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Ratziu V. Cirrhose métabolique : une entité en plein essor. BULLETIN DE L'ACADÉMIE NATIONALE DE MÉDECINE 2024. [DOI: 10.1016/j.banm.2024.11.012] [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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Pliszka M, Szablewski L. Associations between Diabetes Mellitus and Selected Cancers. Int J Mol Sci 2024; 25:7476. [PMID: 39000583 PMCID: PMC11242587 DOI: 10.3390/ijms25137476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 06/15/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
Cancer is one of the major causes of mortality and is the second leading cause of death. Diabetes mellitus is a serious and growing problem worldwide, and its prevalence continues to grow; it is the 12th leading cause of death. An association between diabetes mellitus and cancer has been suggested for more than 100 years. Diabetes is a common disease diagnosed among patients with cancer, and evidence indicates that approximately 8-18% of patients with cancer have diabetes, with investigations suggesting an association between diabetes and some particular cancers, increasing the risk for developing cancers such as pancreatic, liver, colon, breast, stomach, and a few others. Breast and colorectal cancers have increased from 20% to 30% and there is a 97% increased risk of intrahepatic cholangiocarcinoma or endometrial cancer. On the other hand, a number of cancers and cancer therapies increase the risk of diabetes mellitus. Complications due to diabetes in patients with cancer may influence the choice of cancer therapy. Unfortunately, the mechanisms of the associations between diabetes mellitus and cancer are still unknown. The aim of this review is to summarize the association of diabetes mellitus with selected cancers and update the evidence on the underlying mechanisms of this association.
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Affiliation(s)
- Monika Pliszka
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego Str. 5, 02-004 Warsaw, Poland
| | - Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego Str. 5, 02-004 Warsaw, Poland
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Hu TH, Luh DL, Tsao YY, Lin TY, Chang CJ, Su WW, Yang CC, Yang CJ, Chen HP, Liao PY, Su SL, Chen LS, Hsiu-Hsi Chen T, Yeh YP. Using the Diabetes Care System for a County-Wide Hepatitis C Elimination: An Integrated Community-Based Shared Care Model in Taiwan. Am J Gastroenterol 2024; 119:883-892. [PMID: 38084857 PMCID: PMC11062613 DOI: 10.14309/ajg.0000000000002624] [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: 06/21/2023] [Accepted: 10/16/2023] [Indexed: 01/30/2024]
Abstract
INTRODUCTION Despite the serious risks of diabetes with hepatitis C virus (HCV) infection, this preventable comorbidity is rarely a priority for HCV elimination. We aim to examine how a shared care model could eliminate HCV in patients with diabetes (PwD) in primary care. METHODS There were 27 community-based Diabetes Health Promotion Institutes in each township/city of Changhua, Taiwan. PwD from these institutes from January 2018 to December 2020 were enrolled. HCV screening and treatment were integrated into diabetes structured care through collaboration between diabetes care and HCV care teams. Outcome measures included HCV care continuum indicators. Township/city variation in HCV infection prevalence and care cascades were also examined. RESULTS Of the 10,684 eligible PwD, 9,984 (93.4%) underwent HCV screening, revealing a 6.18% (n = 617) anti-HCV seroprevalence. Among the 597 eligible seropositive individuals, 507 (84.9%) completed the RNA test, obtaining 71.8% positives. Treatment was initiated by 327 (89.8%) of 364 viremic patients, and 315 (86.5%) completed it, resulting in a final cure rate of 79.4% (n = 289). Overall, with the introduction of antivirals in this cohort, the prevalence of viremic HCV infection dropped from 4.44% to 1.34%, yielding a 69.70% (95% credible interval 63.64%-77.03%) absolute reduction. DISCUSSION Although HCV prevalence varied, the care cascades achieved consistent results across townships/cities. We have further successfully implemented the model in county-wide hospital-based diabetes clinics, eventually treating 89.6% of the total PwD. A collaborative effort between diabetes care and HCV elimination enhanced the testing and treatment in PwD through an innovative shared care model.
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Affiliation(s)
- Tsung-Hui Hu
- Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung City, Taiwan
| | - Dih-Ling Luh
- Department of Public Health, Chung Shan Medical University, Taichung, Taiwan
- Department of Family and Community Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Yo-Yu Tsao
- Changhua Public Health Bureau, Changhua, Taiwan
| | - Ting-Yu Lin
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | | | - Wei-Wen Su
- Changhua Christian Hospital, Changhua, Taiwan
| | - Chih-Chao Yang
- Changhua Hospital, Ministry of Health and Welfare, Changhua, Taiwan
| | - Chang-Jung Yang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | | | | | - Shih-Li Su
- Changhua Christian Hospital, Changhua, Taiwan
| | - Li-Sheng Chen
- School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan
| | - Tony Hsiu-Hsi Chen
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Yen-Po Yeh
- Changhua Public Health Bureau, Changhua, Taiwan
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
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Genetic Susceptibility to Hepatocellular Carcinoma in Patients with Chronic Hepatitis Virus Infection. Viruses 2023; 15:v15020559. [PMID: 36851773 PMCID: PMC9964813 DOI: 10.3390/v15020559] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk factors, individual genetic predisposition is a major determinant of HCC risk. Familial clustering of HCC has been observed, and a hereditary factor likely contributes to the risk of HCC development. The familial aggregation may depend on a shared environment and genetic background as well as the interactions of environmental and genetic factors. Genome-wide association studies (GWASs) are one of the most practical tools for mapping the patterns of inheritance for the most common form of genomic variation, single nucleotide polymorphisms. This approach is practical for investigating genetic variants across the human genome, which is affected by thousands of common genetic variants that do not follow Mendelian inheritance. This review article summarizes the academic knowledge of GWAS-identified genetic loci and their association with HCC. We summarize the GWASs in accordance with various chronic hepatitis virus infection statuses. This genetic profiling could be used to identify candidate biomarkers to refine HCC screening and management by enabling individual risk-based personalization and stratification. A more comprehensive understanding of the genetic mechanisms underlying individual predisposition to HCC may lead to improvements in the prevention and early diagnosis of HCC and the development of effective treatment strategies.
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Xu R, Zheng T, Ouyang C, Ding X, Ge C. Causal associations between site-specific cancer and diabetes risk: A two-sample Mendelian randomization study. Front Endocrinol (Lausanne) 2023; 14:1110523. [PMID: 36860363 PMCID: PMC9968794 DOI: 10.3389/fendo.2023.1110523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 02/03/2023] [Indexed: 02/17/2023] Open
Abstract
BACKGROUND Both cancer and diabetes are complex chronic diseases that have high economic costs for society. The co-occurrence of these two diseases in people is already well known. The causal effects of diabetes on the development of several malignancies have been established, but the reverse causation of these two diseases (e.g., what type of cancer can cause T2D) has been less investigated. METHODS Multiple Mendelian randomization (MR) methods, such as the inverse-variance weighted (IVW) method, weighted median method, MR-Egger, and MR pleiotropy residual sum and outlier test, were performed to evaluate the causal association of overall and eight site-specific cancers with diabetes risk using genome-wide association study summary data from different consortia, such as Finngen and UK biobank. RESULTS A suggestive level of evidence was observed for the causal association between lymphoid leukaemia and diabetes by using the IVW method in MR analyses (P = 0.033), indicating that lymphoid leukaemia increased diabetes risk with an odds ratio of 1.008 (95% confidence interval, 1.001-1.014). Sensitivity analyses using MR-Egger and weighted median methods showed consistent direction of the association compared with the IVW method. Overall and seven other site-specific cancers under investigation (i.e., multiple myeloma, non-Hodgkin lymphoma, and cancer of bladder, brain, stomach, lung, and pancreas) were not causally associated with diabetes risk. CONCLUSIONS The causal relationship between lymphoid leukaemia and diabetes risk points to the necessity of diabetes prevention amongst leukaemia survivors as a strategy for ameliorating the associated disease burden.
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Affiliation(s)
- Rong Xu
- Department of Pharmacy, Quanzhou Medical College, Quanzhou, China
- *Correspondence: Rong Xu, ; Chenjin Ge,
| | - Tingjin Zheng
- Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China
| | - Chaoqun Ouyang
- Department of Pharmacy, Quanzhou Medical College, Quanzhou, China
| | - Xiaoming Ding
- Department of Basic Medicine, Quanzhou Medical College, Quanzhou, China
| | - Chenjin Ge
- Department of Medical Imaging, Shanghai Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- *Correspondence: Rong Xu, ; Chenjin Ge,
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Nakatsuka T, Tateishi R. Development and prognosis of hepatocellular carcinoma in patients with diabetes. Clin Mol Hepatol 2023; 29:51-64. [PMID: 35903020 PMCID: PMC9845683 DOI: 10.3350/cmh.2022.0095] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/03/2022] [Indexed: 02/02/2023] Open
Abstract
The incidence of diabetes mellitus and hepatocellular carcinoma (HCC) has been increasing worldwide during the last few decades, in the context of an increasing prevalence of obesity and non-alcoholic fatty liver disease (NAFLD). Epidemiologic studies have revealed that patients with diabetes have a 2- to 3-fold increased risk of developing HCC, independent of the severity and cause of the underlying liver disease. A bidirectional relationship exists between diabetes and liver disease: advanced liver disease promotes the onset of diabetes, and HCC is an important cause of death in patients with diabetes; conversely, diabetes is a risk factor for liver fibrosis progression and HCC development, and may worsen the long-term prognosis of patients with HCC. The existence of close interconnections among diabetes, obesity, and NAFLD causes insulin resistance-related hyperinsulinemia, increased oxidative stress, and chronic inflammation, which are assumed to be the underlying causes of hepatocarcinogenesis in patients with diabetes. No appropriate surveillance methods for HCC development in patients with diabetes have been established, and liver diseases, including HCC, are often overlooked as complications of diabetes. Although some antidiabetic drugs are expected to prevent HCC development, further research on the optimal use of antidiabetic drugs aimed at hepatoprotection is warranted. Given the increasing medical and socioeconomic impact of diabetes on HCC development, diabetologists and hepatologists need to work together to develop strategies to address this emerging health issue. This article reviews the current knowledge on the impact of diabetes on the development and progression of HCC.
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Affiliation(s)
- Takuma Nakatsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan,Corresponding author : Ryosuke Tateishi Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan Tel: +81-3-3815-5411, Fax: +81-3-3814-0021, E-mail:
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Kumar A, Rajani D, Kumar S. Letter to the editor: Hepatitis B virus genotype: A significant risk factor in determining which patients with chronic hepatitis B virus infection should undergo surveillance for hepatocellular carcinoma: The hepatitis B Alaska study. Hepatology 2022; 76:E63-E64. [PMID: 35478185 DOI: 10.1002/hep.32544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 04/11/2022] [Indexed: 12/08/2022]
Affiliation(s)
- Aashish Kumar
- Shaheed Mohtarma Benazir Bhutto Medical College Liyari, Karachi, Pakistan
| | - Deepak Rajani
- Shaheed Mohtarma Benazir Bhutto Medical College Liyari, Karachi, Pakistan
| | - Satesh Kumar
- Shaheed Mohtarma Benazir Bhutto Medical College Liyari, Karachi, Pakistan
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Yang C, Wan M, Lu Y, Yang X, Yang L, Wang S, Sun G. Associations between diabetes mellitus and the risk of hepatocellular carcinoma in Asian individuals with hepatitis B and C infection: systematic review and a meta-analysis of cohort studies. Eur J Cancer Prev 2022; 31:107-116. [PMID: 35103624 DOI: 10.1097/cej.0000000000000669] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
We aim to further analyze and compare associations between diabetes mellitus and the risk of hepatocellular carcinoma (HCC) in Asian individuals with hepatitis B or C virus infection by conducting an updated meta-analysis of cohort studies. Literature search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library from the beginning of indexing for each database to January 1, 2020. A total of 22 articles met the inclusion criteria, in which 18 were cohort studies and 4 were case-control studies. We identified eight cohort studies and three case-control studies that presented results on diabetes mellitus and the risk of HCC in Asian subjects with hepatitis B virus (HBV) infection: the cumulative relative risk (RR) with 95% confidence interval (CI) was 1.37 (95% CI: 1.24 to 1.51; I2 = 27.8%) for cohort studies and cumulative odds ratio (OR) with 95% CI was 1.99 (95% CI: 0.73 to 5.48; I2 = 88.4%) for case-control studies. Thirteen cohort studies and two case-control studies presented results on the association between diabetes mellitus and the risk of HCC in Asian subjects with hepatitis C virus (HCV) infection: the RR with 95% CI was 1.76 (95% CI: 1.42 to 2.17; I2 = 62.8%) for cohort studies and OR with 95% CI was 1.77 (95% CI: 1.18 to 2.64; I2 = 0.0%) for case-control studies. In summary, our meta-analysis strongly supports the association between coexistent HCV and diabetes with the increasing risk of HCC; although the results equally support diabetes mellitus being significantly associated with increased risk of HCC among patients with HBV infection, this correlation is weaker than the former.
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Affiliation(s)
- Chao Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
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Puri P, Kotwal N. An Approach to the Management of Diabetes Mellitus in Cirrhosis: A Primer for the Hepatologist. J Clin Exp Hepatol 2022; 12:560-574. [PMID: 35535116 PMCID: PMC9077234 DOI: 10.1016/j.jceh.2021.09.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 09/07/2021] [Indexed: 12/12/2022] Open
Abstract
The management of diabetes in cirrhosis and liver transplantation can be challenging. There is difficulty in diagnosis and monitoring of diabetes as fasting blood sugar values are low and glycosylated hemoglobin may not be a reliable marker. The challenges in the management of diabetes in cirrhosis include the likelihood of cognitive impairment, risk of hypoglycemia, altered drug metabolism, frequent renal dysfunction, risk of lactic acidosis, and associated malnutrition and sarcopenia. Moreover, calorie restriction and an attempt to lose weight in obese diabetics may be associated with a worsening of sarcopenia. Many commonly used antidiabetic drugs may be unsafe or be associated with a high risk of hypoglycemia in cirrhotics. Post-transplant diabetes is common and may be contributed by immunosuppressive medication. There is inadequate clinical data on the use of antidiabetic drugs in cirrhosis, and the management of diabetes in cirrhosis is hampered by the lack of guidelines focusing on this issue. The current review aims at addressing the practical management of diabetes by a hepatologist.
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Key Words
- ADA, American Diabetes Association
- AGI, Alfa Glucosidase inhibitors
- BMI, Body mass index
- CLD, Chronic liver disease
- CYP-450, Cytochrome P-450
- Dipeptidyl-peptidase 4, DPP-4
- GLP-1, Glucagon-like peptide-1
- HCC, Hepatocellular carcinoma
- HCV, Hepatitis C virus
- HbA1c, Hemoglobin A1c
- IGF, Insulin-like growth factor
- MALA, Metformin-associated lactic acidosis
- NASH, Nonalcoholic steatohepatitis
- NPL, Neutral protamine lispro
- OGTT, Oral glucose tolerance test
- SMBG, Self-monitoring of blood glucose
- Sodium-glucose cotransporter 2, SGLT2
- VEGF, Vascular endothelial growth factor
- antidiabetic agents
- antihyperglycemic drugs
- chronic liver disease
- cirrhosis
- diabetes mellitus
- eGFR, estimated glomerular filtration rates
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Affiliation(s)
- Pankaj Puri
- Fortis Escorts Liver and Digestive Diseases Institute, New Delhi, 110025, India
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Shigematsu Y, Kanda H, Amori G, Takahashi Y, Takazawa Y, Inamura K. Nonalcoholic non-virus-related hepatocellular carcinoma arising from nonsteatotic liver: Clinical and pathological features. Medicine (Baltimore) 2022; 101:e28746. [PMID: 35119029 PMCID: PMC8812618 DOI: 10.1097/md.0000000000028746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 01/07/2022] [Indexed: 01/04/2023] Open
Abstract
Nonalcoholic non-virus-related hepatocellular carcinoma (NANV-HCC) is considered to occur in steatotic livers; however, emerging evidence indicates that a subset of NANV-HCC occurs in nonsteatotic livers. Currently, little information is available regarding this subset. This study sought to provide the clinical and pathological features of NANV-HCC in nonsteatotic livers.We retrospectively investigated the clinicopathological features of 101 consecutive patients with NANV-HCC treated with a curative-intent hepatectomy. A background liver with <5% steatosis by area was regarded as a nonsteatotic liver. Survivals of patient subgroups were estimated using the Kaplan-Meier method, and log-rank tests were conducted to assess the survival difference. Multivariate analysis was performed with the Cox proportional hazards method.Overall, 34 of 101 patients with NANV-HCC were found to have a nonsteatotic liver. Vascular invasion of the tumor was more frequently observed in patients with a nonsteatotic liver than in those with a steatotic liver (P = .03). The extent of lobular inflammation and fibrosis did not differ between patients with and without steatosis in the liver. NANV-HCC with a nonsteatotic liver was independently associated with a shorter disease-free survival (DFS) (hazard ratio [HR] 2.14; 95% confidence interval [CI] 1.21-3.80; P = .009) and a shorter overall survival (OS) (HR 2.79; 95% CI 1.27-6.16; P = .01) than NANV-HCC with a steatotic liver.The absence of steatosis in the liver is independently associated with shorter DFS and OS in patients with NANV-HCC. Our findings indicate that nonsteatotic liver can be a surrogate phenotype of aggressive NANV-HCC.
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Affiliation(s)
- Yasuyuki Shigematsu
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
| | - Hiroaki Kanda
- Department of Pathology, Saitama Cancer Center, 780 Komuro, Ina, Kita-adachi-gun, Saitama, Japan
| | - Gulanbar Amori
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
| | - Yu Takahashi
- Division of Hepatobiliary and Pancreatic Surgery, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
| | - Yutaka Takazawa
- Department of Pathology, Toranomon Hospital, 2-2-2 Toranomon Minato, Tokyo, Japan
| | - Kentaro Inamura
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto, Tokyo, Japan
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Chang JCJ, Yang HY. Epidemiology of chronic kidney disease of undetermined aetiology in Taiwanese farmers: a cross-sectional study from Changhua Community-based Integrated Screening programme. Occup Environ Med 2021; 78:849-858. [PMID: 34108255 DOI: 10.1136/oemed-2021-107369] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 04/09/2021] [Accepted: 05/03/2021] [Indexed: 01/27/2023]
Abstract
OBJECTIVES Chronic kidney disease of undetermined or non-traditional aetiology (CKDu or CKDnT) has been reported in Mesoamerica among farmers under heat stress. Epidemiological evidence was lacking in Asian countries with similar climatic conditions. The objective of this study was to investigate the prevalence of CKDu and possible risk factors. METHODS We used the data from the Changhua Community-based Integrated Screening programme from 2005 to 2014, which is the annual screening for chronic diseases in Taiwan's largest rice-farming county since 2005. Our study population included farmers and non-farmers aged 15-60 years. CKDu was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 at age under 60 years without hypertension, diabetes, proteinuria, haematuria or using Chinese herbal medicine. We estimated the adjusted prevalence OR (POR) of CKDu by farmers, age, sex, education, urbanisation, smoking, body mass index, hyperuricaemia, hyperlipidaemia, heart disease and chronic liver disease. RESULTS 5555 farmers and 35 761 non-farmers were included in this study. CKDu accounted for 48.9% of all CKD cases. The prevalence of CKDu was 2.3% in the farmers and 0.9% in the non-farmers. The crude POR of CKDu in farmers compared with non-farmers was 2.73 (2.13-3.50), and the adjusted POR was 1.45 (1.10-1.90). Dehydration (blood urea nitrogen-to-creatinine ratio >20) was found in 22% of the farmers and 14% of the non-farmers. CONCLUSIONS Farmers in subtropical Asian countries are at increased risk of CKDu. Governments should take the CKDu epidemics seriously and provide farmers with occupational health education programmes on thermal hazards.
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Affiliation(s)
- Jerry Che-Jui Chang
- Institute of Occupational and Environmental Health Sciences, National Taiwan University College of Public Health, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiao-Yu Yang
- Institute of Occupational and Environmental Health Sciences, National Taiwan University College of Public Health, Taipei, Taiwan .,Department of Public Health, National Taiwan University College of Public Health, Taipei, Taiwan.,Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Shi GY, Sun Y, Liang XC, Xie JD. Clinical significance of expression of serum insulin-like growth factor-1 in patients with primary liver cancer and diabetes mellitus. Shijie Huaren Xiaohua Zazhi 2021; 29:236-241. [DOI: 10.11569/wcjd.v29.i5.236] [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] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Studies have reported that serum insulin like growth factor 1 (IGF-1) levels decrease in patients with primary liver cancer or type 2 diabetes, but there are also reports that serum IGF-1 levels increase in these patients. Whether primary liver cancer and type 2 diabetes have a mutual promotion effect remains unclear. Evaluating the prognostic effect of serum IGF-1 in these patients will provide a theoretical basis for early detection of liver cancer and liver cancer with type 2 diabetes.
AIM To investigate the IGF-1 expression in patients with hepatocellular carcinoma (HCC) complicated with type 2 diabetes mellitus (DM2).
METHODS From 2014 to 2018, 80 patients with DM2, 80 patients with HCC, and 80 patients with HCC complicated with DM2 were collected from Xinjiang Hospitals. Serum IGF-1, alpha-fetoprotein (AFP), and carbohydrate antigen 199 (CA199) were measured in all patients.
RESULTS The three groups had significantly different levels of serum IGF-1, AFP, and CA199. The level of serum IGF-1 was significantly higher in the DM2 group and HCC complicated with DM2 group than in the HCC group (P < 0.05). The levels of serum AFP and CA199 were significantly higher in the HCC group and HCC complicated with DM2 group than in the DM2 group (P < 0.05). The levels of serum IGF-1, AFP, and CA199 in the HCC complicated with DM2 group did not differ significantly among patients with different HCC stages (P > 0.05).
CONCLUSION The levels of IGF-1 in patients with HCC complicated with DM2 group are higher than those of patients with HCC alone. This finding may be used to guide the early screening of patients with HCC complicated with DM2.
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Affiliation(s)
- Guang-Ying Shi
- Department of Hepatology, Xinjiang Production and Construction Corps Hospital, Urumqi 830002, Xinjiang Uygur Autonomous Region, China
| | - Yu Sun
- Second Department of Internal Medicine, Qitai Hospital, 6th Division, Xinjiang Production and Construction Corps, Qitai 831800, Xinjiang Uygur Autonomous Region, China
| | - Xing-Chen Liang
- Shihezi University School of Medicine, Shihezi 832003, Xinjiang Uygur Autonomous Region, China
| | - Jing-Dong Xie
- Department of Infection, Ruijin Hospital, School of medicine, Shanghai Jiaotong University, Shanghai 200025, China
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Chen M, Xiao H, Chen B, Bian Z, Kwan HY. The advantages of using Scutellaria baicalensis and its flavonoids for the management of non-viral hepatocellular carcinoma. J Funct Foods 2021. [DOI: 10.1016/j.jff.2021.104389] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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Campbell C, Wang T, McNaughton AL, Barnes E, Matthews PC. Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: a systematic review and meta-analysis. J Viral Hepat 2021; 28:493-507. [PMID: 33305479 PMCID: PMC8581992 DOI: 10.1111/jvh.13452] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 11/19/2020] [Accepted: 11/23/2020] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide and is a leading cause of death in individuals with chronic hepatitis B virus (HBV) infection. It is uncertain how the presence of other metabolic factors and comorbidities influences HCC risk in HBV. Therefore, we performed a systematic literature review and meta-analysis to seek evidence for significant associations. MEDLINE, EMBASE and Web of Science databases were searched from 1 January 2000 to 24 June 2020 for studies investigating associations of metabolic factors and comorbidities with HCC risk in individuals with chronic HBV infection, written in English. We extracted data for meta-analysis and generated pooled effect estimates from a fixed-effects model. Pooled estimates from a random-effects model were also generated if significant heterogeneity was present. We identified 40 observational studies reporting on associations of diabetes mellitus (DM), hypertension, dyslipidaemia and obesity with HCC risk. Only DM had a sufficient number of studies for meta-analysis. DM was associated with >25% increase in hazards of HCC (fixed-effects hazards ratio [HR] 1.26, 95% confidence interval (CI) 1.20-1.32, random-effects HR 1.36, 95% CI 1.23-1.49). This association was attenuated towards the null in a sensitivity analysis restricted to studies adjusted for metformin use. In conclusion, in adults with chronic HBV infection, DM is a significant risk factor for HCC, but further investigation of the influence of antidiabetic drug use and glycaemic control on this association is needed. Enhanced screening of individuals with HBV and diabetes may be warranted.
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Affiliation(s)
- Cori Campbell
- Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | - Tingyan Wang
- Nuffield Department of MedicineUniversity of OxfordOxfordUK
| | | | - Eleanor Barnes
- Nuffield Department of MedicineUniversity of OxfordOxfordUK,Department of HepatologyOxford University NHS Foundation TrustJohn Radcliffe HospitalOxfordUK
| | - Philippa C. Matthews
- Nuffield Department of MedicineUniversity of OxfordOxfordUK,Department of Infectious Diseases and MicrobiologyOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxfordUK,NIHR BRCJohn Radcliffe HospitalOxfordUK
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15
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Wang M, Yang Y, Liao Z. Diabetes and cancer: Epidemiological and biological links. World J Diabetes 2020; 11:227-238. [PMID: 32547697 PMCID: PMC7284016 DOI: 10.4239/wjd.v11.i6.227] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2020] [Revised: 04/24/2020] [Accepted: 05/05/2020] [Indexed: 02/06/2023] Open
Abstract
The incidence of diabetes and cancer has increased significantly in recent years. Furthermore, there are many common risk factors for both diabetes and cancer, such as obesity, sedentary lifestyle, smoking, and ageing. A large body of epidemiological evidence has indicated that diabetes is considered as an independent risk factor for increased rates of heterogeneous types of cancer occurrence and death. The incidence and mortality of various types of cancer, such as pancreas, liver, colorectal, breast, endometrial, and bladder cancers, have a modest growth in diabetics. However, diabetes may work as a protective factor for prostate cancer. Although the underlying biological mechanisms have not been totally understood, studies have validated that insulin/insulin-like growth factor (IGF) axis (including insulin resistance, hyperinsulinemia, and IGF), hyperglycemia, inflammatory cytokines, and sex hormones provide good circumstances for cancer cell proliferation and metastasis. Insulin/IGF axis activates several metabolic and mitogenic signaling pathways; hyperglycemia provides energy for cancer cell growth; inflammatory cytokines influence cancer cell apoptosis. Thus, these three factors affect all types of cancer, while sex hormones only play important roles in breast cancer, endometrial cancer, and prostate cancer. This minireview consolidates and discusses the epidemiological and biological links between diabetes and various types of cancer.
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Affiliation(s)
- Mina Wang
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- The Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing 100010, China
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Yingying Yang
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna 17177, Sweden
- Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Zehuan Liao
- School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
- Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Solna 17177, Sweden
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16
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Sanchez-Torrijos Y, Ampuero J. The Spectrum of NAFLD: From the Organ to the System. NAFLD AND NASH 2020:1-10. [DOI: 10.1007/978-3-030-37173-9_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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17
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Abudawood M. Diabetes and cancer: A comprehensive review. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2019; 24:94. [PMID: 31741666 PMCID: PMC6856544 DOI: 10.4103/jrms.jrms_242_19] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 06/30/2019] [Accepted: 08/26/2019] [Indexed: 02/06/2023]
Abstract
Diabetes mellitus (DM) is a common worldwide endocrine disorder characterized by hyperglycemia resulting from defects in insulin secretion and insulin action or both. A number of clinical studies have investigated diabetes and its causal relation with neoplasm. Several epidemiological studies have found that diabetic patients have an increased risk of different types of cancers, for example liver, pancreas, gastric (stomach), colorectum, kidney, and breast, and it is predicted that hyperglycemic state observed in diabetic milieu enhances the cancer risk in prediabetic and diabetic individuals. To explore the strength of evidence and biases in the claimed associations between type 2 DM (T2DM) and risk of developing cancer, an umbrella review of the evidence across published meta-analyses or systematic reviews is performed. The concurrence of T2DM with the growing burden of cancer globally has generated interest in defining the epidemiological and biological relationships between these medical conditions. Through this review, it was found that diabetes could be related to cancer. Yet, the results from most of the studies are obscure and conflicting and need a robust research so that the link between diabetes and cancer could be firmly and impeccably documented.
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Affiliation(s)
- Manal Abudawood
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, KSA
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18
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Tan Y, Zhang X, Zhang W, Tang L, Yang H, Yan K, Jiang L, Yang J, Li C, Yang J, Wen T, Tang H, Yan L. The Influence of Metabolic Syndrome on the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection in Mainland China. Cancer Epidemiol Biomarkers Prev 2019; 28:2038-2046. [PMID: 31533942 DOI: 10.1158/1055-9965.epi-19-0303] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 06/15/2019] [Accepted: 09/12/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The association between metabolic syndrome (MS), both in terms of its components and as a whole, and the risk of hepatocellular carcinoma (HCC) in subjects with hepatitis B virus (HBV) infection remains unclear, especially in mainland China. METHODS We prospectively included 6,564 individuals with HBV infection from an initial cohort of 105,397 civil servants. The multivariate-adjusted HR and 95% confidence interval (95% CI) were evaluated using Cox proportional hazards models to explore the potential connection between HCC risk and MS. Cumulative incidences were plotted using Kaplan-Meier curves. RESULTS After a 45,668.0 person-year follow-up (76.0 ± 30.8 months) of 6,564 subjects who were seropositive for hepatitis B surface antigen, 89 incident HCC cases were identified. MS as a whole was independently associated with a 2-fold increased HCC risk (HR, 2.25; 95% CI, 1.41-3.60) after adjusting for age (in 1-year increments), gender, cigarette smoking, alcohol consumption, liver cirrhosis, and elevated aspartate aminotransferase levels (≥40 U/L). Subjects with three or more factors and those with one or two factors had adjusted increased HCC risks of 2.12-fold (95% CI, 1.16-3.89) and 1.28-fold (95% CI, 0.74-2.22), respectively, in comparison with those without any metabolic factors. Central obesity and type 2 diabetes were associated with significantly increased HCC risk, whereas this association was not observed in obese subjects (body mass index ≥30 kg/m2; 95% CI, 0.73-3.44). CONCLUSIONS MS as a whole, central obesity, and type 2 diabetes were independently associated with increased HCC risk in a population with HBV infection in mainland China. IMPACT MS may be a risk factor for HCC.
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Affiliation(s)
- Yifei Tan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Xiaoyun Zhang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Wei Zhang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Li Tang
- Department of Intense Care Unit, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Hanwei Yang
- Physical Examination Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Ke Yan
- West China School of Public Health, Sichuan University, Chengdu, Sichuan Province, China
| | - Li Jiang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jian Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Chuan Li
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
| | - Jiayin Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
| | - Tianfu Wen
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
| | - Huairong Tang
- Physical Examination Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
| | - Lunan Yan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
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19
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Chronic Viral Hepatitis Signifies the Association of Premixed Insulin Analogues with Liver Cancer Risks: A Nationwide Population-Based Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16122097. [PMID: 31200528 PMCID: PMC6616640 DOI: 10.3390/ijerph16122097] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 06/09/2019] [Accepted: 06/12/2019] [Indexed: 02/07/2023]
Abstract
This study sought to determine whether chronic hepatitis B or C would modify the association between insulin analogues and hepatocellular carcinoma (HCC) risks. We conducted a nationwide nested case-control study for HCC cases and matched controls from 2003 to 2013 among newly diagnosed type 2 diabetes patients on any antidiabetic agents in Taiwan before and after exclusion of chronic viral hepatitis, respectively. A total of 5832 and 1237 HCC cases were identified before and after exclusion of chronic viral hepatitis, respectively. Incident HCC risks were positively associated with any use of premixed insulin analogues (adjusted odds ratio (OR), 1.27; 95% CI 1.04 to 1.55) among total participants, especially among current users (adjusted OR, 1.45; 95% CI 1.12 to 1.89). However, the association between HCC occurrence and premixed insulin analogues diminished among participants without chronic viral hepatitis (adjusted OR, 1.35; 95% CI 0.92 to 1.98). We also observed a significant multiplicative interaction between chronic viral hepatitis and premixed insulin analogues on HCC risks (P = 0.010). Conclusions: Chronic viral hepatitis signifies the role of premixed insulin analogues in HCC oncogenesis. We recommend a closer liver surveillance among patients prescribed premixed insulin analogues with concomitant chronic viral hepatitis.
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20
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Diabetes mellitus as a risk factor of hepatocellular carcinoma in patients with chronic hepatitis B on nucleot(s)ide analogues. J Hepatol 2019; 70:795-796. [PMID: 30630598 DOI: 10.1016/j.jhep.2018.11.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Accepted: 11/16/2018] [Indexed: 12/04/2022]
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21
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Carnovale C, Pozzi M, Dassano A, D'Addio F, Gentili M, Magni C, Clementi E, Radice S, Fiorina P. The impact of a successful treatment of hepatitis C virus on glyco-metabolic control in diabetic patients: a systematic review and meta-analysis. Acta Diabetol 2019; 56:341-354. [PMID: 30478781 DOI: 10.1007/s00592-018-1257-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2018] [Accepted: 11/06/2018] [Indexed: 01/06/2023]
Abstract
AIMS The effect of HCV eradication following the use of direct-acting antiviral drugs (DAAs) on the glyco-metabolic control is unknown. Through a meta-analysis of available clinical studies, we investigated whether eradication of HCV infection with interferon-free DAAs is associated with improved glyco-metabolic control in diabetic patients. METHODS We searched the PubMed, MEDLINE and Embase, up to 08th June 2018, for all studies evaluating whether eradication of HCV infection with DAAs is associated with changes in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) levels from baseline in human subjects, without restrictions for study type and language. Data were independently extracted by two researchers using pre-specified forms. Random effects meta-analyses were conducted on HbA1c and FPG levels before/after HCV eradication. RESULTS We found a significant mean reduction in HbA1c levels of - 0.45% (95% CI - 0.60 to - 0.30%; P < 0.001) and in FPG levels of - 22.03 mg/dL (95% CI - 41.61 to - 2.44 mg/dL; P = 0.03), with high heterogeneity between studies (χ2 = 20.4, P < 0.001, I2 = 80% and χ2 = 35.8, P = 0.001, I2 = 94%, respectively). The number of available manuscripts did not allow conducting a meta-regression to elucidate the role of sustained virological response and other confounders in determining the effect of direct-acting antiviral agents on HbA1c reduction. CONCLUSIONS We found a significant improvement in glyco-metabolic control after HCV eradication (in terms of glycated haemoglobin and fasting plasma glucose levels reduction) following direct-acting antiviral treatment in patients with established diabetes, including a consequent positive impact on anti-diabetic therapies.
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Affiliation(s)
- Carla Carnovale
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy
| | - Marco Pozzi
- Scientific Institute IRCCS Eugenio Medea, 23842, Bosisio Parini, Lecco, Italy
| | - Alice Dassano
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, Università di Milano, 20157, Milan, Italy
| | - Francesca D'Addio
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, Università di Milano, 20157, Milan, Italy
| | - Marta Gentili
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy
| | - Carlo Magni
- 1st Division of Infectious Diseases, ASST Fatebenefratelli-Sacco, 20157, Milan, Italy
| | - Emilio Clementi
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy
- Scientific Institute IRCCS Eugenio Medea, 23842, Bosisio Parini, Lecco, Italy
| | - Sonia Radice
- Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy
| | - Paolo Fiorina
- International Center for T1D, Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, Department of Biomedical and Clinical Science L. Sacco, Università di Milano, 20157, Milan, Italy
- Nephrology Division, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
- Division of Endocrinology, ASST Fatebenefratelli-Sacco, 20157, Milan, Italy
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22
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Tan Y, Wei S, Zhang W, Yang J, Yang J, Yan L. Type 2 diabetes mellitus increases the risk of hepatocellular carcinoma in subjects with chronic hepatitis B virus infection: a meta-analysis and systematic review. Cancer Manag Res 2019; 11:705-713. [PMID: 30679924 PMCID: PMC6338123 DOI: 10.2147/cmar.s188238] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background Type 2 diabetes mellitus has been proved to be a risk factor of hepatocellular carcinoma, but how diabetes affects incidence of hepatocellular carcinoma among patients with chronic hepatitis B virus infection remains controversial. Methods A comprehensive search of Medline and Embase was performed. Incidence of hepatocellular carcinoma in chronic hepatitis B patients was the primary outcome. Pooled HRs and 95% CIs were calculated to assess the correlation between diabetes and incidence of hepatocellular carcinoma. Results Five cohort studies and two case–control studies were identified, with a total of 21,842 chronic hepatitis B patients. The diabetes mellitus cohort was found to have increased incidence of hepatocellular carcinoma (pooled HR 1.77, 95% CI 1.28–2.47; fixed effect) and worse overall mortality (pooled RR 1.93, 95% CI 1.64–2.27; fixed effect) in comparison with those without diabetes. In case–control studies, hepatocellular carcinoma cases were found to have an insignificantly elevated diabetes mellitus rate in comparison with the control group. Conclusion Type 2 diabetes mellitus is significantly associated with increased risk of hepatocellular carcinoma among patients with chronic hepatitis B virus infection, and aggressive management of diabetes mellitus is strongly suggested.
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Affiliation(s)
- Yifei Tan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
| | - Shiyou Wei
- Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Wei Zhang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
| | - Jian Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
| | - Jiayin Yang
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
| | - Lunan Yan
- Liver Transplantation Center, Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China,
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23
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Miura K, Ohnishi H, Morimoto N, Minami S, Ishioka M, Watanabe S, Tsukui M, Takaoka Y, Nomoto H, Isoda N, Yamamoto H. Ezetimibe suppresses development of liver tumors by inhibiting angiogenesis in mice fed a high-fat diet. Cancer Sci 2019; 110:771-783. [PMID: 30520543 PMCID: PMC6361611 DOI: 10.1111/cas.13902] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Revised: 11/20/2018] [Accepted: 11/23/2018] [Indexed: 12/11/2022] Open
Abstract
Nonalcoholic steatohepatitis (NASH) is a common cause of liver cirrhosis and hepatocellular carcinoma (HCC). However, effective therapeutic strategies for preventing and treating NASH‐mediated liver cirrhosis and HCC are lacking. Cholesterol is closely associated with vascular endothelial growth factor (VEGF), a key factor that promotes HCC. Recent reports have demonstrated that statins could prevent HCC development. In contrast, we have little information on ezetimibe, an inhibitor of cholesterol absorption, in regards to the prevention of NASH‐related liver cirrhosis and HCC. In the present study, a steatohepatitis‐related HCC model, hepatocyte‐specific phosphatase and tensin homolog (Pten)‐deficient (PtenΔhep) mice were fed a high‐fat (HF) diet with/without ezetimibe. In the standard‐diet group, ezetimibe did not reduce the development of liver tumors in PtenΔhep mice, in which the increase of serum cholesterol levels was mild. Feeding of a HF diet increased serum cholesterol levels markedly and subsequently increased serum levels of VEGF, a crucial component of angiogenesis. The HF diet increased the number of VEGF‐positive cells and vascular endothelial cells in the tumors of PtenΔhep mice. Kupffer cells, macrophages in the liver, increased VEGF expression in response to fat overload. Ezetimibe treatment lowered cholesterol levels and these angiogenetic processes. As a result, ezetimibe also suppressed inflammation, liver fibrosis and tumor growth in PtenΔhep mice on the HF diet. Tumor cells were highly proliferative with HF‐diet feeding, which was inhibited by ezetimibe. In conclusion, ezetimibe suppressed development of liver tumors by inhibiting angiogenesis in PtenΔhep mice with hypercholesterolemia.
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Affiliation(s)
- Kouichi Miura
- Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Hirohide Ohnishi
- Department of Gastroenterology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.,Japan Organization of Occupational Health and Safety, Kanagawa, Japan
| | - Naoki Morimoto
- Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Shinichiro Minami
- Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan
| | - Mitsuaki Ishioka
- Department of Gastroenterology, Akita University Graduate School of Medicine, Akita, Japan
| | - Shunji Watanabe
- Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Mamiko Tsukui
- Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Yoshinari Takaoka
- Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Hiroaki Nomoto
- Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Norio Isoda
- Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
| | - Hironori Yamamoto
- Division of Gastroenterology, Department of Medicine, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan
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24
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Li X, Xu H, Gao P. Diabetes Mellitus is a Risk Factor for Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Infection in China. Med Sci Monit 2018; 24:6729-6734. [PMID: 30245503 PMCID: PMC6178879 DOI: 10.12659/msm.911702] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND This study aimed to investigate whether diabetes mellitus (DM) increased the risk of developing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. MATERIAL AND METHODS Individuals with a confirmed diagnosis of HCC and chronic HBV infection (n=112), and non-diabetic individuals with both chronic HBV infection and HCC (n=210), were matched by age, sex, and degree of liver cirrhosis. Demographic, lifestyle, and clinical data were reviewed. Data were analyzed by univariate and multiple logistic regression analysis to identify the risk factors for HCC. RESULTS Of the 112 patients with HCC (median age, 52.0 years; range, 46.3-56.0 years), 18.8% were men, and the prevalence of cirrhosis was 90.2%. Of the 210 patients without HCC (median age, 51.0 years; range, 47.0-58.0 years), 26.2% were men, and the prevalence of cirrhosis was 91.9%. Diabetes mellitus was more prevalent among individuals with HCC (16.1%) compared with those without HCC (7.6%) and increased the risk for HCC by two-fold to three-fold (adjusted odds ratio [AOR]: 2.402; 95% confidence interval [CI], 1.150-5.018). Multivariate analysis showed that cigarette smoking significantly increased the risk of HBV-related HCC (AOR: 1.665; 95% CI, 1.031-2.690), as did increased levels of HBV DNA (≥10³ IU/mL) (AOR: 1.753; 95% CI, 1.079-2.849). CONCLUSIONS In a Chinese population with chronic HBV infection, DM increased the risk of HCC, as did cigarette smoking and high levels of HBV DNA. Screening patients with known risk factors for HCC might improve early detection rates and treatment to prevent tumor progression.
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Affiliation(s)
- Xu Li
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, China (mainland)
| | - Hongqin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, China (mainland).,Jilin Province Key Laboratory of Infectious Disease, Laboratory of Molecular Virology, Changchun, Jilin, China (mainland)
| | - Pujun Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, China (mainland)
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25
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Kim K, Choi S, Park SM. Association of fasting serum glucose level and type 2 diabetes with hepatocellular carcinoma in men with chronic hepatitis B infection: A large cohort study. Eur J Cancer 2018; 102:103-113. [PMID: 30189372 DOI: 10.1016/j.ejca.2018.07.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 07/09/2018] [Accepted: 07/13/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND It is unclear whether elevated fasting serum glucose level and type 2 diabetes (T2DM) are associated with an increased risk of hepatocellular carcinoma (HCC), irrespective of obesity in patients with chronic hepatitis B. PATIENTS AND METHODS Our study population comprised 214,167 Korean men with chronic hepatitis B in the National Health Insurance Service (NHIS) database between January 2002 and December 2006. Data on new events of HCC were obtained by records of the NHIS during the follow-up. We used Cox proportional hazards models adjusted for sociodemographic, lifestyle, health status and clinical conditions to estimate the hazard ratio (HR) and 95% confidence intervals (95% CIs) of HCC associated with different categories of fasting serum glucose level and T2DM, using fasting serum glucose <90 mg/dL as reference. RESULTS During the 8 years of follow-up, there were 11,241 HCCs in men with chronic hepatitis B. Compared with the reference group, fasting serum glucose level of more than 140 mg/dL (HR = 1.46; 95% CI: 1.36-1.57; p < 0.001) and presence of T2DM (HR = 1.23; 95% CI: 1.15-1.34; p < 0.001) were associated with an increased risk of HCC after controlling for potential confounders. Significant association with fasting serum glucose and HCC was found for both non-obese (<25 kg/m2) and obese (≥25.0 kg/m2) patients (Ptrend < 0.001). CONCLUSION In this cohort of men with chronic hepatitis B infection, elevated fasting serum glucose level and T2DM were significantly associated with an increased risk of HCC, regardless of obesity. Glycaemic control in men with chronic hepatitis B patients should be considered in clinical practice to prevent HCC.
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Affiliation(s)
- Kyuwoong Kim
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Seulggie Choi
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Sang Min Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea; Department of Family Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea.
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26
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Pan XF, He M, Yu C, Lv J, Guo Y, Bian Z, Yang L, Chen Y, Wu T, Chen Z, Pan A, Li L. Type 2 Diabetes and Risk of Incident Cancer in China: A Prospective Study Among 0.5 Million Chinese Adults. Am J Epidemiol 2018; 187:1380-1391. [PMID: 29304221 PMCID: PMC6153481 DOI: 10.1093/aje/kwx376] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 12/09/2017] [Accepted: 12/14/2017] [Indexed: 12/20/2022] Open
Abstract
Using data from the China Kadoorie Biobank Study, we conducted a prospective investigation on the association between type 2 diabetes mellitus (T2DM) and cancer risk in Chinese adults. A total of 508,892 participants (mean age = 51.5 (standard deviation, 10.7) years) without prior cancer diagnosis at baseline (2004-2008) were included. We documented 17,463 incident cancer cases during follow-up through December 31, 2013. Participants with T2DM had increased risks of total and certain site-specific cancers; hazard ratios were 1.13 (95% confidence interval (CI): 1.07, 1.19) for total cancer, 1.51 (95% CI: 1.29, 1.76) for liver cancer, 1.86 (95% CI: 1.43, 2.41) for pancreatic cancer, and 1.21 (95% CI: 1.01, 1.47) for female breast cancer. The associations were largely consistent when physician-diagnosed and screen-detected T2DM were analyzed separately, except for colorectal cancer (for physician-diagnosed T2DM, HR = 0.91 (95% CI: 0.73, 1.13), and for screen-detected T2DM, HR = 1.44 (95% CI: 1.18, 1.77)). In participants without a prior diagnosis of T2DM, higher random blood glucose levels were positively associated with risks of total cancer, liver cancer, and female breast cancer (all P's for trend ≤ 0.02). In conclusion, T2DM is associated with an increased risk of new-onset cancer in China, particularly cancers of the liver, pancreas, and female breast.
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Affiliation(s)
- Xiong-Fei Pan
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health
| | - Meian He
- Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health
| | - Canqing Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
| | - Jun Lv
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
| | - Yu Guo
- Chinese Academy of Medical Sciences, Beijing, China
| | - Zheng Bian
- Chinese Academy of Medical Sciences, Beijing, China
| | - Ling Yang
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Yiping Chen
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Tangchun Wu
- Department of Occupational and Environmental Health, Ministry of Education Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health
| | - Zhengming Chen
- Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - An Pan
- Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health and State Key Laboratory of Environmental Health
| | - Liming Li
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
- Chinese Academy of Medical Sciences, Beijing, China
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Nam SY. Obesity-Related Digestive Diseases and Their Pathophysiology. Gut Liver 2018; 11:323-334. [PMID: 27890867 PMCID: PMC5417774 DOI: 10.5009/gnl15557] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2015] [Accepted: 12/25/2015] [Indexed: 12/13/2022] Open
Abstract
Obesity is a growing medical and public health problem worldwide. Many digestive diseases are related to obesity. In this article, the current state of our knowledge of obesity-related digestive diseases, their pathogenesis, and the medical and metabolic consequences of weight reduction are discussed. Obesity-related digestive diseases include gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, colon polyp and cancer, nonalcoholic fatty liver disease, hepatitis C-related disease, hepatocellular carcinoma, gallstone, cholangiocarcinoma, and pancreatic cancer. Although obesity-related esophageal diseases are associated with altered mechanical and humoral factors, other obesity-related digestive diseases seem to be associated with obesity-induced altered circulating levels of adipocytokines and insulin resistance. The relationship between functional gastrointestinal disease and obesity has been debated. This review provides a comprehensive evaluation of the obesity-related digestive diseases, including pathophysiology, obesity-related risk, and medical and metabolic effects of weight reduction in obese subjects.
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Affiliation(s)
- Su Youn Nam
- Department of Gastroenterology, Gastric Cancer Center, Kyungpook National University Medical Center, Daegu, Korea
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28
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Diabetes Mellitus and Risk of Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2017; 2017:5202684. [PMID: 29379799 PMCID: PMC5742888 DOI: 10.1155/2017/5202684] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 11/22/2017] [Indexed: 02/06/2023]
Abstract
The occurrence of hepatocellular carcinoma (HCC) is two to three times higher in patients with diabetes mellitus (DM), the prevalence of which is increasing sharply worldwide. The purpose of this review was to describe clinical links between DM and HCC and potential biological mechanisms that may account for this association. We evaluated the role of potential pathways that could account for the development of HCC with different etiologies in the presence of DM. In addition, we also briefly discuss the potential effect of other factors such as type and dosage of antidiabetic medicines and duration of DM on HCC risk.
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29
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Ciancio A, Bosio R, Bo S, Pellegrini M, Sacco M, Vogliotti E, Fassio G, Bianco Mauthe Degerfeld AGF, Gallo M, Giordanino C, Terzi di Bergamo L, Ribaldone D, Bugianesi E, Smedile A, Rizzetto M, Saracco GM. Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents. J Med Virol 2017; 90:320-327. [DOI: 10.1002/jmv.24954] [Citation(s) in RCA: 75] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 09/19/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Alessia Ciancio
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Roberta Bosio
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Simona Bo
- Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Marianna Pellegrini
- Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Marco Sacco
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Edoardo Vogliotti
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Giulia Fassio
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | | | - Monica Gallo
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Chiara Giordanino
- Gastroenterology Unit; San Luigi Hospital; University of Turin; Torino Italy
| | - Lodovico Terzi di Bergamo
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Davide Ribaldone
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Elisabetta Bugianesi
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Antonina Smedile
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Mario Rizzetto
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
| | - Giorgio Maria Saracco
- Gastroenterology Unit; Department of Medical Sciences; AOU Città della Salute e della Scienza di Torino; University of Turin; Torino Italy
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30
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Nishida T. Diagnosis and Clinical Implications of Diabetes in Liver Cirrhosis: A Focus on the Oral Glucose Tolerance Test. J Endocr Soc 2017; 1:886-896. [PMID: 29264539 PMCID: PMC5686620 DOI: 10.1210/js.2017-00183] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Accepted: 05/18/2017] [Indexed: 02/08/2023] Open
Abstract
The liver and skeletal muscles are responsible for maintaining glucose metabolism. As chronic liver disease progresses to cirrhosis, the loss of liver function is exacerbated and leads to the deterioration of skeletal muscle. Consequently, impaired glucose tolerance (IGT) and insulin resistance are often observed in patients with liver cirrhosis. Early stage cirrhosis with hepatogenous diabetes is characterized by marked postprandial hyperglycemia and hyperinsulinemia. Generally, it is possible to underestimate IGT when using either the conventional fasting plasma glucose (FPG) criterion or hemoglobin A1c (HbA1c) levels despite their status as the gold standard for diagnosing diabetes. The number of cirrhotic patients with diabetes tends to be underestimated because many of these patients show lower FPG levels or HbA1c, which masks their IGT. In such cases, the oral glucose tolerance test is recommended to evaluate patients with suspected postprandial hyperglycemia who present with a normal FPG. Moreover, in addition to the Child-Pugh score, the early detection of diabetes may be a useful prognostic marker for patients with liver cirrhosis.
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Affiliation(s)
- Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, Osaka 560-8565 Japan
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31
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Kim JH, Sinn DH, Gwak GY, Kang W, Paik YH, Choi MS, Lee JH, Koh KC, Paik SW. Insulin resistance and the risk of hepatocellular carcinoma in chronic hepatitis B patients. J Gastroenterol Hepatol 2017; 32:1100-1106. [PMID: 27862289 DOI: 10.1111/jgh.13647] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 10/25/2016] [Accepted: 11/06/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIM We analyzed whether insulin resistance (IR) assessed by homeostasis model assessment (HOMA2-IR) index can stratify hepatocellular carcinoma (HCC) risk in patients with chronic hepatitis B virus (HBV) infection. METHODS A retrospective cohort of 1696 chronic HBV-infected patients (age: 50.0 ± 7.8 years, men = 964 [56.8%]) who underwent detailed health checkup program including C-peptide and fasting blood glucose measurement and followed up for more than a year were analyzed. RESULTS During a median follow-up of 5.0 years (range, 1.0-10.5 years), 24 patients (1.4%) developed HCC. The HCC incidence rate was higher for patients with higher HOMA2-IR value than those with lower HOMA2-IR value (1.7% vs 0.5% for HOMA2-IR >1.200 vs ≤1.200, P = 0.009). HOMA2-IR was a significant factor associated with HCC development in multivariable-adjusted model (HR [95% CI]: 3.25 [1.13-9.31], adjusted for age, sex, cirrhosis, and HBV DNA levels). The association between HOMA2-IR and HCC was markedly attenuated and became no longer statistically significant (HR [95% CI]: 1.93 [0.57-6.51]) when further adjusted for obesity, hypertension, and diabetes. In subgroup analysis, HOMA2-IR value was an independent factor associated with HCC in patients without overt metabolic abnormalities (hypertension, diabetes, and metabolic syndrome) but not for those with overt metabolic abnormalities. CONCLUSION Insulin resistance assessed by HOMA2 was associated with the risk of HCC, indicating that HOMA2-IR can be a useful tool for stratifying the risk of HCC in chronic HBV-infected patients, particularly in patients without overt metabolic abnormalities.
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Affiliation(s)
- Jung Hee Kim
- Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Kwang Cheol Koh
- Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul, Korea
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32
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Desbois AC, Cacoub P. Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review. World J Gastroenterol 2017; 23:1697-1711. [PMID: 28321170 PMCID: PMC5340821 DOI: 10.3748/wjg.v23.i9.1697] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 11/10/2016] [Accepted: 02/08/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To summarise the literature data on hepatitis C virus (HCV)-infected patients concerning the prevalence of glucose abnormalities and associated risk.
METHODS We conducted a PubMed search and selected all studies found with the key words "HCV" or "hepatitis C virus" and "diabetes" or "insulin resistance". We included only comparative studies written in English or in French, published from January 2000 to April 2015. We collected the literature data on HCV-infected patients concerning the prevalence of glucose abnormalities [diabetes mellitus (DM) and insulin resistance (IR)] and associated risk [i.e., severe liver fibrosis, response to antivirals, and the occurrence of hepatocellular carcinoma (HCC)].
RESULTS HCV infection is significantly associated with DM/IR compared with healthy volunteers and patients with hepatitis B virus infection. Glucose abnormalities were associated with advanced liver fibrosis, lack of sustained virologic response to interferon alfa-based treatment and with a higher risk of HCC development. As new antiviral therapies may offer a cure for HCV infection, such data should be taken into account, from a therapeutic and preventive point of view, for liver and non-liver consequences of HCV disease. The efficacy of antidiabetic treatment in improving the response to antiviral treatment and in decreasing the risk of HCC has been reported by some studies but not by others. Thus, the effects of glucose abnormalities correction in reducing liver events need further studies.
CONCLUSION Glucose abnormalities are strongly associated with HCV infection and show a negative impact on the main liver related outcomes.
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33
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Zignego AL, Ramos-Casals M, Ferri C, Saadoun D, Arcaini L, Roccatello D, Antonelli A, Desbois AC, Comarmond C, Gragnani L, Casato M, Lamprecht P, Mangia A, Tzioufas AG, Younossi ZM, Cacoub P. International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement. Autoimmun Rev 2017; 16:523-541. [PMID: 28286108 DOI: 10.1016/j.autrev.2017.03.004] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 02/26/2017] [Indexed: 02/06/2023]
Abstract
Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility.
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Affiliation(s)
- Anna Linda Zignego
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
| | - Manuel Ramos-Casals
- Department of Autoimmune Diseases, ICMiD Josep Font Autoimmune Lab, CELLEX-IDIBAPS, Hospital Clinic, Barcelona, Spain
| | - Clodoveo Ferri
- Chair and Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria, Policlinico di Modena, 41124 Modena, Italy
| | - David Saadoun
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Luca Arcaini
- Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Dario Roccatello
- Department of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Center of Research of Immunopathology and Rare Diseases, and Nephrology and Dialysis Unit, San G. Bosco Hospital and University of Turin, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, Pisa 56126, Italy
| | - Anne Claire Desbois
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Cloe Comarmond
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
| | - Laura Gragnani
- Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Milvia Casato
- Department of Clinical Medicine, Sapienza University of Rome, Viale dell'Università 37, 00185 Rome, Italy.
| | - Peter Lamprecht
- Klinik für Rheumatologie Oberarzt, Ratzeburger Allee 160 (Haus 40), 23538 Lübeck, Germany.
| | - Alessandra Mangia
- Liver Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy.
| | - Athanasios G Tzioufas
- Department of Pathophysiology, School of Medicine, University of Athens, 75 M. Asias st, Building 16, Room, 32 11527 Athens, Greece.
| | - Zobair M Younossi
- Center for Liver Diseases, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA; Beatty Liver and Obesity Program, Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
| | - Patrice Cacoub
- Sorbonne University, UPMC Univ Paris 06, UMR 7211, and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France; INSERM, UMR S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France
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34
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GFD-Net: A novel semantic similarity methodology for the analysis of gene networks. J Biomed Inform 2017; 68:71-82. [PMID: 28274758 DOI: 10.1016/j.jbi.2017.02.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 02/08/2017] [Accepted: 02/22/2017] [Indexed: 02/06/2023]
Abstract
Since the popularization of biological network inference methods, it has become crucial to create methods to validate the resulting models. Here we present GFD-Net, the first methodology that applies the concept of semantic similarity to gene network analysis. GFD-Net combines the concept of semantic similarity with the use of gene network topology to analyze the functional dissimilarity of gene networks based on Gene Ontology (GO). The main innovation of GFD-Net lies in the way that semantic similarity is used to analyze gene networks taking into account the network topology. GFD-Net selects a functionality for each gene (specified by a GO term), weights each edge according to the dissimilarity between the nodes at its ends and calculates a quantitative measure of the network functional dissimilarity, i.e. a quantitative value of the degree of dissimilarity between the connected genes. The robustness of GFD-Net as a gene network validation tool was demonstrated by performing a ROC analysis on several network repositories. Furthermore, a well-known network was analyzed showing that GFD-Net can also be used to infer knowledge. The relevance of GFD-Net becomes more evident in Section "GFD-Net applied to the study of human diseases" where an example of how GFD-Net can be applied to the study of human diseases is presented. GFD-Net is available as an open-source Cytoscape app which offers a user-friendly interface to configure and execute the algorithm as well as the ability to visualize and interact with the results(http://apps.cytoscape.org/apps/gfdnet).
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35
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Seto WK, Lau EHY, Wu JTK, Hung IFN, Leung WK, Cheung KS, Fung J, Lai CL, Yuen MF. Effects of nucleoside analogue prescription for hepatitis B on the incidence of liver cancer in Hong Kong: a territory-wide ecological study. Aliment Pharmacol Ther 2017; 45:501-509. [PMID: 27976416 DOI: 10.1111/apt.13895] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 10/27/2016] [Accepted: 11/18/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND The temporal relationship between nucleoside analogue therapy for chronic hepatitis B (CHB) and liver cancer development has not been evaluated at a population level. AIM To investigate the impact of nucleoside analogue prescription on liver cancer incidence in a CHB-prevalent region. METHODS We obtained territory-wide nucleoside analogue prescription data from 1999, when nucleoside analogue was first available in Hong Kong, to 2012 and the population-based liver cancer incidence data from 1990 to 2012. We compared the liver cancer incidences from 1990 to 1998 and 1999 to 2012 with adjustment for local hepatitis B surface antigen seroprevalence. RESULTS Nucleoside analogue prescription patient headcount increased from 2006 per year in 1999 to 26 411 in 2012. Prescription volume in 2012 was highest among 55-64 years (30.3%), higher than 65-74 years (13.0%) and ≥75 years (5.8%). Age-standardised liver cancer incidence 1999-2012 decreased by 1.88%/year (95% CI 3.34% to 0.42%/year). NA therapy was associated with decline in age-adjusted liver cancer incidence (2.7 per 100 000 persons, P < 0.001, 95% CI 1.4-4.0 per 100 000 persons). Fifty-five to sixty-four years age group had the most significant decline (men: 24.0 per 100 000 persons, P = 0.001, 95% CI 11.4-36.6 per 100 000 persons; women: 8.5 per 100 000 persons, P = 0.009, 95% CI 2.3-14.6 per 100 000 persons). No significant association was noted in age groups 65-74 years and ≥75 years (both P > 0.05). CONCLUSIONS Nucleoside analogue prescription was associated with a reduction of overall liver cancer incidence in a CHB-prevalent region. The lack of association among individuals of ≥65 years was consistent with the low nucleoside analogue prescription volume in elderly patients, mitigating the impact of CHB treatment on liver cancer.
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Affiliation(s)
- W-K Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - E H Y Lau
- School of Public Health, The University of Hong Kong, Hong Kong
| | - J T K Wu
- School of Public Health, The University of Hong Kong, Hong Kong
| | - I F N Hung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - W K Leung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - K-S Cheung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - J Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - C-L Lai
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
| | - M-F Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.,State Key Laboratory for Liver Research, The University of Hong Kong, Queen Mary Hospital, Hong Kong
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36
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Si WK, Chung JW, Cho J, Baeg JY, Jang ES, Yoon H, Kim J, Shin CM, Park YS, Hwang JH, Jeong SH, Kim N, Lee DH, Lim S, Kim JW. Predictors of Increased Risk of Hepatocellular Carcinoma in Patients with Type 2 Diabetes. PLoS One 2016; 11:e0158066. [PMID: 27359325 PMCID: PMC4928920 DOI: 10.1371/journal.pone.0158066] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Accepted: 06/09/2016] [Indexed: 12/20/2022] Open
Abstract
Epidemiological data indicate that type 2 diabetes is associated with increased risk of hepatocellular carcinoma (HCC). However, risk stratification for HCC has not been fully elucidated in diabetic population. The aim of this study was to identify potential predictors of HCC in diabetic patients without chronic viral hepatitis. A cohort of 3,544 diabetic patients without chronic viral hepatitis or alcoholic cirrhosis was established and subjects were randomly allocated into a derivation and a validation set. A scoring system was developed by using potential predictors of increased risk of HCC from the Cox proportional hazards model. The performance of the scoring system was tested for validation by using receiver operating characteristics analysis. During median follow-up of 55 months, 36 cases of HCC developed (190 per 100,000 person-years). The 5- and 10-year cumulative incidences of HCC were 1.0%, and 2.2%, respectively. Multivariate Cox regression analysis showed that age > 65 years, low triglyceride levels and high gamma-glutamyl transferase levels were independently associated with an increased risk of HCC. DM-HCC risk score, a weighted sum of scores from these 3 parameters, predicted 10-year development of HCC with area under the receiver operating characteristics curve of 0.86, and discriminated different risk categories for HCC in the derivation and validation cohort. In conclusion, old age, low triglyceride level and high gamma-glutamyl transferase level may help to identify individuals at high risk of developing HCC in diabetic patients without chronic viral hepatitis or alcoholic cirrhosis.
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Affiliation(s)
- Won Keun Si
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Jung Wha Chung
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Junhyeon Cho
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Joo Yeong Baeg
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Eun Sun Jang
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyuk Yoon
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jaihwan Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Cheol Min Shin
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young Soo Park
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Hyeok Hwang
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sook-Hyang Jeong
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Nayoung Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dong Ho Lee
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Soo Lim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Wook Kim
- Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- * E-mail:
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Roujun C, Yanhua Y, Bixun L. High prevalence of diabetes mellitus and impaired glucose tolerance in liver cancer patients: A hospital based study of 4610 patients with benign tumors or specific cancers. F1000Res 2016; 5:1397. [PMID: 27610222 PMCID: PMC4995685 DOI: 10.12688/f1000research.8457.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/24/2016] [Indexed: 01/07/2023] Open
Abstract
Objective: The prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were hypothesised to be different among different tumor patients. This study aimed to study the association between the prevalence of DM, IGT and IFG and liver cancer, colorectal cancer, breast cancer, cervical cancer, nasopharyngeal cancer and benign tumor. Methods: A hospital based retrospective study was conducted on 4610 patients admitted to the Internal Medical Department of the Affiliated Tumor Hospital of Guangxi Medical University, China. Logistic regression was used to examine the association between gender, age group, ethnicity , cancer types or benign tumors and prevalence of DM, IFG, IGT. Results: Among 4610 patients, there were 1000 liver cancer patients, 373 breast cancer patients, 415 nasopharyngeal cancer patients, 230 cervical cancer patients, 405 colorectal cancer patients, and 2187 benign tumor patients. The prevalence of DM and IGT in liver cancer patients was 14.7% and 22.1%, respectively. The prevalence of DM and IGT was 13.8% and 20%, respectively, in colorectal cancer patients, significantly higher than that of benign cancers. After adjusting for gender, age group, and ethnicity, the prevalence of DM and IGT in liver cancers patients was 1.29 times (CI :1.12-1.66) and 1.49 times (CI :1.20-1.86) higher than that of benign tumors, respectively. Conclusion: There was a high prevalence of DM and IGT in liver cancer patients.
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Affiliation(s)
- Chen Roujun
- Department of Internal Medicine, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi, China
| | - Yi Yanhua
- School for International Education, Guangxi Medical University, Guangxi, China
| | - Li Bixun
- Department of Internal Medicine, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi, China
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38
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NAFLD-Associated Hepatocellular Carcinoma: a Threat to Patients with Metabolic Disorders. ACTA ACUST UNITED AC 2016. [DOI: 10.1007/s11901-016-0297-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Kumar DBU, Chen CL, Liu JC, Feldman DE, Sher LS, French S, DiNorcia J, French SW, Naini BV, Junrungsee S, Agopian VG, Zarrinpar A, Machida K. TLR4 Signaling via NANOG Cooperates With STAT3 to Activate Twist1 and Promote Formation of Tumor-Initiating Stem-Like Cells in Livers of Mice. Gastroenterology 2016; 150:707-19. [PMID: 26582088 PMCID: PMC4766021 DOI: 10.1053/j.gastro.2015.11.002] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Revised: 10/30/2015] [Accepted: 11/01/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS Obesity and alcohol consumption contribute to steatohepatitis, which increases the risk for hepatitis C virus (HCV)-associated hepatocellular carcinomas (HCCs). Mouse hepatocytes that express HCV-NS5A in liver up-regulate the expression of Toll-like receptor 4 (TLR4), and develop liver tumors containing tumor-initiating stem-like cells (TICs) that express NANOG. We investigated whether the TLR4 signals to NANOG to promote the development of TICs and tumorigenesis in mice placed on a Western diet high in cholesterol and saturated fat (HCFD). METHODS We expressed HCV-NS5A from a transgene (NS5A Tg) in Tlr4-/- (C57Bl6/10ScN), and wild-type control mice. Mice were fed a HCFD for 12 months. TICs were identified and isolated based on being CD133+, CD49f+, and CD45-. We obtained 142 paraffin-embedded sections of different stage HCCs and adjacent nontumor areas from the same patients, and performed gene expression, immunofluorescence, and immunohistochemical analyses. RESULTS A higher proportion of NS5A Tg mice developed liver tumors (39%) than mice that did not express HCV NS5A after the HCFD (6%); only 9% of Tlr4-/- NS5A Tg mice fed HCFD developed liver tumors. Livers from NS5A Tg mice fed the HCFD had increased levels of TLR4, NANOG, phosphorylated signal transducer and activator of transcription (pSTAT3), and TWIST1 proteins, and increases in Tlr4, Nanog, Stat3, and Twist1 messenger RNAs. In TICs from NS5A Tg mice, NANOG and pSTAT3 directly interact to activate expression of Twist1. Levels of TLR4, NANOG, pSTAT3, and TWIST were increased in HCC compared with nontumor tissues from patients. CONCLUSIONS HCFD and HCV-NS5A together stimulated TLR4-NANOG and the leptin receptor (OB-R)-pSTAT3 signaling pathways, resulting in liver tumorigenesis through an exaggerated mesenchymal phenotype with prominent Twist1-expressing TICs.
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Affiliation(s)
| | | | | | | | - Linda S. Sher
- Department of Surgery, Keck School of Medicine of University of Southern California
| | | | - Joseph DiNorcia
- Department of Surgery, Keck School of Medicine of University of Southern California
| | - Samuel W. French
- Department of Pathology and Laboratory Medicine of University of California Los Angeles,Jonsson Comprehensive Cancer Center UCLA
| | - Bita V. Naini
- Department of Pathology and Laboratory Medicine of University of California Los Angeles
| | | | | | | | - Keigo Machida
- Department of Molecular Microbiology and Immunology, Keck School of Medicine of University of Southern California, Los Angeles, California; Southern California Research Center for Alcoholic Liver and Pancreatic Disease and Cirrhosis, Los Angeles, California.
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40
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Chiang CH, Lu CW, Han HC, Hung SH, Lee YH, Yang KC, Huang KC. The Relationship of Diabetes and Smoking Status to Hepatocellular Carcinoma Mortality. Medicine (Baltimore) 2016; 95:e2699. [PMID: 26871803 PMCID: PMC4753898 DOI: 10.1097/md.0000000000002699] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The relationship of diabetes and smoking status to hepatocellular carcinoma (HCC) mortality is not clear. We aimed to investigate the association of smoking cessation relative to diabetes status with subsequent deaths from HCC.We followed up 51,164 participants (aged 44-94 years) without chronic hepatitis B or C from 1 January 1998 to 31 December 2008 enrolled from nationwide health screening units in a prospective cohort study. The primary outcomes were deaths from HCC.During the study period, there were 253 deaths from HCC. History of diabetes was associated with deaths from HCC for both total participants (adjusted hazard ratio [HR], 2.97; 95% confidence interval [CI], 2.08-4.23) and ever smokers with current or past smoking habits (HR, 1.92; 95% CI, 1.10-3.34). Both never smokers (HR, 0.46; 95% CI, 0.32-0.65) and quitters (HR, 0.62; 95% CI, 0.39-0.97) had a lower adjusted risk of HCC deaths compared with current smokers. Among all ever smokers with current or past smoking habits, as compared with diabetic smokers, only quitters without diabetes had a lower adjusted risk of HCC deaths (HR, 0.37; 95% CI, 0.18-0.78). However, quitters with diabetes were observed to have a similar risk of deaths from HCC when compared with smokers with diabetes. Regarding the interaction between diabetes and smoking status on adjusted HCC-related deaths, with the exception of quitters without history of diabetes, all groups had significantly higher HRs than nondiabetic never smokers. There was also a significant multiplicative interaction between diabetes and smoking status on risk of dying from HCC (P = 0.033). We suggest clinicians should promote diabetes prevention and never smoking to associate with reduced subsequent HCC mortality even in adults without chronic viral hepatitis.
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Affiliation(s)
- Chien-Hsieh Chiang
- From the Department of Family Medicine, National Taiwan University College of Medicine, Taipei (C-HC, S-HH, K-CH); Department of Community and Family Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin (C-HC, S-HH); Department of Family Medicine, National Taiwan University Hospital (C-HC, C-WL, S-HH, K-CH); Research Center for Applied Sciences, Academia Sinica (H-CH); Community and Geriatric Medicine Research Center, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan (Y-HL, K-CH); Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, MA (Y-HL); Department of Community and Family Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu (K-CY); Institute of Epidemiology and Preventive Medicine, National Taiwan University (K-CY); and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan (K-CH)
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41
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Vanni E, Bugianesi E, Saracco G. Treatment of type 2 diabetes mellitus by viral eradication in chronic hepatitis C: Myth or reality? Dig Liver Dis 2016; 48:105-11. [PMID: 26614641 DOI: 10.1016/j.dld.2015.10.016] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 10/05/2015] [Accepted: 10/16/2015] [Indexed: 12/15/2022]
Abstract
Chronic hepatitis C is a systemic disease inducing metabolic alterations leading to extrahepatic consequences. In particular, hepatitis C virus (HCV) infection seems to increase the risk of incident type 2 diabetes mellitus in predisposed individuals, independently of liver disease stage. The mechanisms through which hepatitis C induces T2DM involve direct viral effects, insulin resistance, pro-inflammatory cytokines and other immune-mediated processes. Many studies have reported the clinical consequences of type 2 diabetes mellitus on hepatitis C outcome, but very few studies have addressed the issue of microangiopathic complications among patients with hepatitis C only, who develop type 2 diabetes mellitus. Moreover, clinical trials in HCV-positive patients have reported improvement in glucose metabolism after antiviral treatment; recent studies have suggested that this metabolic amelioration might have a clinical impact on type 2 diabetes mellitus-related complications. These observations raise the question as to whether the HCV eradication may also have an impact on the future morbidity and mortality due to type 2 diabetes mellitus. The scope of this review is to summarise the current evidence linking successful antiviral treatment and the prevention of type 2 diabetes mellitus and its complications in hepatitis C-infected patients.
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Affiliation(s)
- Ester Vanni
- Gastro-hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Elisabetta Bugianesi
- Gastro-hepatology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giorgio Saracco
- Gastroenterology Unit, Oncology Department, University of Turin, Italy.
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42
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Metformin inhibits angiogenesis induced by interaction of hepatocellular carcinoma with hepatic stellate cells. Cell Biochem Biophys 2015; 71:931-6. [PMID: 25326336 DOI: 10.1007/s12013-014-0287-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Accumulated evidences indicate metformin is associated with reduced risk of hepatocellular carcinoma (HCC) in diabetic patients, which inspired researchers to explore its therapeutic potentials in HCC. Since Hepatic stellate cells (HSCs) are believed to be the key contributors to tumor microenvironment in HCC and promotes tumor development, here, we explored the effect of metformin on tumor angiogenesis induced by interplay of HCC and HSCs. Our results showed that conditional medium from co-culture of HCC/HSCs induced VEGF secretions and stimulated human umbilical vein endothelial cells (HUVEC) tube formation. However, 25 µM metformin could inhibit this angiogenesis effect. Furthermore, knockdown AMPK of HSCs, not HCC, could abolish inhibition caused by metformin. Our finding suggested that metformin could inhibit HCC angiogenesis through targeting on HSCs through AMPK pathway.
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43
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Huang YW, Wang TC, Yang SS, Lin SY, Fu SC, Hu JT, Liu CJ, Kao JH, Chen DS. Increased risk of hepatocellular carcinoma in chronic hepatitis C patients with new onset diabetes: a nation-wide cohort study. Aliment Pharmacol Ther 2015. [PMID: 26211742 DOI: 10.1111/apt.13341] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The impact of diabetes for hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients remains controversial. AIM To investigate the risk of HCC in CHC patients who develop new onset diabetes. METHODS We conducted a nation-wide cohort study by using Taiwanese National Health Insurance Research Database, which comprised of data from >99% of entire population. Among randomly sampled one million enrollees, 6251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in the patient who was given the diagnosis in the years 1999-2009 but not in 1997-1998. The cohorts of CHC with new onset diabetes (n = 1100) and 1:1 ratio age-, gender-, and inception point (onset date of diabetes) matched nondiabetes (n = 1087) were followed up from the inception point until the development of HCC, withdrawal from insurance, or December 2009. RESULTS After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC (Relative Risk = 1.544, 95% CI = 1.000-2.387, modified log-rank test, P = 0.047) as compared to those without. After adjustment for age, gender, cirrhosis, hyperlipidaemia, CHC treatment, diabetes treatment, comorbidity index, obesity and statins therapy by Cox proportional hazard model, diabetes was still an independent predictor for HCC (hazard ratio (HR) = 1.906, 95% CI = 1.102-3.295, P = 0.021). The risk for HCC was increased in those who were 40-59 years old, independent of other variables (HR = 3.086, 95% CI = 1.045-9.112, P = 0.041), and after adjustment for competing mortality (modified log-rank test, P = 0.009). CONCLUSION Chronic hepatitis C patients who develop diabetes are at an increased risk of hepatocellular carcinoma over time.
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Affiliation(s)
- Y-W Huang
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.,School of Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - T-C Wang
- Department of Medical Research, Cathay General Hospital Medical Center, Taipei, Taiwan
| | - S-S Yang
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.,School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei, Taiwan
| | - S-Y Lin
- Department of General Medicine, School of Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan
| | - S-C Fu
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan
| | - J-T Hu
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.,School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei, Taiwan
| | - C-J Liu
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - J-H Kao
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan
| | - D-S Chen
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Genomics Research Center, Academia Sinica, Nankang, Taiwan
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Shen Y, Zhang J, Cai H, Shao JG, Zhang YY, Liu YM, Qin G, Qin Y. Identifying patients with chronic hepatitis B at high risk of type 2 diabetes mellitus: a cross-sectional study with pair-matched controls. BMC Gastroenterol 2015; 15:32. [PMID: 25887997 PMCID: PMC4387579 DOI: 10.1186/s12876-015-0263-9] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 03/04/2015] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The presence of diabetes mellitus (DM) is associated with increased liver morbidity and mortality risk in patients with chronic hepatitis B (CHB). Aim of this study was to identify factors associated with type 2 diabetes mellitus (T2DM) in CHB patients. METHODS A cross-sectional study with pair-matched controls was conducted in Nantong Third People's Hospital, Nantong University, China. From January 2008 to December 2012, a total of 1783 CHB patients were screened for study subjects, among whom 207 patients with T2DM were enrolled as cases and 207 sex- and age-matched non-DM patients as controls. Demographic, anthropometric, lifestyle, clinical, and laboratory data were obtained from each subject. RESULTS In the univariate model, thirteen variables showed marked differences between the DM group and non-DM group. Patients with longer duration of CHB (≥15 years) and alcoholic steatosis showed the highest likelihood of T2DM (odds ratio = 5.39 and 4.95; 95% confidence intervals 2.76-10.53 and 1.65-14.91). In the multivariate adjusted analysis, three CHB-related factors, namely high viral load, long duration of illness, and presence of cirrhosis, contributed to substantially increase the likelihood of T2DM, in addition to the other five risk factors including family history of DM, low education level, elevated triglycerides (TG), gamma-glutamyl transferase (GGT) levels, and presence of alcoholic steatosis. CONCLUSIONS Our findings suggest that high viral load, long duration of CHB, presence of cirrhosis, alcoholic steatosis and several other factors may be potential risk factors for development of T2DM in CHB patients. It is of vital importance to monitor glucose in high-risk CHB patients and aggressively intervene on modifiable risk factors.
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Affiliation(s)
- Yi Shen
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China. .,Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, 226006, China.
| | - Jian Zhang
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China.
| | - Hui Cai
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China.
| | - Jian-Guo Shao
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, 226006, China.
| | - You-Yi Zhang
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, 226006, China.
| | - Yan-Mei Liu
- Department of Epidemiology and Medical Statistics, School of Public Health, Nantong University, Nantong, Jiangsu, 226019, China.
| | - Gang Qin
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, Jiangsu, 226006, China.
| | - Yan Qin
- Department of Internal Medicine, Singapore General Hospital, Singapore, 169608, Singapore.
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Hsiang JC, Gane EJ, Bai WW, Gerred SJ. Type 2 diabetes: a risk factor for liver mortality and complications in hepatitis B cirrhosis patients. J Gastroenterol Hepatol 2015; 30:591-9. [PMID: 25250942 DOI: 10.1111/jgh.12790] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/11/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM The effect of type 2 diabetes mellitus (DM) on morbidity and mortality among hepatitis B virus (HBV) cirrhosis patients is poorly defined. We assess the effect of DM on the HBV cirrhosis outcomes and survival. METHODS A retrospective study of HBV cirrhosis patients who sought care at a sole public hospital in a geographically defined region, from year 2000 to 2012. Cirrhosis complications, liver transplantations, and mortality were reviewed. Primary outcome is the composite of liver-related and overall mortality or orthotopic liver transplantation (OLT). RESULTS Two hundred twenty-three patients entered into the final analysis; 50 patients (22.4%) have DM at cirrhosis diagnosis. Seventy-two percent of DM patients have DM for more than 5 years at cirrhosis diagnosis. The incidence of hepatocellular carcinoma (HCC) was 25.4 and 60.5 per 1000 patient-years for non-DM and DM patients, respectively (P = 0.006). In multivariate analysis, DM was a predictor of HCC (hazard ratio [HR] 2.36, [1.14-4.85], P = 0.02), hepatic complications (HR 2.04, [1.16-3.59], P = 0.01), liver mortality or OLT (HR 2.26, [1.05-4.86], P = 0.04), and overall mortality or OLT (HR 2.25, [1.96-4.22], P = 0.01). Insulin and/or sulphonylurea use and poor diabetic control (glycosylated hemoglobin ≥ 7.0%) were predictors of HCC and cirrhosis complications (all P < 0.05). The 5-year liver-related mortality or OLT rate was 23.4% for DM patients and 9.4% for non-DM patients, respectively (P = 0.009). CONCLUSION The presence of DM and poor diabetic control at cirrhosis diagnosis significantly increase the rate of cirrhosis complications and reduced survival in patients with HBV cirrhosis. Improving diabetic control should be essential part of the cirrhosis care in these patients.
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Affiliation(s)
- John C Hsiang
- Middlemore Hospital, Counties Manukau District Health Board, South Auckland, New Zealand
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Raff EJ, Kakati D, Bloomer JR, Shoreibah M, Rasheed K, Singal AK. Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases. J Clin Transl Hepatol 2015; 3:9-16. [PMID: 26356325 PMCID: PMC4542082 DOI: 10.14218/jcth.2015.00001] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 02/19/2015] [Accepted: 02/22/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND AIMS Alcohol abuse and nonalcoholic fatty liver disease (NAFLD) are common causes of liver disease. Diabetes mellitus (DM) is a common comorbidity among NAFLD patients. We performed this study with the specific aim to examine the impact of DM on progression of alcoholic liver disease (ALD) liver and NAFLD. METHODS Medical charts of 480 patients with ALD or NAFLD (2004-2011) managed at a tertiary center were retrospectively reviewed. NAFLD was diagnosed based on exclusion of other causes of liver disease and alcohol use of <10 g/d. ALD was diagnosed based on alcohol use of >40 g/d in women or >60 g/d in men for >5 years. RESULTS Of 480 patients (307 NAFLD), 200 diabetics differed from nondiabetics for: age (52±11 vs. 49±11 years; p=0.004); male gender (48% vs. 57%; p=0.03); metabolic syndrome (49% vs. 30%; p=0.0002); NAFLD (80% vs. 56%; p<0.0001); cirrhosis (70% vs. 59%; p=0.005); and hepatocellular carcinoma (HCC; 8% vs. 3%; p=0.009). Over a 3 year median follow-up period, diabetics relative to nondiabetics had a higher probability to develop cirrhosis (60% vs. 41%; p=0.022) and HCC (27% vs. 10%; p=0.045). There was a trend for increased development of hepatic encephalopathy in diabetics compared to nondiabetics (55% vs. 39%; p=0.053), and there was no difference between the two groups in survival or other liver disease complications. CONCLUSIONS DM increased risk for cirrhosis and HCC among patients with ALD and NAFLD. Prospective studies with longer follow-up periods are needed to examine the impact of DM on survival and the role of aggressive HCC screening in diabetic cirrhotics.
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Affiliation(s)
- Evan J. Raff
- Department of Internal Medicine, UAB, Birmingham, AL, USA
| | - Donny Kakati
- Department of Internal Medicine, UAB, Birmingham, AL, USA
| | - Joseph R. Bloomer
- Division of Gastroenterology and Hepatology, UAB, Birmingham, AL, USA
| | - Mohamed Shoreibah
- Division of Gastroenterology and Hepatology, UAB, Birmingham, AL, USA
| | - Khalid Rasheed
- Department of Internal Medicine, UAB Montgomery Program, Huntsville, AL, USA
| | - Ashwani K. Singal
- Division of Gastroenterology and Hepatology, UAB, Birmingham, AL, USA
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Tateishi R, Okanoue T, Fujiwara N, Okita K, Kiyosawa K, Omata M, Kumada H, Hayashi N, Koike K. Clinical characteristics, treatment, and prognosis of non-B, non-C hepatocellular carcinoma: a large retrospective multicenter cohort study. J Gastroenterol 2015; 50:350-60. [PMID: 24929638 PMCID: PMC4352653 DOI: 10.1007/s00535-014-0973-8] [Citation(s) in RCA: 125] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Accepted: 06/02/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND The number of hepatocellular carcinoma (HCC) patients with non-viral etiologies is increasing in Japan. We conducted a nation-wide survey to examine the characteristics of those patients. METHODS After we assessed the trend of patients who were first diagnosed with HCC at 53 tertiary care centers in Japan from 1991 to 2010, we collected detailed data of 5326 patients with non-viral etiology. The etiologies were categorized as autoimmune hepatitis, primary biliary cirrhosis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), unclassified, and other. Baseline characteristics at initial diagnosis, the modality of the initial treatment, and survival status were collected via a website. Survival of the patients was assessed by the Kaplan-Meier method and Cox proportional hazard regression. RESULTS The proportion of patients with non-viral etiologies increased from 10.0% in 1991 to 24.1% in 2010. Of the patients, 92% were categorized as ALD, NAFLD, or unclassified. Body mass index (BMI) was ≥ 25 kg/m(2) in 39%. Diabetes was most prevalent in NAFLD (63%), followed by unclassified etiology (46%) and ALD (45%). Approximately 80% of patients underwent radical therapy, including resection, ablation, or transarterial chemoembolization. Survival rates at 3, 5, 10, 15, and 20 years were 58.2, 42.6, 21.5, 15.2, and 15.2%, respectively. Multivariate analysis revealed that patients with BMI > 22 and ≤ 25 kg/m(2) showed the best prognosis versus other BMI categories, after adjusting by age, gender, tumor-related factors, and Child-Pugh score. CONCLUSIONS Most cases of non-B, non-C HCC are related to lifestyle factors, including obesity and diabetes. Slightly overweight patients showed the best prognosis.
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MESH Headings
- Aged
- Body Mass Index
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/etiology
- Carcinoma, Hepatocellular/therapy
- Cohort Studies
- Female
- Hepatitis, Autoimmune/complications
- Hepatitis, Autoimmune/epidemiology
- Hepatitis, Viral, Human/complications
- Hepatitis, Viral, Human/epidemiology
- Humans
- Japan/epidemiology
- Liver Cirrhosis, Biliary/complications
- Liver Cirrhosis, Biliary/epidemiology
- Liver Diseases, Alcoholic/complications
- Liver Diseases, Alcoholic/epidemiology
- Liver Neoplasms/diagnosis
- Liver Neoplasms/epidemiology
- Liver Neoplasms/etiology
- Liver Neoplasms/therapy
- Male
- Middle Aged
- Non-alcoholic Fatty Liver Disease/complications
- Non-alcoholic Fatty Liver Disease/epidemiology
- Prognosis
- Retrospective Studies
- Risk Factors
- Survival Analysis
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Affiliation(s)
- Ryosuke Tateishi
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan,
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Chen CI, Kuan CF, Fang YA, Liu SH, Liu JC, Wu LL, Chang CJ, Yang HC, Hwang J, Miser JS, Wu SY. Cancer risk in HBV patients with statin and metformin use: a population-based cohort study. Medicine (Baltimore) 2015; 94:e462. [PMID: 25674734 PMCID: PMC4602747 DOI: 10.1097/md.0000000000000462] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Chronic infection with hepatitis B virus (HBV) often causes chronic inflammation of the liver with an increased incidence of hepatocellular carcinoma (HCC). HBV-infected individuals may also have an increased incidence of nonliver cancers. Taking statin or metformin may decrease inflammation and infiltration, which may, as a result, reduce the risk of liver cancer or other major cancers in patients with HBV infection. The purpose of this study was to evaluate the hypothesis that statin and metformin could reduce the incidence of liver cancer (HCC) or nonliver cancers in patients with HBV.Using the Taiwan Longitudinal Health Insurance Database 2000 to 2008, this cohort study comprised patients with a recorded diagnosis of HBV (N = 71,847) between January 1, 2000 and December 31, 2008. Each patient was followed-up until the end of 2008. The occurrence of HCC or a nonliver cancer was evaluated in patients who either were or were not taking statin or metformin. Cox proportional hazard regressions were used to evaluate the cancer incidence after adjusting for known confounding factors.In total, 71,824 HBV-infected patients comprised the study cohort. Our study showed that either metformin or statin use was associated with a reduction in the incidence of cancer. This was most prominent in patients taking both statin and metformin. The adjusted hazard ratios (HRs) for patients using only statin were 0.52 (95% confidence interval [CI], 0.48-0.57) for all cancers, 0.28 (95% CI, 0.23-0.35) for liver cancer, and 0.63 (95% CI, 0.57-0.70) for nonliver cancers. Patients taking only metformin had risk-adjusted HRs of 0.82 (95% CI, 0.75-0.90) for all cancers, 0.97 (95% CI, 0.84-1.14) for liver cancer, and 0.75 (95% CI, 0.67-0.84) for nonliver cancers. A dose-dependent effect of statin use for chemoprevention was observed for all cancers, including both liver cancer and nonliver cancers. A dose-dependent effect of metformin was also seen in liver cancer and nonliver cancers without stratification into different cumulative daily doses of statin use.This population-based cohort study investigated the protective effect of statin and metformin against cancer events in patients with HBV infection. Our study demonstrated that either statin or metformin served as independent chemopreventive agents with a dose-response effect in reducing the incidence of cancer with a dose-response effect of the agents and an additive or synergistic effect of combining statin and metformin use in reducing the incidence of many cancers.
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Affiliation(s)
- Chang-I Chen
- From the Graduate Institute of Medical Science (C-IC); Center of Excellence for Cancer Research (C-IC, Y-AF); Cancer Center (C-IC), Wan Fang Hospital, Taipei Medical University, Taipei; Department of Health care Administration (C-FK), Central Taiwan University of Science and Technology, Taichung; Graduate Institute of Toxicology (S-HL), College of Medicine, National Taiwan University, Taipei; Division of Cardiovascular Medicine (J-CL), Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City; Department of Ophthalmology (L-LW), National Taiwan University Hospital; Section of Endocrinology and Metabolism (C-JC), Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei; Institute of Biomedical Informatics (H-CY), National Yang Ming University; Department of Biochemistry (JH), School of Medicine, Taipei Medical University, Taipei, Taiwan; City of Hope National Medical Center (JSM), Duarte, CA; College of Medical Science and Technology (JSM), Taipei Medical University; Graduate Institute of Toxicology (SYW), College of Medicine, National Taiwan University, Taipei; Department of Internal Medicine (SYW), School of Medicine, College of Medicine; Department of Radiation Oncology (SYW), Wan Fang Hospital, Taipei Medical University, Taipei; Department of Biotechnology (SYW), Hung Kuang University, Taichung, Taiwan
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49
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Chen CF, Liu PH, Lee YH, Tsai YJ, Hsu CY, Huang YH, Chiou YY, Huo TI. Impact of renal insufficiency on patients with hepatocellular carcinoma undergoing radiofrequency ablation. J Gastroenterol Hepatol 2015; 30:192-8. [PMID: 25039567 DOI: 10.1111/jgh.12669] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/18/2014] [Indexed: 12/25/2022]
Abstract
BACKGROUND AND AIM Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). We aimed to investigate the impact of RI on the long-term survival of HCC patients undergoing radiofrequency ablation (RFA) and to determine the optimal staging strategy for these patients. METHODS RI was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) . A total of 123 and 344 patients with and without RI undergoing RFA, respectively, were enrolled. A one-to-one propensity score matching analysis with preset caliper width was performed. The prognostic ability of four currently used staging systems was compared by the Akaike information criterion (AIC). RESULTS HCC patients with RI undergoing RFA were older (P < 0.001) and had significantly different baseline characteristics. Of all patients, RI was significantly associated with a decreased long-term survival (P = 0.03). After matching in the propensity model, the baseline characteristics were similar between patients with (n = 92) and without (n = 92) RI. In the propensity model, RI was not significantly associated with a shortened survival (P = 0.273). In the Cox multivariate analysis, Child-Turcotte-Pugh class B or C was identified as the only independent predictor of poor prognosis. Among patients with RI undergoing RFA, the Taipei Integrated Scoring (TIS) system provided the highest homogeneity and lowest AIC value among the currently used staging systems. CONCLUSIONS The long-term survival of HCC patients undergoing RFA is not affected by RI. The TIS staging system may provide a better prognostic prediction for HCC patients with RI undergoing RFA.
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Affiliation(s)
- Chuan-Fu Chen
- Division of Gastroenterology, Wei Gong Memorial Hospital, Miaoli, Taiwan
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El-Eshmawy MM, Kandil TS, El-Hafez HAA, El yazid AYA, El Hadidy EHM. Type 2 diabetes mellitus is a risk factor for hepatocellular carcinoma in Egyptian patients with HCV-related cirrhosis. Int J Diabetes Dev Ctries 2014. [DOI: 10.1007/s13410-013-0186-3] [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: 11/30/2022] Open
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