced area were retrospectively collected. Imaging data were reviewed by two experienced ultrasound doctors. Patients were randomly assigned to training and validation sets. Chi-squared test followed by LASSO regression was performed on ultrasonographic features in the training set to identify the most valuable features that distinguish HCC from IPT, based on which the sonographic score formula was generated. With the significant clinical and ultrasonographic indicators, a nomogram was developed. The performance of the nomogram was verified by ROC curve and decision curve analysis (DCA) with the comparison with sonographic score and the ultrasound doctor's diagnosis. RESULTS The most valuable ultrasonographic features that distinguish between HCC and IPT were enhancement degree during arterial phase, early washout, peritumoral vessels, peritumoral enhancement, and liver background. The sonographic score based on these features was verified to be an independent factor that predicts the diagnosis (p = 0.003). Among the clinical indicators, AFP (p = 0.009) and viral hepatitis infection (p = 0.004) were significant. Sonographic score, AFP, and viral hepatitis were used to construct a predictive nomogram. The AUC of the nomogram was 0.989 and 0.984 in training and validation sets, respectively, which were higher than those of sonographic score alone (0.938 and 0.958) or the ultrasound doctor's diagnosis (0.794 and 0.832). DCA showed the nomogram provided the greatest clinical usefulness. CONCLUSION A predictive nomogram based on a sonographic signature improved the diagnostic performance in distinguishing HCC and IPT, which may help with individualized diagnosis and treatment in clinical practice.
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Affiliation(s)
- Mengting Liao
- Department of Ultrasonography, Xiangya Hospital, Central South University, Changsha, China
- Health Management Center, Xiangya Hospital, Central South University, Changsha, China
| | - Chenshan Wang
- Department of Ultrasonography, Xiangya Hospital, Central South University, Changsha, China
- Department of Medical Ultrasound, Wuhan First Hospital, Wuhan, China
| | - Bo Zhang
- Department of Ultrasonography, Xiangya Hospital, Central South University, Changsha, China
| | - Qin Jiang
- Department of Ultrasonography, Xiangya Hospital, Central South University, Changsha, China
| | - Juan Liu
- Department of Ultrasonography, Xiangya Hospital, Central South University, Changsha, China
| | - Jintang Liao
- Department of Ultrasonography, Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Jintang Liao,
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