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Qiu C, Yu C, Yang L, Liu S, Zhang Q, Jia S, Wang W, Jin Z, Yu D. The neutrophil-lymphocyte ratio as a risk factor for all-cause mortality among individuals with resolved HBV infection: evidence from the NHANES 1999-2018. Front Public Health 2025; 12:1493439. [PMID: 39882122 PMCID: PMC11775152 DOI: 10.3389/fpubh.2024.1493439] [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: 09/09/2024] [Accepted: 12/23/2024] [Indexed: 01/31/2025] Open
Abstract
Background Inflammation is a critical component in the process of resolved hepatitis B virus (HBV) infection. The neutrophil-to-lymphocyte ratio (NLR) serves as a sensitive indicator of systemic inflammation and immune activation. Our study aimed to investigate the correlation between elevated NLR levels and the risk of all-cause mortality in patients with resolved HBV infection. Additionally, we evaluated the potential mediating effect of diabetes mellitus (DM) on this correlation. Methods Our study enrolled 1,146 adult patients with resolved HBV infection from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. We utilized the Restricted Cubic Splines (RCS) and Maximum Selection Rank Statistical Method (MSRSM) to analyze the relationship between the NLR and the risk of all-cause mortality. The impact of NLR was evaluated using a weighted multivariate Cox regression model, and the model's predictive accuracy was assessed using time-dependent Receiver Operating Characteristic (ROC) curves. An intermediary analysis was conducted to explore the potential influence of DM on the observed relationship. Results During follow-up period of 103.54 ± 4.90 months, we recorded 207 deaths among the study participants. The analysis using the RCS method revealed a significant positive correlation between the NLR and the risk of all-cause mortality. Those with elevated NLR levels faced a substantially higher mortality risk compared to those with lower levels, as indicated by a Hazard Ratio (HR) of 1.84, with a 95% Confidence Interval (CI) of 1.17 to 2.89 (p < 0.05). The predictive accuracy of the model was substantial, as evidenced by the Area Under the Curve (AUC) for ROC curves at 3, 5, and 10 years, which were 0.873, 0.870, and 0.862, respectively. Furthermore, mediation analysis indicated that DM significantly influenced the relationship between the NLR and mortality, with a mediation effect of 6.57% (95% Confidence Interval [CI]: 0.64 to 15%; p = 0.02). Conclusion Elevated NLR is significantly associated with an increased risk of all-cause mortality in patients with resolved HBV infection. Concurrently, DM acts as a partial mediator of this association.
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Affiliation(s)
- Chen Qiu
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Chaojie Yu
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Lanlan Yang
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Siqi Liu
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Qian Zhang
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Shengnan Jia
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Wenrui Wang
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Zhenjing Jin
- Digestive Disease Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital, Jilin University, Changchun, Jilin, China
| | - Dongdong Yu
- Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
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Wang N, Shen Q, Zhou PS, Wang MD, Zhang JL, Sheng YH, Qian GJ. Association of diabetes mellitus with long-term prognosis after ablation therapy for patients with hepatocellular carcinoma: A single-center cohort study. J Cancer Res Ther 2024; 20:2118-2124. [PMID: 39792423 DOI: 10.4103/jcrt.jcrt_2708_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 11/18/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND This study investigated the clinical efficacy and prognostic factors of ablative treatment in hepatocellular carcinoma (HCC) patients with and without diabetes mellitus (DM). METHODS Retrospective data were collected from HCC patients who underwent ablation between January 2016 and December 2019. The baseline clinicopathological characteristics and long-term outcomes, such as overall survival (OS) and recurrence-free survival (RFS), were compared between those with and without DM. Predictive factors associated with survival and recurrence were identified through univariable and multivariable Cox regression analyses. RESULTS Of the 3528 patients enrolled in the study, 588 (16.7%) had concurrent DM. The 1-, 3-, and 5-year RFS rates in patients with DM (73.8%, 33.7%, and 5.8%, respectively) were significantly (P < 0.001) lower than those in the non-DM patients (70.4%, 37.6%, and 18.6%, respectively). Likewise, significant differences (P < 0.001) in the 1-, 3-, and 5-year OS rates were observed between the DM (99.9%, 78.1%, and 29.1%, respectively) and non-DM (99.9%, 85.9%, and 54.3%, respectively) patients. Multivariable Cox regression analysis identified DM as an independent risk factor for OS [hazard ratio (HR), 1.982; P < 0.001] and RFS (HR, 1.175; P = 0.002). CONCLUSION Patients with DM exhibited a poorer oncological prognosis than those without DM following ablation for HCC. DM was identified as an independent factor influencing the prognosis of HCC patients after curative ablation. Thus, active therapies targeting DM might enhance oncological outcomes and facilitate individualized treatment decisions.
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Affiliation(s)
- Neng Wang
- Department of Ultrasonic Intervention, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Qiang Shen
- Department of Ultrasonic Intervention, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Ping-Sheng Zhou
- Department of Ultrasonic Intervention, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Jing-Lei Zhang
- Department of Ultrasonic Intervention, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Yue-Hong Sheng
- Department of Ultrasonic Intervention, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
| | - Guo-Jun Qian
- Department of Ultrasonic Intervention, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China
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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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Wu Z(E, Xu D, Hu PJH, Huang TS. A hierarchical multilabel graph attention network method to predict the deterioration paths of chronic hepatitis B patients. J Am Med Inform Assoc 2023; 30:846-858. [PMID: 36794643 PMCID: PMC10114116 DOI: 10.1093/jamia/ocad008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Revised: 12/26/2022] [Accepted: 01/25/2023] [Indexed: 02/17/2023] Open
Abstract
OBJECTIVE Estimating the deterioration paths of chronic hepatitis B (CHB) patients is critical for physicians' decisions and patient management. A novel, hierarchical multilabel graph attention-based method aims to predict patient deterioration paths more effectively. Applied to a CHB patient data set, it offers strong predictive utilities and clinical value. MATERIALS AND METHODS The proposed method incorporates patients' responses to medications, diagnosis event sequences, and outcome dependencies to estimate deterioration paths. From the electronic health records maintained by a major healthcare organization in Taiwan, we collect clinical data about 177 959 patients diagnosed with hepatitis B virus infection. We use this sample to evaluate the proposed method's predictive efficacy relative to 9 existing methods, as measured by precision, recall, F-measure, and area under the curve (AUC). RESULTS We use 20% of the sample as holdouts to test each method's prediction performance. The results indicate that our method consistently and significantly outperforms all benchmark methods. It attains the highest AUC, with a 4.8% improvement over the best-performing benchmark, as well as 20.9% and 11.4% improvements in precision and F-measures, respectively. The comparative results demonstrate that our method is more effective for predicting CHB patients' deterioration paths than existing predictive methods. DISCUSSION AND CONCLUSION The proposed method underscores the value of patient-medication interactions, temporal sequential patterns of distinct diagnosis, and patient outcome dependencies for capturing dynamics that underpin patient deterioration over time. Its efficacious estimates grant physicians a more holistic view of patient progressions and can enhance their clinical decision-making and patient management.
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Affiliation(s)
- Zejian (Eric) Wu
- Department of Operations and Information Systems, David Eccles School of Business, University of Utah, Salt Lake City, Utah, USA
| | - Da Xu
- Department of Information Systems, College of Business, California State University Long Beach, Long Beach, California, USA
| | - Paul Jen-Hwa Hu
- Department of Operations and Information Systems, David Eccles School of Business, University of Utah, Salt Lake City, Utah, USA
| | - Ting-Shuo Huang
- Department of General Surgery, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
- Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
- Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung City, Taiwan
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Li MY, Li TT, Li KJ, Zhou C. Type 2 diabetes mellitus characteristics affect hepatocellular carcinoma development in chronic hepatitis B patients with cirrhosis. World J Clin Cases 2023; 11:1009-1018. [PMID: 36874430 PMCID: PMC9979280 DOI: 10.12998/wjcc.v11.i5.1009] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/24/2022] [Accepted: 01/16/2023] [Indexed: 02/14/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) has been shown to be correlated with hepatocellular carcinoma (HCC) development. However, further investigation is needed to understand how T2DM characteristics affect the prognosis of chronic hepatitis B (CHB) patients.
AIM To assess the effect of T2DM on CHB patients with cirrhosis and to determine the risk factors for HCC development.
METHODS Among the 412 CHB patients with cirrhosis enrolled in this study, there were 196 with T2DM. The patients in the T2DM group were compared to the remaining 216 patients without T2DM (non-T2DM group). Clinical characteristics and outcomes of the two groups were reviewed and compared.
RESULTS T2DM was significantly related to hepatocarcinogenesis in this study (P = 0.002). The presence of T2DM, being male, alcohol abuse status, alpha-fetoprotein > 20 ng/mL, and hepatitis B surface antigen > 2.0 log IU/mL were identified to be risk factors for HCC development in the multivariate analysis. T2DM duration of more than 5 years and treatment with diet control or insulin ± sulfonylurea significantly increased the risk of hepatocarcinogenesis.
CONCLUSION T2DM and its characteristics increase the risk of HCC in CHB patients with cirrhosis. The importance of diabetic control should be emphasized for these patients.
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Affiliation(s)
- Man-Yu Li
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing 100050, China
| | - Ting-Ting Li
- Department of Clinical Laboratory, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Ke-Jian Li
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing 100050, China
| | - Cheng Zhou
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing 100050, China
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Liu X, Zhou Y. Influence of hepatitis B virus on the prevalence of diabetes complications in patients with type 2 diabetes. J Diabetes Investig 2022; 14:429-434. [PMID: 36510700 PMCID: PMC9951573 DOI: 10.1111/jdi.13954] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 11/03/2022] [Accepted: 11/16/2022] [Indexed: 12/15/2022] Open
Abstract
AIMS/INTRODUCTION Diabetes and hepatitis B are both global problems. The influence of diabetes on complications and prognosis of hepatitis B has been widely studied. However, the association between hepatitis B virus (HBV) infection and the prevalence of diabetes-related complications is less documented and is uncertain. MATERIALS AND METHODS This was a retrospective study. We collected information from a large clinical database. A total of 1,090 Chinese inpatients with type 2 diabetes were included. RESULTS The participants were divided into two groups, including 135 patients with HBV infection and 955 patients without HBV infection. Patients with HBV infection were younger and had worse control of blood glucose than those without HBV infection. No significant difference was found in the prevalence of diabetic retinopathy, neuropathy, nephropathy, diabetic ketosis or diabetic ketoacidosis between the patients with HBV infection and the patients without HBV infection. The prevalence of macrovascular complications was 54.1% and 64.4% in diabetes patients complicated with HBV infection and without HBV infection, respectively. The P-value was <0.05. However, through the logistic regression analysis, we found HBV infection was not an independent risk factor for macrovascular complications of diabetes. CONCLUSION There was no significant correlation between the prevalence of macrovascular complications, microvascular complications of diabetes, diabetic ketosis or diabetic ketoacidosis and HBV infection status.
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Affiliation(s)
- Xi‐yu Liu
- Department of EndocrinologyDongyang People's HospitalDongyangChina
| | - Yan Zhou
- Department of EndocrinologyDongyang People's HospitalDongyangChina
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Chi ZC. Progress in understanding of association between metabolic associated fatty liver disease and viral infectious diseases. Shijie Huaren Xiaohua Zazhi 2022; 30:783-794. [DOI: 10.11569/wcjd.v30.i18.783] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Metabolic associated fatty liver disease (MAFLD) is a chronic liver disease with the highest incidence in the world, which affects 1/4-1/3 of the world population and has a serious effect on people's health. As is a multi-systemic disease, MAFLD is closely related to the occurrence and prognosis of many diseases. Studies have shown that MAFLD is associated with viral infectious diseases, and their interaction affects the prognosis of the disease. This paper reviews the research progress in this field in recent years.
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Affiliation(s)
- Zhao-Chun Chi
- Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao 266011, Shandong Province, China
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Zhou G, Chen C, Han G, Jiang H, Cao M. Relationship between different hepatitis B virus infection status and gestational diabetes mellitus prevalence among pregnant women with chronic HBV infection: A retrospective study. J Viral Hepat 2022; 29:596-603. [PMID: 35582862 DOI: 10.1111/jvh.13700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Accepted: 03/18/2022] [Indexed: 12/09/2022]
Abstract
To investigate the relationships between different hepatitis B virus (HBV) infection status and gestational diabetes mellitus (GDM) and analyse the potential risk factors, we conducted an observational retrospective study in HBV-infected pregnant women to compare the differences of GDM prevalence and clinical outcomes between groups divided by HBV infection status. Spearman's correlation coefficient was used to evaluate the correlations among hepatitis B e antigen (HBeAg), HBV DNA and liver function. Logistic regression model was used to analyse the risk factors. In all, 1390 HBsAg-positive pregnant women were enrolled. HBeAg titre and HBV DNA, ALT and AST were correlated (r = 0.743, p < 0.001; r = 0.813, p < 0.001). Overall GDM prevalence was 21%. GDM prevalence of HBV-infected women with abnormal liver function was higher than those with normal liver function (26.8% vs. 20%, p = 0.027). Age over 35 years and abnormal liver function over 5 times ULN and 1-2 times ULN were independent risk factors for GDM prevalence with odds ratio (OR) of 1.858 (95% CI 1.227-2.815), 1.589 (95% CI 1.023-2.468) and 2.203 (95% CI 1.029-4.718), respectively. GDM prevalence in HBV-infected pregnancies with abnormal liver function was higher than those with normal liver function. Age over 35 years and abnormal liver function were independent risk factors for GDM in HBV-infected women.
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Affiliation(s)
- Guanlun Zhou
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chao Chen
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Guorong Han
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongxiu Jiang
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Minkai Cao
- Department of Obstetrics and Gynecology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
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Chen L, Dai J, Xie Q, Wang X, Cai W. Metabolic Risk Factors Are Associated with the Disease Severity and Prognosis of Hepatitis B Virus-Related Acute on Chronic Liver Failure. Gut Liver 2022; 16:456-464. [PMID: 35321957 PMCID: PMC9099392 DOI: 10.5009/gnl210449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 12/12/2021] [Accepted: 12/27/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND/AIMS Metabolic risk factors could accelerate hepatitis B virus (HBV)-related mortality; however, their impacts on disease severity in HBV-related acute on chronic liver failure (HBV-ACLF) patients remain unexplored. In this study, we assessed the effects of metabolic risk factors on the outcome of HBV-ACLF patients. METHODS This study retrospectively enrolled antiviral therapy naïve HBV-ACLF patients from a single center in China. Patients were evaluated according to Child-Turcotte-Pugh score, Model for End-Stage Liver Disease (MELD) score, 30-day, 90-day mortality and survival rate to estimate the prognosis of HBV-ACLF. The impacts of different metabolic risk factors were further analyzed. RESULTS A total of 233 patients, including 158 (67.8%) with metabolic risk factors and 75 (32.2%) without metabolic risk factors, were finally analyzed. Patients with metabolic risk factors had significantly higher MELD score (22.6±6.1 vs 19.8±3.8, p<0.001), 90-day mortality rate (56.3% vs 38.7%, p=0.017), and shorter median survival time (58 days vs 75 days: hazard ratio, 1.553; 95% confidence interval, 1.061 to 2.274; p=0.036) than patients without them. Moreover, metabolic risk factors were independently associated with patients' 90-day mortality (hazard ratio, 1.621; 95% confidence interval, 1.016 to 2.585; p=0.043). Prediabetes/diabetes and hypertension were related to higher rates of infection and worse renal function in HBV-ACLF patients. CONCLUSIONS HBV-ACLF patients with metabolic risk factors, especially prediabetes/diabetes or hypertension, could have more severe disease and lower survival rates. In addition, the existence of metabolic disorder is an independent risk factor for HBV-ACLF patients' 90-day mortality.
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Affiliation(s)
- Lu Chen
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinjin Dai
- Department of Infectious Disease, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui Province), Suzhou, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaolin Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Cai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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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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Prognosis Comparison Between Chronic Hepatitis B Patients Receiving a Finite Course of Tenofovir and Entecavir Treatment: A Nationwide Cohort Study in Taiwan. Clin Ther 2022; 44:403-417.e6. [DOI: 10.1016/j.clinthera.2022.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 01/13/2022] [Accepted: 01/14/2022] [Indexed: 11/20/2022]
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Hepatocellular Carcinoma in Hepatitis B Virus-Infected Patients and the Role of Hepatitis B Surface Antigen (HBsAg). J Clin Med 2022; 11:jcm11041126. [PMID: 35207397 PMCID: PMC8878376 DOI: 10.3390/jcm11041126] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 02/09/2022] [Accepted: 02/17/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Hepatitis B virus (HBV) infection is among the main risk factors for HCC. The risk of HCC is not eliminated completely after viral suppression, due to HBV DNA integrated into human chromosomes. Cirrhosis, HBV viral DNA levels, age, male gender, the immune response of the host against HBV, and a combination of obesity and diabetes are among the main risk factors for HCC. Active viral replication and long-standing active disease with inflammation are associated with a higher risk of HCC. Treatment of HBV with nucleos(t)ide analogues (NAs) decreased HCC risk by effectively decreasing viral load and inflammation. Similar risk factors have been reported in hepatitis B patients after seroclearance. Studies have reported decreased risk of HCC after seroclearance, but there were also conflicting results from a few studies indicating no difference in risk of developing HCC. The difference in HCC rates could be because of other factors such as coinfection, occult HBV infection, family history, HBV genotype, and other comorbidities. Due to the persistent risk of HCC after seroclearance, HCC surveillance is critical for early detection, especially in high-risk patients. However, long-term studies might be needed to further validate the results.
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Huang R, Liu J, Wang J, Li J, Wu C. Letter to the Editor: Is HBV genotype strongly associated with HCC risk in patients with chronic hepatitis B? Hepatology 2022; 75:233-234. [PMID: 34519071 DOI: 10.1002/hep.32155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 07/31/2021] [Indexed: 01/15/2023]
Affiliation(s)
- Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.,Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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Siphepho PY, Liu YT, Shabangu CS, Huang JF, Huang CF, Yeh ML, Yu ML, Wang SC. The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments. Biomedicines 2021; 9:1491. [PMID: 34680608 PMCID: PMC8533513 DOI: 10.3390/biomedicines9101491] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/12/2021] [Accepted: 10/13/2021] [Indexed: 02/07/2023] Open
Abstract
Metabolic derangement is characteristic in patients with hepatitis C virus (HCV) infection. Aside from established liver injury, various extrahepatic metabolic disorders impact the natural history of the disease, clinical outcomes, and the efficacy of antiviral therapy. The presence of steatosis, recently redefined as metabolic-associated fatty liver disease (MAFLD), is a common feature in HCV-infected patients, induced by host and/or viral factors. Most chronic HCV-infected (CHC) patients have mild steatosis within the periportal region of the liver with an estimated prevalence of 40% to 86%. Indeed, this is higher than the 19% to 50% prevalence observed in patients with other chronic liver diseases such as chronic hepatitis B (CHB). The histological manifestations of HCV infection are frequently observed in genotype 3 (G-3), where relative to other genotypes, the prevalence and severity of steatosis is also increased. Steatosis may independently influence the treatment efficacy of either interferon-based or interferon-free antiviral regimens. This review aimed to provide updated evidence of the prevalence and risk factors behind HCV-associated steatosis, as well as explore the impact of steatosis on HCV-related outcomes.
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Affiliation(s)
- Phumelele Yvonne Siphepho
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
| | - Yi-Ting Liu
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
| | - Ciniso Sylvester Shabangu
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Jee-Fu Huang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Ming-Lung Yu
- Program in Tropical Medicine, Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (P.Y.S.); (M.-L.Y.)
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.-F.H.); (M.-L.Y.)
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
| | - Shu-Chi Wang
- Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan; (C.S.S.); (J.-F.H.)
- Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan;
- Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
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15
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Wang L, Lin N, Lin K, Xiao C, Wang R, Chen J, Zhou W, Liu J. The Clinical Value of Postoperative Transarterial Chemoembolization for Resectable Patients with Intermediate Hepatocellular Carcinoma After Radical Hepatectomy: a Propensity Score-Matching Study. J Gastrointest Surg 2021; 25:1172-1183. [PMID: 32440804 DOI: 10.1007/s11605-020-04588-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 03/25/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND AND AIMS Surgical resection for patients with intermediate hepatocellular carcinoma (HCC) is preferred in China, but the prognosis remains far from satisfactory. Postoperative transarterial chemoembolization (p-TACE) has been conducted prevalently to prevent recurrence, but its efficacy remains controversial. Hence, we collected the data from primary liver cancer big data (PLCBD) to investigate the clinical value of p-TACE for patients with intermediate HCC and identify the potential beneficiaries. METHODS Patients who were diagnosed with intermediate HCC between December 2012 and December 2015 were identified through the PLCBD. Disease-free survival (DFS) of patients who received p-TACE or not following radical resection was evaluated using Kaplan-Meier survival curves before and after 1:1 propensity scoring match (PSM). Subgroup analysis was conducted stratified by risk factors associated with recurrence. RESULTS A total of 325 intermediate HCC patients receiving radical resection were eligible in this study, including 123 patients in the p-TACE group and 202 in the non-TACE group. Median DFS in the p-TACE group was significantly longer than in the non-TACE group (23.3 months vs. 18.0 months, P = 0.016) in the whole cohort with no severe complicates, which was confirmed in a well-matched cohort (17.4 months vs. 23.3 months, P = 0.012). In addition, p-TACE was identified as an independent risk factors of DFS by multivariate Cox regression analysis before and after PSM (both P < 0.05). After adjusting for other prognostic variables, patients were found to significantly benefit from p-TACE in DFS if they were male, or had hepatitis, diabetes, cirrhosis, AFP ≤ 400 ng/ml, anatomic hepatectomy, no severe surgical complication, no intraoperative transfusion, tumor number = 2, differentiation grading III, capsule, or had no transfusion (all P < 0.05). CONCLUSION With the current data, we concluded that p-TACE was safe and efficient for the patients with intermediate HCC following radical resection, and male patients with hepatitis, diabetes, cirrhosis, AFP ≤ 400 ng/ml, anatomic hepatectomy, no severe surgical complication, no intraoperative transfusion, tumor number = 2, differentiation grading III, and capsule would benefit more from p-TACE.
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Affiliation(s)
- Lei Wang
- Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian, People's Republic of China
| | | | | | - Chunhong Xiao
- Department of General Surgery, 900th Hospital of PLA, 305 Zhongshan East Road,, Nanjing, Jiangsu Province, China
| | - Ren Wang
- Department of Pediatric Surgery, Huai'an Women and Children's Hospital, Huai'an, Jiangsu, China
| | - Jingbo Chen
- Department of Oncology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, Fujian, China
| | - Weiping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Secondary Military Medical University, Shanghai, China
| | - Jingfeng Liu
- Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, Fujian, People's Republic of China.
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16
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Chon HY, Lee JS, Lee HW, Chun HS, Kim BK, Park JY, Kim DY, Ahn SH, Kim SU. Impact of antiviral therapy on risk prediction model for hepatocellular carcinoma development in patients with chronic hepatitis B. Hepatol Res 2021; 51:406-416. [PMID: 33242365 DOI: 10.1111/hepr.13600] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 10/27/2020] [Accepted: 11/08/2020] [Indexed: 02/08/2023]
Abstract
AIM Risk prediction models for hepatocellular carcinoma (HCC) development are available. However, the influence of antiviral therapy (AVT) on these models in patients with chronic hepatitis B is unknown. METHODS The dynamic changes in risk prediction models during AVT and the association between risk prediction model and the risk of chronic hepatitis B-related HCC development were investigated. Between 2005 and 2017, 4917 patients with chronic hepatitis B (3361 noncirrhotic, 1556 cirrhotic) were recruited. RESULTS The mean age of the study population was 49.3 years and 60.6% (n = 2980) of the patients were male. The mean Chinese University-HCC (CU-HCC) score was 12.7 at baseline in the overall study population, and decreased significantly (mean, 8.7) after 1 year of AVT (p < 0.001). The score was maintained throughout 5 years of AVT (mean, 8.4-8.8; p > 0.05). The proportion of high-risk patients (CU-HCC score ≥ 20) was 28.9% at baseline, and decreased significantly after 1 year of AVT (5.0%; p < 0.001), and remained stable through 5 years of AVT (2.2%-3.6%; p > 0.05). In addition to the score at baseline, the CU-HCC score at 1 year of AVT independently predicted the risk of HCC development (hazard ratio = 1.072; p < 0.001), together with male gender and platelet count (all p < 0.05). CONCLUSIONS The CU-HCC score significantly decreased at 1 year of AVT and was maintained thereafter. The CU-HCC score after 1 year of AVT independently predicted the risk of HCC development in patients with chronic hepatitis B.
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Affiliation(s)
- Hye Yeon Chon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ho Soo Chun
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
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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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19
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Zhang H, Li H, Lan X, Liu F, Li B, Wei Y. Diabetes mellitus affects long-term survival in hepatitis B virus-related hepatocellular carcinoma patients: A propensity score-matched analysis. Medicine (Baltimore) 2021; 100:e24354. [PMID: 33530229 PMCID: PMC7850751 DOI: 10.1097/md.0000000000024354] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 11/12/2020] [Accepted: 12/22/2020] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) increases the risk of developing hepatocellular carcinoma (HCC), and how DM affects the prognosis of HCC have not been elucidated. The aim of this study was to compare clinicopathological characteristics and survival between hepatitis B virus (HBV)-related HCC patients with and without DM and to determine risk factors for overall survival after hepatectomy.Among 474 patients with HBV-related HCC, 119 patients had DM. Patients were divided into the diabetic group and nondiabetic group. The short-term and long-term outcomes were evaluated by using propensity score matching analysis.After 1:2 propensity score matching, there were 107 patients in diabetic group, 214 patients in nondiabetic group. The proportion of vessels invasion were higher in diabetic group. The overall survival rate in the diabetic group was 44.7% at 3 years, which was lower than that in the nondiabetic group (56.1%, P = .025). The multivariate analysis indicated that fasting blood glucose >7.0, capsular invasion, microvascular invasion and satellite were independent risk factor of poor prognosis in HCC.DM dose affect the recurrence-free survival and overall survival in HBV-related HCC patients after hepatectomy. One of the more significant findings to emerge from this study is that DM induced higher proportion of major vessel invasion in HCC patients implied unfavorable prognosis.
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Affiliation(s)
- Haili Zhang
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu
| | - Hongyu Li
- Liver transplantation center, Beijing friendship hospital, capital medical university. 101 Luyuan east road, Tongzhou district, Beijing, China
| | - Xiang Lan
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu
| | - Fei Liu
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu
| | - Bo Li
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu
| | - Yonggang Wei
- Department of Liver Surgery, West China Hospital of Sichuan University, Chengdu
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20
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Du Y, Du B, Fang X, Shu M, Zhang Y, Chung H, Sun Y, Teng J, Visalath P, Qiu H, Cai W. ALT Flare Predicts Hepatocellular Carcinoma Among Antiviral Treated Patients With Chronic Hepatitis B: A Cross-Country Cohort Study. Front Oncol 2021; 10:615203. [PMID: 33552989 PMCID: PMC7859526 DOI: 10.3389/fonc.2020.615203] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Accepted: 12/04/2020] [Indexed: 12/21/2022] Open
Abstract
Objectives Alanine aminotransferase (ALT) level is one of the crucial indexes to evaluate disease status for chronic hepatitis B (CHB) patients. However, whether the ALT level after nucleos(t)ide analog (NA) treatment is associated with hepatocellular carcinoma (HCC) development remains unclear. Materials and Methods We evaluated the association between ALT level and HCC occurrence in NA-treated patients and investigated the predictive value of ALT flare for HCC. The associations between ALT level and HCC were analyzed by logistic regression and Cox proportional hazards models. Results There were 21,223 CHB patients at Ruijin Hospital of China and 16,737 CHB patients in the Optum electronic health records (EHR) in the United States (US) treated with NAs between 2010 and 2018. Among them, 8,152 and 4,893 patients who achieved a normal ALT value were included in the study cohorts, respectively. A significant positive dose-dependent correlation between the peak ALT level and HCC was identified in both cohorts. Within the China cohort, ALT flare was significantly associated with increased risks of HCC compared to normal ALT (HR 2.55, 95%CI 1.45-4.50). Stronger increased risks associated with ALT flare were observed in the US cohort (HR 7.62, 95%CI 4.85-11.98). Conclusions ALT flare is a strong predictor for HCC occurrence in the CHB patients treated with NAs. Elevation of ALT, especially ALT flare warrants close monitoring for early HCC detection.
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Affiliation(s)
- Yanan Du
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bingying Du
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyan Fang
- Department of Epidemiology, Janssen Research and Development, Shanghai, China
| | - Meng Shu
- Department of Epidemiology, Janssen Research and Development, Shanghai, China
| | - Yongjing Zhang
- Department of Epidemiology, Janssen Research and Development, Shanghai, China
| | - Hsingwen Chung
- Global Epidemiology, Janssen Research and Development, Titusville, NJ, United States
| | - Ye Sun
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiaming Teng
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Phimphone Visalath
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong Qiu
- Global Epidemiology, Janssen Research and Development, Titusville, NJ, United States
| | - Wei Cai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Amponsah-Dacosta E, Tchuem CT, Anderson M. Chronic hepatitis B-associated liver disease in the context of human immunodeficiency virus co-infection and underlying metabolic syndrome. World J Virol 2020; 9:54-66. [PMID: 33362998 PMCID: PMC7747023 DOI: 10.5501/wjv.v9.i5.54] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 09/24/2020] [Accepted: 10/12/2020] [Indexed: 02/06/2023] Open
Abstract
Globally, a shift in the epidemiology of chronic liver disease has been observed. This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection (CHB), with the greatest burden restricted to the Western Pacific and sub-Saharan African regions. Amidst this is a growing burden of metabolic syndrome (MetS) worldwide. A disproportionate co-burden of human immunodeficiency virus (HIV) infection is also reported in sub-Saharan Africa, which poses a further risk of liver-related morbidity and mortality in the region. We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection. While the mechanistic association between CHB and MetS remains poorly resolved, the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB. Among HIV infected individuals, MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy (ART). It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection. However, this remains to be explored through rigorous longitudinal studies, especially in sub-Saharan Africa. Ultimately, there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV co-infected individuals.
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Affiliation(s)
- Edina Amponsah-Dacosta
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town, Cape Town 7925, Western Cape, South Africa
| | - Cynthia Tamandjou Tchuem
- Health Economics Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town 7925, Western Cape, South Africa
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Kim SU, Chon YE, Seo YS, Lee HW, Lee HA, Kim MN, Min IK, Park JY, Kim DY, Ahn SH, Tak WY, Kim BK, Park SY. A multi-centre study of trends in hepatitis B virus-related hepatocellular carcinoma risk over time during long-term entecavir therapy. J Viral Hepat 2020; 27:1352-1358. [PMID: 32852880 DOI: 10.1111/jvh.13384] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/22/2020] [Accepted: 06/28/2020] [Indexed: 12/13/2022]
Abstract
The risk of developing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is reduced by antiviral therapy. Here, we evaluated the chronological trends in HCC development risk starting in 2007, when entecavir reimbursement was first initiated in South Korea. Treatment-naïve patients with chronic hepatitis B (CHB) receiving entecavir 0.5 mg/d were stratified into three groups according to entecavir start time: early (2007-2010), middle (2011-2012) and late (2013-2014) cohorts Among 2442 patients, cumulative probabilities of developing HCC after 1, 3 and 5 years were, respectively, 1.7%, 5.1%, and 8.2% (early cohort; n = 672); 1.5%, 5.1% and 8.9% (middle cohort; n = 757); and 1.2%, 5.3% and 10.6% (late cohort; n = 1013; P > .05 between each pair). Older age, male, positive hepatitis B e antigen, liver cirrhosis, Child-Pugh class B (vs A) and lower platelet count significantly predicted HCC development in univariate analysis (P < .001), whereas entecavir start time (early vs middle vs late cohorts) did not affect the risk of HCC development (P = .457). A multivariate analysis revealed that older age (adjusted hazard ratio [aHR]=1.041), male gender (aHR = 2.069), liver cirrhosis (aHR = 3.771) and Child-Pugh class B (vs A, aHR = 1.548) were independently associated with an increased risk of HCC development, whereas higher platelet count was independently associated with a reduced risk of HCC development (aHR = 0.993; all P < .05). In conclusion, the risk of developing HCC among patients receiving entecavir in South Korea has been stable since 2007. To establish more effective HCC surveillance programs, further studies regarding the carcinogenic roles of nonviral factors are required.
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Affiliation(s)
- Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yong Eun Chon
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Mi Na Kim
- Department of Internal Medicine, Cha Bundang Medical Center, Cha University, Seongnam, Korea
| | - In Kyung Min
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Kyungpook National University, Daegu, Korea
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Sheen YJ, Kung PT, Sheu WHH, Kuo WY, Tsai WC. Impact of Liver Cirrhosis on Incidence of Dialysis Among Patients with Type 2 Diabetes. Diabetes Ther 2020; 11:2611-2628. [PMID: 32901421 PMCID: PMC7547941 DOI: 10.1007/s13300-020-00919-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Indexed: 12/27/2022] Open
Abstract
INTRODUCTION Renal injury is a common complication of liver cirrhosis and type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the association between cirrhosis and dialysis in patients with T2DM. METHODS This was a retrospective study of specific patient populations using data collected from the National Health Insurance Research Database, National Health Research Institutes, Taiwan on patients treated between 1999 and 2007. The study population comprised 1271,759 patients with T2DM without cirrhosis, 38,860 patients with cirrhosis without T2DM, 11,487 patients with T2DM and cirrhosis, and 579,173 patients without T2DM and cirrhosis (non-cirrhotic control group). RESULTS The average incidence of dialysis in patients with T2DM and liver cirrhosis (2.466%) was 10.6-, 2.3-, and 102.7-fold higher than that in patients with T2DM without cirrhosis (0.232%), with cirrhosis without T2DM (1.071%), and patients without both T2DM and cirrhosis (0.024%), respectively. Adjusted odds ratio (OR) for dialysis risk was 3.19 in patients with T2DM and cirrhosis, 2.16 in patients with T2DM without cirrhosis, and 1.98 in patients with cirrhosis without T2DM, compared to that in patients without T2DM and cirrhosis. Male sex (adjusted hazard ratio [HR] 1.15), age (45-49 vs. 20-34 years [reference]; adjusted HR 1.34), low-income households (adjusted HR 1.46), cirrhosis (adjusted HR 3.42), and diabetic complications severity index (adjusted HR 1.71) were predictors of dialysis in T2DM patients. In addition, those with T2DM participating in the pay-for-performance (P4P) program had a significantly lower relative risk for requiring dialysis (HR 0.64). CONCLUSION Liver cirrhosis is an independent risk factor for dialysis in patients with T2DM. Participating in the P4P program for diabetes care may reduce the risk of requiring dialysis in patients with T2DM.
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Affiliation(s)
- Yi-Jing Sheen
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Public Health, China Medical University, Taichung, Taiwan
| | - Pei-Tseng Kung
- Department of Healthcare Administration, Asia University, Taichung, Taiwan
- Department of Medical Research, China Medical University Hospital-China Medical University, Taichung, Taiwan
| | - Wayne H-H Sheu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Institute of Medical Technology, College of Life Science, National Chung-Hsing University, Taichung, Taiwan
- School of Medicine, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Yin Kuo
- Department of Health Services Administration, China Medical University, Taichung, Taiwan
| | - Wen-Chen Tsai
- Department of Health Services Administration, China Medical University, Taichung, Taiwan.
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Expression and Significance of Insulin Receptor Substrate 1 in Human Hepatocellular Carcinoma. DISEASE MARKERS 2020; 2020:7174062. [PMID: 32695243 PMCID: PMC7368964 DOI: 10.1155/2020/7174062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 05/14/2020] [Accepted: 05/26/2020] [Indexed: 12/24/2022]
Abstract
Background Insulin receptor substrate 1 (IRS-1) is an important molecule of the insulin signal transduction pathway and has been associated with the occurrence and development of many tumors, including hepatocellular carcinoma (HCC). Our study was designed to determine the expression and significance of IRS-1 in human HCC. Methods Two hundred and forty specimens were drawn from 140 patients, including 100 HCC tissues and 100 paracancerous (PC) tissues from 100 HCC patients, 20 liver cirrhosis (LC) tissues from 20 LC patients, and 20 chronic hepatitis (CH) tissues from 20 CH patients. Baseline and pathological characteristics were included, and the expression of IRS-1 was examined by immunohistochemical (IHC) staining. Binary logistic regression model calculation was used for multivariate analysis. Results The total positive rates of IRS-1 expression were 41.0%, 17.0%, 15.0%, and 10.0% in HCC, PC, LC and CH tissues, respectively. IRS-1-positive signals were brown in color and located in the nucleus and cytoplasm. Compared with PC, LC, and CH tissues, a significantly increased expression was observed in human HCC tissues (P < 0.001, P = 0.028, and P = 0.008). Eight of the total 240 specimens had the strong immunostaining of IRS-1 expression, and all of them were HCC tissues. After control of the age, gender, and HBV and HCV infection, IRS-1 expression was independently associated with the diagnosis of HCC (OR 6.60, 95% CI 2.243-19.425, P = 0.001). Conclusions Positive expression of IRS-1 in HCC was increased significantly and may play an important role in the occurrence and development of human HCC.
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Shi Z, Xiao Z, Hu L, Gao Y, Zhao J, Liu Y, Shen G, Xu Q, Huang D. The genetic association between type 2 diabetic and hepatocellular carcinomas. ANNALS OF TRANSLATIONAL MEDICINE 2020; 8:380. [PMID: 32355824 PMCID: PMC7186634 DOI: 10.21037/atm.2020.02.13] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Type 2 diabetes mellitus (T2DM) and hepatocellular carcinoma (HCC) are both major health problems throughout the world. It has been reported that T2DM is an independent risk factor for HCC, although the pathophysiology is still unclear. Methods In order to identify differentially expressed genes (DEGs) in T2DM and HCC, gene expression datasets for T2DM (GSE15653), HCC (GSE60502) and metformin-treated cells (GSE69850) were obtained from the Gene Expression Omnibus database repository. Protein-protein interaction (PPI) networks for the DEGs were constructed and gene clusters selected for functional enrichment analysis. Ten genes with the highest degree of connectivity were selected as hub genes and prognostic analysis together with analysis of gene expression and protein distribution were performed for these genes. Lastly, we investigated associations between the hub genes and genes associated with metformin treatment in hepatocarcinoma cells. Results In total, 256 common DEGs, including 155 up-regulated genes and 101 down-regulated genes, were identified. Enrichment analyses showed that the genes of the major module were largely associated with the cell cycle. All of the 10 hub genes (CCNA2, CCNB1, MAD2L1, BU1B, RACGAP1, CHEK1, BUB1, ASPM, NCAPG and TTK) have a strong association with lower overall survival in liver cancer patients and four genes (CCNA2, CCNB1, CHEK1 and BUB1) have reduced expression in metformin-treated samples. Conclusions This study identified a number of genes that may play important roles in the association of T2DM and HCC, including four genes which may be the target of metformin treatment for diabetes and HCC. The specific mechanisms involved remain to be identified.
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Affiliation(s)
- Zhan Shi
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310014, China
| | - Zunqiang Xiao
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou 310014, China
| | - Linjun Hu
- The Medical College of Qingdao University, Qingdao 266071, China
| | - Yuling Gao
- Department of Genetic Laboratory, Shaoxing Women and Children Hospital, Shaoxing 312030, China
| | - Junjun Zhao
- Graduate Department, Bengbu Medical College, Bengbu 233030, China
| | - Yang Liu
- The Medical College of Qingdao University, Qingdao 266071, China
| | - Guoliang Shen
- Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Hangzhou 310014, China
| | - Qiuran Xu
- The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou 310014, China
| | - Dongsheng Huang
- The Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou 310014, China
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Doycheva I, Zhang T, Amjad W, Thuluvath PJ. Diabetes and Hepatocellular Carcinoma: Incidence Trends and Impact of Liver Disease Etiology. J Clin Exp Hepatol 2020; 10:296-303. [PMID: 32655232 PMCID: PMC7335702 DOI: 10.1016/j.jceh.2019.11.004] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2019] [Accepted: 11/14/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS Hepatocellular carcinoma (HCC) remains the leading cause of cancer-related death among patients with type 2 diabetes mellitus (T2DM). We aimed to assess the independent role of T2DM on HCC risk among patients with different liver disease etiologies. METHODS We analyzed the United Network for Organ Sharing database of all adults registered for liver transplantation (LT) between February 27, 2002 and December 31, 2017. For initial analyses, patients were divided into four groups: nonalcoholic steatohepatitis (NASH) and all other etiologies with or without T2DM. For additional analyses, we divided them based on underlying etiology. Logistic regression was used to evaluate the impact of T2DM with NASH and other etiologies on HCC risk. RESULTS Overall, 24,149 (21.6%) of the listed patients had HCC. Of those, 23.9% had T2DM. When compared with nondiabetics, patient with NASH and T2DM had the highest risk of HCC (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.52-1.86), followed by patients with other etiologies and diabetes. After adjusting for other risk factors, these associations remained unchanged. Registrants with T2DM and NASH, cryptogenic cirrhosis, hepatitis C, and alcoholic liver disease were at higher risk of HCC than those without diabetes, but in patients with chronic hepatitis B or primary biliary cholangitis, diabetes did not increase the HCC risk. Between 2004 and 2016, the annual percentage change of HCC incidence increased for all patients with NASH and hepatitis C regardless of their diabetes status. For those with hepatitis B, this trend was significant only for diabetics. CONCLUSIONS The additive risk of T2DM for HCC development was highest in patients with NASH. HCC risk may vary depending on the underlying etiology.
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Key Words
- ALD, alcoholic liver disease
- APC, annual percentage change
- CI, confidence interval
- HBV, hepatitis B virus
- HCC incidence
- HCC, hepatocellular carcinoma
- HCV, hepatitis C virus
- LT, liver transplantation
- MELD, Model for End-Stage Liver Disease
- NAFLD, nonalcoholic liver disease
- NASH, nonalcoholic steatohepatitis
- OR, odds ratio
- PBC, primary biliary cholangitis
- T2DM, type 2 diabetes mellitus
- UNOS
- UNOS, United Network for Organ Sharing
- fatty liver
- liver cancer
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Affiliation(s)
- Iliana Doycheva
- Institute of Digestive Heath and Liver Diseases, Mercy Medical Center, Baltimore, MD, USA
| | - Talan Zhang
- Institute of Digestive Heath and Liver Diseases, Mercy Medical Center, Baltimore, MD, USA
| | - Waseem Amjad
- Institute of Digestive Heath and Liver Diseases, Mercy Medical Center, Baltimore, MD, USA
| | - Paul J. Thuluvath
- Institute of Digestive Heath and Liver Diseases, Mercy Medical Center, Baltimore, MD, USA,University of Maryland School of Medicine, Baltimore, MD, USA,Address for correspondence. Paul J Thuluvath, Institute of Digestive Health and Liver Diseases Mercy Medical Center, 301 St. Paul Place, Baltimore, MD, 21202, USA.
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Wang CC, Cheng PN, Kao JH. Systematic review: chronic viral hepatitis and metabolic derangement. Aliment Pharmacol Ther 2020; 51:216-230. [PMID: 31746482 DOI: 10.1111/apt.15575] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 08/08/2019] [Accepted: 10/17/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND The liver has a critical role in the metabolism of glucose and lipids. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection leads to a spectrum of liver disease including chronic hepatitis, cirrhosis and hepatocellular carcinoma. Metabolic syndrome (MetS) has a rising incidence owing to an epidemic of type 2 diabetes mellitus (T2DM) and obesity. Non-alcoholic fatty liver disease is a liver manifestation of MetS and has become the most common cause of chronic liver disease worldwide. AIM To summarise the interplay among hepatitis viruses, MetS and its components. METHODS We searched the literature about HBV, HCV infection, MetS, fatty liver and its components from PubMed. RESULTS With respect to the viral replication cycle, lipids are important mediators between viral entry and hepatocyte in HCV infection, but not in HBV infection. Thus, HCV infection is inversely associated with hyperlipidaemia and lipid rebound occurs following sustained viral response induced by interferon-based therapy or direct antiviral agents. In addition, HCV infection is positively associated with insulin resistance, hepatic steatosis, MetS and the risk of T2DM and atherosclerosis. In contrast, HBV infection may protect infected subjects from the development of MetS and hepatic steatosis. Accumulating evidence suggests that HBV infection is inversely associated with lipid metabolism, and exhibits no conclusive association with insulin resistance or the risk of T2DM and arteriosclerosis. CONCLUSIONS In patients with viral hepatitis and concurrent metabolic diseases, a multidisciplinary approach should be given rather than simply antiviral treatment.
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Affiliation(s)
- Chia-Chi Wang
- Department of Gastroenterology and Hepatology, Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, Hualien, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, Department of Medical Research and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
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Merza M. Seroprevalence and risk factors of hepatitis B and C viruses among diabetes mellitus patients in Duhok province, Iraqi Kurdistan. J Family Med Prim Care 2020; 9:642-646. [PMID: 32318396 PMCID: PMC7114067 DOI: 10.4103/jfmpc.jfmpc_1158_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 01/10/2020] [Accepted: 01/23/2020] [Indexed: 01/08/2023] Open
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The Pre- and Postoperative FIB-4 Indexes Are Good Predictors to the Outcomes of HBV-Related HCC Patients after Resection. Gastroenterol Res Pract 2019; 2019:8945798. [PMID: 31885547 PMCID: PMC6914978 DOI: 10.1155/2019/8945798] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 09/24/2019] [Indexed: 12/21/2022] Open
Abstract
Background and Aim Liver fibrosis is associated with the prognosis of patients with hepatocellular carcinoma (HCC) after resection. The fibrosis-4 (FIB-4) index is an accurate and noninvasive marker to determine the degree of liver fibrosis. Here, we evaluated the effect of pre- and postoperative FIB-4 index in predicting the outcomes after resection of HCC in patients who have chronic hepatitis B (CHB) infection. Methods A total of 534 CHB patients with HCC who received curative hepatectomy between 2001 and 2016 at Kaohsiung Chang Gung Memorial Hospital, Taiwan, were enrolled in this study. The impact of the FIB-4 index (preoperative and the 1st year after operation) on overall survival (OS) and recurrence-free survival (RFS) was evaluated. Results There was a significant association between the preoperative FIB-4 index and Metavir fibrosis stage (p < 0.01). The multivariate analysis showed that preoperative FIB‐4 > 2 is an independent risk factor for RFS and OS after HCC curative resection [hazard ratio (HR), 1.902; 95% CI, 1.491–2.460; p < 0.001, and HR, 2.207; 95% CI, 1.420–3.429; p < 0.001, respectively]. Notably, preoperative FIB-4 is also an independent risk factor for RFS (HR, 1.219; p = 0.035) in noncirrhotic patients. Furthermore, patients had deteriorated FIB-4 1 year after operation [definition: the value (the 1st year FIB‐4 after operation minus preoperative FIB‐4) > 1] and had an adverse outcome in RFS and OS (p < 0.001, both). Conclusion The pre and postoperative FIB-4 indexes are useful clinical markers to predict the prognosis in HBV-HCC patients after curative hepatectomy.
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