|
1
|
Tarar ZI, Farooq U, Inayat F, Basida SD, Ibrahim F, Gandhi M, Nawaz G, Afzal A, Chaudhary AJ, Kamal F, Ali AH, Ghouri YA. Statins decrease the risk of hepatocellular carcinoma in metabolic dysfunction-associated steatotic liver disease: A systematic review and meta-analysis. World J Exp Med 2024; 14:98543. [PMID: 39713070 PMCID: PMC11551700 DOI: 10.5493/wjem.v14.i4.98543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 10/02/2024] [Accepted: 10/24/2024] [Indexed: 10/31/2024] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease with a significant risk of developing hepatocellular carcinoma (HCC). Recent clinical evidence indicates the potential benefits of statins in cancer chemoprevention and therapeutics. However, it is still unclear if these drugs can lower the specific risk of HCC among patients with MASLD. AIM To investigate the impact of statin use on the risk of HCC development in patients with MASLD. METHODS A systematic review and meta-analysis of all the studies was performed that measured the effect of statin use on HCC occurrence in patients with MASLD. The difference in HCC risk between statin users and non-users was calculated among MASLD patients. We also evaluated the risk difference between lipophilic versus hydrophilic statins and the effect of cumulative dose on HCC risk reduction. RESULTS A total of four studies consisting of 291684 patients were included. MASLD patients on statin therapy had a 60% lower pooled risk of developing HCC compared to the non-statin group [relative risk (RR) = 0.40, 95%CI: 0.31-0.53, I 2 = 16.5%]. Patients taking lipophilic statins had a reduced risk of HCC (RR = 0.42, 95%CI: 0.28-0.64), whereas those on hydrophilic statins had not shown the risk reduction (RR = 0.57, 95%CI: 0.27-1.20). The higher (> 600) cumulative defined daily doses (cDDD) had a 70% reduced risk of HCC (RR = 0.30, 95%CI: 0.21-0.43). There was a 29% (RR = 0.71, 95%CI: 0.55-0.91) and 43% (RR = 0.57, 95%CI: 0.40-0.82) decreased risk in patients receiving 300-599 cDDD and 30-299 cDDD, respectively. CONCLUSION Statin use lowers the risk of HCC in patients with MASLD. The higher cDDD and lipophilicity of statins correlate with the HCC risk reduction.
Collapse
Affiliation(s)
- Zahid Ijaz Tarar
- Department of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| | - Umer Farooq
- Department of Gastroenterology and Hepatology, St. Louis University, St. Louis, MO 63104, United States
| | - Faisal Inayat
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore, Punjab 54550, Pakistan
| | - Sanket D Basida
- Department of Internal Medicine, University of Missouri, Columbia, MO 65212, United States
| | - Faisal Ibrahim
- Department of Internal Medicine, Wexham Park Hospital, Wexham SL24HL, Slough, United Kingdom
| | - Mustafa Gandhi
- Department of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| | - Gul Nawaz
- Department of Internal Medicine, Allama Iqbal Medical College, Lahore, Punjab 54550, Pakistan
| | - Arslan Afzal
- Department of Hospital Medicine, ECU Health Medical Center, Greenville, NC 27834, United States
| | - Ammad J Chaudhary
- Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, United States
| | - Faisal Kamal
- Department of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - Ahmad H Ali
- Department of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| | - Yezaz A Ghouri
- Department of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, United States
| |
Collapse
|
|
2
|
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.
Collapse
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
| |
Collapse
|
|
3
|
Scarlata GGM, Cicino C, Spagnuolo R, Marascio N, Quirino A, Matera G, Dumitrașcu DL, Luzza F, Abenavoli L. Impact of diet and gut microbiota changes in the development of hepatocellular carcinoma. HEPATOMA RESEARCH 2024. [DOI: 10.20517/2394-5079.2023.122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2025]
Abstract
Hepatocellular carcinoma (HCC) is a primary liver cancer that occurs with a frequency of 85% in patients with liver cirrhosis. It is the sixth most common type of cancer globally. Asia is the continent with the highest incidence (72%), followed by Europe (8%) and Africa (5%). Men are four times more likely than women to develop this cancer, especially in the 70-80 age group. Risk factors include alcoholic liver disease, tobacco use, genetic predisposition, dysmetabolic comorbidities such as type 2 diabetes mellitus and obesity, hepatitis B virus and hepatitis C virus infections, and non-alcoholic fatty liver disease. Unhealthy dietary regimens and gut dysbiosis are additional risk factors that have been recently investigated. These two factors are closely related because the gut microbiota performs several biological functions, including nutrient metabolism, a process that promotes gut homeostasis, known as eubiosis. With regard to the correlation between diet, gut microbiota, and HCC development, there are several mechanisms that have not yet been fully elucidated. This narrative review aims to evaluate the impact of diet and gut microbiota changes in the development of HCC. Our analysis, performed on several clinical and pre-clinical studies, showed that a high-fat diet promotes gut dysbiosis and hepatic fat accumulation, leading to the progression from simple steatosis to HCC, while the Mediterranean diet, rich in fiber and monounsaturated fatty acids, had a protective role. For this reason, international employment of this dietary regimen for therapeutic purposes should be encouraged.
Collapse
|
|
4
|
Okita Y, Sobue T, Zha L, Kitamura T, Iwasaki M, Inoue M, Yamaji T, Tsugane S, Sawada N. Long-term use of anti-cholesterol drugs and cancer risks in a Japanese population. Sci Rep 2024; 14:2896. [PMID: 38316869 PMCID: PMC10844312 DOI: 10.1038/s41598-024-53252-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 01/30/2024] [Indexed: 02/07/2024] Open
Abstract
Several studies have investigated the association between the use of anti-cholesterol drugs and cancer risks, of which results have been inconsistent. This study included 67,768 participants from the Japan Public Health Center-based Prospective Study. The data on anti-cholesterol drug use was collected using three questionnaires of the survey conducted every five years. We divided the participants into three groups according to the duration of the anti-cholesterol drug use. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). During the 893,009 person-years of follow-up from the 10-year follow-up survey, 8,775 participants (5,387 men and 3,388 women) were newly diagnosed with cancers. The duration of anti-cholesterol drug use was significantly associated with a decreased risk of liver cancer (HR:0.26, 95% CI 0.11-0.64 in > 5 y group) and with an increased risk of pancreatic cancer (HR:1.59, 95% CI 1.03-2.47 in > 5 y group). Moreover, a different trend was observed between men and women in the association with the risk of lung cancer. This study suggested that long-term use of anti-cholesterol drugs may have associations with a decreased incidence of liver cancer and with an increased incidence of pancreatic cancers.
Collapse
Affiliation(s)
- Yuki Okita
- Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Tomotaka Sobue
- Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan.
| | - Ling Zha
- Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Tetsuhisa Kitamura
- Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka, 565-0871, Japan
| | - Motoki Iwasaki
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Manami Inoue
- Division of Prevention, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Shoichiro Tsugane
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
- National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Shinjuku-Ku, Tokyo, 162-8636, Japan
| | - Norie Sawada
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Chuo-Ku, Tokyo, 104-0045, Japan
| |
Collapse
|
|
5
|
Zhang X, Lou D, Fu R, Wu F, Zheng D, Ma X. Association between Statins Types with Incidence of Liver Cancer: An Updated Meta-analysis. Curr Med Chem 2024; 31:762-775. [PMID: 37393552 PMCID: PMC10661961 DOI: 10.2174/0929867330666230701000400] [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: 11/04/2022] [Revised: 03/21/2023] [Accepted: 04/23/2023] [Indexed: 07/04/2023]
Abstract
BACKGROUND Previous studies have found a potential role for statins in liver cancer prevention. OBJECTIVE This study aimed to explore the effect of different types of statins on the incidence of liver cancer. METHODS Relevant articles were systematically retrieved from PubMed, EBSCO, Web of Science, and Cochrane Library databases from inception until July 2022 to explore the relationship between lipophilic statins or hydrophilic statins exposure and the incidence of liver cancer. The main outcome was the incidence of liver cancer. RESULTS Eleven articles were included in this meta-analysis. The pooled results showed a reduced incidence of liver cancer in patients exposed to lipophilic statins (OR=0.54, p < 0.001) and hydrophilic statins (OR=0.56, p < 0.001) compared with the non-exposed cohort. Subgroup analysis showed that both exposures to lipophilic (Eastern countries: OR=0.51, p < 0.001; Western countries: OR=0.59, p < 0.001) and hydrophilic (Eastern countries: OR=0.51, p < 0.001; Western countries: OR=0.66, p=0.019) statins reduced the incidence of liver cancer in Eastern and Western countries, and the reduction was most significant in Eastern countries. Moreover, atorvastatin (OR=0.55, p < 0.001), simvastatin (OR=0.59, p < 0.001), lovastatin (OR=0.51, p < 0.001), pitavastatin (OR=0.36, p=0.008) and rosuvastatin (OR=0.60, p=0.027) could effectively reduce the incidence of liver cancer, unlike fluvastatin, cerivastatin and pravastatin. CONCLUSION Both lipophilic and hydrophilic statins contribute to the prevention of liver cancer. Moreover, the efficacy was influenced by the region and the specific type of statins used.
Collapse
Affiliation(s)
- Xingfen Zhang
- Department of Liver Disease, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
| | - Dandi Lou
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Rongrong Fu
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Feng Wu
- Department of General Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
| | - Dingcheng Zheng
- Department of General Surgery, Ningbo No. 2 Hospital, Ningbo, Zhejiang, China
| | - Xueqiang Ma
- Department of Hepatobiliary Surgery, Zhuji People's Hospital, Shaoxing, Zhejiang, China
| |
Collapse
|
|
6
|
Khaghani A, Kasiri K, Heidari-Soureshjani S, Sherwin CMT, Mardani-Nafchi H. A Systematic Review and Meta-analysis of the Relationship between Statin Intake and Esophageal Cancer. Anticancer Agents Med Chem 2024; 24:1029-1037. [PMID: 38812422 DOI: 10.2174/0118715206292712240522043350] [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: 01/16/2024] [Revised: 04/14/2024] [Accepted: 04/25/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Esophageal cancer is a malignant tumor with a low survival rate. Statins, commonly prescribed for their lipid-lowering effects, have been suggested to possess potential chemopreventive properties against various cancers, including esophageal cancer. OBJECTIVES This systematic review studied the association between statin intake and esophageal cancer. METHODS To conduct this systematic review and meta-analysis, we reviewed studies published between 1980 and June 2023 in Web of Science (WOS), Embase, MEDLINE/PubMed, Scopus, and Cochrane Library databases according to the PRISMA guidelines. Data extraction, quality assessment, and statistical analyses were performed using predefined protocols. We used various statistical tests conducted by Stata statistical software. Statistical significance was considered significant at p < 0.05. RESULTS Twenty-one studies were collected and analyzed. The meta-analysis demonstrated that the odds ratio (OR) of esophageal cancer in patients treated with statins was 0.65 (95% CI: 0.57-0.75, p < 0.001) compared to the non-receiving group. The ORs for case-control and cohort studies were 0.67 (95% CI:0.54-0.83, p < 0.001) and 0.62 (95% CI:0.55-0.71, p < 0.001), respectively. The investigation into the relationship between the statins intake and the incidence of esophageal cancer did not reveal any indication of publication bias according to both Begg's test (p = 0.966) and Egger's test (p = 0.113). CONCLUSION The results revealed that the odds of esophageal cancer in patients treated with statins decreased by 35% compared to patients not treated with statins. However, further well-designed prospective studies are needed to validate these findings and understand the underlying mechanisms of statins in preventing esophageal cancer.
Collapse
Affiliation(s)
- Armin Khaghani
- Skin Diseases and Leishmaniasis Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Karamali Kasiri
- Department of Pediatrics, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | | | - Catherine M T Sherwin
- Pediatric Clinical Pharmacology and Toxicology, Department of Pediatrics, Wright State University Boonshoft School of Medicine, Dayton Children's Hospital, One Children's Plaza, Dayton, Ohio, USA
| | - Hossein Mardani-Nafchi
- Department of Pharmacology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
7
|
Statin can reduce the risk of hepatocellular carcinoma among patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2023; 35:353-358. [PMID: 36719824 DOI: 10.1097/meg.0000000000002517] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Currently, nonalcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease and liver-related mortality worldwide. Hepatocellular carcinoma (HCC) is a fatal complication in patients with NAFLD. However, whether statins can reduce the risk of HCC in patients with NAFLD remains controversial. We aimed to determine the relationship between statin use and HCC occurrence among patients with NAFLD. We independently retrieved related studies from PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrial.gov (from 1 January 2000 to 27 February 2022). The main outcome was the development of HCC. A fixed-effects model was used to merge odds ratio (OR) in the meta-analysis. Five studies involving 684 363 patients were included. The results of the meta-analysis suggested a significantly lower risk of HCC among statin users with NAFLD [OR = 0.59; 95% confidence interval (CI), 0.39-0.89; I2 = 87.90%]. Additionally, a lower risk of HCC was observed among patients with NAFLD aged less than 65 years (OR = 0.59; 95% CI, 0.46-0.77; I2 = 20.50%). Statins can reduce the risk of HCC in patients aged less than 65 years with NAFLD.
Collapse
|
|
8
|
Deza Z, Caimi GR, Noelia M, Coli L, Ridruejo E, Alvarez L. Atorvastatin shows antitumor effect in hepatocellular carcinoma development by inhibiting angiogenesis via TGF-β1/pERK signaling pathway. Mol Carcinog 2023; 62:398-407. [PMID: 36575946 DOI: 10.1002/mc.23494] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/19/2022] [Accepted: 10/21/2022] [Indexed: 12/29/2022]
Abstract
Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins may reduce HCC incidence. Its antitumor activities may be mediated by disrupting several hepatocarcinogenic pathways. To evaluate in vivo and in vitro the antiproliferative and antiangiogenic action of atorvastatin (AT) in the development of HCC as well as its mechanisms of action. In vivo model: hexachlorobenzene (HCB) was used to promote the development of HCC in Balb/C nude mice. Number of hepatic tumor, liver cell proliferation parameters (proliferating cell nuclear antigen, PCNA), angiogenesis, and VEGF levels were analyzed. In vitro model: Hep-G2 and Ea-hy926 cells were used to evaluate the effect of different doses of AT on HCB induced cell proliferation, migration, and vasculogenesis and to analyze proliferative parameters. In vivo: AT prevented liver growth and tumor development and inhibited PCNA, TGF-β1, and pERK levels increase. AT prevented skin blood vessel formation. In vitro, AT prevented cell proliferation and migration as well as tubular formation in the endothelial cell line by inhibiting the MAPK ERK pathway. We were able to demonstrate the potential AT antiproliferative and antiangiogenic effects in an HCC model and the involvement of TGF-β1 and pERK pathways.
Collapse
Affiliation(s)
- Zahira Deza
- Laboratory of Biological Effects of Environmental Contaminants, Department of Human Biochemistry, School of Medicine, Ciudad Autónoma de Buenos Aires, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Giselle Romero Caimi
- Laboratory of Biological Effects of Environmental Contaminants, Department of Human Biochemistry, School of Medicine, Ciudad Autónoma de Buenos Aires, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Miret Noelia
- Laboratory of Biological Effects of Environmental Contaminants, Department of Human Biochemistry, School of Medicine, Ciudad Autónoma de Buenos Aires, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Lucia Coli
- Laboratory of Biological Effects of Environmental Contaminants, Department of Human Biochemistry, School of Medicine, Ciudad Autónoma de Buenos Aires, Universidad de Buenos Aires, Buenos Aires, Argentina
| | - Ezequiel Ridruejo
- Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno" (CEMIC), Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina
| | - Laura Alvarez
- Laboratory of Biological Effects of Environmental Contaminants, Department of Human Biochemistry, School of Medicine, Ciudad Autónoma de Buenos Aires, Universidad de Buenos Aires, Buenos Aires, Argentina
| |
Collapse
|
|
9
|
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.
Collapse
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
| |
Collapse
|
|
10
|
Prediction of hepatocellular carcinoma risk in patients with type-2 diabetes using supervised machine learning classification model. Heliyon 2022; 8:e10772. [PMID: 36203910 PMCID: PMC9529545 DOI: 10.1016/j.heliyon.2022.e10772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2022] [Revised: 05/26/2022] [Accepted: 09/22/2022] [Indexed: 11/21/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) among type-2 diabetes (T2D) patients is an increasing burden to diabetes management. This study aims to develop and select the best machine learning (ML) classification model for predicting HCC in T2D for HCC early detection. Methods A case-control study was conducted utilising computerised medical records in two hepatobiliary centres. The predictors were chosen using multiple logistic regression. IBM SPSS Modeler® was used to assess the discriminative performance of support vector machine (SVM), logistic regression (LR), artificial neural network (ANN), chi-square automatic interaction detection (CHAID), and their ensembles. Results Subjects (N = 424) were split into 60% training (n = 248) and 40% testing (n = 176) groups. The independent predictors identified were race, viral hepatitis, abdominal pain/discomfort, unintentional weight loss, statins, alcohol consumption, non-alcoholic fatty liver, platelet <150 ×103/μL, alkaline phosphatase >129 IU/L, and alanine transaminase ≥25 IU/L. The performances of all models differed significantly (Cochran’s Q-test,p = 0.001) but not between the ensembled and SVM model (McNemar test, p = 0.687). SVM model was selected as the best model due to its simplicity, high accuracy (85.28%), and high AUC (0.914). A web-based application was developed using the best model’s algorithm for HCC prediction. Conclusions If further validation studies confirm these results, the SVM model’s application potentially augments early HCC detection in T2D patients.
Hepatocellular carcinoma (HCC) in type-2 diabetes (T2D) is increasing. A web-based application using a machine learning model has been developed. The model has 85.28% accuracy and high AUC (0.914) in HCC prediction. Potential risk stratification tool in T2D clinic to predict HCC. HCC prediction in T2D clinic may aid early detection and improve survival.
Collapse
|
|
11
|
Benhammou JN, Sinnett-Smith J, Pisegna JR, Rozengurt EJ. Interplay Between Fatty Acids, Stearoyl-Co-A Desaturase, Mechanistic Target of Rapamycin, and Yes-Associated Protein/Transcriptional Coactivator With PDZ-Binding Motif in Promoting Hepatocellular Carcinoma. GASTRO HEP ADVANCES 2022; 2:232-241. [PMID: 39132609 PMCID: PMC11308718 DOI: 10.1016/j.gastha.2022.07.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/17/2022] [Indexed: 08/13/2024]
Abstract
Nonalcoholic fatty liver disease has reached pandemic proportions with one of its most consequential complications being hepatocellular carcinoma (HCC). Nonalcoholic fatty liver disease-related HCC is becoming the leading indication for liver transplantation in the United States. Given the scarcity of available organs, early detection and prevention remain key in prevention and management of the disease. Over the years, the yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) pathway emerged as a key signal transduction pathway in the pathogenesis of HCC. In this review, we explore the interplay between the YAP/TAZ pathway as a point of convergence in HCC pathogenesis. We review the evidence of how lipid reprogramming and key lipid pathways, saturated and monounsaturated fatty acids (through the rate-limiting enzyme stearoyl Co-A desaturase), the mevalonic acid pathway (the role of statins), and mechanistic target of rapamycin all play critical roles in intricate and complex networks that tightly regulate the YAP/TAZ pro-oncogenic pathway.
Collapse
Affiliation(s)
- Jihane N. Benhammou
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California
| | - Jim Sinnett-Smith
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California
| | - Joseph R. Pisegna
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California
| | - Enrique J. Rozengurt
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at the University of California, Los Angeles, California
- Division of Gastroenterology, Hepatology and Parenteral Nutrition, Greater Los Angeles Veterans Affairs Healthcare System, Los Angeles, California
| |
Collapse
|
|
12
|
Chavez-Tapia NC, Murúa-Beltrán Gall S, Ordoñez-Vázquez AL, Nuño-Lambarri N, Vidal-Cevallos P, Uribe M. Understanding the Role of Metabolic Syndrome as a Risk Factor for Hepatocellular Carcinoma. J Hepatocell Carcinoma 2022; 9:583-593. [PMID: 35818404 PMCID: PMC9270896 DOI: 10.2147/jhc.s283840] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Accepted: 06/23/2022] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) and metabolic syndrome (MetS) have a rising prevalence worldwide. The relationship between these two entities has long been studied and understanding it has become a public health and clinical priority. This association follows, in most patients, the path through non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis and finally HCC. Nonetheless, increasing evidence has been found, that shows MetS as an independent risk factor for the development of HCC. This review brings together the clinical evidence of the relationship between these highly prevalent diseases, with a particular interest in the impact of each component of MetS on HCC; It aims to summarize the complex physiopathological pathways that explain this relationship, and to shed light on the different clinical scenarios of this association, the impact of treating the different components of MetS on the risk of HCC and what is known about screening for HCC in patients with MetS. By doing so, it hopes to improve awareness on this topic.
Collapse
Affiliation(s)
- Norberto C Chavez-Tapia
- Gastroenterology Department, Medica Sur Clinic & Foundation, Mexico City, Mexico
- Transational Research Department, Medica Sur Clinic & Foundation, Mexico City, Mexico
| | | | | | - Natalia Nuño-Lambarri
- Transational Research Department, Medica Sur Clinic & Foundation, Mexico City, Mexico
| | | | - Misael Uribe
- Gastroenterology Department, Medica Sur Clinic & Foundation, Mexico City, Mexico
| |
Collapse
|
|
13
|
Wang Y, Wang W, Wang M, Shi J, Jia X, Dang S. A Meta-Analysis of Statin Use and Risk of Hepatocellular Carcinoma. Can J Gastroenterol Hepatol 2022; 2022:5389044. [PMID: 35356132 PMCID: PMC8958112 DOI: 10.1155/2022/5389044] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 02/25/2022] [Accepted: 02/26/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The use of statins is a potential protective factor against the development of hepatocellular carcinoma. Therefore, we conducted a meta-analysis to evaluate the contribution of statins to the risk of hepatocellular carcinoma. METHODS We searched for PubMed and EMBASE through January 2021. RESULTS Thirty-two studies (eighteen cohort, eleven case-control, and three randomized controlled trials) reporting 56,838 cases of hepatocellular carcinoma in 4,963,518 persons were included. Statin users were less likely to develop hepatocellular carcinoma than nonusers (adjusted odds ratio, 0.58; 95% CI: 0.51-0.67). Stratified analysis showed that statins reduced the risk of hepatocellular carcinoma in Asian and Western populations (odds ratio, 0.54 vs. 0.60). Besides, statins have protective effects against hepatocellular carcinoma after hepatitis B virus (odds ratio, 0.44; 95% CI: 0.22-0.85) and hepatitis C virus infections (odds ratio, 0.53; 95% CI: 0.49-0.57). Statins have protective effects on people with chronic liver disease (odds ratio, 0.52; 95% CI: 0.40-0.68) and on the general population (odds ratio, 0.60; 95% CI: 0.50-0.72). Lipophilic statins can prevent hepatocellular carcinoma (odds ratio, 0.51, 95% CI: 0.46-0.57), while hydrophilic statins cannot (odds ratio, 0.77, 95% CI: 0.58-1.02). The single-drug analyses showed that simvastatin (odds ratio, 0.53, 95% CI: 0.48-0.59), atorvastatin (odds ratio, 0.54, 95% CI: 0.45-0.64), rosuvastatin (odds ratio, 0.55, 95% CI: 0.37-0.83), lovastatin (odds ratio, 0.30, 95% CI: 0.15-0.62), and pitavastatin (odds ratio, 0.36, 95% CI: 0.17-0.75) had significant benefits. Further studies have shown that those in the high-dose group experienced better effects in preventing hepatocellular carcinoma (adjusted hazard ratio, 0.38 vs. 0.55). Further research found that the combined use of aspirin did not increase the chemoprevention effect of liver cancer (odds ratio, 0.57; 95% CI: 0.40-0.81). In addition, the preventive effect of statins improved with the extension of follow-up time (odds ratio, 0.54 vs. 0.65). CONCLUSION Our meta-analysis shows that the use of statins is associated with a lower risk of liver cancer.
Collapse
Affiliation(s)
- Yikai Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Muqi Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Juanjuan Shi
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Xiaoli Jia
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China
| |
Collapse
|
|
14
|
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.
Collapse
|
|
15
|
Goh MJ, Sinn DH. Statin and aspirin for chemoprevention of hepatocellular carcinoma: Time to use or wait further? Clin Mol Hepatol 2022; 28:380-395. [PMID: 35021597 PMCID: PMC9293618 DOI: 10.3350/cmh.2021.0366] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 01/08/2022] [Indexed: 11/20/2022] Open
Abstract
Preclinical studies highlighted potential therapeutic applications of aspirin and statins as anticancer agents based on their pleiotropic effects. Epidemiologic studies suggested the role of aspirin and statins in the chemoprevention of hepatocellular carcinoma (HCC). However, observational data is prone to bias, and no prospective randomized trials are currently available to assess the risks and benefits of statin or aspirin therapy for chemoprevention of HCC. It is therefore important for clinicians and researchers to be aware of the quality of current evidence regarding this issue. In this review, we summarize currently available evidence to assist clinicians with their decision to use statin or aspirin and provide information for further clinical investigations.
Collapse
Affiliation(s)
- Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| |
Collapse
|
|
16
|
Azit NA, Sahran S, Voon Meng L, Subramaniam M, Mokhtar S, Mohammed Nawi A. Risk factors of hepatocellular carcinoma in type 2 diabetes patients: A two-centre study in a developing country. PLoS One 2021; 16:e0260675. [PMID: 34882716 PMCID: PMC8659343 DOI: 10.1371/journal.pone.0260675] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2021] [Accepted: 11/13/2021] [Indexed: 12/24/2022] Open
Abstract
Type 2 diabetes mellitus (T2DM) is increasingly known as a risk factor of hepatocellular carcinoma (HCC). In this study, we determined the risk factors associated with HCC in T2DM patients. This was a matched case-control study conducted at two hepatobiliary referral centres in a developing country. Patients' sociodemographic, clinical, and biochemical characteristics between 1 January 2012 and 30 June 2018 were extracted from the electronic medical records and analysed using multivariate logistic regression analysis. A total of 212 case-control pairs were included. Significant risk factors included Chinese and Malay ethnicities that interacted with viral hepatitis (adjusted odds ratio [AOR] = 11.77, 95% confidence interval [CI]: 1.39-99.79) and (AOR = 37.94, 95% CI: 3.92-367.61) respectively, weight loss (AOR = 5.28, 95% CI: 2.29-12.19), abdominal pain/ discomfort (AOR = 6.73, 95% CI: 3.34-13.34), alcohol (AOR = 4.08, 95% CI: 1.81-9.22), fatty liver (AOR = 3.29, 95% CI: 1.40-7.76), low platelet (AOR = 4.03, 95% CI:1.90-8.55), raised alanine transaminase (AOR = 2.11, 95% CI: 1.16-3.86). and alkaline phosphatase (ALP) levels (AOR = 2.17, 95% CI: 1.17-4.00). Statins reduced the risk of HCC by 63% (AOR = 0.37, 95% CI: 0.21-0.65). The identification of these factors aids the risk stratification for HCC among T2DM patients for early detection and decision-making in patient management in the primary care setting.
Collapse
Affiliation(s)
- Noor Atika Azit
- Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Shahnorbanun Sahran
- Faculty of Information Science and Technology, National University of Malaysia, Bangi, Selangor, Malaysia
| | - Leow Voon Meng
- Advanced Medical and Dental Institute (AMDI), USM, Kepala Batas, Penang, Malaysia
- Hepato-Pancreato-Biliary Unit, Department of Surgery, Hospital Sultanah Bahiyah, Ministry of Health Malaysia, Alor Setar, Kedah, Malaysia
| | - Manisekar Subramaniam
- Hepato-Pancreato-Biliary Unit, Department of Surgery, Hospital Sultanah Bahiyah, Ministry of Health Malaysia, Alor Setar, Kedah, Malaysia
| | - Suryati Mokhtar
- Hepato-Pancreato-Biliary Unit, Department of Surgery, Hospital Selayang, Ministry of Health Malaysia, Batu Caves, Selangor, Malaysia
| | - Azmawati Mohammed Nawi
- Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| |
Collapse
|
|
17
|
Orabi D, Berger NA, Brown JM. Abnormal Metabolism in the Progression of Nonalcoholic Fatty Liver Disease to Hepatocellular Carcinoma: Mechanistic Insights to Chemoprevention. Cancers (Basel) 2021; 13:3473. [PMID: 34298687 PMCID: PMC8307710 DOI: 10.3390/cancers13143473] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/01/2021] [Accepted: 07/02/2021] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is on the rise and becoming a major contributor to the development of hepatocellular carcinoma (HCC). Reasons for this include the rise in obesity and metabolic syndrome in contrast to the marked advances in prevention and treatment strategies of viral HCC. These shifts are expected to rapidly propel this trend even further in the coming decades, with NAFLD on course to become the leading etiology of end-stage liver disease and HCC. No Food and Drug Administration (FDA)-approved medications are currently available for the treatment of NAFLD, and advances are desperately needed. Numerous medications with varying mechanisms of action targeting liver steatosis and fibrosis are being investigated including peroxisome proliferator-activated receptor (PPAR) agonists and farnesoid X receptor (FXR) agonists. Additionally, drugs targeting components of metabolic syndrome, such as antihyperglycemics, have been found to affect NAFLD progression and are now being considered in the treatment of these patients. As NAFLD drug discovery continues, special attention should be given to their relationship to HCC. Several mechanisms in the pathogenesis of NAFLD have been implicated in hepatocarcinogenesis, and therapies aimed at NAFLD may additionally harbor independent antitumorigenic potential. This approach may provide novel prevention and treatment strategies.
Collapse
Affiliation(s)
- Danny Orabi
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44106, USA;
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44106, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
- Case Comprehensive Cancer Center, Cleveland, OH 44106, USA;
- Department of General Surgery, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Nathan A. Berger
- Case Comprehensive Cancer Center, Cleveland, OH 44106, USA;
- Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
- Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
- Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
| | - J. Mark Brown
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44106, USA;
- Center for Microbiome and Human Health, Lerner Research Institute of the Cleveland Clinic, Cleveland, OH 44106, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA
- Case Comprehensive Cancer Center, Cleveland, OH 44106, USA;
| |
Collapse
|