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Huang SC, Su TH, Tseng TC, Liao SH, Hsu SJ, Hong CM, Lan TY, Liu CH, Yang HC, Liu CJ, Kao JH. Pre-Existing and New-Onset Metabolic Dysfunctions Increase Cirrhosis and Its Complication Risks in Chronic Hepatitis B. Am J Gastroenterol 2025; 120:401-409. [PMID: 38920306 DOI: 10.14309/ajg.0000000000002915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 06/17/2024] [Indexed: 06/27/2024]
Abstract
INTRODUCTION The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing among the chronic hepatitis B (CHB) population. This study aimed to explore the impact of metabolic dysfunction (MD) on cirrhosis and cirrhotic complication risks in CHB. METHODS Patients with CHB were consecutively recruited between 2006 and 2021. The presence of MD was based on the 5 cardiometabolic criteria specified in the MASLD definition. Patients were categorized into MD/non-MD groups based on these criteria. RESULTS Eleven thousand five hundred two treatment-naive noncirrhotic patients with CHB were included with a median follow-up of 5.3 years. Patients in the MD group (n = 7,314) were older and had lower hepatitis B virus DNA levels than non-MD patients (n = 4,188). After adjustment for clinical and viral factors, MD patients had significantly higher risks of cirrhosis (adjusted hazard ratio [aHR]: 1.82, 95% confidence interval [CI]: 1.40-2.37, P < 0.001) and cirrhotic complications (aHR: 1.30 per MD, 95% CI: 1.03-1.63, P = 0.025) in a dose-dependent manner. Furthermore, new-onset diabetes mellitus during the follow-up aggravated the risk of cirrhotic complications (aHR: 2.87, 95% CI: 1.34-6.11, P = 0.006). Hepatic steatosis was associated with lower risks of cirrhosis (aHR: 0.57 within 5 years, 95% CI: 0.44-0.74, P < 0.001) and cirrhotic complications (aHR: 0.45, 95% CI 0.23-0.88, P = 0.020). Among individuals with hepatic steatosis, patients with MASLD exhibited a higher cirrhosis risk than non-MD patients. DISCUSSION Concurrent and new-onset MDs increase the risks of cirrhosis and cirrhotic complications in patients with CHB, independent of hepatic steatosis. Proactively investigating metabolic comorbidities in CHB is critical to stratify the risk of liver disease progression.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Sih-Han Liao
- Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Yuan Lan
- Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Kim M, Jun BG, Shin HS, Yi JJ, Kim SG, Yi SW. Impact of high body mass index on hepatocellular carcinoma risk in chronic liver disease: A population-based prospective cohort study. PLoS One 2025; 20:e0316175. [PMID: 39841714 PMCID: PMC11753674 DOI: 10.1371/journal.pone.0316175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 12/08/2024] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND AND AIMS We investigated associations between body mass index (BMI) and hepatocellular carcinoma (HCC) in patients with hepatitis B (HBV) C (HCV) virus infection, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and liver cirrhosis (LC). METHODS We followed 350,608 Korean patients with liver disease who underwent routine health examinations from 2003-2006 until December 2018 via national hospital discharge records. Multivariable adjusted hazard ratios (HRs) per 5-kg/m2 BMI increase (BMI ≥25 kg/m2) for HCC risk were calculated using Cox models. HCC developed in 17,752 patients. RESULTS The HRs (95% CI) were 1.17 (1.06-1.28), 1.08 (0.87-1.34), 1.34 (1.14-1.58), 1.51 (1.17-1.94), and 1.11 (1.00-1.23) for HBV, HCV, ALD, NAFLD, and LC, respectively. The HRs for HBV were 1.45 (1.23-1.70) and 1.06 (0.95-1.19) in women and men, respectively; the corresponding HRs for LC were 1.27 (1.07-1.50) and 1.02 (0.90-1.16), respectively. In patients <65 years old with HBV, HCV, and NAFLD, the HRs were 1.17 (1.07-1.29), 1.33 (1.03-1.73), and 1.20 (0.87-1.64), respectively; the corresponding HRs were 1.05 (0.70-1.59), 0.74 (0.50-1.10), and 2.40 (1.62-3.54), respectively, in patients ≥65 years old. A BMI of 27.5-29.9 kg/m2 showed significantly higher HCC risks in patients with HBV, ALD, NAFLD, and LC. CONCLUSIONS Higher BMIs were associated with increased HCC risks in patients with HBV, ALD, NAFLD, and LC. Overweight status increased HCC risk. Women with HBV and LC had stronger BMI-HCC associations than men. The effect of high BMI was stronger in older patients with NAFLD and younger patients with viral hepatitis.
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Affiliation(s)
- Moonho Kim
- Department of Hematology and Oncology, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, Asanseoul Internal Medicine Clinic, Seoul, South Korea
| | - Hwang Sik Shin
- Department of Family Medicine, Soonchunhyang University Hospital Cheonan, Soonchunhyang University College of Medicine, Cheonan, South Korea
| | - Jee-Jeon Yi
- Institute for Occupational and Environmental Health, Catholic Kwandong University, Gangneung, South Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine Bucheon Hospital, Bucheon, South Korea
| | - Sang-Wook Yi
- Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Gangneung, South Korea
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Kim HY, Lee HA, Radu P, Dufour JF. Association of modifiable metabolic risk factors and lifestyle with all-cause mortality in patients with hepatocellular carcinoma. Sci Rep 2024; 14:15405. [PMID: 38965260 PMCID: PMC11224327 DOI: 10.1038/s41598-024-65127-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 06/17/2024] [Indexed: 07/06/2024] Open
Abstract
We aimed to investigate the potential impact of metabolic risk factors and lifestyles on mortality in hepatocellular carcinoma (HCC) patients. From the Korean Central Cancer Registry database (2008-2016), 8,505 HCC patients were included in the analysis. Patients with 2 or more metabolic risk factors (n = 2384, 28.0%) showed significantly worse overall survival (OS, 29 months, 95% confidence interval [CI] 27-33) than patients with 0 (n = 2269 [26.7%]; 41 months, 95% CI 37-47), or 1 (n = 3852 [45.3%]; 42 months; 95% CI 38-46) metabolic risk factor. (P < 0.001) In the multivariable Cox analysis, patients with ≥ 2 metabolic risk factors had significantly elevated risk of overall mortality (adjusted hazards ratio (HR) = 1.14 [95% CI 1.06-1.23], P < 0.001) and HCC-specific mortality (sub-distribution HR = 1.09 [95% CI 1.00-1.09], P = 0.046), compared to those without. Alcohol and smoking were also independent risk factors for worse overall and HCC-specific mortality (all P < 0.05). Metabolic comorbidities were associated with greater risk of mortality in a dose-dependent manner in HCC patients, regardless of tumor stage and liver function. Alcohol intake and smoking significantly increased mortality by themselves and even further with the presence of metabolic risk.
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Affiliation(s)
- Hwi Young Kim
- Department of Internal Medicine, College of Medicine, Ewha Womans University, 1071, Anyangcheon-ro, Yangcheon-gu, Seoul, 07985, Republic of Korea.
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Medical Center, Seoul, Republic of Korea
| | - Pompilia Radu
- University Clinic for Visceral Surgery and Medicine, University of Bern, Inselspital, Bern, Switzerland
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Xie J, Lin X, Fan X, Wang X, Pan D, Li J, Hao Y, Jie Y, Zhang L, Gu J. Global Burden and Trends of Primary Liver Cancer Attributable to Comorbid Type 2 Diabetes Mellitus Among People Living with Hepatitis B: An Observational Trend Study from 1990 to 2019. J Epidemiol Glob Health 2024; 14:398-410. [PMID: 38713342 PMCID: PMC11176116 DOI: 10.1007/s44197-024-00237-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 04/22/2024] [Indexed: 05/08/2024] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) increases the risk of liver cancer among people living with hepatitis B virus (HBV). Our study aimed to estimate the global burden and trends of liver cancer attributable to comorbid T2DM among people living with HBV from 1990 to 2019. METHODS We calculated the population attributable fractions (PAFs) of liver cancer attributable to comorbid T2DM among the burden of HBV-related liver cancer. We applied the PAFs to the burden of HBV-related liver cancer derived from the Global Burden of Disease (GBD) 2019 database to obtain the burden of liver cancer attributable to HBV-T2DM comorbidity. The prevalence, disability-adjusted life year (DALY), and deaths of liver cancer attributable to the comorbidity were assessed at the global, regional, and country levels and then stratified by the sociodemographic index (SDI), sex, and age group. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends. RESULTS In 2019, the global age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity were 9.9 (8.4-11.5) and 182.4 (154.9-212.7) per 10,000,000 individuals, respectively. High-income Asia Pacific and East Asia had the highest age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity, respectively. From 1990 to 2019, age-standardized prevalence and DALY rates increased in 16 out of 21 GBD regions. High-income North America had the largest annual increases in both age-standardized prevalence rates (EAPC = 6.07; 95% UI, 5.59 to 6.56) and DALY rates (EAPC = 4.77; 95% UI, 4.35 to 5.20), followed by Australasia and Central Asia. Across all SDI regions, the high SDI region exhibited the most rapid increase in age-standardized prevalence and DALY rates from 1990 to 2019. Additionally, men had consistently higher disease burdens than women across all age groups. The patterns of mortality burden and trends are similar to those of DALYs. CONCLUSIONS The burden of liver cancer attributable to comorbid T2DM among people living with HBV has exhibited an increasing trend across most regions over the last three decades. Tailored prevention strategies targeting T2DM should be implemented among individuals living with HBV.
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Affiliation(s)
- Jinzhao Xie
- Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Xiao Lin
- Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Xiaoyan Fan
- School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Xu Wang
- Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Deng Pan
- Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Jinghua Li
- Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, China
- Sun Yat-sen Global Health Institute, School of Public Health and Institute of State Governance, Sun Yat-sen University, Guangzhou, China
- Key Laboratory of Health Informatics of Guangdong Province, Sun Yat-sen University, Guangzhou, China
| | - Yuantao Hao
- Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, China
- Sun Yat-sen Global Health Institute, School of Public Health and Institute of State Governance, Sun Yat-sen University, Guangzhou, China
- Key Laboratory of Health Informatics of Guangdong Province, Sun Yat-sen University, Guangzhou, China
- Center for Public Health and Epidemic Preparedness and Response, Peking University, Beijing, China
| | - Yusheng Jie
- Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lei Zhang
- China-Australia Joint Research Centre for Infectious Diseases, School of Public Health, Xi'an Jiaotong University Health Science Centre, Xi'an, China
- Central Clinical School, Faculty of Medicine, Monash University, Melbourne, VIC, Australia
- Artificial Intelligence and Modelling in Epidemiology Program, Melbourne Sexual Health Centre, Alfred Health, Melbourne, VIC, Australia
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Jing Gu
- Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou, China.
- Sun Yat-sen Global Health Institute, School of Public Health and Institute of State Governance, Sun Yat-sen University, Guangzhou, China.
- Key Laboratory of Health Informatics of Guangdong Province, Sun Yat-sen University, Guangzhou, China.
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Luo J, Yuan M, Li S, Chen L, Zhou M, Li H, Bai X, Zhang Z, Zeng W, Sun X, Zhang Q, Chen Y, Zhou L. Dynamic evaluation of liver fibrosis to assess hepatocellular carcinoma risk in patients with chronic hepatitis B receiving nucleoside analogs treatment. Rev Inst Med Trop Sao Paulo 2024; 66:e27. [PMID: 38747848 PMCID: PMC11095248 DOI: 10.1590/s1678-9946202466027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Accepted: 02/28/2024] [Indexed: 05/19/2024] Open
Abstract
Despite good hepatitis B virus (HBV) inhibition by nucleoside analogs (NAs), cases of hepatocellular carcinoma (HCC) still occur. This study proposed a non-invasive predictive model to assess HCC risk in patients with chronic hepatitis B (CHB) receiving NAs treatment. Data were obtained from a hospital-based retrospective cohort registered on the Platform of Medical Data Science Academy of Chongqing Medical University, from 2013 to 2019. A total of 501 patients under NAs treatment had their FIB-4 index updated semiannually by recalculation based on laboratory values. Patients were divided into three groups based on FIB-4 index values: < 1.45, 1.45-3.25, and ≥ 3.25. Subsequently, HCC incidence was reassessed every six months using Kaplan-Meier curves based on the updated FIB-4 index. The median follow-up time of CHB patients after receiving NAs treatment was 2.5 years. HCC incidences with FIB-4 index < 1.45, 1.45-3.25, and ≥ 3.25 were 1.18%, 1.32%, and 9.09%, respectively. Dynamic assessment showed that the percentage of patients with FIB-4 index < 1.45 significantly increased semiannually (P < 0.001), and of patients with FIB-4 index ≥ 3.25 significantly decreased (P < 0.001). HCC incidence was the highest among patients with FIB-4 index ≥ 3.25. The FIB-4 index effectively predicted HCC incidence, and its dynamic assessment could be used for regular surveillance to implement early intervention and reduce HCC risk.
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Affiliation(s)
- Jia Luo
- Chongqing Medical University, School of Public Health, Department of Epidemiology, Chongqing, China
| | - Ming Yuan
- Chongqing Medical and Pharmaceutical College, Chongqing, China
| | - Shan Li
- Chongqing Medical University, School of Public Health, Department of Epidemiology, Chongqing, China
| | - Lijuan Chen
- Chongqing Medical University, School of Public Health, Department of Epidemiology, Chongqing, China
| | - Mingsha Zhou
- Chongqing Medical University, School of Public Health, Department of Epidemiology, Chongqing, China
| | - Hailan Li
- Chongqing Medical University, School of Public Health, Department of Epidemiology, Chongqing, China
| | - Xiuyuan Bai
- Chongqing Medical University, School of Public Health, Chongqing, China
| | - Zhiyu Zhang
- Chongqing Medical University, School of Public Health, Chongqing, China
| | - Weiqi Zeng
- Chongqing Medical University, School of Public Health, Chongqing, China
| | - Xueyi Sun
- Chongqing Medical University, School of Public Health, Chongqing, China
| | - Qiongfang Zhang
- Chongqing Medical University, School of Public Health, Chongqing, China
| | - Yi Chen
- Chongqing Medical University, School of Public Health, Chongqing, China
| | - Li Zhou
- Chongqing Medical University, School of Public Health, Department of Epidemiology, Chongqing, China
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Huang SC, Kao JH. The interplay between chronic hepatitis B and diabetes mellitus: A narrative and concise review. Kaohsiung J Med Sci 2024; 40:6-10. [PMID: 37732697 DOI: 10.1002/kjm2.12762] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Revised: 09/02/2023] [Accepted: 09/05/2023] [Indexed: 09/22/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder among individuals with chronic hepatitis B (CHB), contributing to additional adverse impacts on both hepatic and extrahepatic systems. Existing evidence suggests a potential positive association between CHB and the development of insulin resistance and T2DM. The presence of T2DM in CHB patients is associated with an increased risk of liver fibrosis, cirrhosis, decompensation, and hepatocellular carcinoma (HCC) occurrence. Moreover, it elevates the risk of non-liver cancers and all-cause mortality in this population. T2DM also serves as the key element in metabolic dysfunction-associated steatotic liver disease, which is prevalent in the CHB population. Although specific guidelines for managing T2DM in CHB patients have not been proposed, some studies indicated that intensive glycemic control may benefit the prognosis of these patients. Additionally, specific antidiabetic agents, such as metformin and thiazolidinediones, promise to reduce HCC risk. However, unresolved questions, including the optimal glycemic control target and the selection of antidiabetic agents for CHB patients, remain and thus warrant further investigations through well-designed prospective trials. Implementing a standardized protocol encompassing regular monitoring, risk stratification, and early intervention using a multidisciplinary framework may improve the outcomes of diabetic CHB patients.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Abdalla MMI. Serum resistin and the risk for hepatocellular carcinoma in diabetic patients. World J Gastroenterol 2023; 29:4271-4288. [PMID: 37545641 PMCID: PMC10401662 DOI: 10.3748/wjg.v29.i27.4271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/11/2023] [Accepted: 06/27/2023] [Indexed: 07/13/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the predominant type of liver cancer, is a major contributor to cancer-related fatalities across the globe. Diabetes has been identified as a significant risk factor for HCC, with recent research indicating that the hormone resistin could be involved in the onset and advancement of HCC in diabetic individuals. Resistin is a hormone that is known to be involved in inflammation and insulin resistance. Patients with HCC have been observed to exhibit increased resistin levels, which could be correlated with more severe disease stages and unfavourable prognoses. Nevertheless, the exact processes through which resistin influences the development and progression of HCC in diabetic patients remain unclear. This article aims to examine the existing literature on the possible use of resistin levels as a biomarker for HCC development and monitoring. Furthermore, it reviews the possible pathways of HCC initiation due to elevated resistin and offers new perspectives on comprehending the fundamental mechanisms of HCC in diabetic patients. Gaining a better understanding of these processes may yield valuable insights into HCC’s development and progression, as well as identify possible avenues for prevention and therapy.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
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Mak LY, Hui RWH, Lee CH, Mao X, Cheung KS, Wong DKH, Lui DTW, Fung J, Yuen MF, Seto WK. Glycemic burden and the risk of adverse hepatic outcomes in patients with chronic hepatitis B with type 2 diabetes. Hepatology 2023; 77:606-618. [PMID: 36130882 DOI: 10.1002/hep.32716] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 07/27/2022] [Accepted: 08/08/2022] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Type 2 diabetes (T2D) is common among patients with chronic hepatitis B infection (CHB) and has been associated with increased risk of carcinogenesis, including HCC. We investigated factors associated with HCC and fibrosis progression among patients with CHB with T2D (CHB+T2D). APPROACH AND RESULTS Chinese patients with CHB were prospectively recruited for the incidence of HCC and fibrosis progression defined by transient elastography. Among patients with CHB+T2D, glycemic control was assessed by mean glycated hemoglobin (HbA1c) and HbA1c variability determined using HbA1c measurements in the 5 years preceding recruitment. A total of 2330 patients with CHB were recruited (mean age 54.6 ±11.8 years old, 55.5% male, 57.9% antiviral-treated), with 671 (28.8%) having CHB+T2D (mean T2D duration 7.2 ± 4.6 years, mean HbA1c 7.2 ± 0.9%). T2D was independently associated with HCC (HR 2.080, 95% CI 1.343-3.222) and fibrosis progression (OR 4.305, 95% CI 3.416-5.424) in the overall cohort. In patients with CHB+T2D, factors reflecting glycemic burden (T2D duration [HR 1.107, 95% CI 1.023-1.198]), mean HbA1c (HR 1.851, 95% CI 1.026-3.339), time reaching target HbA1c (HbA1c-TRT; HR 0.978, 95% CI 0.957-0.999), liver stiffness (HR 1.041-1.043), and smoking (HR 2.726-3.344) were independently associated with HCC (all p < 0.05), but not HbA1c variability or controlled attenuation parameter. The same glycemic burden-related factors (T2D duration, mean HbA1c, and HbA1c-TRT), in addition to baseline fasting glucose, baseline HbA1c, AST and antiviral therapy, were independently associated with fibrosis progression at 3 years. CONCLUSIONS High glycemic burden was associated with HCC development and fibrosis progression among patients with CHB+T2D, highlighting the importance of glycemic control in reducing liver-related complications.
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Affiliation(s)
- Lung-Yi Mak
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong.,State Key Laboratory of Liver Research , The University of Hong Kong , Hong Kong
| | - Rex Wan-Hin Hui
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong
| | - Chi-Ho Lee
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong
| | - XianHua Mao
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong
| | - Ka-Shing Cheung
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong.,Department of Medicine , The University of Hong Kong-Shenzhen Hospital , Shenzhen , China
| | - Danny Ka-Ho Wong
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong.,State Key Laboratory of Liver Research , The University of Hong Kong , Hong Kong
| | - David Tak-Wai Lui
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong
| | - James Fung
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong.,State Key Laboratory of Liver Research , The University of Hong Kong , Hong Kong
| | - Man-Fung Yuen
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong.,State Key Laboratory of Liver Research , The University of Hong Kong , Hong Kong
| | - Wai-Kay Seto
- Department of Medicine , Queen Mary Hospital, The University of Hong Kong , Hong Kong.,State Key Laboratory of Liver Research , The University of Hong Kong , Hong Kong.,Department of Medicine , The University of Hong Kong-Shenzhen Hospital , Shenzhen , China
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9
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Yu MW, Lin CL, Liu CJ, Wu WJ, Hu JT, Huang YW. Metabolic-Associated Fatty Liver Disease, Hepatitis B Surface Antigen Seroclearance, and Long-Term Risk of Hepatocellular Carcinoma in Chronic Hepatitis B. Cancers (Basel) 2022; 14:cancers14236012. [PMID: 36497492 PMCID: PMC9736898 DOI: 10.3390/cancers14236012] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/02/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
The value of metabolic-associated fatty liver disease (MAFLD) and its ability to assess hepatocellular carcinoma (HCC) risk remains uncertain for chronic hepatitis B (CHB). We evaluated the impacts of MAFLD and its coincidental metabolic abnormalities and related genetic predisposition on HCC incidence and mortality outcomes in CHB. We analyzed data from 1453 HBsAg-positive men (median age = 49.2 years at baseline) from a cohort of civil servants recruited from 1989−1992. MAFLD was defined as hepatic steatosis on ultrasound with obesity, diabetes, or metabolic dysfunction at baseline. During follow-up (median = 19.3 years), 105 HCC events occurred. MAFLD was not associated with HCC (adjusted hazard ratio (aHR) = 1.02) but was associated with a higher HBsAg seroclearance rate (aHR = 1.43). In mediation analysis, HBsAg seroclearance driven by hepatic steatosis explained 31.6% of the association between MAFLD and HCC. Antiviral treatment or fatty liver disease-associated genetic variants did not influence the MAFLD−HCC association. In contrast, even after adjustment for MAFLD and the other metabolic abnormalities, diabetes (aHR = 2.28), obesity (aHR = 1.72), and metabolic dysfunction (aHR = 3.30) increased the risk of HCC (all p < 0.030). The risk of HCC increased with the number of metabolic abnormalities (vs 0: aHR = 2.05 and 5.72 for 2 and ≥ 3 metabolic abnormalities, respectively), and the cumulative effect of metabolic abnormalities was found across subgroups categorized by hepatic steatosis as well as in participants both with and without HBsAg seroclearance. In conclusion, MAFLD was not associated with increased HCC incidence in CHB. A more informative assessment of HCC risk can be obtained by taking into account the number of metabolic abnormalities.
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Affiliation(s)
- Ming-Whei Yu
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan
- Correspondence:
| | - Chih-Lin Lin
- Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei 10629, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan
| | - Wan-Jung Wu
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei 10055, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital Medical Center, School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei 24352, Taiwan
| | - Yi-Wen Huang
- Clinical Research Center, Liver Center and Division of Gastroenterology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
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10
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Shin HS, Jun BG, Yi SW. Impact of diabetes, obesity, and dyslipidemia on the risk of hepatocellular carcinoma in patients with chronic liver diseases. Clin Mol Hepatol 2022; 28:773-789. [PMID: 35934813 PMCID: PMC9597232 DOI: 10.3350/cmh.2021.0383] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 04/20/2022] [Indexed: 01/05/2023] Open
Abstract
Despite the increasing prevalence of metabolic disorders, the potential effects of metabolic factors on hepatocellular carcinoma (HCC) development in individuals with chronic liver diseases (CLDs) are not well understood. For a metabolic factor to be identified as a risk factor for HCC in patients with CLDs, such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, there should be a strong synergistic interaction between the carcinogenic mechanisms of the metabolic factor and the CLD itself. This review aims to comprehensively summarize the published data on the relationship between metabolic factors such as diabetes mellitus (DM), obesity, and blood lipids and the risk of HCC in patients with CLDs. DM consistently increases the risk of HCC in patients with CLD. When associated with DM, the risk of HCC seems to be highest in HCV and non-alcoholic fatty liver disease (NAFLD), followed by alcoholic liver disease (ALD) and HBV. Obesity may increase the risk of HCC. Among CLDs, the evidence is relatively consistent and clear for ALD, while clear evidence is limited in other CLDs including HBV, HCV, and NAFLD. Total cholesterol, potentially low-density lipoprotein cholesterol and triglyceride, seems to have strong inverse associations with HCC in individuals with CLDs. Despite evidence from observational studies, statins had no effect in preventing HCC in randomized controlled trials. Whether statins have a preventive effect against HCC is unclear. A better understanding and management of metabolic factors may be beneficial to reduce the risk of HCC in patients with CLDs.
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Affiliation(s)
- Hwang Sik Shin
- Department of Family Medicine, Soonchunhyang University Hospital Cheonan, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea,Corresponding author : Baek Gyu Jun Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, 1342 Dongil-ro, Nowon-gu, Seoul 01757, Korea Tel: +82-2-950-8889, Fax: +82-2-950-1955, E-mail:
| | - Sang-Wook Yi
- Department of Preventive Medicine and Public Health, College of Medicine, Catholic Kwandong University, Gangneung, Korea,Sang-Wook Yi Department of Preventive Medicine and Public Health, College of Medicine, Catholic Kwandong University, 24 Beomil-ro 579beon-gil, Gangneung 25601, Korea Tel: +82-33-649-7468, Fax: +82-33-641-1074, E-mail:
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11
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Farshadpour F, Taherkhani R, Saberi F. Molecular evaluation of hepatitis B virus infection and predominant mutations of pre-core, basal core promoter and S regions in an Iranian population with type 2 diabetes mellitus: a case-control study. BMC Infect Dis 2022; 22:553. [PMID: 35715756 PMCID: PMC9206294 DOI: 10.1186/s12879-022-07528-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 06/06/2022] [Indexed: 12/01/2022] Open
Abstract
BACKGROUND This study was designed to evaluate the prevalence, genotypic patterns, and predominant mutations of hepatitis B virus (HBV) infection among diabetic patients. METHODS Serum samples were obtained from 733 patients with type 2 diabetes mellitus and 782 non-diabetic controls. The presence of HBsAg and HBcAb was determined by ELISA. Nested PCR, targeting S and pre-core regions of the HBV genome, followed by sequencing was carried out to determine HBV genotypes and predominant mutations in the S, basal core promoter (BCP), and pre-core regions of the HBV genome. RESULTS Of 733 diabetic patients, 94 cases (12.82%) were positive for HBcAb, 28 cases (3.82%) were positive for HBsAg, and 19 cases (2.59%) had HBV-DNA with genotype D, sub-genotype D1/D3 and subtype ayw2. An occult HBV infection was found in one of the HBV DNA-positive samples, which was positive for HBcAb but negative for HBsAg. P120T/G145R, G1896A/G1899A, and A1762T/G1764T were the most frequent point substitution mutations detected in the S, pre-core, and BCP regions of the HBV genome, respectively. P120T and G145R mutations were associated with low levels or undetectable levels of HBsAg in serum. Therefore, routine tests based on HBsAg detection cannot detect HBsAg-negative infected patients. CONCLUSIONS Relatively high prevalence of HBV infection was found in diabetic patients, while all of the HBV-infected patients were unaware of their infection. Therefore, screening for HBV infection should be included in the management program of diabetes for timely diagnosis and treatment of infected but asymptomatic patients.
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Affiliation(s)
- Fatemeh Farshadpour
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, 751463334, Bushehr, Iran
| | - Reza Taherkhani
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, 751463334, Bushehr, Iran.
| | - Fatemeh Saberi
- Department of Virology, School of Medicine, Bushehr University of Medical Sciences, Moallem Street, 751463334, Bushehr, Iran
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12
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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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13
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Wang J, Li X. Impact of statin use on the risk and prognosis of hepatocellular carcinoma: a meta-analysis. Eur J Gastroenterol Hepatol 2021; 33:1603-1609. [PMID: 33405428 DOI: 10.1097/meg.0000000000002040] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Previous studies have demonstrated that statin use might be associated with a reduced risk of hepatocellular carcinoma (HCC). However, the value of statin on the prognosis still needs to be evaluated. Based on the above considerations, we conducted a meta-analysis regarding the value of statin on the prevention and prognosis of HCC. METHODS Articles regarding the impact of statin use on the risk, prognosis of HCC and published before October 2020 were searched in the five databases. We computed odds ratio (OR)/relative risk (RR) or hazard ratio (HR) and 95% confidence intervals (CIs) regarding the association between statin use and the risk or prognosis of HCC by using STATA 12.0 software. RESULTS Twenty-six studies (including 1772 463 participants) detected the association between statin use and risk of HCC. Additionally, seven studies (including 8925 statin users and 76 487 no-statin users) explored the association between statin use and mortality of HCC. The meta-analysis showed that statin use was associated with lower risk and all-cause mortality of HCC with random effects models (risk: OR/RR = 0.57, 95% CI 0.49-0.65, I2 = 86.0%, P < 0.0001; all-cause mortality: HR = 0.80, 95% CI 0.68-0.94, I2 = 77.6%, P < 0.0001). However, statin use was not associated with cancer-specific mortality of HCC with a random effects model (HR = 0.80, 95% CI 0.62-1.03, I2 = 73.9%, P = 0.002). CONCLUSION In conclusion, our results have demonstrated the salutary effect of statin on the prevention and prognosis of HCC.
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Affiliation(s)
- Jianfeng Wang
- Department of Gastroenterology, Baoshan Branch of Shanghai Renji Hospital, Shanghai, China
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14
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唐 淬, 胡 承, 周 宇, 宋 杨, 李 孟, 廖 敏, 孙 家, 钟 春, 周 琳, 林 志, 周 元. [Risk analysis for hepatocellular carcinoma in patients with chronic hepatitis B-associated cirrhosis complicated by type 2 diabetes mellitus: a 5-year prospective cohort study]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:313-318. [PMID: 33849820 PMCID: PMC8075784 DOI: 10.12122/j.issn.1673-4254.2021.03.01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To elucidate the risk and synergistic factors of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B-associated cirrhosis (CHB-Cir) complicated by type 2 diabetes (T2DM). OBJECTIVE The patients with CHB-Cir who were followed up in Hepatology Center of Nanfang Hospital from June 2010 to June 2019 were divided based on their T2DM status into two cohorts matched for gender, age, HBeAg status and HBV DNA load: CHB-Cir with T2DM group (observation group) and CHB-Cir without T2DM group (control group). All the patients were followed up at a 6-month interval, and the cases with complete clinical data and follow-up data for more than 2 years were included in the analysis. Kaplan- Meier method was used to compare the cumulative incidence of HCC between the two groups. A Cox proportional hazard regression model was used to analyze the relationship between T2DM and the risk of HCC in these patients. OBJECTIVE A total of 467 patients with a mean follow-up time of 4.4±1.62 years were included in the analysis, including 203 in the observation group and 264 in the control group. Sixty-nine and forty-eight new HCC cases occurred in the observation group and control group, respectively, showing a significantly higher incidence rate of HCC in the observation group (P < 0.001). The cumulative incidence of HCC in the observation group was significantly higher than that in the control group (P < 0.001), with a relative risk of 2.096 (P < 0.01). After adjustment for age (≥40 years), family history of liver cancer, previous antiviral therapy, elevated cholesterol and elevated LDL cholesterol, T2DM remained an independent risk factor for HCC in CHB-Cir patients (P=0.000). OBJECTIVE T2DM is an independent risk factor for HCC, and the risk of HCC increases by more than two folds in CHB-Cir patients complicated by T2DM, suggesting the clinical significance of early interventions of diabetes to reduce the risk of HCC in CHB-Cir patients.
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Affiliation(s)
- 淬蓉 唐
- 南方医科大学南方医院消化内科，广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 南方医科大学南方医院感染内科，广东 广州 510515Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 承光 胡
- 南方医科大学南方医院消化内科，广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 南方医科大学南方医院感染内科，广东 广州 510515Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 宇辰 周
- 南方医科大学中西医结合医院肿瘤中心，广东 广州 510310Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510310, China
| | - 杨达 宋
- 南方医科大学南方医院消化内科，广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 南方医科大学南方医院感染内科，广东 广州 510515Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 孟 李
- 南方医科大学南方医院消化内科，广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 南方医科大学南方医院感染内科，广东 广州 510515Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 敏君 廖
- 南方医科大学南方医院消化内科，广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 南方医科大学南方医院感染内科，广东 广州 510515Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 家润 孙
- 南方医科大学南方医院消化内科，广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
- 南方医科大学南方医院感染内科，广东 广州 510515Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 春秀 钟
- 南方医科大学南方医院感染内科，广东 广州 510515Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 琳 周
- 南方医科大学南方医院内分泌科，广东 广州 510515Department of Endocrinology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 志昭 林
- 南方医科大学南方医院消化内科，广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 元平 周
- 南方医科大学南方医院消化内科，广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, 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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16
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Zeng Z, Cao Z, Tang Y. Identification of diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus-associated early stage hepatocellular carcinoma based on RNA-sequencing data. Oncol Lett 2020; 20:231. [PMID: 32968453 PMCID: PMC7499982 DOI: 10.3892/ol.2020.12094] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Accepted: 07/15/2020] [Indexed: 02/07/2023] Open
Abstract
Primary liver cancer is a rapidly progressing neoplasm with high morbidity and mortality rates. The present study aimed to identify potential diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus (HBV)-associated early stage hepatocellular carcinoma (HCC). The gene expression profiles were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), hub genes and the enrichment of signaling pathways were filtered out via a high-throughput sequencing method. The association between hub genes and the effects of the abnormal expression of hub genes on the rate of genetic variation, overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS) and disease-free survival (DSS) of patients with HCC, as well as pathological stage and grade, were analyzed using different databases. A total of 1,582 DEGs were identified. Gene Ontology analysis revealed that the DEGs were mainly involved in the ‘oxidation-reduction process’, ‘steroid metabolic process’, ‘metabolic process’ and ‘fatty acid beta-oxidation’. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways revealed that the DEGs were mainly associated with ‘metabolic pathways’, ‘PPAR signaling pathway’, ‘fatty acid degradation’ and the ‘cell cycle’. A total of 8 hub genes were extracted. Additionally, the abnormal expression levels of hub genes were closely associated with the OS, RFS, PFS and DSS of patients, the pathological stage and the grade. Furthermore, abnormal expression levels of the 8 hub genes were found in >30% of all samples. Several small molecular compounds that may reverse the altered DEGs were identified based on Connectivity Map analysis, including phenoxybenzamine, GW-8510, resveratrol, 0175029-0000 and daunorubicin. In conclusion, the dysfunction of fat metabolic pathways, the cell cycle, oxidation-reduction processes and viral carcinogenesis may serve critical roles in the occurrence of HBV-associated early stage HCC. The identified 8 hub genes may act as robust biomarkers for diagnosis and prognosis. Some small molecular compounds may be promising targeted agents against HBV-associated early stage HCC.
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Affiliation(s)
- Zhili Zeng
- Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Zebiao Cao
- Department of Endocrinology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
| | - Ying Tang
- Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.,Department of Oncology, Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
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17
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Dunachie S, Chamnan P. The double burden of diabetes and global infection in low and middle-income countries. Trans R Soc Trop Med Hyg 2020; 113:56-64. [PMID: 30517697 PMCID: PMC6364794 DOI: 10.1093/trstmh/try124] [Citation(s) in RCA: 104] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 11/02/2018] [Indexed: 12/20/2022] Open
Abstract
Four out of five people in the world with diabetes now live in low- and middle-income countries (LMIC), and the incidence of diabetes is accelerating in poorer communities. Diabetes increases susceptibility to infection and worsens outcomes for some of the world’s major infectious diseases such as tuberculosis, melioidosis and dengue, but the relationship between diabetes and many neglected tropical diseases is yet to be accurately characterised. There is some evidence that chronic viral infections such as hepatitis B and HIV may predispose to the development of type 2 diabetes by chronic inflammatory and immunometabolic mechanisms. Helminth infections such as schistosomiasis may be protective against the development of diabetes, and this finding opens up new territory for discovery of novel therapeutics for the prevention and treatment of diabetes. A greater understanding of the impact of diabetes on risks and outcomes for infections causing significant diseases in LMIC is essential in order to develop vaccines and therapies for the growing number of people with diabetes at risk of infection, and to prioritise research agendas, public health interventions and policy. This review seeks to give an overview of the current international diabetes burden, the evidence for interactions between diabetes and infection, immune mechanisms for the interaction, and potential interventions to tackle the dual burden of diabetes and infection.
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Affiliation(s)
- Susanna Dunachie
- Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, 3rd Floor, 60th Anniversary Chalermprakiat Building, 420/6 Ratchawithi Rd., Ratchathewi District, Bangkok, Thailand.,Centre for Tropical Medicine and Global Health, University of Oxford, Nuffield Department of Medicine Research Building, University of Oxford, Old Road campus, Roosevelt Drie, Headington, Oxford, United Kingdom.,The Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford, United Kingdom
| | - Parinya Chamnan
- Cardiometabolic Research Group, Department of Social Medicine, Sunpasitthiprasong Hospital, Tambon Nai Mueang, Amphoe Mueang Ubon Ratchathani, Chang Wat Ubon Ratchathani, Thailand
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18
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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] [MESH Headings] [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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19
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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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20
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Chronic Viral Hepatitis Signifies the Association of Premixed Insulin Analogues with Liver Cancer Risks: A Nationwide Population-Based Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16122097. [PMID: 31200528 PMCID: PMC6616640 DOI: 10.3390/ijerph16122097] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 06/09/2019] [Accepted: 06/12/2019] [Indexed: 02/07/2023]
Abstract
This study sought to determine whether chronic hepatitis B or C would modify the association between insulin analogues and hepatocellular carcinoma (HCC) risks. We conducted a nationwide nested case-control study for HCC cases and matched controls from 2003 to 2013 among newly diagnosed type 2 diabetes patients on any antidiabetic agents in Taiwan before and after exclusion of chronic viral hepatitis, respectively. A total of 5832 and 1237 HCC cases were identified before and after exclusion of chronic viral hepatitis, respectively. Incident HCC risks were positively associated with any use of premixed insulin analogues (adjusted odds ratio (OR), 1.27; 95% CI 1.04 to 1.55) among total participants, especially among current users (adjusted OR, 1.45; 95% CI 1.12 to 1.89). However, the association between HCC occurrence and premixed insulin analogues diminished among participants without chronic viral hepatitis (adjusted OR, 1.35; 95% CI 0.92 to 1.98). We also observed a significant multiplicative interaction between chronic viral hepatitis and premixed insulin analogues on HCC risks (P = 0.010). Conclusions: Chronic viral hepatitis signifies the role of premixed insulin analogues in HCC oncogenesis. We recommend a closer liver surveillance among patients prescribed premixed insulin analogues with concomitant chronic viral hepatitis.
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21
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Huang Y, Lee C, Hu J, Yang S. New‐onset diabetes increases risk of hepatic encephalopathy in cirrhotics with ascites: A nationwide cohort study. ADVANCES IN DIGESTIVE MEDICINE 2019. [DOI: 10.1002/aid2.13122] [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] [Indexed: 12/13/2022]
Affiliation(s)
- Yi‐Wen Huang
- Liver CenterCathay General Hospital Medical Center Taipei Taiwan
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical University Taipei Taiwan
- Division of Gastroenterology, Department of Internal MedicineNational Taiwan University College of Medicine Taipei Taiwan
- School of MedicineChina Medical University College of Medicine Taichung Taiwan
| | - Chia‐Long Lee
- Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical University Taipei Taiwan
- Division of GastroenterologyCathay General Hospital Medical Center Taipei Taiwan
- School of MedicineFu‐Jen Catholic University College of Medicine Taipei Taiwan
| | - Jui‐Ting Hu
- Liver CenterCathay General Hospital Medical Center Taipei Taiwan
- School of MedicineFu‐Jen Catholic University College of Medicine Taipei Taiwan
| | - Sien‐Sing Yang
- Liver CenterCathay General Hospital Medical Center Taipei Taiwan
- School of MedicineFu‐Jen Catholic University College of Medicine Taipei Taiwan
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22
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Hsu YC, Yip TCF, Wong GLH, Wu CY. Reply to: "Diabetes mellitus as a risk factor of hepatocellular carcinoma in patients with chronic hepatitis B on nucleot(s)ide analogues". J Hepatol 2019; 70:796-797. [PMID: 30635241 DOI: 10.1016/j.jhep.2018.11.031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 11/29/2018] [Indexed: 12/04/2022]
Affiliation(s)
- Yao-Chun Hsu
- Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan; Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
| | - Terry Cheuk-Fung Yip
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong; Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong; State Key Laboratory of Digestive Disease, Chinese University of Hong Kong, Hong Kong
| | - Chun-Ying Wu
- Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan; Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Public Health, China Medical University, Taichung, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan
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23
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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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24
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Hamed AE, Elsahar M, Elwan NM, El-Nakeep S, Naguib M, Soliman HH, Ahmed Aboubakr A, AbdelMaqsod A, Sedrak H, Assaad SN, Elwakil R, Esmat G, Salh S, Mostafa T, Mogawer S, Sadek SE, Saber MM, Ezelarab H, Mahmoud AA, Sultan S, El Kassas M, Kamal E, ElSayed NM, Moussa S. Managing diabetes and liver disease association. Arab J Gastroenterol 2018; 19:166-179. [PMID: 30420265 DOI: 10.1016/j.ajg.2018.08.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/26/2018] [Indexed: 02/05/2023]
Abstract
There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.
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Affiliation(s)
- Abd Elkhalek Hamed
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt.
| | - Medhat Elsahar
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Police Medical Academy, Egypt
| | | | | | | | | | - Ashraf Ahmed Aboubakr
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | | | - Reda Elwakil
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Ain Shams University, Egypt
| | - Gamal Esmat
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Kasr Al Aini, Egypt
| | - Samira Salh
- Department of Pharmacy, Cairo University, Egypt
| | | | | | - Sameh Emil Sadek
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | - Maha M Saber
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Hanan Ezelarab
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Asem Ashraf Mahmoud
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | - Ehab Kamal
- Medical Department, National Research Centre, Egypt
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25
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Seto WK, Lo YR, Pawlotsky JM, Yuen MF. Chronic hepatitis B virus infection. Lancet 2018; 392:2313-2324. [PMID: 30496122 DOI: 10.1016/s0140-6736(18)31865-8] [Citation(s) in RCA: 358] [Impact Index Per Article: 51.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2018] [Revised: 07/28/2018] [Accepted: 08/07/2018] [Indexed: 12/14/2022]
Abstract
Chronic hepatitis B virus infection is a global public health threat that causes considerable liver-related morbidity and mortality. It is acquired at birth or later via person-to-person transmission. Vaccination effectively prevents infection and chronic hepatitis B virus carriage. In chronically infected patients, an elevated serum hepatitis B virus DNA concentration is the main risk factor for disease progression, although there are other clinical and viral parameters that influence disease outcomes. In addition to liver biochemistry, virological markers, and abdominal ultrasonography, non-invasive assessment of liver fibrosis is emerging as an important assessment modality. Long-term nucleos(t)ide-analogue therapy is safe and well tolerated, achieves potent viral suppression, and reduces the incidence of liver-related complications. However, a need to optimise management remains. Promising novel therapies are at the developmental stage. With current vaccines, therapies, and an emphasis on improving linkage to care, WHO's goal of eliminating hepatitis B virus as a global health threat by 2030 is achievable.
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Affiliation(s)
- Wai-Kay Seto
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, Hong Kong Special Administrative Region, China; Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Ying-Ru Lo
- WHO Representative Office in Malaysia, Brunei Darussalam, and Singapore, Cyberjaya, Malaysia
| | - Jean-Michel Pawlotsky
- National Reference Centre for Viral Hepatitis B, C, and Delta, Department of Virology, Henri Mondor Hospital, University of Paris-Est, Créteil, France; Department of Molecular Virology and Immunology, Inserm U955, Créteil, France
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong Queen Mary Hospital, Hong Kong Special Administrative Region, China; Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong Special Administrative Region, China.
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26
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Morisco F, Guarino M, Valvano MR, Auriemma F, Farinati F, Giannini EG, Ciccarese F, Tovoli F, Rapaccini GL, Di Marco M, Caturelli E, Zoli M, Borzio F, Sacco R, Cabibbo G, Felder M, Benvengù L, Gasbarrini A, Svegliati Baroni G, Foschi FG, Biasini E, Masotto A, Virdone R, Marra F, Caporaso N, Trevisani F. Metabolic disorders across hepatocellular carcinoma in Italy. Liver Int 2018; 38:2028-2039. [PMID: 29745475 DOI: 10.1111/liv.13877] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2017] [Accepted: 04/30/2018] [Indexed: 02/05/2023]
Abstract
BACKGROUND Metabolic disorders are well-known risk factors for HCC. Conversely, their impact on the natural history of HCC is not established. This study aimed at evaluating the impact of metabolic disorders on clinical features, treatment and survival of HCC patients regardless of its aetiology. METHODS We analysed the ITA.LI.CA database regarding 839 HCC patients prospectively collected. The following metabolic features were analysed: BMI, diabetes, arterial hypertension, hypercholesterolaemia and hypertriglyceridaemia. According to these features, patients were divided into 3 groups: 0-1, 2 and 3-5 metabolic features. RESULTS As compared with patients with 0-1 metabolic features, patients with 3-5 features showed lower percentage of HCC diagnosis on surveillance (P = .021), larger tumours (P = .038), better liver function (higher percentage of Child-Pugh class A [P = .007] and MELD < 10 [P = .003]), higher percentage of metastasis (P = .024) and lower percentage of portal vein thrombosis (P = .010). The BCLC stage and treatment options were similar among the 3 groups, with the exception of a less frequent access to loco-regional therapies for BCLC stage B patients with 3-5 features (P = .012). Overall survival and survival according to BCLC stage and/or treatment did not significantly differ among the 3 groups. Only using a probabilistic sensitivity analysis, diabetic patients showed a lower survival (P = .046). MELD score, HCC morphology, nodule size, BCLC stage, portal vein thrombosis and metastasis were independent predictors of lead-time adjusted survival. CONCLUSIONS Our "real world" study suggests that metabolic disorders shape the clinical presentation of HCC but do not seem to play a major role in setting patient survival.
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Affiliation(s)
- Filomena Morisco
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Maria Guarino
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Maria R Valvano
- Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy
| | - Francesco Auriemma
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Fabio Farinati
- Section of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Edoardo G Giannini
- Gastroenterology Unit, Department Internal Medicine, Policlinico San Martino, University of Genoa, Genoa, Italy
| | | | - Francesco Tovoli
- Internal Medicine Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Gian Ludovico Rapaccini
- Division of Internal Medicine and Gastroenterology, Complesso Integrato Columbus, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Maria Di Marco
- Division of Medicine, Bolognini Hospital, Seriate, Italy
| | | | - Marco Zoli
- Internal Medicine Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Franco Borzio
- Division of Radiology, Department of Medicine, Fatebenefratelli Hospital, Milan, Italy
| | - Rodolfo Sacco
- Division of Gastroenterology and Metabolic Diseases, University Hospital of Pisa, Pisa, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology, Biomedical Department of Internal and Specialized Medicine (DI.BI.M.I.S.), University of Palermo, Palermo, Italy
| | - Martina Felder
- Division of Gastroenterology, Bolzano Regional Hospital, Bolzano, Italy
| | - Luisa Benvengù
- Medical Unit, Department of Clinical and Experimental Medicine, University of Padua, Paadua, Italy
| | - Antonio Gasbarrini
- Division of Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy
| | | | - Francesco G Foschi
- Department of Internal Medicine, Ospedale per gli Infermi di Faenza, Faenza, Italy
| | - Elisabetta Biasini
- Division of Infectious Diseases and Hepatology, Parma University Hospital, Parma, Italy
| | - Alberto Masotto
- Gastroenterology Unit, Ospedale Sacro Cuore Don Calabria, Negrar, Italy
| | - Roberto Virdone
- Division of Internal Medicine 2, Ospedali Riuniti Villa Sofia Cervello, Palermo, Italy
| | - Fabio Marra
- Department of Clinical and Experimental Medicine, Internal Medicine and Hepatology, University of Firenze, Firenze, Italy
| | - Nicola Caporaso
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
| | - Franco Trevisani
- Semeiotica Medica Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum - University of Bologna, Bologna, Italy
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27
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Chou AH, Chen CC, Lin YS, Lin MS, Wu VCC, Ting PC, Chen SW. A population-based analysis of endovascular aortic stent graft therapy in patients with liver cirrhosis. J Vasc Surg 2018; 69:1395-1404.e4. [PMID: 30528408 DOI: 10.1016/j.jvs.2018.06.225] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Accepted: 06/25/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Endovascular aneurysm repair (EVAR) and thoracic endovascular aortic repair (TEVAR) are effective and minimally invasive treatments for high-risk surgical candidates. However, information about the management of EVAR and TEVAR in liver cirrhosis (LC) is lacking. The aim of our study was to evaluate outcomes after EVAR and TEVAR in patients with LC. METHODS Using Taiwan's National Health Insurance Research Database, we retrospectively evaluated patients who underwent EVAR and TEVAR therapy between January 1, 2006, and December 31, 2013. RESULTS A total of 146 patients with LC and 730 matched patients without LC were eligible for analysis after propensity score matching. In-hospital mortality and perioperative complications were not statistically significantly different between the two cohorts, although the LC group had an increased volume of blood transfusion and a trend toward a lower survival rate (P of stratified Cox = .092). However, patients with LC had a higher adjusted hazard ratio for death (1.66; 95% confidence interval, 1.31-2.12; P < .001) in the sensitivity analysis by traditional multivariable adjustment. The LC cohort had a higher risk of liver-related death (4.1% vs 0.7%; P = .001) and liver-related readmission (6.2% vs 0.3%; P < .001). As expected, the advanced LC group had a higher mortality rate than the early LC group (P = .022). The risk for reintervention, redo open aortic surgery (P = .859), and redo stent graft therapy (P = .179) was not statistically significantly different between the two cohorts. CONCLUSIONS Short-term results after EVAR and TEVAR are promising in patients with LC, despite poor long-term outcomes, because of the nature of LC. Innovations in endovascular therapy for aortic disease have improved surgical outcomes, even in high-risk patients with LC.
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Affiliation(s)
- An-Hsun Chou
- Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taipei, Taiwan; Department of Medicine, Chang Gung University, Taoyuan City, Taipei, Taiwan
| | - Ching-Chang Chen
- Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taipei, Taiwan
| | - Yu-Sheng Lin
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi City, Taiwan
| | - Ming-Shyan Lin
- Department of Cardiology, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi City, Taiwan
| | - Victor Chien-Chia Wu
- Department of Cardiology, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taipei, Taiwan
| | - Pei-Chi Ting
- Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taipei, Taiwan
| | - Shao-Wei Chen
- Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University, Taoyuan City, Taipei, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan City, Taipei, Taiwan.
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Kim K, Choi S, Park SM. Association of fasting serum glucose level and type 2 diabetes with hepatocellular carcinoma in men with chronic hepatitis B infection: A large cohort study. Eur J Cancer 2018; 102:103-113. [PMID: 30189372 DOI: 10.1016/j.ejca.2018.07.008] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 07/09/2018] [Accepted: 07/13/2018] [Indexed: 12/22/2022]
Abstract
BACKGROUND It is unclear whether elevated fasting serum glucose level and type 2 diabetes (T2DM) are associated with an increased risk of hepatocellular carcinoma (HCC), irrespective of obesity in patients with chronic hepatitis B. PATIENTS AND METHODS Our study population comprised 214,167 Korean men with chronic hepatitis B in the National Health Insurance Service (NHIS) database between January 2002 and December 2006. Data on new events of HCC were obtained by records of the NHIS during the follow-up. We used Cox proportional hazards models adjusted for sociodemographic, lifestyle, health status and clinical conditions to estimate the hazard ratio (HR) and 95% confidence intervals (95% CIs) of HCC associated with different categories of fasting serum glucose level and T2DM, using fasting serum glucose <90 mg/dL as reference. RESULTS During the 8 years of follow-up, there were 11,241 HCCs in men with chronic hepatitis B. Compared with the reference group, fasting serum glucose level of more than 140 mg/dL (HR = 1.46; 95% CI: 1.36-1.57; p < 0.001) and presence of T2DM (HR = 1.23; 95% CI: 1.15-1.34; p < 0.001) were associated with an increased risk of HCC after controlling for potential confounders. Significant association with fasting serum glucose and HCC was found for both non-obese (<25 kg/m2) and obese (≥25.0 kg/m2) patients (Ptrend < 0.001). CONCLUSION In this cohort of men with chronic hepatitis B infection, elevated fasting serum glucose level and T2DM were significantly associated with an increased risk of HCC, regardless of obesity. Glycaemic control in men with chronic hepatitis B patients should be considered in clinical practice to prevent HCC.
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Affiliation(s)
- Kyuwoong Kim
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Seulggie Choi
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Sang Min Park
- Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea; Department of Family Medicine, College of Medicine, Seoul National University, Seoul, Republic of Korea.
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Diabetes Mellitus and Risk of Hepatocellular Carcinoma. BIOMED RESEARCH INTERNATIONAL 2017; 2017:5202684. [PMID: 29379799 PMCID: PMC5742888 DOI: 10.1155/2017/5202684] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Accepted: 11/22/2017] [Indexed: 02/06/2023]
Abstract
The occurrence of hepatocellular carcinoma (HCC) is two to three times higher in patients with diabetes mellitus (DM), the prevalence of which is increasing sharply worldwide. The purpose of this review was to describe clinical links between DM and HCC and potential biological mechanisms that may account for this association. We evaluated the role of potential pathways that could account for the development of HCC with different etiologies in the presence of DM. In addition, we also briefly discuss the potential effect of other factors such as type and dosage of antidiabetic medicines and duration of DM on HCC risk.
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Chen X, Yan CC, Zhang X, You ZH. Long non-coding RNAs and complex diseases: from experimental results to computational models. Brief Bioinform 2017; 18:558-576. [PMID: 27345524 PMCID: PMC5862301 DOI: 10.1093/bib/bbw060] [Citation(s) in RCA: 312] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2016] [Indexed: 02/07/2023] Open
Abstract
LncRNAs have attracted lots of attentions from researchers worldwide in recent decades. With the rapid advances in both experimental technology and computational prediction algorithm, thousands of lncRNA have been identified in eukaryotic organisms ranging from nematodes to humans in the past few years. More and more research evidences have indicated that lncRNAs are involved in almost the whole life cycle of cells through different mechanisms and play important roles in many critical biological processes. Therefore, it is not surprising that the mutations and dysregulations of lncRNAs would contribute to the development of various human complex diseases. In this review, we first made a brief introduction about the functions of lncRNAs, five important lncRNA-related diseases, five critical disease-related lncRNAs and some important publicly available lncRNA-related databases about sequence, expression, function, etc. Nowadays, only a limited number of lncRNAs have been experimentally reported to be related to human diseases. Therefore, analyzing available lncRNA–disease associations and predicting potential human lncRNA–disease associations have become important tasks of bioinformatics, which would benefit human complex diseases mechanism understanding at lncRNA level, disease biomarker detection and disease diagnosis, treatment, prognosis and prevention. Furthermore, we introduced some state-of-the-art computational models, which could be effectively used to identify disease-related lncRNAs on a large scale and select the most promising disease-related lncRNAs for experimental validation. We also analyzed the limitations of these models and discussed the future directions of developing computational models for lncRNA research.
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Affiliation(s)
- Xing Chen
- School of Information and Electrical Engineering, China University of Mining and Technology, Xuzhou, China
- Corresponding authors. Xing Chen, School of Information and Electrical Engineering, China University of Mining and Technology, Xuzhou 221116, China. E-mail: ; Zhu-Hong You, School of Computer Science and Technology, China University of Mining and Technology, Xuzhou 221116, China. E-mail:
| | | | - Xu Zhang
- School of Mechanical, Electrical & Information Engineering, Shandong University, Weihai, China
- Corresponding authors. Xing Chen, School of Information and Electrical Engineering, China University of Mining and Technology, Xuzhou 221116, China. E-mail: ; Zhu-Hong You, School of Computer Science and Technology, China University of Mining and Technology, Xuzhou 221116, China. E-mail:
| | - Zhu-Hong You
- School of Computer Science and Technology, China University of Mining and Technology, Xuzhou, China
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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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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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Chou AH, Chen TH, Chen CY, Chen SW, Lee CW, Liao CH, Wang SY. Long-Term Outcome of Cardiac Surgery in 1,040 Liver Cirrhosis Patient - Nationwide Population-Based Cohort Study. Circ J 2017; 81:476-484. [PMID: 28163280 DOI: 10.1253/circj.cj-16-0849] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2025]
Abstract
BACKGROUND Patients with liver cirrhosis (LC) have a higher risk for cardiac surgery, but population-based long-term follow-up studies are lacking. The aim of this study was therefore to validate the long-term outcome of cardiac surgery in patients with LC. METHODS AND RESULTS Data were obtained from Taiwan's National Health Insurance Database, 1997-2011. This study included 1,040 LC patients and 1,040 matched controls without LC. The actuarial survival rate at 1, 5 and 10 years in the LC cohort was 68%, 50% and 41%: significantly lower than that of the control cohort at 81%, 68% and 62% at 1, 5 and 10 years after cardiac surgery. Compared with the matched control cohort, the LC group had a higher risk of liver and heart failure readmission (P<0.001) during the follow-up period. In addition, the LC cohort had a higher risk of liver causes of death than did the control cohort (12.6% vs. 1.2%). In the LC cohort, 51% of deaths were due to hepatocellular carcinoma. And in the LC group, those with valve surgery and advanced cirrhosis had a lower survival rate (P=0.002, P=0.001). CONCLUSIONS Even after successful cardiac surgery, long-term outcome is unsatisfactory in LC patients because of the progressive deterioration of liver function.
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Affiliation(s)
- An-Hsun Chou
- Department of Anesthesiology, Chang Gung Memorial Hospital, Linkou Medical Center, Chang Gung University
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Diabetes mellitus increases the risk of intrahepatic recurrence of hepatocellular carcinoma after surgical resection. TUMORI JOURNAL 2017; 103:279-285. [PMID: 28085178 DOI: 10.5301/tj.5000594] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/04/2016] [Indexed: 12/13/2022]
Abstract
AIMS AND BACKGROUND The relationship between cancer and metabolism has recently been receiving attention. We investigated the prognostic influence of type 2 diabetes mellitus in patients with hepatocellular carcinoma (HCC) treated with curative resection. METHODS AND STUDY DESIGN The records of 58 patients who underwent curative resection for HCC pT1-2N0M0 between 2010 and 2014 were reviewed retrospectively. Fourteen patients (24.1%) had diabetes mellitus at diagnosis. Local control (LC) was defined as time to recurrence in the liver. RESULTS The median follow-up was 23.3 months. Relapses occurred in 20 patients (34.5%) during the follow-up period; 17 of them developed intrahepatic recurrence, which was associated with diabetes mellitus (p = 0.013) and alpha fetoprotein (AFP) levels >500 ng/mL (p = 0.019). Overall relapses (n = 20) were related to T stage (p = 0.044), AFP level (p = 0.005), and diabetes (p = 0.044). The 3-year local control (intrahepatic control), disease-free survival, and overall survival rates were 56.7%, 50.5%, and 84.3%, respectively. LC was affected by diabetes mellitus (p = 0.046), Barcelona Clinic Liver Cancer staging (p<0.001), Milan criteria for transplantation (p = 0.041), serosal invasion (p = 0.032), and microvascular invasion (p = 0.043). Diabetes was also associated with reduced LC in the subgroup with hepatitis B-related HCC (n = 44, p = 0.028). CONCLUSIONS Diabetes mellitus is correlated with intrahepatic HCC recurrence after surgery. Greater attention should be paid to managing patients with HCC and diabetes mellitus.
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Cheng JYK, Wong VWS, Tse YK, Chim AML, Chan HLY, Wong GLH. Metabolic syndrome increases cardiovascular events but not hepatic events and death in patients with chronic hepatitis B. Hepatology 2016; 64:1507-1517. [PMID: 27680510 DOI: 10.1002/hep.28778] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2016] [Accepted: 07/27/2016] [Indexed: 12/21/2022]
Abstract
UNLABELLED Metabolic syndrome is an independent risk factor of liver cirrhosis in chronic hepatitis B (CHB). Whether metabolic syndrome affects the long-term prognosis of CHB patients in terms of hepatic events, cardiovascular events, and death remains unknown. We aimed to determine the incidences of hepatic events, cardiovascular events, and death in CHB patients with or without metabolic syndrome. From 2006 to 2008, we prospectively recruited 1,466 CHB patients for liver stiffness measurement (LSM) with transient elastography together with detailed metabolic profiling as baseline assessment. Patients were prospectively followed for any clinical events. The impact of LSM and metabolic syndrome on hepatic events, cardiovascular events, and death was evaluated. At baseline visit, the mean age was 46 ± 12 years, LSM value was 8.4 ± 6.3 kPa, and 188 patients (12.8%) had metabolic syndrome. At a mean follow-up of 88 ± 20 months, 93 and 44 patients developed hepatic and cardiovascular events, respectively; 70 patients died. Patients with baseline LSM >8.0 kPa had higher cumulative probability of hepatic events than those with LSM ≤8.0kPa at 8 years (12.3% versus 3.1%, P < 0.001). Patients with metabolic syndrome had higher cumulative probability of cardiovascular events than those without (8.0% versus 2.1%, P < 0.001). High LSM had no impact on cardiovascular events; neither did metabolic syndrome on hepatic events. LSM >8.0 kPa but not metabolic syndrome was an independent risk factor of death, with adjusted hazard ratios of 1.9 (95% confidence interval 1.1-3.2, P = 0.023) and 1.3 (95% confidence interval 0.8-2.4, P = 0.310), respectively. CONCLUSIONS Metabolic syndrome increased the risk of cardiovascular events but not hepatic events and death; LSM was the important risk factor of hepatic events and death in CHB patients. (Hepatology 2016;64:1507-1517).
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Affiliation(s)
- Jenny Yeuk-Ki Cheng
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Vincent Wai-Sun Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Yee-Kit Tse
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Angel Mei-Ling Chim
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Henry Lik-Yuen Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
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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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Allaire M, Dupont B, Nahon P, Ganne-Carrié N, Nault JC. Hepatocellular Carcinoma: the Impact of NAFLD. CURRENT HEPATOLOGY REPORTS 2016; 15:190-198. [DOI: 10.1007/s11901-016-0303-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Allaire M, Nault JC. Type 2 diabetes-associated hepatocellular carcinoma: A molecular profile. Clin Liver Dis (Hoboken) 2016; 8:53-58. [PMID: 31041063 PMCID: PMC6490195 DOI: 10.1002/cld.569] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2016] [Revised: 05/26/2016] [Accepted: 06/06/2016] [Indexed: 02/04/2023] Open
Affiliation(s)
- Manon Allaire
- Service d'Hépato‐GastroentérologieCHU Côte de NacreCaenFrance
| | - Jean Charles Nault
- Liver Unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris‐Seine‐Saint‐DenisAssistance‐Publique Hôpitaux de ParisBondyFrance,Unité Mixte de Recherche 1162, Génomique Fonctionnelle des Tumeurs SolidesInstitut National de la Santé et de la Recherche MédicaleParisFrance,Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13Communauté d'Universités et Etablissements Sorbonne Paris CitéParisFrance
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Huang YW, Lee CL, Yang SS, Fu SC, Chen YY, Wang TC, Hu JT, Chen DS. Statins Reduce the Risk of Cirrhosis and Its Decompensation in Chronic Hepatitis B Patients: A Nationwide Cohort Study. Am J Gastroenterol 2016; 111:976-85. [PMID: 27166128 DOI: 10.1038/ajg.2016.179] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2015] [Accepted: 04/13/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The protective effect of statins in cirrhosis and its decompensation in chronic hepatitis B (CHB) patients remains unknown. METHODS We conducted a population-based cohort study using data from the Taiwanese National Health Insurance Research Database from 1997 to 2009. A total of 298,761 CHB patients were identified. CHB patients using statins (n=6,543; defined as ≥28 cumulative defined daily doses (cDDD)) and a 1:1 ratio propensity score and inception point (the date of first use of statins)-matched non-statins (<28 cDDD) were followed up from the inception point until the development of cirrhosis or its decompensation or until withdrawal from insurance or December 2009. RESULTS After adjustment for competing mortality, CHB patients using statins had a significantly lower cumulative incidence of cirrhosis (relative risk)=0.433; 95% confidence interval (CI)=0.344-0.515; modified log-rank test, P<0.001) and decompensated cirrhosis (relative risk=0.468; 95% CI=0.344-0.637; P<0.001) compared with patients not using statins. After adjustment for age, gender, comorbidity index, hypertension, diabetes, hyperlipidemia, hepatocellular carcinoma, obesity, non-alcoholic fatty liver disease, aspirin use, diabetes medication, CHB treatment, non-statin lipid-lowering drugs, and triglyceride lipid-lowering drugs using the Cox proportional hazard model, statins were still an independent protector against cirrhosis (adjusted hazard ratio (AHR)=0.512; 95% CI=0.413-0.634; P<0.001) and its decompensation (AHR=0.534; 95% CI=0.433-0.659; P<0.001). The AHRs for cirrhosis were 0.467 and 0.200, and the AHRs for decompensated cirrhosis were 0.611 and 0.231 with 91-365 and >365 cDDD of statins, respectively. CONCLUSIONS CHB patients who receive statin therapy have a dose-dependent reduction in the risk of cirrhosis and its decompensation.
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Affiliation(s)
- Yi-Wen 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
| | - Chia-Long Lee
- School of Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan.,Division of Gastroenterology, Department of Internal Medicine, Cathay General Hospital Medical Center, Taipei, Taiwan
| | - Sien-Sing Yang
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.,School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei, Taiwan
| | - Szu-Chieh Fu
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan
| | - Yun-Yi Chen
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.,Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan
| | - Ting-Chuan Wang
- Department of Medical Research, Cathay General Hospital Medical Center, Taipei, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan.,School of Medicine, Fu-Jen Catholic University College of Medicine, Taipei, Taiwan
| | - Ding-Shinn 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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Gounder PP, Bulkow LR, Snowball M, Negus S, Spradling PR, Simons BC, McMahon BJ. Nested case-control study: hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance. Aliment Pharmacol Ther 2016; 43:1197-207. [PMID: 27061300 PMCID: PMC5053330 DOI: 10.1111/apt.13621] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 02/29/2016] [Accepted: 03/21/2016] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) risk after resolving chronic hepatitis B virus (HBV) infection is unclear. AIM To compare HCC risk between Alaska Native (AN) patients with and without hepatitis B surface antigen (HBsAg) seroclearance. METHODS We selected persons with (case-patients) and without (control-patients) HBsAg seroclearance from a cohort of 1346 chronically HBV-infected AN patients followed during 1982-2013. We attempted to match two control-patients/case-patient on sex, HBV genotype, and age. Person-years of follow-up for case-patients began on the date of HBsAg resolution and for control-patients began on the date equivalent to the cohort entry date plus the years of HBsAg duration for their corresponding case-patient. We compared HCC risk using a Cox proportional hazards model. RESULTS The 238 case-patients (4 with HCC) and 435 control-patients (9 with HCC) were similar in age [P-value (P) = 0.30], sex (P = 0.53) and HBV genotype (P = 0.99). Case-patients had longer person-years of follow-up than control-patients (11.7 vs. 10.1 years; P = 0.04). The HCC rate/100 000 persons was similar between case- (132) and control-patients (178; P = 0.65). The adjusted hazard ratio comparing case- and control-patients was similar for HCC [0.7; 95% confidence interval (CI): 0.2-2.4], increased for each 1-year increment for age (1.1; CI: 1.0-1.1; P < 0.01), and was greater if the initial HBeAg was positive (3.5; CI: 1.1-11.0; P = 0.03). CONCLUSIONS Hepatitis B surface antigen seroclearance was not associated with reduced HCC risk; the HCC risk estimates are limited by wide 95% confidence intervals. Persons meeting HCC surveillance indications prior to HBsAg seroclearance could benefit from continued surveillance after seroclearance.
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Affiliation(s)
- P P Gounder
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention (CDC), Anchorage, AK, USA
| | - L R Bulkow
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention (CDC), Anchorage, AK, USA
| | - M Snowball
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - S Negus
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - P R Spradling
- Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA, USA
| | - B C Simons
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
| | - B J McMahon
- Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Disease, Centers for Disease Control and Prevention (CDC), Anchorage, AK, USA
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK, USA
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Pang Q, Bi JB, Wang ZX, Xu XS, Qu K, Miao RC, Chen W, Zhou YY, Liu C. Simple models based on gamma-glutamyl transpeptidase and platelets for predicting survival in hepatitis B-associated hepatocellular carcinoma. Onco Targets Ther 2016; 9:2099-109. [PMID: 27110127 PMCID: PMC4835119 DOI: 10.2147/ott.s101465] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Several hepatic cirrhosis-derived noninvasive models have been developed to predict the incidence and outcomes of hepatocellular carcinoma (HCC). We aimed to investigate the prognostic significance of the two novel established cirrhosis-associated models based on gamma-glutamyl transpeptidase (GGT) and platelets in hepatitis B-associated HCC. Methods We retrospectively evaluated 182 HCC patients with positive hepatitis B surface antigen who received radical therapy at a single institution between 2002 and 2012. Laboratory data prior to operation were collected to calculate the GGT to platelets ratio (GPR) and the S-index. Predictive factors associated with overall survival and recurrence-free survival were assessed using log-rank test and multivariate Cox analysis. Additional analyses were performed after patients were stratified based on cirrhosis status, tumor size, therapy methods, and so forth, to investigate the prognostic significance in different subgroups. Results During a median follow-up time of 45.0 months, a total of 88 (48.4%) patients died and 79 (43.4%) patients recurred. The cut-off points for GPR and S-index in predicting death were determined to be 0.76 and 0.56, respectively. Compared with patients with a lower GPR, those with GPR ≥0.76 had a higher probability of cirrhosis and a larger tumor (both P<0.05). GPR and S-index were both found to be significantly associated with survival by univariate log-rank test. Multivariate analysis identified tumor size ≥5 and high level of GPR, but not high Barcelona Clinic Liver Cancer stage or S-index, as independent factors for predicting poor overall survival and recurrence-free survival. Conclusion The GPR is an effective preoperative predictor for outcomes in hepatitis B-associated HCC.
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Affiliation(s)
- Qing Pang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi Province, People's Republic of China
| | - Jian-Bin Bi
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi Province, People's Republic of China
| | - Zhi-Xin Wang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi Province, People's Republic of China
| | - Xin-Sen Xu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi Province, People's Republic of China
| | - Kai Qu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi Province, People's Republic of China
| | - Run-Chen Miao
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi Province, People's Republic of China
| | - Wei Chen
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi Province, People's Republic of China
| | - Yan-Yan Zhou
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi Province, People's Republic of China
| | - Chang Liu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Shaanxi Province, People's Republic of China
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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: 77] [Impact Index Per Article: 8.6] [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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Khalili M, Sanyal A. Is there a relationship between hepatitis B surface antibody status and diabetes? J Diabetes 2016. [PMID: 26201556 DOI: 10.1111/1753-0407.12327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Affiliation(s)
- Mandana Khalili
- University of California San Francisco, San Francisco, California, USA.
| | - Arun Sanyal
- Virginia Commonwealth University, Richmond, VA, USA
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44
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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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45
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Fu SC, Huang YW. Editorial: diabetes and its association with hepatocellular carcinoma in chronic hepatitis B - authors' reply. Aliment Pharmacol Ther 2015; 42:118-9. [PMID: 26040519 DOI: 10.1111/apt.13245] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- S-C Fu
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan
| | - Y-W Huang
- Liver Center, Cathay General Hospital Medical Center, Taipei, Taiwan. , .,School of Medicine, Taipei Medical University, Taipei, Taiwan. , .,Division of Gastroenterology, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. ,
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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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