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Shinkawa H, Kaibori M, Ueno M, Yasuda S, Ikoma H, Aihara T, Nakai T, Kinoshita M, Kosaka H, Hayami S, Matsuo Y, Morimura R, Nakajima T, Nobori C, Ishizawa T. Impact of Diabetes Mellitus and Obesity Comorbidities on Survival Outcomes after Hepatocellular Carcinoma Resection: A Multicenter Retrospective Study. Liver Cancer 2025; 14:80-91. [PMID: 40144468 PMCID: PMC11936440 DOI: 10.1159/000540858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Accepted: 08/07/2024] [Indexed: 01/03/2025] Open
Abstract
Introduction This study aimed to evaluate the association of obesity and diabetes mellitus (DM) comorbidity with hepatocellular carcinoma (HCC) recurrence and survival. Methods We investigated 1,644 patients who underwent hepatic resection for solitary HCC without vascular invasion using computed tomography. Patients were categorized into four groups according to the combination of obesity and DM comorbidities: OB (+) or (-) and DM (+) or (-). Postoperative cumulative recurrence rates within and beyond 2 years and beyond 5 years were assessed. Results Multivariate Cox proportional hazard regression analysis revealed that the adjusted hazard ratios (HRs) of reduced recurrence-free survival was 1.10 (95% confidence interval [CI]: 0.91-1.33; p = 0.31), 0.94 (95% CI: 0.78-1.12; p = 0.48), and 1.24 (95% CI: 1.01-1.54; p = 0.045) in the OB(+)DM(-), OB(-)DM(+), and OB(+)DM(+) groups compared with the OB(-)DM(-) group, respectively. Additionally, the corresponding adjusted HRs of reduced overall survival were 0.93 (p = 0.57), 0.97 (p = 0.76), and 1.38 (p = 0.013) for OB(+)DM(-), OB(-)DM(+), and OB(+)DM(+) groups, respectively. No significant difference in the early recurrence rate was determined among the four groups. The OB(+)DM(+) group demonstrated an increased risk for late recurrence beyond 2 years and 5 years postoperatively compared with the OB(-)DM(-) group (HR: 1.51; p = 0.024 and HR: 2.53; p = 0.046, respectively). The OB(+)DM(-) and OB(-)DM(+) groups demonstrated an increased risk for late recurrence beyond 5 years postoperatively (HR: 3.83; p < 0.001 and HR: 1.95; p = 0.037, respectively). Conclusions Obesity and DM coexistence increased late recurrence and worsened prognosis in patients with HCC undergoing hepatic resection. The results help surgeons develop possible different surveillance protocol and need to focus on diabetes/obesity control during life-long surveillance for patients with HCC.
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Affiliation(s)
- Hiroji Shinkawa
- Department of Hepatobiliary Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Masaki Kaibori
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Japan
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Satoshi Yasuda
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Hisashi Ikoma
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | | | - Takuya Nakai
- Department of Surgery, Faculty of Medicine, Kindai University, Sayama, Japan
| | - Masahiko Kinoshita
- Department of Hepatobiliary Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Hisashi Kosaka
- Department of Surgery, Hirakata Hospital, Kansai Medical University, Hirakata, Japan
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Yasuko Matsuo
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Ryo Morimura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | | | - Chihoko Nobori
- Department of Surgery, Faculty of Medicine, Kindai University, Sayama, Japan
| | - Takeaki Ishizawa
- Department of Hepatobiliary Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
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Jespersen S, Fritt-Rasmussen A, Madsbad S, Pedersen BK, Krogh-Madsen R, Weis N. Prevalence of cardiometabolic co-morbidities in patients with vs persons without chronic hepatitis B: The FitLiver cohort study. World J Hepatol 2025; 17:97797. [PMID: 39871902 PMCID: PMC11736484 DOI: 10.4254/wjh.v17.i1.97797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Revised: 08/29/2024] [Accepted: 09/19/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) affects > 300 million people worldwide. The combination of CHB and cardiometabolic co-morbidities increases the risk of liver-related morbidity and mortality. However, international guidelines for CHB treatment do not provide recommendations for follow-up examinations or treatment of patients with CHB and cardiometabolic comorbidities. In studies investigating cardiometabolic co-morbidity in patients with CHB, inconsistent findings have been observed, and both lower and higher prevalence of cardiometabolic co-morbidities compared to the general population have been reported. It is unclear whether patients with CHB living in Denmark have an increased prevalence of cardiometabolic co-morbidities. AIM To investigate the prevalence of cardiometabolic comorbidities in patients with CHB and matched non-CHB comparison group. METHODS We examined patients with CHB and age-, sex-, body mass index (BMI)-, and country-of-birth matched comparison group. Defining cardiometabolic co-morbidity: Obesity (BMI > 25 kg/m2/abnormal waist-to-hip ratio), metabolic dysfunction-associated steatotic liver disease (MASLD), hypercholesterolemia (total-cholesterol > 5 mmol/L/statin use), hypertension (systolic ≥ 135 mmHg/ diastolic ≥ 85 mmHg/antihypertensive medication) and type 2 diabetes (T2D) (2-hour oral glucose tolerance test glucose > 11.1 mmol/L/HbA1c > 48 mmol/mol/ antidiabetic medication). Physical activity was evaluated using maximal oxygen consumption (VO2max), activity monitors, and a questionnaire. RESULTS We included 98 patients with CHB and 49 persons in the comparison group. The two groups were well-matched, showing no significant differences in age, sex, BMI, country-of-birth, education, or employment. Among patients with CHB, the following prevalence of cardiometabolic co-morbidity was found: 77% were obese, 45% had MASLD, 38% had hypercholesterolemia, 26% had hypertension, and 7% had T2D, which did not differ significantly from the comparison group, apart from lower prevalence of hemoglobin A1c (HbA1c) ≥ 48 mmol/L or known T2D. Both groups had low VO2max of 27 mL/kg/minute in the patients with CHB and 30 mL/kg/minute in the comparison group, and the patients with CHB had a shorter self-assessed sitting time. CONCLUSION The patients with CHB and the comparison group were well-matched and had a similar prevalence of cardiometabolic comorbidities. Furthermore, both groups had low levels of physical fitness.
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Affiliation(s)
- Sofie Jespersen
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
- Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Denmark.
| | - Asmita Fritt-Rasmussen
- Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Denmark
| | - Sten Madsbad
- Department of Endocrinology, Copenhagen University Hospital, Hvidovre, Denmark
| | - Bente K Pedersen
- Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Denmark
| | - Rikke Krogh-Madsen
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
- Centre for Physical Activity Research, Copenhagen University Hospital, Rigshospitalet, Denmark
| | - Nina Weis
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
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Yan LJ, Yang LS, Yan YC, Tan SY, Ding ZN, Liu H, Wang DX, Dong ZR, Li T. Anthropometric indicators of adiposity and risk of primary liver cancer: A systematic review and dose-response meta-analysis. Eur J Cancer 2023; 185:150-163. [PMID: 36996625 DOI: 10.1016/j.ejca.2023.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 01/29/2023] [Accepted: 03/01/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND AND AIMS Adiposity is associated with an increased risk of primary liver cancer (PLC). As the most commonly used indicator of adiposity, the body mass index (BMI) has been questioned for its limitations in reflecting visceral fat. This study aimed to investigate the role of different anthropometric indicators in identifying the risk of PLC by accounting for potential non-linear associations. METHODS Systematic searches were conducted in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, and CNKI databases. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship was assessed using a restricted cubic spline model. RESULTS Sixty-nine studies involving more than 30 million participants were included in the final analysis. Regardless of the indicator used, adiposity was strongly associated with an increased risk of PLC. When comparing the HRs per 1-standard deviation increment across indicators of adiposity, the association was strongest for waist-to-height ratio (WHtR) (HR = 1.39), followed by waist-to-hip ratio (WHR) (HR = 1.22), BMI (HR = 1.13), waist circumference (WC) (HR = 1.12), and hip circumference (HC) (HR = 1.12). A strong non-linear association was observed between each anthropometric parameter and the risk of PLC, regardless of whether the original or decentralised value was used. The positive association between WC and PLC risk remained substantial after adjusting for BMI. The incidence of PLC was higher with central adiposity (52.89 per 100,000 person-years, 95% CI = 50.33-55.44) than general adiposity (39.01 per 100,000 person-years, 95% CI = 37.26-40.75). CONCLUSION Central adiposity seems to contribute more to the development of PLC than general adiposity. A larger WC, independent of BMI, was strongly associated with the risk of PLC and might be a more promising predictive indicator than BMI.
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Affiliation(s)
- Lun-Jie Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Long-Shan Yang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Yu-Chuan Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Si-Yu Tan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China.
| | - Tao Li
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China; Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan 250012, PR China.
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Chang SS, Hu HY, Chen YC, Yen YF, Huang N. Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case–control study. BMC Gastroenterol 2022; 22:425. [PMID: 36115934 PMCID: PMC9482748 DOI: 10.1186/s12876-022-02504-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 09/13/2022] [Indexed: 12/09/2022] Open
Abstract
Abstract
Background
New direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan.
Methods
We conducted a population-based unmatched case–control study. 2008–2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis.
Results
A decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis.
Conclusions
Elderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.
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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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Sufyan M, Ali Ashfaq U, Ahmad S, Noor F, Hamzah Saleem M, Farhan Aslam M, El-Serehy HA, Aslam S. Identifying key genes and screening therapeutic agents associated with diabetes mellitus and HCV-related hepatocellular carcinoma by bioinformatics analysis. Saudi J Biol Sci 2021; 28:5518-5525. [PMID: 34588861 PMCID: PMC8459114 DOI: 10.1016/j.sjbs.2021.07.068] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 07/19/2021] [Accepted: 07/24/2021] [Indexed: 01/05/2023] Open
Abstract
Objective Incidence of both Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) are rapidly increasing worldwide. One of the leading causes of HCC is hepatitis C virus (HCV), which is a resource of blood-borne viral infection. HCV increases the risk for HCC probably by promoting fibrosis and cirrhosis. Association among T2DM and HCV related HCC remains significant, indicating that such association is clinically reliable and robust. Lawson was the first who uncovered HCC in person suffered from T2DM. Until now, genetic association between HCV related HCC and T2DM is poorly known. Current work was designed to figure out the molecular mechanisms of both diseases by identifying the hub genes and therapeutic drugs using integrated bioinformatics analysis. Methods Four microarray datasets were downloaded from GEO database and analyzed using R in order to obtain different expressed genes (DEGs). Protein–protein interaction (PPI) networks was constructed using STRING tool and visualized by Cytoscape. Moreover, hub genes were identified on the basis of their degree of connectivity. Finally, Networkanalyst and DGIdb were used for the identification of transcription factors (TFs) and selection of candidate drugs, respectively. Results A total of 53 DEGs were identified, of which 41 were upregulated genes and 12 were downregulated genes. PPI network obtained from STRING were subjected to Cytoscape plugin cytoHubba, and top 10 genes (AURKA, JUN, AR, MELK, NCOA2, CENPF, NCAPG, PCK1, RAD51AP1, and GTSE1) were chosen as the target hub genes based on the highest degree of connectivity. Furthermore, 47 drugs of AURKA, JUN, AR, MELK, and NCOA2 were found having therapeutic potential to treat HCV-HCC in patients with T2DM. Conclusion This study updates the information and yield a new perspective in context of understanding the pathogenesis and development of HCV related HCC in affected persons with T2DM. In vivo and in vitro investigation of hub genes and pathway interaction is essential to delineate the specific roles of the novel hub genes, which may help to reveal the genetic association between HCV-HCC and T2DM. In future, hub genes along with their candidate drugs might be capable of improving the personalized detection and therapies for both diseases.
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Affiliation(s)
- Muhammad Sufyan
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), Allama Iqbal Road, Faisalabad-38000, Pakistan
| | - Usman Ali Ashfaq
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), Allama Iqbal Road, Faisalabad-38000, Pakistan
| | - Sajjad Ahmad
- Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan
| | - Fatima Noor
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), Allama Iqbal Road, Faisalabad-38000, Pakistan
| | - Muhammad Hamzah Saleem
- MOA Key Laboratory of Crop Ecophysiology and Farming System in the Middle Reaches of the Yangtze River, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
| | | | - Hamed A El-Serehy
- Department of Zoology, King Saud University, Riyadh 11451, Saudi Arabia
| | - Sidra Aslam
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), Allama Iqbal Road, Faisalabad-38000, Pakistan
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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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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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Sohn W, Lee HW, Lee S, Lim JH, Lee MW, Park CH, Yoon SK. Obesity and the risk of primary liver cancer: A systematic review and meta-analysis. Clin Mol Hepatol 2020; 27:157-174. [PMID: 33238333 PMCID: PMC7820201 DOI: 10.3350/cmh.2020.0176] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 08/31/2020] [Indexed: 12/14/2022] Open
Abstract
Background/Aims In this systematic review and meta-analysis, we aimed to clarify the effect of obesity on the occurrence of and mortality from primary liver cancer. Methods This study was conducted using a systematic literature search of MEDLINE, EMBASE, and the Cochrane Library until November 2018 using the primary keywords “obesity,” “overweight,” “body mass index (BMI),” “body weight,” “liver,” “cancer,” “hepatocellular carcinoma,” “liver cancer,” “risk,” and “mortality.” Studies assessing the relationship between BMI and occurrence of or mortality from primary liver cancer in prospective cohorts and those reporting hazard ratios (HRs) or data that allow HR estimation were included. Results A total of 28 prospective cohort studies with 8,135,906 subjects were included in the final analysis. These included 22 studies with 6,059,561 subjects for cancer occurrence and seven studies with 2,077,425 subjects for cancer-related mortality. In the meta-analysis, an increase in BMI was associated with the occurrence of primary liver cancer (HR, 1.69; 95% confidence interval, 1.50–1.90, I2=56%). A BMI-dependent increase in the risk of occurrence of primary liver cancer was reported. HRs were 1.36 (95% CI, 1.02–1.81), 1.77 (95% CI, 1.56–2.01), and 3.08 (95% CI, 1.21–7.86) for BMI >25 kg/m2, >30 kg/m2, and >35 kg/m2, respectively. Furthermore, increased BMI resulted in enhanced liver cancer-related mortality (HR, 1.61; 95% CI, 1.14–2.27, I2=80%). Conclusions High BMI increases liver cancer mortality and occurrence of primary liver cancer. Obesity is an independent risk factor for the occurrence of and mortality from primary liver cancer.
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Affiliation(s)
- Won Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sangheun Lee
- Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Jin Hong Lim
- Department of General Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Min Woo Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University College of Medicine, Seoul, Korea
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Montemurro N, Perrini P, Rapone B. Clinical Risk and Overall Survival in Patients with Diabetes Mellitus, Hyperglycemia and Glioblastoma Multiforme. A Review of the Current Literature. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E8501. [PMID: 33212778 PMCID: PMC7698156 DOI: 10.3390/ijerph17228501] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 11/11/2020] [Accepted: 11/15/2020] [Indexed: 12/15/2022]
Abstract
The relationship between type 2 diabetes mellitus (DM2) and hyperglycemia with cancer patients remains controversial also in the setting of patients with glioblastoma multiforme (GBM), the most common and aggressive form of astrocytoma with a short overall survival (OS) and poor prognosis. A systematic search of two databases was performed for studies published up to 19 August 2020, reporting the OS of patients with DM2 or high blood sugar level and GBM and the clinical risk of diabetic patients for development of GBM. According to PRISMA guidelines, we included a total of 20 papers reporting clinical data of patients with GBM and diabetes and/or hyperglycemia. The aim of this review was to investigate the effect of DM2, hyperglycemia and metformin on OS of patients with GBM. In addition, we evaluated the effect of these factors on the risk of development of GBM. This review supports accumulating evidence that hyperglycemia, rather than DM2, and elevated BMI are independent risk factors for poor outcome and shorter OS in patients with GBM. GBM patients with normal weight compared to obese, and diabetic patients on metformin compared to other therapies, seems to have a longer OS. Further studies are needed to understand better these associations.
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Affiliation(s)
- Nicola Montemurro
- Department of Neurosurgery, Azienda Ospedaliera Universitaria Pisana (AOUP), 56126 Pisa, Italy;
- Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy
| | - Paolo Perrini
- Department of Neurosurgery, Azienda Ospedaliera Universitaria Pisana (AOUP), 56126 Pisa, Italy;
- Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy
| | - Biagio Rapone
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, “Aldo Moro” University of Bari, 70121 Bari, Italy;
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11
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Phan DV, Chan CL, Li AHA, Chien TY, Nguyen VC. Liver cancer prediction in a viral hepatitis cohort: A deep learning approach. Int J Cancer 2020; 147:2871-2878. [PMID: 32761609 DOI: 10.1002/ijc.33245] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/15/2020] [Accepted: 07/28/2020] [Indexed: 12/14/2022]
Abstract
Viral hepatitis is the primary cause of liver diseases, among which liver cancer is the leading cause of death from cancer. However, this cancer is often diagnosed in the later stages, which makes treatment difficult or even impossible. This study applied deep learning (DL) models for the early prediction of liver cancer in a hepatitis cohort. In this study, we surveyed 1 million random samples from the National Health Insurance Research Database (NHIRD) to analyze viral hepatitis patients from 2002 to 2010. Then, we used DL models to predict liver cancer cases based on the history of diseases of the hepatitis cohort. Our results revealed the annual prevalence of hepatitis in Taiwan increased from 2002 to 2010, with an average annual percentage change (AAPC) of 5.8% (95% CI: 4.2-7.4). However, young people (aged 16-30 years) exhibited a decreasing trend, with an AAPC of -5.6 (95% CI: -8.1 to -2.9). The results of applying DL models showed that the convolution neural network (CNN) model yielded the best performance in terms of predicting liver cancer cases, with an accuracy of 0.980 (AUC: 0.886). In conclusion, this study showed an increasing trend in the annual prevalence of hepatitis, but a decreasing trend in young people from 2002 to 2010 in Taiwan. The CNN model may be applied to predict liver cancer in a hepatitis cohort with high accuracy.
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Affiliation(s)
- Dinh-Van Phan
- Department of Information Management, Yuan Ze University, Taoyuan, Taiwan.,University of Economics, The University of Danang, Danang, Vietnam.,Teaching and Research Team for Business Intelligence, University of Economics, The University of Danang, Danang, Vietnam
| | - Chien-Lung Chan
- Department of Information Management, Yuan Ze University, Taoyuan, Taiwan.,Innovation Center for Big Data and Digital Convergence, Yuan Ze University, Taoyuan, Taiwan
| | - Ai-Hsien Adams Li
- Division of Cardiology, Far Eastern Memorial Hospital, Taipei, Taiwan
| | - Ting-Ying Chien
- Department of Computer Science and Engineering, Yuan Ze University, Taoyuan, Taiwan
| | - Van-Chuc Nguyen
- University of Economics, The University of Danang, Danang, Vietnam.,Teaching and Research Team for Business Intelligence, University of Economics, The University of Danang, Danang, Vietnam
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12
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Yang HI, Yeh ML, Wong GL, Peng CY, Chen CH, Trinh HN, Cheung KS, Xie Q, Su TH, Kozuka R, Lee DH, Ogawa E, Zhao C, Ning HB, Huang R, Li J, Zhang JQ, Ide T, Xing H, Iwane S, Takahashi H, Wong C, Wong C, Lin CH, Hoang J, Le A, Henry L, Toyoda H, Ueno Y, Gane EJ, Eguchi Y, Kurosaki M, Wu C, Liu C, Shang J, Furusyo N, Enomoto M, Kao JH, Yuen MF, Yu ML, Nguyen MH. Real-World Effectiveness From the Asia Pacific Rim Liver Consortium for HBV Risk Score for the Prediction of Hepatocellular Carcinoma in Chronic Hepatitis B Patients Treated With Oral Antiviral Therapy. J Infect Dis 2020; 221:389-399. [PMID: 31550363 DOI: 10.1093/infdis/jiz477] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 09/13/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Patients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort. METHODS Adult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was <1 year. Patients were randomized to derivation and validation cohorts on a 2:1 ratio. Statistically significant predictors from multivariate modeling formed the Real-world Effectiveness from the Asia Pacific Rim Liver Consortium for HBV (REAL-B) score. RESULTS A total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0-3 low risk, 4-7 moderate risk, and 8-13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001). CONCLUSIONS The REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy.
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Affiliation(s)
- Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan.,Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Lun Yeh
- Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Grace L Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Cheng-Yuan Peng
- Department of Gastroenterology, China Medical University Hospital, Taichung, Taiwan
| | - Chien-Hung Chen
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Huy N Trinh
- San Jose Gastroenterology, San Jose, California, USA
| | - Ka-Shing Cheung
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, Peopole's Republic of China
| | - Tung-Hung Su
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Ritsuzo Kozuka
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Dong-Hyun Lee
- Department of Gastroenterology, Good Gang-An Hospital, Busan, South Korea
| | - Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Changqing Zhao
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Peopole's Republic of China
| | - Hui-Bin Ning
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, Peopole's Republic of China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, Peopole's Republic of China
| | - Jiayi Li
- Palo Alto Medical Foundation, Mountain View Division, Mountain View, California, USA
| | - Jian Q Zhang
- Chinese Hospital, San Francisco, California, USA
| | - Tatsuya Ide
- Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan
| | - Huichun Xing
- Beijing Ditan Hospital, Capital Medical University, Beijing, Peopole's Republic of China
| | - Shinji Iwane
- Department of Internal Medicine, Saga University Hospital, Saga, Japan
| | | | | | | | - Chia-Hsin Lin
- Department of Gastroenterology, China Medical University Hospital, Taichung, Taiwan
| | - Joseph Hoang
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - An Le
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Linda Henry
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Yamagata University, Yamagata, Japan
| | - Edward J Gane
- Liver Transplant Unit, University of Auckland, Auckland, New Zealand
| | - Yuichiro Eguchi
- Department of Internal Medicine, Saga University Hospital, Saga, Japan
| | - Masayuki Kurosaki
- Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, Peopole's Republic of China
| | - Chenghai Liu
- Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, Peopole's Republic of China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, Peopole's Republic of China
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masaru Enomoto
- Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Jia-Horng Kao
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Hong Kong
| | - Ming-Lung Yu
- Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, USA
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13
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Lim CT, Goh GBB, Li H, Lim TKH, Leow WQ, Wan WK, Azhar R, Chow WC, Kumar R. Presence of Hepatic Steatosis Does Not Increase the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Over Long Follow-Up. Microbiol Insights 2020; 13:1178636120918878. [PMID: 32435130 PMCID: PMC7223198 DOI: 10.1177/1178636120918878] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Accepted: 03/16/2020] [Indexed: 12/11/2022] Open
Abstract
Background Chronic hepatitis B (CHB) infection and nonalcoholic fatty liver disease (NAFLD) are liver diseases which may lead to hepatocellular carcinoma (HCC) formation. Both disease entities have been attributed independently to increase risk of HCC development. While concomitant hepatic steatosis in patients with CHB are becoming more frequent in view of increasing NAFLD prevalence, there is no conclusive evidence linking presence of hepatic steatosis and increased HCC risk in patients with CHB infection. This study explores the association of hepatic steatosis among CHB-infected individuals in HCC development. Methods This is a retrospective study on a cohort of patients with CHB who underwent liver biopsy between January 2000 and December 2014. They were stratified according to presence and severity of histologically proven hepatic steatosis and subsequently followed up to evaluate the association between hepatic steatosis and HCC development. Results Among 289 patients with a median follow-up of 111.1 months, hepatic steatosis was present in 185 patients (64.0%). In all, 27 patients developed HCC on follow-up and 21 of them had hepatic steatosis. Univariate Cox analysis showed that age (hazard ratio [HR] = 1.08, 95% CI = 1.042-1.12), type 2 diabetes mellitus (T2DM) (HR = 4.00, 95% CI = 1.622-9.863), and Ishak score (HR = 1.221, 95% CI = 1.014-1.472) were associated with HCC development, whereas multivariate Cox analysis demonstrated that age and T2DM (HR = 2.69, 95% CI = 1.072-6.759) were significant risk factors for development of HCC. Conclusions Concurrent hepatic steatosis in patients with CHB infection is not a risk factor for hepatocellular carcinoma formation.
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Affiliation(s)
- Chong Teik Lim
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - George Boon Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.,Duke-NUS Graduate Medical School, Singapore
| | - Huihua Li
- Department of Health Services Research Unit, Singapore General Hospital, Singapore.,Centre of Quantitative Medicine, Duke-NUS Medical School, Singapore
| | - Tony Kiat-Hon Lim
- Duke-NUS Graduate Medical School, Singapore.,Department of Pathology, Singapore General Hospital, Singapore
| | - Wei Qiang Leow
- Duke-NUS Graduate Medical School, Singapore.,Department of Pathology, Singapore General Hospital, Singapore
| | - Wei Keat Wan
- Duke-NUS Graduate Medical School, Singapore.,Department of Pathology, Singapore General Hospital, Singapore
| | - Rafay Azhar
- Duke-NUS Graduate Medical School, Singapore.,Department of Pathology, Singapore General Hospital, Singapore
| | - Wan Cheng Chow
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.,Duke-NUS Graduate Medical School, Singapore
| | - Rajneesh Kumar
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.,Duke-NUS Graduate Medical School, Singapore
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14
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Jeong E, Park N, Kim Y, Jeon JY, Chung WY, Yoon D. Temporal trajectories of accompanying comorbidities in patients with type 2 diabetes: a Korean nationwide observational study. Sci Rep 2020; 10:5535. [PMID: 32218498 PMCID: PMC7099011 DOI: 10.1038/s41598-020-62482-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Accepted: 03/11/2020] [Indexed: 12/22/2022] Open
Abstract
Type 2 diabetes mellitus is a major concern globally and well known for increasing risk of complications. However, diabetes complications often remain undiagnosed and untreated in a large number of high-risk patients. In this study based on claims data collected in South Korea, we aimed to explore the diagnostic progression and sex- and age-related differences among patients with type 2 diabetes using time-considered patterns of the incidence of comorbidities that evolved after a diagnosis of type 2 diabetes. This study compared 164,593 patients who met the full criteria for type 2 diabetes with age group-, sex-, encounter type-, and diagnosis date-matched controls who had not been diagnosed with type 2 diabetes. We identified 76,423 significant trajectories of four diagnoses from the dataset. The top 30 trajectories with the highest average relative risks comprised microvascular, macrovascular, and miscellaneous complications. Compared with the trajectories of male groups, those of female groups included relatively fewer second-order nodes and contained hubs. Moreover, the trajectories of male groups contained diagnoses belonging to various categories. Our trajectories provide additional information about sex- and age-related differences in the risks of complications and identifying sequential relationships between type 2 diabetes and potentially complications.
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Affiliation(s)
- Eugene Jeong
- Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Namgi Park
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.,Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Gyeonggi-do, Republic of Korea
| | - Yujeong Kim
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea
| | - Ja Young Jeon
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea
| | - Wou Young Chung
- Department of Pulmonology and Critical Care Medicine, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea
| | - Dukyong Yoon
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Gyeonggi-do, Republic of Korea. .,Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Gyeonggi-do, Republic of Korea.
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15
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Muñoz Díaz HA, Lúquez Mindiola AJ, Gómez Aldana AJ. Fisiopatología de la hepatitis C y diabetes mellitus. Hacia la cura de dos epidemias en el siglo XXI. REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2019; 34:277-287. [DOI: 10.22516/25007440.322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/01/2024]
Abstract
La infección crónica por virus de la hepatitis C (VHC) y la diabetes mellitus (DM) son dos problemas de salud pública que impactan los sistemas de salud, con una alta carga económica global. La infección por VHC produce manifestaciones hepáticas tales como hepatitis, cirrosis y carcinoma hepatocelular; asimismo, se ha involucrado en la patogénesis de manifestaciones extrahepáticas, entre las cuales se ha asociado con alteraciones metabólicas como la DM. Estudios longitudinales y transversales han reportado mayor incidencia y prevalencia de DM en pacientes con infección crónica por VHC. La DM acelera la progresión histológica y clínica en pacientes con infección crónica por VHC y las complicaciones cardiovasculares. Recientemente se ha avanzado en el tratamiento y la introducción de nuevos medicamentos como los antivirales de acción directa, que mejoran el control glucémico en estos pacientes.
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16
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Yang C, Lu Y, Xia H, Liu H, Pan D, Yang X, Sun G. Excess Body Weight and the Risk of Liver Cancer: Systematic Review and a Meta-Analysis of Cohort Studies. Nutr Cancer 2019; 72:1085-1097. [PMID: 31544511 DOI: 10.1080/01635581.2019.1664602] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Objective: To update and expand the previous meta-analysis including all prospective studies on the issue of the associations between overweight, obesity, and liver cancer risk. We also performed a meta-regression to investigate a potential nonlinear and/or linear association between body mass index (BMI) and liver cancer risk.Methods: Literature search was conducted in four libraries from the beginning of indexing for each database to 1st September, 2018.Results: The summary risk estimate was statistically significant on the association between overweight and the risk of liver cancer incidence (relative ratio [RR] = 1.19). The RRs were significantly stronger in people with known liver disease with overweight than in the general population with overweight (RR = 1.50 vs. RR = 1.10; Pdifference = .02). The meta-analysis showed an increase by 87% on the risk of liver cancer incidence in obesity categories, relative to categories of normal BMI (RR = 1.87, P < .01). Moreover, the results showed that, overweight was associated with 9% increased and obesity with 66% increased for risk of liver cancer mortality. In linear model, the relative risks of liver cancer were 1.32 for continuous BMI per 5 kg/m2 increase.Conclusion: This meta-analysis supports the hypothesis that overweight, obesity may significantly increase liver cancer risk.
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Affiliation(s)
- Chao Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China.,Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Yifei Lu
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China.,Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Hui Xia
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China.,Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Hechun Liu
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China.,Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Da Pan
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China.,Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Xian Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China.,Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
| | - Guiju Sun
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, Southeast University, Nanjing, P.R. China.,Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, P.R. China
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17
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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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18
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Shyu YC, Huang TS, Chien CH, Yeh CT, Lin CL, Chien RN. Diabetes poses a higher risk of hepatocellular carcinoma and mortality in patients with chronic hepatitis B: A population-based cohort study. J Viral Hepat 2019; 26:718-726. [PMID: 30739359 DOI: 10.1111/jvh.13077] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 01/08/2019] [Indexed: 12/12/2022]
Abstract
Diabetes mellitus may be a risk factor of HCC development in chronic hepatitis B infected patients and affect the all-cause mortality. This study aimed to examine whether DM was associated with the development of HCC with CHB and affected the all-cause mortality. A total of 2966 CHB patients newly diagnosed with DM in 2000 were retrieved from the Longitudinal Cohort of Diabetes Patients database and used propensity scores matching based on age, sex-gender, alcohol-related liver disease and baseline liver cirrhosis to compare with the non-DM patients from the Taiwanese National Health Insurance Research Database. The CHB patients with DM compared to the non-DM had significantly increased (3.3%) risk for HCC development and significantly increased (2.8%) risk of HCC-related mortality. Interestingly, the all-cause mortality was significantly higher in the DM cohort (16.9%) compared to the non-DM cohort (8.2%). In a multivariable transition-specific Cox model to investigate the adjusted hazard ratio of CHB patients with DM or non-DM during the transitions from start to HCC was 1.35; 95% CI (1.16-1.57) and from HCC to death was 1.31; 95% CI (1.06-1.62). All-cause mortality between CHB patients with DM or non-DM during the transitions from start to death was 2.32; 95% CI (1.84-2.92). Taken together, DM is an independent risk factor associated with increasing disease development of HCC, HCC-related mortality and all-cause mortality in CHB patients. This study may provide a clinical strategy for strict DM control in order to reduce the risk of disease development in CHB patients.
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Affiliation(s)
- Yu-Chiau Shyu
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.,Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan.,Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan
| | - Ting-Shuo Huang
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.,Department of General Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan.,School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Hung Chien
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.,Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chau-Ting Yeh
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
| | - Chih-Lang Lin
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.,Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan.,School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Division of Gastroenterology, Department of Internal Medicine Chang-Gung Memorial Hospital, Keelung, Taiwan
| | - Rong-Nan Chien
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.,Liver Research Unit, Chang Gung Memorial Hospital, Keelung, Taiwan.,School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Division of Gastroenterology, Department of Internal Medicine Chang-Gung Memorial Hospital, Keelung, Taiwan
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19
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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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20
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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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21
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Fabiani S, Fallahi P, Ferrari SM, Miccoli M, Antonelli A. Hepatitis C virus infection and development of type 2 diabetes mellitus: Systematic review and meta-analysis of the literature. Rev Endocr Metab Disord 2018; 19:405-420. [PMID: 29322398 DOI: 10.1007/s11154-017-9440-1] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Type 2 diabetes mellitus (T2DM) is an endocrine disorder encompassing multifactorial mechanisms, and chronic hepatitis C virus infection (CHC) is a multifaceted disorder, associated with extrahepatic manifestations, including endocrinological disorders. CHC and T2DM are associated, but the subject remains controversial. We performed a systematic review and meta-analysis evaluating such association, searching on PubMed until February 29, 2016. Inclusion criteria were: 1) presence of at least one internal control group age- and gender-matched (non-hepatopathic controls; and/or hepatopathic, not HCV-positive, controls); 2) sufficient data to calculate odds ratio and relative risk. Exclusion criteria were: 1) literature reviews on the topic; 2) publications regarding special populations [human immunodeficiency virus and human T-lymphotropic virus-1 coinfections, hepatocellular carcinoma (HCC), post-transplantation DM, gender selection]; 3) no clear differentiation among HCV patients with CHC, cirrhosis or HCC. Data from each study were independently extracted by two reviewers and cross-checked by AA. Our systematic review returned 544 records, and 33 were included in our meta-analysis. HCV infection is associated with an increased risk of T2DM independently from the severity of the associated liver disease, in CHC and cirrhotic HCV patients. As expected T2DM risk is higher in cirrhotic HCV patients, than CHC, and the prevalence of HCV infection in T2DM patients is higher than in non-diabetic controls. Regarding HBV infection prevalence, no difference exists in diabetic and non-diabetic subjects. An unequivocal CHC and T2DM association was shown. A proactive, integrated approach to HCV and T2DM therapies should maximize benefits of both diseases treatment.
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Affiliation(s)
- Silvia Fabiani
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy
| | - Poupak Fallahi
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy
| | - Silvia Martina Ferrari
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy
| | - Mario Miccoli
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, School of Medicine, University of Pisa, Via Savi 10, I-56126, Pisa, Italy.
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22
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El Sagheer G, Soliman E, Ahmad A, Hamdy L. Study of changes in lipid profile and insulin resistance in Egyptian patients with chronic hepatitis C genotype 4 in the era of DAAs. Libyan J Med 2018; 13:1435124. [PMID: 29451090 PMCID: PMC5827781 DOI: 10.1080/19932820.2018.1435124] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group. Lipid profile changes and IR were analyzed at baseline and after the end of treatment, and any effect of these changes on the response to treatment was studied. Before treatment, the levels of serum triglycerides were significantly higher in patients than in the control, and the levels of fasting insulin showed a progressive increase with advancing stage of fibrosis. At the end of treatment, there were a significant reduction in serum triglycerides, FBS, fasting insulin, and homeostasis model for the assessment of IR (P < 0.001), and a significant elevation of serum cholesterol and low-density lipoprotein (LDL)-c, high-density lipoprotein (HDL)-c, and LDL/HDL ratio (P = 0.001). An end-of-treatment response (week 12) was achieved in (99%) of the treated cases with 99% sustained viral response for 12 weeks post-treatment (week 24). Significant lipid profile changes were detected at the end of treatment. Serum lipid levels and IR are no longer predictors of response to DAAs. Follow-up of the lipid profile is warranted to avoid any possible remote effect of atherosclerotic heart disease.
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Affiliation(s)
- Ghada El Sagheer
- a Endocrinology Unit, Department of Internal Medicine, Minia School of Medicine , Minia University , Minia , Egypt
| | - Elwy Soliman
- b Hepatology Unit, Department of Internal Medicine, Minia School of Medicine , Minia University , Minia , Egypt
| | - Asmaa Ahmad
- a Endocrinology Unit, Department of Internal Medicine, Minia School of Medicine , Minia University , Minia , Egypt
| | - Lamiaa Hamdy
- c Department of Clinical Pathology, Minia School of Medicine , Minia University , Minia , Egypt
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23
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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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24
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Ferreira GLC, Marano C, De Moerlooze L, Guignard A, Feng Y, El Hahi Y, van Staa T. Incidence and prevalence of hepatitis B in patients with diabetes mellitus in the UK: A population-based cohort study using the UK Clinical Practice Research Datalink. J Viral Hepat 2018; 25:571-580. [PMID: 29220868 DOI: 10.1111/jvh.12841] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 10/19/2017] [Indexed: 01/16/2023]
Abstract
We assessed the incidence and prevalence of hepatitis B (Hep B) in patients with or without diabetes mellitus (DM) using the UK Clinical Practice Research Datalink (CPRD). This was a retrospective, observational study of diabetic and nondiabetic cohorts aged 0-80 years using CPRD (NCT02324218). Incidence rates (IR) for each cohort were calculated. Crude and adjusted (Poisson regression) IR ratios (IRR) were estimated with 95% confidence intervals (CI) to compare the cohorts. Hep B prevalence stratified by age, and hospitalization related to Hep B was also calculated. Of 7 712 043 subjects identified, 4 839 770 were included (DM: 160 760; non-DM: 4 679 010). Mean ages were 54.4 and 32.0 years, and 57.20% and 50.14% were male in the diabetic and nondiabetic cohorts, respectively. Hep B was identified in 29 diabetic and 845 nondiabetic subjects; IR was 4.03 per 100 000 person-years and 2.88 per 100 000 person-years, respectively. The adjusted IRR was 1.00 (95% CI: 0.70-1.50) between diabetic and nondiabetic cohorts. Hep B prevalence was higher in the diabetic cohort (0.01%-0.26%) than in the nondiabetic cohort (0.00%-0.03%) across the different age groups. Hep B-associated hospitalization IR was higher in the diabetic cohort (4.98-10.91) than the nondiabetic cohort (0.26-2.44). The Hep B IR, hospitalization and prevalence were higher in males in both cohorts. In conclusion, the risk of incident Hep B diagnosis in the diabetic cohort was not different from that in the nondiabetic cohort. However, prevalence of Hep B and Hep B-associated hospitalization rate was higher in the diabetic than in the nondiabetic cohort.
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Affiliation(s)
| | | | | | | | | | | | - T van Staa
- Health and Research Centre, Farr Institute for Health Informatics Research, University of Manchester, Manchester, UK
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25
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Abstract
Molecular pathological epidemiology (MPE) is a new discipline which emerged as an integrated approach of molecular pathology and epidemiology and was introduced for the first time by Professor Shuji Ogino and Professor Meir Stampfer in the year of 2010. MPE studies in hepatocellular carcinoma (HCC) investigate the relationship among risk factors, molecular biomarkers, and initiation, progression, and prognosis of HCC, which can be used for exploring the molecular mechanisms of HCC and for the molecular classification of the high risk population. Type 2 diabetes mellitus (DM) has been confirmed as an established risk factor for HCC, and MPE can be helpful to better understand the underlying molecular mechanisms. On December 20, 2017, the first China-Japan Symposium on HCC-MPE was held successfully in Beijing. HCC-MPE provides the opportunities and challenges to solve some problems of HCC, and I believe that it can be helpful to improve the early diagnosis, molecular typing, personalized prevention and treatment, and prognosis of HCC.
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26
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Wang CS, Chang TT, Yao WJ, Wang ST, Chou P. The impact of smoking on incident type 2 diabetes in a cohort with hepatitis B but not hepatitis C infection. J Viral Hepat 2017; 24:1114-1120. [PMID: 20819148 DOI: 10.1111/j.1365-2893.2010.01337.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Smoking may be a risk factor for diabetes, and it has been suggested that viral hepatitis may predispose to diabetes. We studied diabetes and smoking histories in people with viral hepatitis. From 1997 to 2004, we studied the risk of incident diabetes in a community cohort with hyperendemic HBV and HCV infection in southern Taiwan. The cohort involved 3539 people (40-70 years old) without diabetes. Four hundred and twenty-three individuals developed diabetes. Those who were ≥65 years old, frequently consumed alcohol, had a BMI ≥25, had <9 years of education, were anti-HCV+ or smoked ≥1 pack per day were more likely to develop diabetes (P < 0.05). A cumulative hazard function test showed that the higher the smoking levels, the greater the cumulative incidence rate of diabetes in HBsAg+ participants only (P = 0.03 by log-rank test). A multiple Cox proportional hazards model analysis in different hepatitis statuses showed smoking levels were strong predictors of diabetes with a dose-response relationship for type 2 diabetes in those with HBsAg+ : hazard ratio (HR) = 3.8, (95% CI: 1.2, 12.3) for light smokers (<1 pack per day) and HR = 4.4 (95% CI: 1.5, 13.3) for heavy smokers (≥1 pack per day). Increasing BMI was a common predictor in all people. Smoking is a strong predictor for diabetes with a dose-response relationship in HBsAg+ individuals and a mild predictor for seronegative individuals but not significant in anti-HCV+ individuals.
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Affiliation(s)
- C-S Wang
- Community Medicine Research Center and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan.,A-Lein Community Health Center, Kaohsiung County, Taiwan
| | - T-T Chang
- Division of Gastroenterology, Department of Internal Medicine and Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan
| | - W-J Yao
- Department of Radiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - S-T Wang
- Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - P Chou
- Community Medicine Research Center and Institute of Public Health, National Yang-Ming University, Taipei, Taiwan
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27
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Risk Assessment of Hepatocellular Carcinoma in Patients with Hepatitis C in China and the USA. Dig Dis Sci 2017; 62:3243-3253. [PMID: 28948495 DOI: 10.1007/s10620-017-4776-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2017] [Accepted: 09/19/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND Hepatitis C (HCV) infection is an increasingly common cause of hepatocellular carcinoma (HCC) in China. AIMS We aimed to determine differences in demographic and behavioral profiles associated with HCC in HCV+ patients in China and the USA. METHODS Consecutive HCV+ patients were recruited from centers in China and the USA. Clinical data and lifestyle profiles were obtained through standardized questionnaires. Multivariable analysis was conducted to determine factors associated with HCC diagnosis within groups. RESULTS We included 41 HCC patients from China and 71 from the USA, and 931 non-HCC patients in China and 859 in China. Chinese patients with HCC were significantly younger, less likely to be male and to be obese than US patients with HCC (all p < 0.001). Chinese patients with HCC had a significantly lower rate of cirrhosis diagnosis (36.6 vs. 78.9%, p < 0.001); however, they also had a higher rate of hepatitis B core antibody positivity (63.4 vs. 36.8%, p = 0.007). In a multivariable analysis of the entire Chinese cohort, age > 55, male sex, the presence of diabetes, and time from maximum weight were associated with HCC, while tea consumption was associated with a decreased HCC risk (OR 0.37, 95% CI 0.16-0.88). In the US cohort, age > 55, male sex, and cirrhosis were associated with HCC on multivariable analysis. CONCLUSIONS With the aging Chinese population and increasing rates of diabetes, there will likely be continued increase in the incidence of HCV-related HCC in China. The protective effect of tea consumption on HCC development deserves further validation.
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28
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Shen Y, Zhang S, Wang X, Wang Y, Zhang J, Qin G, Li W, Ding K, Zhang L, Liang F. Comparison of type 2 diabetes mellitus incidence in different phases of hepatitis B virus infection: A meta-analysis. Liver Int 2017; 37:1451-1460. [PMID: 27753241 DOI: 10.1111/liv.13275] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2016] [Accepted: 10/11/2016] [Indexed: 12/15/2022]
Abstract
BACKGROUND Because whether hepatitis B virus infection increases the risk of type 2 diabetes mellitus has been a controversial topic, pair-wise and network meta-analyses of published literature were carried out to accurately evaluate the association between different phases of hepatitis B virus infection and the risk of type 2 diabetes mellitus. METHODS A comprehensive literature retrieval was conducted from the PubMed, Embase, Cochrane Library and Chinese Database to identify epidemiological studies on the association between hepatitis B virus infection and the risk of type 2 diabetes mellitus that were published from 1999 to 2015. A pair-wise meta-analysis of direct evidence was performed to estimate the pooled odds ratios and 95% confidence intervals. A network meta-analysis was conducted, including the construction of a network plot, inconsistency plot, predictive interval plot, comparison-adjusted funnel plot and rank diagram, to graphically link the direct and indirect comparisons between different hepatitis B virus infective phases. RESULTS Eighteen publications (n=113 639) describing 32 studies were included in this meta-analysis. In the pair-wise meta-analysis, the pooled odds ratio for type 2 diabetes mellitus in chronic hepatitis B cirrhosis patients was 1.76 (95% confidence interval: 1.44-2.14) when compared with non-cirrhotic chronic hepatitis B patients. In the network meta-analysis, six comparisons of four hepatitis B virus infectious states indicated the following descending order for the risk of type 2 diabetes mellitus: hepatitis B cirrhosis patients, non-cirrhotic chronic hepatitis B patients, hepatitis B virus carriers and non-hepatitis B virus controls. CONCLUSION This study suggests that hepatitis B virus infection is not an independent risk factor for type 2 diabetes mellitus, but the development of cirrhosis may increase the incidence of type 2 diabetes mellitus cirrhosis.
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Affiliation(s)
- Yi Shen
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Sheng Zhang
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Xulin Wang
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Yuanyuan Wang
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Jian Zhang
- Analysis and testing center, Nantong University, Nantong, China
| | - Gang Qin
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Wenchao Li
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Kun Ding
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Lei Zhang
- Research Centre for Public Health, Tsinghua University, Beijing 100084, China.,Melbourne Sexual Health Centre, Alfred Health, Melbourne, Australia.,Central Clinical School, Faculty of Medicine, Monash University, Melbourne, Australia.,School of Public Health and Preventive Medicine, Faculty of Medicine, Monash University, Melbourne, Australia
| | - Feng Liang
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China.,Qidong Third People's Hospital, Nantong, China
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29
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Younossi Z, Kochems K, de Ridder M, Curran D, Bunge EM, de Moerlooze L. Should adults with diabetes mellitus be vaccinated against hepatitis B virus? A systematic review of diabetes mellitus and the progression of hepatitis B disease. Hum Vaccin Immunother 2017; 13:2695-2706. [PMID: 28742983 PMCID: PMC5703367 DOI: 10.1080/21645515.2017.1353850] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Despite the burden of diabetes mellitus (DM), little is known about the role of this and other metabolic syndromes on the severity of hepatitis B virus (HBV) chronicity and liver disease progression. The value of hepatitis B vaccination and its impact on liver diseases and HCC has been largely demonstrated, adult vaccination coverage is however suboptimal and DM diagnosis represents an opportunity for the HCP to discuss hepatitis B and other adult vaccinations. We performed a systematic literature search to identify studies (January 2000 to January 2017) describing liver disease progression among patients with HBV by DM status. Risk factors were assessed including the relationship between HBV and non-alcoholic steatohepatitis (NASH). Data were extracted systematically and assessed descriptively. Twenty articles described liver disease progression and one article evaluated NASH among subjects with HBV by DM status. Fourteen articles reported that DM as a predictor for the outcome, including delayed seroclearance, cirrhosis, hepatocellular carcinoma, transplant/mortality and death, whereas no association on liver outcomes was found in 7 studies. In summary, our review suggests that DM is associated with the progression of severe liver outcomes in adults with HBV, although more studies are needed to understand the benefits of HBV vaccination in adults with DM and liver-diseases.
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Affiliation(s)
- Zobair Younossi
- a Center for Liver Disease, Department of Medicine , Inova Fairfax Hospital , Falls Church , VA , USA
| | - Katrin Kochems
- b Pallas Health Research and Consultancy , Rotterdam , The Netherlands
| | - Marc de Ridder
- c Faculté de Pharmacie, Université Libre de Bruxelles , Bruxelles , Belgium
| | | | - Eveline M Bunge
- b Pallas Health Research and Consultancy , Rotterdam , The Netherlands
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30
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Han H, Deng H, Han T, Zhao H, Hou F, Qi X. Association Between Hepatocellular Carcinoma and Type 2 Diabetes Mellitus in Chinese Hepatitis B Virus Cirrhosis Patients: A Case-Control Study. Med Sci Monit 2017; 23:3324-3334. [PMID: 28689209 PMCID: PMC5515116 DOI: 10.12659/msm.902440] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Accepted: 12/15/2016] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Whether the presence of type 2 diabetes mellitus (T2DM) increases the risk of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) cirrhosis patients is controversial. We conducted a retrospective case-control study to evaluate this issue. MATERIAL AND METHODS We considered all patients diagnosed with HBV-related liver cirrhosis at our hospital from July 2011 to June 2014. The case (n=91) and control (n=91) groups were HBV cirrhosis patients with and without T2DM, respectively. They were matched at a ratio of 1: 1 according to the individual age (±2 years) and same sex and Child-Pugh score. RESULTS None of the baseline data were significantly different between the 2 groups. The percentage of HCC was similar between the 2 groups (case versus control group: 34.1% versus 46.2%, P=0.13). In the case group, sex (P=0.002), alkaline phosphatase (P<0.001), g-glutamine transferase (P=0.001), and sodium (P=0.003) were associated with the risk of HCC. In the control group, platelet (P=0.041), alanine aminotransferase (P=0.034), aspartate aminotransferase (P=0.026), alkaline phosphatase (P<0.001), and γ-glutamine transferase (P<0.001) were associated with the risk of HCC. CONCLUSIONS T2DM may not be a risk factor for the presence of HCC in HBV cirrhosis.
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Affiliation(s)
- Huixian Han
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, P.R. China
- Postgraduate College, Dalian Medical University, Dalian, Liaoning, P.R. China
| | - Han Deng
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, P.R. China
- Postgraduate College, Dalian Medical University, Dalian, Liaoning, P.R. China
| | - Tao Han
- Department of Oncology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, P.R. China
| | - Haitao Zhao
- Medical Ethical Committee, General Hospital of Shenyang Military Area, Shenyang, Liaoning, P.R. China
| | - Feifei Hou
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, P.R. China
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Shenyang Military Area, Shenyang, Liaoning, P.R. China
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31
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Barami K, Lyon L, Conell C. Type 2 Diabetes Mellitus and Glioblastoma Multiforme-Assessing Risk and Survival: Results of a Large Retrospective Study and Systematic Review of the Literature. World Neurosurg 2017; 106:300-307. [PMID: 28698089 DOI: 10.1016/j.wneu.2017.06.164] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2017] [Revised: 06/27/2017] [Accepted: 06/29/2017] [Indexed: 01/25/2023]
Abstract
OBJECTIVE Despite studies showing a positive correlation between type 2 diabetes mellitus (DM2), a modifiable risk factor, and various cancer types, the link remains controversial in the setting of glioblastoma multiforme (GBM). In this study, we assessed whether DM2 and DM2-associated factors were associated with a higher risk of developing GBM and also determined if DM2 affected the survival of patients with GBM. METHODS A cross-sectional case-control study of 1144 GBM cases diagnosed between 2000 and 2013 of which 969 patients matched for age and sex was performed to assess the association between DM2, hyperlipidemia, and obesity with the incidence of GBM. A longitudinal study of the patients with GBM was also performed to assess the association between the effect of DM2 and GBM survival. RESULTS No association was seen between DM2, hyperlipidemia, obesity, and GBM. DM2 was associated with poorer survival in univariate testing yet not in multivariate testing. Diabetic patients with GBM had good glycemic control. Older patients had poorer survival and overall survival improved over years of study. CONCLUSIONS DM2, hyperlipidemia, and obesity were not associated with increased risk of developing GBM, and DM2 itself does not seem to influence survival among these patients. This finding might be related to good glycemic control in this cohort. Survey of the literature consistently shows that hyperglycemia is associated with poorer survival. Our findings suggest that rather than the presence or absence of DM2, glycemic control seems to be more important in the survival of patients with GBM, which warrants future investigation.
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Affiliation(s)
- Kaveh Barami
- Department of Neurosurgery, Kaiser Permanente Northern California, Sacramento, California, USA.
| | - Liisa Lyon
- The Kaiser Permanente Northern California Division of Research, Oakland, California, USA
| | - Carol Conell
- The Kaiser Permanente Northern California Division of Research, Oakland, California, USA
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Zhang Q, Deng YL, Liu C, Huang LH, Shang L, Chen XG, Wang LT, Du JZ, Wang Y, Wang PX, Zhang H, Shen ZY. Diabetes mellitus may affect the long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after liver transplantation. World J Gastroenterol 2016; 22:9571-9585. [PMID: 27920478 PMCID: PMC5116601 DOI: 10.3748/wjg.v22.i43.9571] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2016] [Revised: 08/02/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To determine whether diabetes mellitus (DM) affects prognosis/recurrence after liver transplantation (LT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).
METHODS A retrospective study was conducted between January 2000 and August 2013 on 1631 patients with HBV-related HCC who underwent LT with antiviral prophylaxis. Patient data were obtained from the China Liver Transplant Registry (https://www.cltr.org/). To compare the outcomes and tumor recurrence in the HBV-related HCC patients with or without DM, statistical analyses were conducted using χ2 tests, Mann-Whitney tests, the Kaplan-Meier method, log-rank tests and multivariate step-wise Cox regression analysis.
RESULTS Univariate analysis of 1631 patients who underwent LT found overall 1-, 3- and 5-year survival rates of 79%, 73% and 71% respectively in the DM patients, and 84%, 78% and 76% in the non-DM patients respectively. Overall survival rate differences after LT between the two groups were significant (P = 0.041), but recurrence-free survival rates were not (P = 0.096). By stratified analysis, the overall survival rates in DM patients for age > 50 years (P = 0.002), the presence of vascular invasion (P = 0.096), tumors ≤ 3 cm (P = 0.047), two to three tumor nodules (P = 0.007), Child-Pugh grade B (P = 0.018), and pre-LT alanine aminotransferase levels between 40 and 80 IU/L (P = 0.017) were significantly lower than in non-DM patients. Additionally, serum α-fetoprotein level > 2000 ng/mL (P = 0.052) was associated with a significant survival difference trend between DM and non-DM patients. Multivariate analysis showed that the presence of DM (P < 0.001, HR = 1.591; 95%CI: 1.239-2.041) was an independent predictor associated with poor survival after LT.
CONCLUSION HBV-related HCC patients with DM have decreased long-term overall survival and poor LT outcomes. Prevention strategies for HCC patients with DM are recommended.
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Gao C. Molecular pathological epidemiology in diabetes mellitus and risk of hepatocellular carcinoma. World J Hepatol 2016; 8:1119-1127. [PMID: 27721917 PMCID: PMC5037325 DOI: 10.4254/wjh.v8.i27.1119] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2016] [Revised: 06/28/2016] [Accepted: 08/08/2016] [Indexed: 02/06/2023] Open
Abstract
Molecular pathological epidemiology (MPE) is a multidisciplinary and transdisciplinary study field, which has emerged as an integrated approach of molecular pathology and epidemiology, and investigates the relationship between exogenous and endogenous exposure factors, tumor molecular signatures, and tumor initiation, progression, and response to treatment. Molecular epidemiology broadly encompasses MPE and conventional-type molecular epidemiology. Hepatocellular carcinoma (HCC) is the third most common cause of cancer-associated death worldwide and remains as a major public health challenge. Over the past few decades, a number of epidemiological studies have demonstrated that diabetes mellitus (DM) is an established independent risk factor for HCC. However, how DM affects the occurrence and development of HCC remains as yet unclearly understood. MPE may be a promising approach to investigate the molecular mechanisms of carcinogenesis of DM in HCC, and provide some useful insights for this pathological process, although a few challenges must be overcome. This review highlights the recent advances in this field, including: (1) introduction of MPE; (2) HCC, risk factors, and DM as an established independent risk factor for HCC; (3) molecular pathology, molecular epidemiology, and MPE in DM and HCC; and (4) MPE studies in DM and risk of HCC. More MPE studies are expected to be performed in future and I believe that this field can provide some very important insights on the molecular mechanisms, diagnosis, personalized prevention and treatment for DM and risk of HCC.
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Lee J, Yoo SH, Sohn W, Kim HW, Choi YS, Won JH, Heo JY, Park SJ, Park YM. Obesity and hepatocellular carcinoma in patients receiving entecavir for chronic hepatitis B. Clin Mol Hepatol 2016; 22:339-349. [PMID: 27729627 PMCID: PMC5066372 DOI: 10.3350/cmh.2016.0021] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 06/13/2016] [Accepted: 06/29/2016] [Indexed: 12/11/2022] Open
Abstract
Background/Aims This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. Methods This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). Results The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm2 (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m2 (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm2 (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602). Conclusion HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.
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Affiliation(s)
- Jaemin Lee
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Sun Hong Yoo
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Won Sohn
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Hyung Woo Kim
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Yong Sun Choi
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Jung Ho Won
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Jin Young Heo
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Sang Jong Park
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
| | - Young Min Park
- Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea.,Liver Center, Bundang Jesaeng Hospital, Seongnam, Korea
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Raffetti E, Fattovich G, Donato F. Incidence of hepatocellular carcinoma in untreated subjects with chronic hepatitis B: a systematic review and meta-analysis. Liver Int 2016; 36:1239-51. [PMID: 27062182 DOI: 10.1111/liv.13142] [Citation(s) in RCA: 115] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Accepted: 03/31/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS In the natural history of hepatitis B virus (HBV) chronic infection, the hepatocellular carcinoma (HCC) risk is unclear. We assessed incidence and predictors of HCC by a systematic review and meta-analysis. METHODS We included longitudinal studies and randomized controlled trials assessing HCC incidence in untreated patients with HBV chronic infection. Incidence rates and their 95% confidence intervals were extracted by each study and pooled together in random effects models. RESULTS Sixty-six studies were included with a total of 347 859 patients. According to liver disease status, the summary incidence rates were in Europe, North America and East Asia, respectively: (a) asymptomatic carriers: 0.07 (95% confidence interval: 0.05-0.09), 0.19 (0.07-0.31) and 0.42 (0.21-0.63) per 100 person-years, respectively; (b) inactive carriers: 0.03 (0.0-0.10), 0.17 (0.02-0.62) and 0.06 (0.02-0.10), respectively; (c) chronic hepatitis: 0.12 (0.0-0.27), 0.48 (0.22-0.91) and 0.49 (0.32-0.66), respectively; (d) compensated cirrhosis (Child-Pugh A): 2.03 (1.30-2.77), 2.89 (1.23-4.55) and 3.37 (2.48-4.26) respectively. Multivariate meta-regression showed a significant increase in incidence rates for age, and for status of a symptomatic carrier, chronic hepatitis and compensated cirrhosis compared to inactive carrier, but not for geographical area after adjusting for age. An increase in the incidence rates was also observed for alcohol intake ≥60 g/dl, HBV genotype C with respect to B and HBV-DNA serum levels >2000 IU/ml, in Asian studies. CONCLUSIONS Hepatocellular carcinoma risk in untreated subjects with HBV chronic infection is strongly related with age and liver disease status.
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Affiliation(s)
- Elena Raffetti
- Unit of Hygiene, Epidemiology and Public Health, University of Brescia, Brescia, Italy
| | | | - Francesco Donato
- Unit of Hygiene, Epidemiology and Public Health, University of Brescia, Brescia, Italy
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36
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Flores YN, Auslander A, Crespi CM, Rodriguez M, Zhang ZF, Durazo F, Salmerón J. Longitudinal association of obesity, metabolic syndrome and diabetes with risk of elevated aminotransferase levels in a cohort of Mexican health workers. J Dig Dis 2016; 17:304-12. [PMID: 26991251 PMCID: PMC4956543 DOI: 10.1111/1751-2980.12341] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2015] [Revised: 12/14/2015] [Accepted: 03/07/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVE In Mexico, chronic liver disease have been increasingly found along with the rapidly growing prevalence of obesity, diabetes and metabolic syndrome (MS). We aimed to investigate the longitudinal association between these three factors and risk of elevated alanine aminotransferase (ALT) levels (>40 U/L), a marker for liver damage, in a cohort of Mexican adults. METHODS Data were obtained from two separate waves of the Mexican Health Worker Cohort Study: Wave 1 (2004-2006) and Wave 2 (2011-2013). Unconditional logistic regression models were employed to determine the cross-sectional and longitudinal association between these risk factors and elevated ALT levels. RESULTS The prevalence of elevated ALT was significantly higher among men, individuals aged under 60 years, those who were overweight or obese, diabetic, with MS or heavy/binge drinkers. The longitudinal results indicated that weight gain between waves that resulted in a change in body mass index, along with remaining overweight or obese, were significantly associated with an increased risk of elevated ALT levels. A significantly increased risk of developing elevated ALT was also observed among those who acquired diabetes or MS from Wave 1 to Wave 2. CONCLUSIONS Weight gain and acquiring diabetes or MS are associated with a significant risk of having elevated ALT. These results, within the context of the rapid increase in global obesity rates, call urgently for programs to help to prevent chronic liver disease.
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Affiliation(s)
- Yvonne N Flores
- Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, México
- Department of Health Policy and Management, Center for Cancer Prevention and Control Research, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, Los Angeles, California, USA
| | - Allyn Auslander
- Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, California, USA
| | - Catherine M Crespi
- Department of Biostatistics, Center for Cancer Prevention and Control Research, Fielding School of Public Health and Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, USA
| | - Michael Rodriguez
- Department of Family Medicine, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
| | - Zuo-Feng Zhang
- Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, California, USA
| | - Francisco Durazo
- Department of Digestive Diseases, David Geffen School of Medicine and Pfleger Liver Institute, UCLA, Los Angeles, California, USA
| | - Jorge Salmerón
- Unidad de Investigación Epidemiológica y en Servicios de Salud, Instituto Mexicano del Seguro Social, Cuernavaca, Morelos, México
- Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico
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Ballestri S, Nascimbeni F, Romagnoli D, Baldelli E, Targher G, Lonardo A. Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection--Liver: The "Musketeer" in the Spotlight. Int J Mol Sci 2016; 17:355. [PMID: 27005620 PMCID: PMC4813216 DOI: 10.3390/ijms17030355] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 02/29/2016] [Accepted: 03/02/2016] [Indexed: 02/07/2023] Open
Abstract
The pathogenesis of type 2 diabetes (T2D) involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR), which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty (simple steatosis and steatohepatitis) and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC)) that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV) infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a "vicious circle", eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved.
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Affiliation(s)
- Stefano Ballestri
- Operating Unit Internal Medicine, Pavullo General Hospital, Azienda USL Modena, ViaSuore di San Giuseppe Benedetto Cottolengo, 5, Pavullo, 41026 Modena, Italy.
| | - Fabio Nascimbeni
- Outpatient Liver Clinic and Operating Unit Internal Medicine, NOCSAE, Azienda USL Modena, Via P. Giardini, 1355, 41126 Modena, Italy.
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via P. Giardini, 1355, 41126 Modena, Italy.
| | - Dante Romagnoli
- Outpatient Liver Clinic and Operating Unit Internal Medicine, NOCSAE, Azienda USL Modena, Via P. Giardini, 1355, 41126 Modena, Italy.
| | - Enrica Baldelli
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via P. Giardini, 1355, 41126 Modena, Italy.
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani, 1, 37126 Verona, Italy.
| | - Amedeo Lonardo
- Outpatient Liver Clinic and Operating Unit Internal Medicine, NOCSAE, Azienda USL Modena, Via P. Giardini, 1355, 41126 Modena, Italy.
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Dyal HK, Aguilar M, Bartos G, Holt EW, Bhuket T, Liu B, Cheung R, Wong RJ. Diabetes Mellitus Increases Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Virus Patients: A Systematic Review. Dig Dis Sci 2016; 61:636-45. [PMID: 26703125 DOI: 10.1007/s10620-015-3983-3] [Citation(s) in RCA: 72] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Accepted: 11/26/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Rising rates of obesity, diabetes mellitus (DM), and nonalcoholic fatty liver disease (NAFLD) among chronic hepatitis C (HCV) patients may contribute to higher hepatocellular carcinoma (HCC) risk. AIM To perform a systematic review evaluating the impact of DM, body mass index (BMI), or steatosis on HCC risk among chronic HCV patients. METHODS A structured keyword search of PubMed from January 1, 2001, to July 1, 2014, was performed to identify original articles evaluating the association of DM, BMI, or steatosis with HCC among adults with chronic HCV. Studies involving HCV patients co-infected with human immunodeficiency virus, hepatitis B virus, or other chronic liver diseases with the exception of NAFLD were excluded. Quality assessment utilized the Newcastle-Ottawa scale. RESULTS Nine studies (seven cohorts, two case-controls) met inclusion criteria for the final analysis. Five of seven studies analyzing DM demonstrated significantly increased HCC risk associated with concurrent DM with effect sizes ranging from HR 1.73 (95 % CI 1.30-2.30) to RR 3.52 (95 % CI 1.29-9.24). One of three studies analyzing BMI demonstrated a significant association with HCC risk (BMI ≥ 30.0 vs. BMI < 23: RR 4.13, 95 % CI 1.38-12.40). Two of the three studies analyzing steatosis demonstrated significantly higher risk of HCC associated with steatosis ranging from RR 2.81 (95 % CI 1.49-4.41) to OR 6.39 (95 % CI 1.04-39.35). CONCLUSIONS Concurrent DM is associated with increased HCC risk among chronic HCV patients. BMI and steatosis may also increase HCC risk, but the limitations of the current studies do not allow us to draw strong conclusions.
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Affiliation(s)
- Harleen K Dyal
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Highland Hospital - Highland Care Pavilion 5th Floor, Endoscopy Unit, 1411 East 31st Street, Oakland, CA, 94602, USA.
| | - Maria Aguilar
- Department of Medicine, Alameda Health System - Highland Hospital, 1411 East 31st Street, Oakland, CA, USA.
| | - Gabriella Bartos
- Department of Medicine, Alameda Health System - Highland Hospital, 1411 East 31st Street, Oakland, CA, USA.
| | - Edward W Holt
- Division of Hepatology, Department of Transplantation, California Pacific Medical Center, 2340 Clay Street, 3rd Floor, San Francisco, CA, 94115, USA.
| | - Taft Bhuket
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Highland Hospital - Highland Care Pavilion 5th Floor, Endoscopy Unit, 1411 East 31st Street, Oakland, CA, 94602, USA.
| | - Benny Liu
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Highland Hospital - Highland Care Pavilion 5th Floor, Endoscopy Unit, 1411 East 31st Street, Oakland, CA, 94602, USA.
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, 750 Welch Road, Stanford, CA, 94305, USA.
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Alameda Health System - Highland Hospital, Highland Hospital - Highland Care Pavilion 5th Floor, Endoscopy Unit, 1411 East 31st Street, Oakland, CA, 94602, USA.
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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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Alcohol consumption and liver cancer risk: a meta-analysis. Cancer Causes Control 2015; 26:1205-31. [PMID: 26134046 DOI: 10.1007/s10552-015-0615-3] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 06/09/2015] [Indexed: 02/07/2023]
Abstract
PURPOSE Alcohol is a confirmed risk factor of liver cancer. Yet, its dose-response function and synergistic effects with other risk factors remain unclear. METHODS We performed a meta-analysis on publications up to May 2014. A total of 112 publications were identified. The meta-relative risk (mRR) and the dose-response trend were calculated. Tests for heterogeneity, publication bias, and sensitivity analyses were performed. The synergy index (SI) was recorded or calculated, whenever possible. RESULTS Compared to individuals who never drank or drank at very low frequencies, the mRR for ever drinkers was 1.29 (95% confidence interval, CI 1.16-1.42) and 1.46 (95% CI 1.27-1.65) for case-control studies, and 1.07 (95% CI 0.87-1.27) for cohort studies. Being a current drinker was associated with an increased liver cancer risk in case-control studies (mRR = 1.55, 95% CI 0.38-2.73), but not in cohort studies (mRR = 0.86, 95% CI 0.74-0.97). The dose-response relation between alcohol and liver cancer was apparent with RR = 1.08 (95% CI 1.04-1.11) for 12 g/day (~1 drink), 1.54 (95% CI 1.36-1.74) for 50 g/day, 2.14 (95% CI 1.74-2.62) for 75 g/day, 3.21 (95% CI 2.34-4.40) for 100 g/day, and 5.20 (95% CI 3.25-8.29) for 125 g/day of alcohol consumption. There were synergistic effects of alcohol consumption with hepatitis (S = 2.14, 95% CI 1.31-2.98) and with diabetes (S = 3.57, 95% CI 2.29-4.84) on the risk of liver cancer, although this may be subject to publication bias. CONCLUSION Overall, one alcoholic drink per day (~12 g/day) may be associated with a 1.1 times higher liver cancer risk. Further studies on the synergistic effects of alcohol consumption and other major risk factors are warranted.
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42
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Konerman M, Loomba R. Editorial: diabetes and its association with hepatocellular carcinoma in chronic hepatitis B. Aliment Pharmacol Ther 2015; 42:117-8. [PMID: 26040518 PMCID: PMC4534719 DOI: 10.1111/apt.13225] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Monica Konerman
- Division of Gastroenterology and Hepatology, Department of
Medicine, University of Michigan, University of California at San Diego, La Jolla,
CA 92093-0063
| | - Rohit Loomba
- NAFLD Translational Research Unit, University of California
at San Diego, La Jolla, CA 92093-0063,Division of Gastroenterology, Department of Medicine,
University of California at San Diego, La Jolla, CA 92093-0063,Division of Epidemiology, Department of Family and
Preventive Medicine, University of California at San Diego, La Jolla, CA
92093-0063
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43
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Type 2 diabetes mellitus and risk of oral cancer and precancerous lesions: a meta-analysis of observational studies. Oral Oncol 2015; 51:332-40. [PMID: 25650271 DOI: 10.1016/j.oraloncology.2015.01.003] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Revised: 12/22/2014] [Accepted: 01/02/2015] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Associations between type 2 diabetes mellitus (type 2 DM) and risk of oral cancer and precancerous lesions have been reported with controversial findings. We performed a meta-analysis to explore these associations. METHODS We identified studies by a literature search of MEDLINE and EMBASE through May 31, 2014, and by searching the reference lists of pertinent articles. Summary relative risk (SRR) with 95% confidence interval (CI) was calculated with a random-effects model. Between- study heterogeneity was assessed using the Cochran's Q and I(2) statistics. RESULTS A total of 13 studies (4 case-control and 9 cohort studies) on the association between type 2 DM and oral cancer were included. Overall analysis found that compared with non-diabetic individuals, individuals with type 2 DM had a significantly elevated incidence of oral cancer (SRR=1.15, 95% CI: 1.02-1.29; Pheterogeneity=0.277, I(2)=15.4%; 10 studies). Subgroup analyses found that duration of follow-up (⩾11years) significantly altered this positive association. Type 2 DM was associated with increased oral cancer mortality (SRR=1.41, 95% CI: 1.16-1.72; 4 studies). Meta-analysis of the four case-control studies showed a positive association between type 2 DM and risk of oral precancerous lesions (SRR=1.85, 95%CI: 1.23-2.80; Pheterogeneity=0.038, I(2)=57.5%). No significant public bias was found across these studies. CONCLUSIONS These findings of this meta-analysis indicate that compared with non-diabetic individuals, individuals with type 2 DM have an elevated risk of oral cancer and precancerous lesions development.
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Herrigel DJ, Moss RA. Diabetes mellitus as a novel risk factor for gastrointestinal malignancies. Postgrad Med 2015; 126:106-18. [PMID: 25414939 DOI: 10.3810/pgm.2014.10.2825] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Evidence of an emerging etiologic link between diabetes mellitus and several gastrointestinal malignancies is presented. Although a correlation between pancreatic cancer and diabetes mellitus has long been suspected, the potential role diabetes mellitus plays in the pathogenicity of both hepatocellular carcinoma and colon cancer is becoming increasingly well defined. Further supporting the prospect of etiologic linkage, the association of diabetes mellitus with colon cancer is consistently demonstrated to be independent of obesity. An increasing incidence of diabetes and obesity in the United States has led to a recent surge in incidence of hepatocellular cancer on the background of nonalcoholic fatty liver disease, and this disease is expected to commensurately grow in incidence. Widespread recognition of this emerging risk factor may lead to a change in screening practices. Although the mechanisms underlying the correlation are still under investigation, the role of insulin, the insulin-like growth factor-I, and related binding and signaling pathways as regulators of cell growth and cell proliferation are implicated in carcinogenesis and tumor growth. The potential role of metformin and other medications for diabetes mellitus in the chemoprevention, carcinogenesis, and treatment of gastrointestinal malignancies is also presented.
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Affiliation(s)
- Dana J Herrigel
- Department of Internal Medicine, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, New Brunswick, NJ
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Antonelli A, Ferrari SM, Giuggioli D, Di Domenicantonio A, Ruffilli I, Corrado A, Fabiani S, Marchi S, Ferri C, Ferrannini E, Fallahi P. Hepatitis C virus infection and type 1 and type 2 diabetes mellitus. World J Diabetes 2014; 5:586-600. [PMID: 25317237 PMCID: PMC4138583 DOI: 10.4239/wjd.v5.i5.586] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 04/10/2014] [Accepted: 07/12/2014] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients.
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Starup-Linde J, Karlstad O, Eriksen SA, Vestergaard P, Bronsveld HK, de Vries F, Andersen M, Auvinen A, Haukka J, Hjellvik V, Bazelier MT, Boer AD, Furu K, De Bruin ML. CARING (CAncer Risk and INsulin analoGues): the association of diabetes mellitus and cancer risk with focus on possible determinants - a systematic review and a meta-analysis. Curr Drug Saf 2014; 8:296-332. [PMID: 24215312 PMCID: PMC5421136 DOI: 10.2174/15748863113086660071] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Revised: 10/27/2013] [Accepted: 10/30/2013] [Indexed: 12/11/2022]
Abstract
Background: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. Objective: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. Data Sources: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: “Diabetes mellitus”, “Neoplasms”, and “Risk of cancer”. Study Eligibility Criteria: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. Results: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). Limitations: Publication bias seemed to be present. Only published data were used in the analyses. Conclusions: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | | | | | - Marie L De Bruin
- Department of Endocrinology and Internal Medicine (MEA), Aarhus University Hospital, Tage Hansens Gade 2, 8000 Aarhus C, Denmark.
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Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is traditionally associated with chronic liver injury resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) infection or excessive consumption of alcohol. In addition, recent evidence links HCC to diabetes. AIMS Since these risk factors are prevalent among US veterans, we analyzedcontribution of various etiologies toHCC incidence in this population. METHODS Clinicopathological correlates of 150 male US veterans diagnosed with HCC between 2001 and 2010 were analyzed and compared to frequency-matched (2:1) non-cancer controls in a single center. RESULTS HCC was associated with cirrhosis (odds ratio [OR], 250.84; 95 % confidence interval [CI], 86.92-723.88; p < 0.0001), chronic hepatitis B (OR, 34.30 95 % CI, 1.97-598.47; p = 0.015), chronic hepatitis C (OR, 6.84; 95 % CI, 3.89-12.04; p < 0.0001), alcohol use (OR, 6.76; 95 % CI, 4.35-10.52; p < 0.0001), and smoking (OR, 1.83; 95 % CI, 1.23-2.89; p = 0.009), but surprisingly not with diabetes. Only in a subgroup of HCC patients with no "traditional" risk factors did diabetes become a strong independent predictor of HCC when compared to HCC patients with at least one such risk factor (OR, 10.69; 95 % CI, 1.88-60.63, p = 0.007). This subgroup was further distinguished by older age, increased prevalence of hypertension, nonsmoking, and a trend to develop noncirrhotic HCC. CONCLUSIONS While HCC in US veterans is overwhelmingly linked to cirrhosis due to "traditional" risk factors, it also occurs with a separate clinical profile characterized by diabetes and no evidence of cirrhosis, suggesting distinct mechanisms of hepatocarcinogenesis and needs for surveillance.
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Pais R, Rusu E, Ratziu V. The impact of obesity and metabolic syndrome on chronic hepatitis B and drug-induced liver disease. Clin Liver Dis 2014; 18:165-78. [PMID: 24274872 DOI: 10.1016/j.cld.2013.09.015] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Steatosis and insulin resistance (IR) are no more frequent in chronic hepatitis B (CHB) than in the general population. Although experimental studies suggest that the HBx protein induces liver fat, human studies have shown that steatosis and IR are related to coexistent metabolic risk factors, thus epidemiologically linked rather than virally induced. Diabetes and obesity are associated with advanced fibrosis and increased risk of hepatocellular carcinoma in CHB. Despite abundant experimental data showing that fatty liver is more susceptible to liver injury, drug-induced liver disease seems no more frequent in NAFLD patients, except, possibly, a higher incidence but not severity of acetaminophen hepatotoxicity.
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Affiliation(s)
- Raluca Pais
- Department of Hepatogastroenterology, Université Pierre et Marie Curie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Inserm UMR_S 938, Paris 75013, France
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Zheng Z, Zhang C, Yan J, Ruan Y, Zhao X, San X, Mao Y, Sun Q, Zhang K, Fan Z. Diabetes mellitus is associated with hepatocellular carcinoma: a retrospective case-control study in hepatitis endemic area. PLoS One 2013; 8:e84776. [PMID: 24386416 PMCID: PMC3873428 DOI: 10.1371/journal.pone.0084776] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Accepted: 11/19/2013] [Indexed: 12/14/2022] Open
Abstract
Background A number of case-control patient studies have been conducted to investigate the association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC). Despite some controversial reports, it has been suggested that DM is associated with HCC. The previous studies on this subject vary in the selection of populations, sample sizes, methodology, and analysis results. Therefore, it is necessary to further delineate the involvement of DM, together with other related risk factors, in HCC with large sample size and strict analysis methodology. Methods We conducted a hospital-based retrospective case-control study at Perking Union Medical College Hospital, China. A total of 1,568 patients with liver diseases were enrolled in the statistical study to evaluate the association of DM and other risk factors with HCC. Among these patients, 716 of them were diagnosed with benign liver diseases, and 852 patients were diagnosed as HCC. We utilized binary logistic regression and stepwise logistic regression to investigate the associations among DM, hypertension, fatty liver, cirrhosis, gallstone, HBV infection, HCV infection, and HCC. Results Statistical analysis through the stepwise regression model indicated that the prevalence of DM, male gender, cirrhosis, HCV infection, or HBV infection is higher in the HCC patient group compared to the control group. However, the prevalence of gallstone is negatively associated with HCC cases. DM co-exists with HBV infection, male gender, and age in the HCC cases. Binary logistic regression analysis suggested that DM may synergize with HBV infection in HCC development. Conclusion DM is strongly associated with the increased risk of HCC regardless of the prevalence of HBV infection, HCV infection, cirrhosis, male gender, and age. However, the synergistic interaction between DM and HBV in HCC occurrence is significant. Therefore, DM patients with HBV infection represent a very high HCC risk population and should be considered for HCC close surveillance program.
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Affiliation(s)
- Ze Zheng
- Center for Molecular Medicine & Genetics, Wayne State University School of Medicine, Detroit, Michigan, United States of America
| | - Chao Zhang
- Center for Molecular Medicine & Genetics, Wayne State University School of Medicine, Detroit, Michigan, United States of America
| | - Jianhua Yan
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yanping Ruan
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyi Zhao
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xingting San
- Department of Hepatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Yilei Mao
- Department of Hepatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Qinghua Sun
- Division of Cardiovascular Medicine, Davis Heart & Lung Research Institute, College of Medicine, Ohio State University, Columbus, Ohio, United States of America
- Division of Environmental Health Sciences, College of Public Health, Ohio State University, Columbus, Ohio, United States of America
- * E-mail: (KZ); (QS); (ZF)
| | - Kezhong Zhang
- Center for Molecular Medicine & Genetics, Wayne State University School of Medicine, Detroit, Michigan, United States of America
- Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan, United States of America
- * E-mail: (KZ); (QS); (ZF)
| | - Zhongjie Fan
- Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
- * E-mail: (KZ); (QS); (ZF)
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Younossi Z, Negro F, Serfaty L, Pol S, Diago M, Zeuzem S, Andreone P, Lawitz EJ, Roberts S, Focaccia R, Foster GR, Horban A, Lonjon-Domanec I, Coate B, DeMasi R, Picchio G, Witek J. Homeostasis model assessment of insulin resistance does not seem to predict response to telaprevir in chronic hepatitis C in the REALIZE trial. Hepatology 2013; 58:1897-906. [PMID: 24382638 DOI: 10.1002/hep.26437] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Accepted: 03/31/2013] [Indexed: 12/26/2022]
Abstract
UNLABELLED Baseline homeostasis model assessment-estimated insulin resistance (HOMA-IR), a marker for insulin resistance, has been associated with poor virologic response to peginterferon alpha/ribavirin (PR) in chronic hepatitis C. We evaluated the association between baseline HOMA-IR and pretreatment factors on sustained virologic response (SVR) to telaprevir (TVR) in genotype 1 patients with hepatitis C and prior peginterferon/ribavirin (PR) treatment failure. Patients were randomized to 12 weeks of TVR (750 mg q8h) plus peginterferon (180 μg/week) and ribavirin (1,000-1,200 mg/day) (with or without a 4-week lead-in) followed by PR, or PR alone (PR48), for 48 weeks. Univariate and multiple logistic regression analyses explored the prognostic significance of baseline HOMA-IR alone and adjusted for other pretreatment factors and SVR. The TVR arms were pooled for the purposes of this analysis. In all, 662 patients were randomized; 578 had baseline HOMA-IR and other prognostic data and were included in this analysis. Median baseline HOMA-IR was 2.6 (interquartile range [IQR] 1.7-4.3); 207 (36%), 206 (36%), and 165 (29%) patients had baseline HOMA-IR <2, 2 to <4, and ≥ 4, respectively. Male gender, higher body mass index, triglycerides, gamma-glutamyl transpeptidase, maximum alanine aminotransferase/aspartate aminotransferase, and fibrosis stage were associated with higher baseline HOMA-IR. Baseline HOMA-IR was associated with SVR in univariate analysis, but not after adjustment for other baseline prognostic factors (TVR: OR = 0.95, 95% confidence interval [CI]: 0.71,1.29; PR48: 0.60; 95% CI: 0.25,1.43). CONCLUSION In patients with prior PR treatment failure, baseline HOMA-IR correlated with SVR in univariate but not multivariate analyses, suggesting other factors have a more direct causal relationship with virologic response to TVR-based therapy than HOMA-IR.
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Affiliation(s)
- Zobair Younossi
- Center for Liver Diseases and Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA
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