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Wu Y, Ren L, Mao C, Shen Z, Zhu W, Su Z, Lin X, Lin X. Small hepatitis B virus surface antigen (SHBs) induces dyslipidemia by suppressing apolipoprotein-AII expression through ER stress-mediated modulation of HNF4α and C/EBPγ. J Virol 2024; 98:e0123924. [PMID: 39470210 PMCID: PMC11575332 DOI: 10.1128/jvi.01239-24] [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: 07/15/2024] [Accepted: 09/26/2024] [Indexed: 10/30/2024] Open
Abstract
Persistent infection with hepatitis B virus (HBV) often leads to disruptions in lipid metabolism. Apolipoprotein AII (apoAII) plays a crucial role in lipid metabolism and is implicated in various metabolic disorders. However, whether HBV could regulate apoAII and contribute to HBV-related dyslipidemia and the underlying mechanism remain unclear. This study revealed significant reductions in apoAII expression in HBV-expressing cell lines, the serum, and liver tissues of HBV-transgenic mice. The impact of HBV on apoAII is related to small hepatitis B virus surface antigen (SHBs). Overexpression of SHBs decreased apoAII levels in SHBs-expressing hepatoma cells, transgenic mice, and the serum of HBV-infected patients, whereas suppression of SHBs increased apoAII expression. Mechanistic investigations demonstrated that SHBs repressed the apoAII promoter activity through a HNF4α- and C/EBPγ-dependent manner; SHBs simultaneously upregulated C/EBPγ and downregulated HNF4α by inhibiting the PI3K/AKT signaling pathway through activating endoplasmic reticulum (ER) stress. Serum lipid profile assessments revealed notable decreases in high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) in SHBs-transgenic mice compared to control mice. However, concurrent overexpression of apoAII in these mice effectively counteracted these reductions in lipid levels. In HBV patients, SHBs levels were negatively correlated with serum levels of HDL-C, LDL-C, TC, and TG, whereas apoAII levels positively correlated with lipid content. This study underscores that SHBs contributes to dyslipidemia by suppressing the PI3K/AKT pathway via inducing ER stress, leading to altered expression of HNF4α and C/EBPγ, and subsequently reducing apoAII expression.IMPORTANCEThe significance of this study lies in its comprehensive examination of how the hepatitis B virus (HBV), specifically through its small hepatitis B virus surface antigen (SHBs), impacts lipid metabolism-a key aspect often disrupted by chronic HBV infection. By elucidating the role of SHBs in regulating apolipoprotein AII (apoAII), a critical player in lipid processes and associated metabolic disorders, this research provides insights into the molecular pathways contributing to HBV-related dyslipidemia. Discovering that SHBs downregulates apoAII through mechanisms involving the repression of the apoAII promoter via HNF4α and C/EBPγ, and the modulation of the PI3K/AKT signaling pathway via endoplasmic reticulum (ER) stress, adds critical knowledge to HBV pathogenesis. The research also shows an inverse correlation between SHBs expression and key lipid markers in HBV-infected individuals, suggesting that apoAII overexpression could counteract the lipid-altering effects of SHBs, offering new avenues for understanding and managing the metabolic implications of HBV infection.
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Affiliation(s)
- Yunli Wu
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
| | - Lan Ren
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Chenglei Mao
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Zhiqing Shen
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Wenyu Zhu
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Zhijun Su
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Xinjian Lin
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
| | - Xu Lin
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China
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Zhang L, Wu HD, Qian YF, Xu HY. Prevalence of nonalcoholic fatty liver disease in patients with hepatitis B: A meta-analysis. World J Clin Cases 2024; 12:5749-5760. [PMID: 39247728 PMCID: PMC11263053 DOI: 10.12998/wjcc.v12.i25.5749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 06/27/2024] [Accepted: 07/03/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has increased in recent clinical practice; however, the relationship between CHB and hepatic steatosis (HS) remains controversial. AIM To shed light on the potential association between NAFLD and hepatitis B virus (HBV) infection. METHODS We conducted a systematic literature search using multiple databases, including PubMed, the Cochrane Library, Web of Science, and EMBASE, to identify relevant studies. Predefined inclusion criteria were used to determine the eligibility of the studies for further analysis. RESULTS Comprehensive meta-analysis software was used for statistical analysis, which covered 20 studies. The results indicated a lower NAFLD susceptibility in HBV-infected individuals (pooled OR = 0.87; 95%CI = 0.69-1.08; I 2 = 91.1%), with diabetes (P = 0.015), body mass index (BMI; P = 0.010), and possibly age (P = 0.061) as heterogeneity sources. Of note, in four studies (6197 HBV patients), HBV-infected individuals had a reduced NAFLD risk (OR = 0.68, 95%CI = 0.51-0.89, P = 0.006). A positive link between hyperlipidemia and metabolic syndrome emerged in hepatitis B patients, along with specific biochemical indicators, including BMI, creatinine, uric acid, fasting blood glucose, and homeostasis model assessment of insulin resistance. CONCLUSION HBV infection may provide protection against HS; however, the occurrence of HS in patients with HBV infection is associated with metabolic syndrome and specific biochemical parameters.
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Affiliation(s)
- Li Zhang
- Department of Infectious Diseases, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
| | - Hong-Di Wu
- Department of Infectious Diseases, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
| | - Yuan-Fang Qian
- Department of Nursing, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
| | - Hong-Yan Xu
- Department of Nursing, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
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Yu Y, Tong K, Hu G, Yang X, Wu J, Bai S, Yu R. Love-hate relationship between hepatitis B virus and type 2 diabetes: a Mendelian randomization study. Front Microbiol 2024; 15:1378311. [PMID: 38646627 PMCID: PMC11026703 DOI: 10.3389/fmicb.2024.1378311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Accepted: 03/15/2024] [Indexed: 04/23/2024] Open
Abstract
Objective The impact of hepatitis B virus (HBV) on the risk of type 2 diabetes (T2D) remains a controversial topic. This study aims to analyze the causal relationship between HBV and T2D using Mendelian randomization (MR). Methods Single nucleotide polymorphisms on chronic hepatitis B (CHB), liver fibrosis, liver cirrhosis, and T2D were obtained from BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Mendelian randomization was utilized to evaluate exposure-outcome causality. Inverse variance weighted was used as the primary method for MR analysis. To assess horizontal pleiotropy and heterogeneity, we conducted MR-Egger intercept analysis and Cochran's Q test, and the robustness of the MR analysis results was evaluated through leave-one-out sensitivity analysis. Results MR analysis revealed that CHB was associated with a decreased genetic susceptibility to T2D (OR, 0.975; 95% CI, 0.962-0.989; p < 0.001) while liver cirrhosis (OR, 1.021; 95% CI, 1.007-1.036; p = 0.004) as well as liver cirrhosis and liver fibrosis (OR, 1.015; 95% CI, 1.002-1.028; p = 0.020) were associated with an increased genetic susceptibility to T2D. MR-Egger intercept showed no horizontal pleiotropy (p > 0.05). Cochran's Q showed no heterogeneity (p > 0.05). Leave-one-out sensitivity analysis showed that the results were robust. Conclusion CHB has the potential to act as a protective factor for T2D, but its effectiveness is constrained by viral load and disease stage. This protective effect diminishes or disappears as viral load decreases, and it transforms into a risk factor with the progression to liver fibrosis and cirrhosis.
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Affiliation(s)
- Yunfeng Yu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Keke Tong
- The Hospital of Hunan University of Traditional Chinese Medicine, Changde, China
| | - Gang Hu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Xinyu Yang
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Jingyi Wu
- The Third School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Siyang Bai
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, China
| | - Rong Yu
- The First Hospital of Hunan University of Chinese Medicine, Changsha, China
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Kim HN, Cheong HS, Kim B, Sohn W, Cho YK, Kwon MJ, Kim J, Song Y, Joo EJ. Human gut microbiota from hepatitis B virus-infected individuals is associated with reduced triglyceride level in mice: faecal transplantation study. Microbes Infect 2024; 26:105281. [PMID: 38128750 DOI: 10.1016/j.micinf.2023.105281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 12/09/2023] [Accepted: 12/18/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND AND AIMS Chronic hepatitis B virus (HBV) infection is associated with a reduced risk of dyslipidaemia. Using a human faecal microbiota transplantation (FMT), we compared changes in gut microbiota and lipid profiles in mice transplanted with human faeces from HBV-infected and non-infected individuals. APPROACH AND RESULTS A total of 19 mice received human FMT from four HBV-infected individuals and were categorised into the HBV-positive mice group, while 20 mice received FMT from four HBV-non-infected individuals into the HBV-negative one. In the analysis of gut microbiota in FMT mice, we observed a robust increase in alpha diversity and abundance of Akkermansia muciniphila in HBV-positive mice, compared to that in HBV-negative. Functional inference analysis revealed that the pathways involved in glycerolipid metabolism were more enriched in HBV-positive mice. At 5 weeks of FMT, the reduced triglyceride (TG) level was predominantly observed in HBV-positive mice. CONCLUSIONS Altered gut microbiota accompanied by HBV infection was associated with a robust increase in alpha diversity and butyrate producers, which resulted in a reduced level of TG at 5 weeks post-FMT. This indicates that the reduced risk of dyslipidaemia in chronic HBV infection may be due to the altered gut microbiota accompanied by HBV infection.
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Affiliation(s)
- Han-Na Kim
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 115 Irwon-ro, Gangnam-gu, Seoul 06355, Republic of Korea; Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Gangnam-gu, Seoul 06351, Republic of Korea
| | - Hae Suk Cheong
- Division of Infectious Diseases, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Bomi Kim
- Division of Infectious Diseases, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Won Sohn
- Division of Gastroenterology and Hepatology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Yong Kyun Cho
- Division of Gastroenterology and Hepatology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Min-Jung Kwon
- Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Juhee Kim
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea
| | - Youngmi Song
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea.
| | - Eun-Jeong Joo
- Division of Infectious Diseases, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, 29 Saemunan-ro, Jongno-gu, Seoul 03181, Republic of Korea.
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Yu YF, Hu G, Tong KK, Yang XY, Wu JY, Yu R. Effect of viral hepatitis on type 2 diabetes: A Mendelian randomization study. World J Diabetes 2024; 15:220-231. [PMID: 38464364 PMCID: PMC10921171 DOI: 10.4239/wjd.v15.i2.220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 12/13/2023] [Accepted: 01/17/2024] [Indexed: 02/04/2024] Open
Abstract
BACKGROUND The effects of viral hepatitis (VH) on type 2 diabetes (T2D) remain controversial. AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization (MR). METHODS Single nucleotide polymorphisms of VH, chronic hepatitis B (CHB), chronic hepatitis C (CHC) and T2D were obtained from the BioBank Japan Project, European Bioinformatics Institute, and FinnGen. Inverse variance weighted, MR-Egger, and weighted median were used to test exposure-outcome associations. The MR-Egger intercept analysis and Cochran's Q test were used to assess horizontal pleiotropy and heterogeneity, respectively. Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results. RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans [odds ratio (OR) = 1.028; 95% confidence interval (CI): 0.995-1.062, P = 0.101]. There was a negative causal association between CHB and T2D among East Asians (OR = 0.949; 95%CI: 0.931-0.968, P < 0.001), while there was no significant causal association between CHC and T2D among East Asians (OR = 1.018; 95%CI: 0.959-1.081, P = 0.551). Intercept analysis and Cochran's Q test showed no horizontal pleiotropy or heterogeneity (P > 0.05). Sensitivity analysis showed that the results were robust. CONCLUSION Among East Asians, CHB is associated with a reduced T2D risk, but this association is limited by HBV load and cirrhosis. Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D, focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHC-mediated pathways of hepatic steatosis, liver fibrosis, and cirrhosis.
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Affiliation(s)
- Yun-Feng Yu
- The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
| | - Gang Hu
- The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
| | - Ke-Ke Tong
- The Hospital of Hunan University of Traditional Chinese Medicine, Changde 415213, Hunan Province, China
| | - Xin-Yu Yang
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Jing-Yi Wu
- The Third Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Rong Yu
- The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
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Luo J, Liu Z, Wang Q, Tan S. Liver iron overload and fat content analyzed by magnetic resonance contribute to evaluatingthe progression of chronic hepatitis B. Biomed Rep 2024; 20:23. [PMID: 38169881 PMCID: PMC10758915 DOI: 10.3892/br.2023.1711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 11/22/2023] [Indexed: 01/05/2024] Open
Abstract
Chronic hepatitis B (CHB) and its complications still have a major role in liver-related mortality. It has been indicated that hepatic iron and steatosis may influence liver fibrosis and carcinogenesis. The present study aimed to assess the liver iron and fat in patients with CHB by MRI in order to estimate the associations among liver iron, fat and the severity and progression of liver fibrosis. In the present retrospective study, consecutive patients with CHB examined from August 2018 to August 2020 were analyzed. Liver iron and fat content were assessed by MRI, which was measured as liver iron content (LIC) and proton density fat fraction (PDFF). A total of 340 patients were included in the current study. For LIC, the median value was 1.68 mg/g and elevated LIC was seen in 122 patients (35.9%). For liver fat content, the median value of PDFF was 3.1%, while only 15.0% of patients had liver steatosis (PDFF ≥5%). Age, total bilirubin and sex were independent predictive factors of liver iron overload [odds ratio (OR)=1.036, 1.005 and 8.834, respectively]. A higher platelet count (OR=1.005) and no portal hypertension (OR=0.381) independently predicted liver steatosis. The areas under the receiver operating characteristic curves of PDFF for the identification of liver cirrhosis estimated by different non-invasive tools ranged from 0.629 to 0.704. It was concluded that iron overload was common in patients with CHB, particularly in those with older age, male sex and high total bilirubin level, and liver steatosis was less common in CHB. Liver iron and fat content analyzed by MRI may contribute to the evaluation of the severity and progression of CHB.
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Affiliation(s)
- Jinni Luo
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Zhenzhen Liu
- Department of Radiology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Qian Wang
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Siwei Tan
- Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510630, P.R. China
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Du X, Shi X, Han M, Gao X, Wang C, Jiang C, Pu C. SCD1 inhibits HBV replication by regulating autophagy under high lipid conditions. Virus Genes 2023; 59:801-816. [PMID: 37644346 DOI: 10.1007/s11262-023-02028-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 08/20/2023] [Indexed: 08/31/2023]
Abstract
Chronic hepatitis B virus (HBV) infection remains a significant public health concern worldwide. Several metabolic processes regulate HBV DNA replication, including autophagy and lipid metabolism. In this study, we clarified the effect of lipids on HBV replication and elucidated possible mechanisms. We discovered that lipid metabolic gene expression levels were negatively correlated with the HBV DNA in plasma. Our data showed that fatty acid stimulation significantly reduced HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) levels in HepG2.2.15 cells, which are human hepatoma cell cultures transfected with HBV DNA. The Stearoyl coenzyme A desaturase 1 (SCD1)-autophagy pathway has also been implicated in inhibiting HBV replication by fatty acids stimulation. SCD1 knockdown deregulates the inhibitory effect of fatty acids on HBV by enhancing autophagy. When 3 methyladenine (3MA) was added, the inhibitory effects of specific autophagy inhibitors eliminated the positive effects of SCD1 knockdown on HBV replication. Our results indicate that SCD1 participates in the regulation of inhibition of HBV replication by fatty acids stimulation through regulating autophagy.
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Affiliation(s)
- Xuan Du
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China
| | - Xiaoyi Shi
- Graduate School of Dalian Medical University, Dalian, 116000, China
| | - Mei Han
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China
| | - Xiaoyun Gao
- Department of Geriatric, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116000, China
| | - Chuang Wang
- Graduate School of Dalian Medical University, Dalian, 116000, China
| | - Chunmeng Jiang
- Department of Gastroenterology, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
| | - Chunwen Pu
- Department of Biobank, The Affiliated Sixth People's Hospital of Dalian Medical University, Dalian, 116000, China.
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Tan YW, Wang JM, Zhou XB. Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease. World J Hepatol 2023; 15:237-254. [PMID: 36926239 PMCID: PMC10011903 DOI: 10.4254/wjh.v15.i2.237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 12/14/2022] [Accepted: 01/17/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Although many studies have investigated the impact of chronic hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) on liver disease, few have investigated the relationship between nonalcoholic steatohepatitis (NASH) defined by liver pathology and the prognosis of chronic HBV infection. Most patients were followed up for a short time. This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection. AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events [cirrhosis, hepatocellular carcinoma (HCC), and death] in patients with chronic hepatitis B (CHB) virus infection. METHODS We enrolled patients with chronic hepatitis B virus (HBV) infection who underwent liver biopsy at the Third People's Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020. Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected. Propensity score matching (PSM) was used to balance baseline parameters, Kaplan-Meier (K-M) survival analysis was used to evaluate the risk of clinical events, and Cox regression was used to analyze the risk factors of events. RESULTS Overall, 456 patients with chronic HBV infection were included in the study, of whom 152 (33.3%) had histologically confirmed NAFLD. The median follow-up time of the entire cohort was 70.5 mo. Thirty-four patients developed cirrhosis, which was diagnosed using ultrasound during the follow-up period. K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis (log-rank test, P > 0.05). Patients with CHB with fibrosis at baseline were more prone to cirrhosis (log-rank test, P = 0.046). After PSM, multivariate analysis showed that diabetes mellitus, ballooning deformation (BD), and platelet (PLT) were independent risk factors for cirrhosis diagnosed using ultrasound (P < 0.05). A total of 10 patients (2.2%) developed HCC, and six of these patients were in the combined NAFLD group. K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher (log-rank test, P < 0.05). Hepatocyte ballooning, and severe liver fibrosis were also associated with an increased risk of HCC (log-rank test, all P < 0.05). Cox multivariate analysis revealed that hepatocyte ballooning, liver fibrosis, and diabetes mellitus were independent risk factors for HCC. CONCLUSION There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD. Diabetes mellitus, BD, and PLT were independent risk factors for liver cirrhosis. Patients with chronic HBV infection and NASH have an increased risk of HCC. BD, liver fibrosis, and diabetes mellitus are independent risk factors for HCC.
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Affiliation(s)
- You-Wen Tan
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China.
| | - Jia-Min Wang
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
| | - Xing-Bei Zhou
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212003, Jiangsu Province, China
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Chen JW, Cao XY, Qi X, Zhang JM. Effect of nucleos(t)ide analogues on blood lipid profiles in patients with chronic hepatitis B: A cross-sectional survey. Medicine (Baltimore) 2022; 101:e31980. [PMID: 36550809 PMCID: PMC9771272 DOI: 10.1097/md.0000000000031980] [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] [Indexed: 12/24/2022] Open
Abstract
This study aimed to explore the effects of the 3 nucleos(t)ide analogues (NAs) on lipid levels. We retrospectively included patients treated with NAs at 2 centers and collected their clinical data at their visiting points. Differences in blood lipid levels were analyzed by statistical methods, and factors related to hyperlipidemia were discussed. In these 2 centers, the prevalence rates of hypercholesterolemia were 12/181 (6.6%) for tenofovir alafenamide fumarate (TAF)-, 0/158 (0%) for tenofovir disoproxil fumarate (TDF)-, and 13/182 (7.1%) for entecavir (ETV)-treated individuals (P = .003). The prevalence rates of hypertriglyceridemia were 30/181 (16.6%) for TAF-, 11/158 (7.0%) for TDF-, and 26/182 (14.3%) for ETV-treated individuals (P = .025). In TAF (n = 181, 10 [6, 15] months), TDF (n = 158, 18 [7.5, 45] months), and ETV (n = 182, 24 [10, 60] months) groups, total cholesterol (TC) levels were 4.63 ± 0.91 mmol/L, 3.86 ± 0.61 mmol/L, and 4.53 ± 0.87 mmol/L, respectively; triglyceride (TG) levels were 1.27 ± 0.76 mmol/L, 0.87 ± 0.51 mmol/L, and 1.14 ± 0.67 mmol/L, respectively (P < .001). In multivariate regression analysis, factors associated with hypercholesterolemia were age (adjusted hazard risk [HR] = 1.055 [1.018-1.094]; P = .003) and body mass index (BMI) (adjusted HR = 0.817 [0.669-0.998]; P = .048). Factors associated with hypertriglyceridemia were TAF group (vs. TDF group) (adjusted HR = 0.405 [0.167-0.980]; P = .045), age (adjusted HR = 1.028 [1.002-1.055]; P = .038), and sex (adjusted HR = 0.190 [0.079-0.456]; P < .001). Among the patients treated with TAF (10 [6, 15] months), TDF (18 [7.5, 45] months), and ETV (24 [10, 60] months), the blood lipid levels in the TDF group were lower than those in the TAF group and ETV group, and the occurrence of hyperlipidemia was associated with age, sex, BMI, and different treatment.
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Affiliation(s)
- Jing Wen Chen
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiong Yue Cao
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Xun Qi
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Ji Ming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
- * Correspondence: Ji Ming Zhang, MD, PhD, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China (e-mail: )
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Clinical impact and mechanisms of hepatitis B virus infection concurrent with non-alcoholic fatty liver disease. Chin Med J (Engl) 2022; 135:1653-1663. [PMID: 35940901 PMCID: PMC9509100 DOI: 10.1097/cm9.0000000000002310] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
ABSTRACT Chronic hepatitis B (CHB) virus infection is an important threat to global health despite the administration of vaccines and the use of antiviral treatments. In recent years, as the prevalence of obesity and metabolic syndrome has increased, non-alcoholic fatty liver disease (NAFLD) in patients with CHB has become more common. Both diseases can lead to liver fibrosis and even hepatocellular carcinoma, but the risk of dual etiology, outcome, and CHB combined with NAFLD is not fully elucidated. In this review, we assess the overlapping prevalence of NAFLD and CHB, summarize recent studies of clinical and basic research related to potential interactions, and evaluate the progressive changes of treatments for CHB patients with NAFLD. This review increases the understanding of the relationship and mechanisms of interaction between steatosis and hepatitis B virus infection, and it provides new strategies for the future clinical management and treatment of CHB combined with NAFLD.
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Chiang CH, Cheng CY, Lien YT, Huang KC, Lin WW. P2X7 Activation Enhances Lipid Accumulation During Adipocytes Differentiation Through Suppressing the Expression of Sirtuin-3, Sirtuin-5, and Browning Genes. Front Pharmacol 2022; 13:852858. [PMID: 35462937 PMCID: PMC9019299 DOI: 10.3389/fphar.2022.852858] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 03/18/2022] [Indexed: 11/24/2022] Open
Abstract
P2X7 signaling has been explored in adipose tissue because of its potential to promote ATP-activated inflammatory cascades during obesogenic environments. However, limited literature has investigated the role of the P2X7 receptor in lipid metabolism during adipocyte differentiation. This study sought to explore the regulatory roles of P2X7 in adipocytes. This study utilized the in vitro 3T3-L1 differentiation model. Lipid accumulation, intracellular triglyceride, and extracellular glycerol were determined. The selective P2X7 agonist BzATP and antagonist A438079 were administered to investigate the functions of P2X7. We found that the expression of P2X7 and the lipid accumulation increased during adipocyte differentiation from D0 to D4. When administered at D0/D2, A438079 attenuated, while BzATP enhanced the degree of lipid accumulation during adipocyte differentiation. Neither did BzATP and A438079 administration affect the expression of PPARγ and C/EBPα genes that increased at D4. In addition, both intracellular triglyceride and extracellular glycerol levels at D4 were reduced by A438079 treatment and enhanced by BzATP administration. When administered at stage 2 of adipocyte differentiation, BzATP consistently enhanced lipid accumulation and intracellular triglyceride and extracellular glycerol levels without affecting mRNA and protein levels of PPARγ and C/EBPα that increased at D4. However, treating A438079 or BzATP at D4 did not affect intracellular triglyceride formation and extracellular glycerol release in differentiated adipocytes at D7. Notably, BzATP administration at stage 2 exerted a concentration-dependent inhibition on the enhanced expression of PRDM16, PGC-1α, and UCP-1 at D4. Furthermore, BzATP administration at D0/D2 inhibited the protein and mRNA levels of sirtuin-3/5 at D4. BzATP treatment at stage 2 also suppressed the mRNA levels of sirtuin-3/5 genes upregulated by insulin. In conclusion, this study demonstrated P2X7 enhances lipid accumulation during adipogenesis by suppressing the expression of sirtuin-3/5 and the browning genes.
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Affiliation(s)
- Chien-Hsieh Chiang
- Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.,Department of Family Medicine, National Taiwan University Hospital & College of Medicine, Taipei, Taiwan
| | - Ching-Yuan Cheng
- Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Ting Lien
- Department of Family Medicine, National Taiwan University Hospital & College of Medicine, Taipei, Taiwan
| | - Kuo-Chin Huang
- Department of Family Medicine, National Taiwan University Hospital & College of Medicine, Taipei, Taiwan
| | - Wan-Wan Lin
- Graduate Institute of Pharmacology, National Taiwan University College of Medicine, Taipei, Taiwan.,Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
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Li H, Xu QY, Xie Y, Luo JJ, Cao HX, Pan Q. Effects of chronic HBV infection on lipid metabolism in non-alcoholic fatty liver disease: A lipidomic analysis. Ann Hepatol 2022; 24:100316. [PMID: 33515803 DOI: 10.1016/j.aohep.2021.100316] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/04/2021] [Accepted: 01/06/2021] [Indexed: 02/04/2023]
Abstract
INTRODUCTION AND OBJECTIVES Chronic hepatitis B virus (HBV) infection exerts an impact on lipid metabolism, but its interaction with dysmetabolism-based non-alcoholic fatty liver disease (NAFLD) remains uncertain. The purpose of the study was to investigate the effects of HBV infection on lipid metabolism, hepatic steatosis and related impairments of NAFLD patients. METHODS Biopsy-proven Chinese NAFLD patients with (NAFLD-HBV group, n = 21) or without chronic HBV infection (NAFLD group, n = 41) were enrolled in the case-control study. Their serum lipidomics was subjected to individual investigation by ultra-performance liquid chromatography-tandem mass spectrometry. Steatosis, activity, and fibrosis (SAF) scoring revealed the NAFLD-specific pathological characteristics. RESULTS Chronic HBV infection was associated with global alteration of serum lipidomics in NAFLD patients. Upregulation of phosphatidylcholine (PCs), choline plasmalogen (PC-Os) and downregulation of free fatty acids (FFAs), lysophosphatidylcholine (LPCs) dominated the HBV-related lipidomic characteristics. Compared to those of NAFLD group, the levels of serum hepatoxic lipids (FFA16:0, FFA16: 1, FFA18:1, FFA18:2) were significantly lowered in the NAFLD-HBV group. These low-level FFAs demonstrated correlation to statistical improvements in aspartate aminotransferase activity (FFA16:0, r = 0.33; FFA16:1, r = 0.37; FFA18:1, r = 0.32; FFA18:2, r = 0.42), hepatocyte steatosis (FFA16: 1, r = 0.39; FFA18:1, r = 0.39; FFA18:2, r = 0.32), and ballooning (FFA16:0, r = 0.30; FFA16:1, r = 0.45; FFA18:1, r = 0.36; FFA18:2, r = 0.30) (all P < 0.05). CONCLUSION Chronic HBV infection may impact on the serum lipidomics and steatosis-related pathological characteristics of NAFLD.
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Affiliation(s)
- Han Li
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Qing-Yang Xu
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Yang Xie
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Ji-Jun Luo
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Hai-Xia Cao
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
| | - Qin Pan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
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Iacob SA, Iacob DG. Non-Alcoholic Fatty Liver Disease in HIV/HBV Patients - a Metabolic Imbalance Aggravated by Antiretroviral Therapy and Perpetuated by the Hepatokine/Adipokine Axis Breakdown. Front Endocrinol (Lausanne) 2022; 13:814209. [PMID: 35355551 PMCID: PMC8959898 DOI: 10.3389/fendo.2022.814209] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 01/10/2022] [Indexed: 12/11/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is strongly associated with the metabolic syndrome and is one of the most prevalent comorbidities in HIV and HBV infected patients. HIV plays an early and direct role in the development of metabolic syndrome by disrupting the mechanism of adipogenesis and synthesis of adipokines. Adipokines, molecules that regulate the lipid metabolism, also contribute to the progression of NAFLD either directly or via hepatic organokines (hepatokines). Most hepatokines play a direct role in lipid homeostasis and liver inflammation but their role in the evolution of NAFLD is not well defined. The role of HBV in the pathogenesis of NAFLD is controversial. HBV has been previously associated with a decreased level of triglycerides and with a protective role against the development of steatosis and metabolic syndrome. At the same time HBV displays a high fibrogenetic and oncogenetic potential. In the HIV/HBV co-infection, the metabolic changes are initiated by mitochondrial dysfunction as well as by the fatty overload of the liver, two interconnected mechanisms. The evolution of NAFLD is further perpetuated by the inflammatory response to these viral agents and by the variable toxicity of the antiretroviral therapy. The current article discusses the pathogenic changes and the contribution of the hepatokine/adipokine axis in the development of NAFLD as well as the implications of HIV and HBV infection in the breakdown of the hepatokine/adipokine axis and NAFLD progression.
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Affiliation(s)
- Simona Alexandra Iacob
- Department of Infectious Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Infectious Diseases, National Institute of Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania
| | - Diana Gabriela Iacob
- Department of Infectious Diseases, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
- Department of Infectious Diseases, Emergency University Hospital, Bucharest, Romania
- *Correspondence: Diana Gabriela Iacob,
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The interplay between non-alcoholic fatty liver disease and innate immunity in hepatitis B virus patients. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00084-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is the most epidemic liver disorder worldwide as a result of rapid lifestyle transformation over the past few decades and is expected to elevate in the next few years as well as it is ranging from plain hepatic steatosis via non-alcoholic steatohepatitis (NASH) to liver cirrhosis and hepatocellular carcinoma (HCC).
Main text
NAFLD can also stimulate the diseases progression as diabetes and cardiovascular. Therefore, understanding the NAFLD pathogenesis is of vital clinical interest additionally is a crucial for disease treatment and prevention. After analyzing NAFLD and liver diseases prevalence, it has been a belief regarding the interaction between NAFLD and chronic hepatitis B (CHB).
Conclusion
The liver is an essential innate immune organ with large numbers of innate immune cells that contribute in NAFLD pathogenesis, additionally play the influential role that control NAFLD progression in the hepatitis B patients. Here, we summarized the recent advances in understanding and managing the NAFLD patients with chronic hepatitis B infection and interplay with innate immunity.
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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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Zhang J, Lin S, Jiang D, Li M, Chen Y, Li J, Fan J. Chronic hepatitis B and non-alcoholic fatty liver disease: Conspirators or competitors? Liver Int 2020; 40:496-508. [PMID: 31903714 DOI: 10.1111/liv.14369] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 12/16/2019] [Accepted: 01/02/2020] [Indexed: 02/06/2023]
Abstract
Despite the widespread use of vaccines and antiviral drugs, approximately 350-400 million patients with chronic hepatitis B (CHB) remain worldwide, who carry high risk of cirrhosis and liver carcinoma. Moreover, owing to improvements in global living standards and lifestyle changes, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. Coexistence of NAFLD and CHB is commonly observed, especially in Asian CHB populations; however, little is known regarding the relationship between these two diseases as comorbidities. In this review, we summarize recent advances in clinical and basic researches related to the underlying mutual interactions, as well as potential animal models to facilitate further investigation.
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Affiliation(s)
- Jianbin Zhang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Shuangzhe Lin
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Daixi Jiang
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Mengting Li
- Department of Gastroenterology, Yinzhou People's Hospital, Zhejiang, China
| | - Yuanwen Chen
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Jun Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jiangao Fan
- Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
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Azarkar G, Doosti Z, Osmani F, Ziaee M. Analysis Of Risk Factors For Nonalcoholic Fatty-Liver Disease In Hepatitis B Virus Infection: A Case-Control Study. Hepat Med 2019; 11:153-158. [PMID: 31749640 PMCID: PMC6818534 DOI: 10.2147/hmer.s211106] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 09/17/2019] [Indexed: 12/29/2022] Open
Abstract
Background Nonalcoholic fatty-liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Although NAFLD has been studied extensively, potential risk factors for NAFLD among chronic hepatitis B (CHB) patients and their comparison with healthy individuals have remained understudied in Iran. As such, we examined the association between HBV infection and the development of NAFLD in two groups. Methods A case-control study was done on 376 CHB patients and 447 healthy subjects randomly selected from Birjand, South Khorasan province, Iran. We used logistic regression to estimate adjusted ORs with 95% CIs for incidence of NAFLD. Potential risk factors for NAFLD were evaluated while adjusting for age, sex, marital status, and educational level. Also, χ 2 was used to compare demographic characteristics between the two groups. Results A total of 373 CHB patients (mean age 40.1±12.9 years) versus 447 individuals in the control group (mean age 39.8±13.9 years) were included in this study (p=0.337). Liver characteristics were found to be significantly different in CHB and healthy groups (p<0.05). According to the results obtained from logistic regression, the adjusted OR (95% CI) for NAFLD incidence of comparing HBsAg-positive to HBsAg-negative participants was 0.62 (0.45-0.84). Conclusion The results suggested that HBsAg seropositivity was associated with lower risk of developing NAFLD. This study also revealed that mild cases of fatty liver in carriers of hepatitis B are more common than in healthy subjects. However, moderate and severe cases of this condition are more common in healthy people than in hepatitis B carriers.
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Affiliation(s)
- Ghodsiyeh Azarkar
- Infectious Diseases Research Center, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Zahra Doosti
- Infectious Diseases and Tropical medicine Research center, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Freshteh Osmani
- Department of Epidemiology and Biostatistics, Faculty of Health, Birjand University of Medical Sciences, Birjand, Iran
| | - Masood Ziaee
- Infectious Diseases Research Center, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
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Xiao B, Liu A, Zhang M, Xue H, Zhu Y. Observation of the effect of the pregnancy complicated with the hepatitis B infection on the lying-in women and neonates. Saudi J Biol Sci 2019; 26:1978-1981. [PMID: 31889781 PMCID: PMC6923461 DOI: 10.1016/j.sjbs.2019.08.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 08/15/2019] [Accepted: 08/27/2019] [Indexed: 12/20/2022] Open
Abstract
Objective To investigate the effect of pregnancy complicated with the hepatitis B infection on the pregnancy outcome, immunological factors and the subgroup of lymphocytes in neonates. Methods Subjects admitting to this hospital between January 1, 2016 and January 1, 2018 in this study were divided into two groups according to the hepatitis B infection, i.e. the observation group (infection) and the control group (healthy), with 60 subjects in each group. Pregnancy complications and the neonatal complications were all recorded, and furthermore, the subgroups of lymphocytes and the levels of immunoglobin in the umbilical cord blood were measured. Results The incidence rates of the premature rupture of fetal membranes, premature delivery, postpartum hemorrhage and pregnancy-induced hypertension syndrome in the observation group were all higher than those in the control group, and the differences had statistical significance. In the observation group, the incidence rates of the neonatal distress and asphyxia, and the levels of neonatal CD3＋, CD4＋, CD19＋, IgA and IgM varied significantly from those in the control group, and the differences showed statistical significance. However, no significant differences were identified in comparison of the incidence rate of the cesarean delivery, neonatal deformity, neonatal death, or levels of neonatal CD8+ and IgG. Conclusion During pregnancy, complications of hepatitis B infection results in the increases in the incidence rates of the premature rupture of fetal membranes and neonatal asphyxia, with influences on the levels of immunological factors and lymphocyte subgroups in the umbilical cord blood.
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Affiliation(s)
- Bo Xiao
- Department of Obstetrics, Hanyang Hospital Affiliated to Wuhan University of Science and Technology, Wuhan 430053, China
| | - Ailing Liu
- Clinical Laboratory, The People's Hospital of Longhua District of Shenzhen, Shenzhen 518109, China
| | - Ming Zhang
- Clinical Laboratory, Zhucheng Maternal and Child Health Hospital, Zhucheng 262200, China
| | - Hui Xue
- Department of Gynecology, The Qingdao Hiser Hospital, Qingdao 266000, China
| | - Yi Zhu
- Hospital Infection Management Office, The Hospital of Xinjiang Production and Construction Corps, Urumqi 830002, China
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Suliman I, Abdelgelil N, Kassamali F, Hassanein TI. The Effects of Hepatic Steatosis on the Natural History of HBV Infection. Clin Liver Dis 2019; 23:433-450. [PMID: 31266618 DOI: 10.1016/j.cld.2019.05.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Fatty liver prevalence is increasing and becoming a global health burden. Chronic hepatitis B infection (CHB) is one of the most common chronic viral infections. Steatosis in CHB patients increases risk of cirrhosis and hepatocellular carcinoma. Data from studies on the interaction between CHB and nonalcoholic fatty liver disease are not conclusive. Liver biopsy is the gold standard for diagnosis of fatty liver; however, noninvasive diagnostic tests have been developed to diagnose and predict fibrosis in CHB/NAFLD. Treatment guidelines are not clear.
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Affiliation(s)
- Idrees Suliman
- Blake Medical Center Internal Medicine, 2020 59th St W, Bradenton, FL 34209, USA
| | - Noha Abdelgelil
- Southern California Research Center, 131 Orange Avenue, Suite 101, Coronado, CA 92118, USA
| | - Farah Kassamali
- St. Mary's Medical Center, 450 Stanyan St, San Francisco, CA 94117, USA
| | - Tarek I Hassanein
- Southern California Liver Centers, 131 Orange Avenue, Suite 101, Coronado, CA 92118, USA.
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Chen CJ, Tsay PK, Huang SF, Tsui PH, Yu WT, Hsu TH, Tai J, Tai DI. Effects of Hepatic Steatosis on Non-Invasive Liver Fibrosis Measurements Between Hepatitis B and Other Etiologies. APPLIED SCIENCES 2019; 9:1961. [DOI: 10.3390/app9091961] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Fibrosis-4 (FIB4), transient elastography (TE), and acoustic radiation force impulse (ARFI) are popular modalities to assess liver fibrosis. Their cutoff values for degrees of fibrosis vary between studies. The influence of hepatic steatosis on fibrosis measurements for different etiologies was evaluated. Data from a consecutive series of patients who received fibrosis measurement were included for the training group. An additional series with histology served as the validation group. A standardized protocol was performed for both TE and ARFI, mostly by a single technician. Patients with alcoholism, autoimmune disease, active inflammation, or who were receiving therapy were excluded. The training group included 215 patients and the validation group included 221. The correlation of liver stiffness between TE and ARFI was good (R2 linear = 0.798; p < 0.001). Different correlations between ARFI and TE were noted between high and low control attenuation parameter (CAP) values (cutoff: 290 dB/m), especially in the non-hepatitis B subgroups. Relatively lower FIB4 and TE values were seen in the high CAP versus low CAP in patients with histology-proven non-alcoholic fatty liver disease and chronic hepatitis C. FIB4 cutoff values were >25% lower among F2-F4 stages and the TE cutoff value for F4 was 8.5% lower in the high versus low CAP group. Such findings were not observed in chronic hepatitis B. Different fibrogenesis mechanisms between hepatitis B and non-B are discussed. We conclude that hepatic steatosis significantly impacts FIB4 and TE fibrosis measurements in non-hepatitis B-related liver diseases. Fibrosis grade should be interpreted with caution in severe steatosis.
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Affiliation(s)
- Cheng-Jen Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
| | - Pei-Kwei Tsay
- Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan 333, Taiwan
| | - Shiu-Feng Huang
- Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei 115, Taiwan
| | - Po-Hsiang Tsui
- Department of Medical imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan
| | - Wan-Ting Yu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
| | - Tse-Hwa Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
| | - Jennifer Tai
- Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
| | - Dar-In Tai
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
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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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Xiong J, Zhang H, Wang Y, Wang A, Bian J, Huang H, Zheng Y, Sang X, Xu Y, Lu X, Zhao H. Hepatitis B virus infection and the risk of nonalcoholic fatty liver disease: a meta-analysis. Oncotarget 2017; 8:107295-107302. [PMID: 29291029 PMCID: PMC5739814 DOI: 10.18632/oncotarget.22364] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 09/04/2017] [Indexed: 12/20/2022] Open
Abstract
Some studies have reported that hepatitis B virus (HBV) infection affects the risk of nonalcoholic fatty liver disease (NAFLD). However, this association is controversial. We conducted a systematic review and meta-analysis to investigate the relationship between HBV infection and NAFLD. Relevant studies published before May 2017 were identified by searching PubMed, EMBASE, and ISI Web of Science. We used the random-effects model proposed by DerSimonian and Laird to quantify the relationship between HBV infection and risk of NAFLD. We also conducted subgroup and sensitivity analyses to validate the stability of the results. Five articles, comprising 8,272 HBV-infected patients and 111,631 uninfected controls, were included in our research. Our meta-analysis suggested that the risk of NAFLD was significantly lower in HBV-infected patients than in uninfected controls, with heterogeneity between studies (summary odds ratio [OR] = 0.71; confidence interval [CI] = 0.53–0.90; I2 = 75.2%). However, the inverse relationship was observed in only cohort (OR = 0.83; 95% CI = 0.73–0.94) and cross-sectional studies (OR = 0.63; 95% CI = 0.47–0.79), not case-control studies (OR = 3.96; 95% CI = 2.10–7.48). In conclusion, HBV infection was inversely associated with the risk of NAFLD.
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Affiliation(s)
- Jianping Xiong
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haoaohai Zhang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yaqin Wang
- Department of Interventional Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Anqiang Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jin Bian
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hanchun Huang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ying Zheng
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macau SAR, China
| | - Xinting Sang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yiyao Xu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Lu
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Haitao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Unawareness of Hepatitis B Virus Infection confers on Higher Rate of Metabolic Syndrome: A Community-based Study. Sci Rep 2017; 7:9869. [PMID: 28852048 PMCID: PMC5575015 DOI: 10.1038/s41598-017-10029-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 08/02/2017] [Indexed: 12/15/2022] Open
Abstract
The objective of this study was to determine whether awareness of hepatitis B virus (HBV) serostatus was discordant with metabolic syndrome (MetS) among people with chronic HBV infection. We conducted a community-based study in four Taiwanese districts. A total of 3493 adult participants were recruited. Participants who were hepatitis B surface antigen (HBsAg) seropositive and had self-reported HBV infection were considered aware of hepatitis B (aHB); those who denied a history of HBV infection were considered unaware of hepatitis B (uaHB). Among the 454 participants who were HBsAg seropositive, 275 (60.6%) were aHB and 179 (39.3%) were uaHB. Hypertriglyceridemia showed significant inverse association with HBsAg seropositive, especially among those who were aHB. Insulin resistance was significantly, positively associated with HBsAg seropositive, especially among participants who were uaHB. Those who were uaHB had a higher risk of central obesity, hyperglycemia, insulin resistance, and MetS than those who were aHB (odds ratio = 2.33, 1.64, 2.15, 1.85, respectively, all p < 0.05). The association among the prevalence of MetS, its individual components and HBsAg seropositivity varies according to awareness of HBV infection. It is important to recognize an individual's risk for MetS, especially who were unaware of HBV infection.
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Changes in the Prevalence of HBsAg and HBeAg: a Study of 8696 Parturients in a Well Vaccinated Area. Sci Rep 2017; 7:1212. [PMID: 28450703 PMCID: PMC5430794 DOI: 10.1038/s41598-017-01234-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 03/24/2017] [Indexed: 12/18/2022] Open
Abstract
To elucidate the impact of a hepatitis B (HB) vaccination program on the prevalence of HB surface antigen (HBsAg) and HB envelope antigen (HBeAg) as well as the success rate of HBeAg clearance among parturients, we collected data on parturients who gave birth between 2000 and 2010, and recorded the HB status postpartum of those with positive HBeAg before birth. A total of 8696 parturients were enrolled, of whom 113 with prenatal positive HBeAg were invited back. The prevalence of HBsAg decreased over the study period, particularly in the vaccinated cohort, while there was no change in the prevalence of HBeAg. Foreign parturients had a higher HBeAg-positive rate and delayed HBeAg clearance, and those with a higher body mass index (>24 kg/m2) had earlier HBeAg clearance (51.9% vs. 23.9%, p = 0.005). Only 30% of the subjects who were positive for HBeAg before birth became negative 5 years after delivery. In conclusion, the downward trend in HB infection with more significance among vaccinated parturients reflects effective prevention and the impact of universal HB immunization. Nonetheless, aggressive follow-up is necessary for parturients who are persistently positive for HBeAg postpartum, as well as developing different public health policies for foreign parturients from endemic areas.
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Joo EJ, Chang Y, Yeom JS, Ryu S. Hepatitis B virus infection and decreased risk of nonalcoholic fatty liver disease: A cohort study. Hepatology 2017; 65:828-835. [PMID: 28035771 DOI: 10.1002/hep.28917] [Citation(s) in RCA: 110] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 09/14/2016] [Accepted: 10/16/2016] [Indexed: 12/11/2022]
Abstract
UNLABELLED The presence of an association between chronic hepatitis B virus (HBV) infection and fatty liver is controversial. We examined the association between HBV infection and the development of nonalcoholic fatty liver disease (NAFLD). We conducted a cohort study of 83,339 participants without NAFLD at baseline who underwent serologic testing for hepatitis B surface antigen (HBsAg) between 2002 and 2006 and were followed annually or biennially until December 2014. NAFLD was defined as the presence of ultrasonographic fatty liver in the absence of excessive alcohol use or other identifiable causes. We used a parametric Cox model to estimate adjusted hazard ratios with 95% confidence intervals of incident NAFLD. During 484,736.1 person-years of follow-up, 20,200 incident NAFLD cases were identified. In models adjusted for age, sex, year of visit, smoking status, alcohol intake, regular exercise, education level, and body mass index, the adjusted hazard ratio (95% confidence interval) for incident NAFLD comparing HBsAg-positive to HBsAg-negative participants was 0.83 (0.73-0.94). After introducing HBV infection and confounders (including homeostasis model assessment of insulin resistance and metabolic factors) as time-dependent exposures, the association between HBV infection and decreased risk of incident NAFLD was attenuated but persisted. These associations were consistently observed across clinically relevant, prespecified subgroups. CONCLUSION In this large cohort of apparently healthy Korean adults, HBsAg seropositivity was associated with lower risk of developing NAFLD, indicating a possible effect of HBV infection on the pathogenesis of NAFLD development. (Hepatology 2017;65:828-835).
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Affiliation(s)
- Eun-Jeong Joo
- Division of Infectious Diseases, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Yoosoo Chang
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.,Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.,Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
| | - Joon-Sup Yeom
- Division of Infectious Diseases, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea
| | - Seungho Ryu
- Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.,Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, Seoul, South Korea.,Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, South Korea
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Eslam M, Mangia A, Berg T, Chan HLY, Irving WL, Dore GJ, Abate ML, Bugianesi E, Adams LA, Najim MAM, Miele L, Weltman M, Mollison L, Cheng W, Riordan S, Fischer J, Romero-Gomez M, Spengler U, Nattermann J, Rahme A, Sheridan D, Booth DR, McLeod D, Powell E, Liddle C, Douglas MW, van der Poorten D, George J. Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes. Hepatology 2016; 64:34-46. [PMID: 26822232 DOI: 10.1002/hep.28475] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 01/27/2016] [Indexed: 01/03/2023]
Abstract
UNLABELLED A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (P = 0.02) but not different in cohorts with CHC (n = 2023) and chronic hepatitis B (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted ≥F2 fibrosis in CHC and NAFLD assessed cross-sectionally (odds ratio = 1.39, 95% confidence interval 1.04-1.87, and odds ratio = 1.62, 95% confidence interval 1.03-2.52, respectively; P < 0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. CONCLUSION The TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (Hepatology 2016;64:34-46).
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Affiliation(s)
- Mohammed Eslam
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
| | - Alessandra Mangia
- Division of Hepatology, Ospedale Casa Sollievo della Sofferenza, IRCCS, San Giovanni Rotondo, Italy
| | - Thomas Berg
- Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany
| | - Henry Lik Yuen Chan
- Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
| | - William L Irving
- NIHR Biomedical Research Unit in Gastroenterology and the Liver, University of Nottingham, Nottingham, UK
| | - Gregory J Dore
- Kirby Institute, The University of New South Wales, Sydney, NSW, Australia
- St. Vincent's Hospital, Sydney, NSW, Australia
| | - Maria Lorena Abate
- Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy
| | - Elisabetta Bugianesi
- Division of Gastroenterology and Hepatology, Department of Medical Science, University of Turin, Turin, Italy
| | - Leon A Adams
- School of Medicine and Pharmacology, Sir Charles Gairdner Hospital Unit, University of Western Australia, Nedlands, WA, Australia
| | - Mustafa A M Najim
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
- Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia
| | - Luca Miele
- Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - Martin Weltman
- Department of Gastroenterology and Hepatology, Nepean Hospital, Sydney, NSW, Australia
| | - Lindsay Mollison
- Department of Gastroenterology and Hepatology, Fremantle Hospital, Fremantle, WA, Australia
| | - Wendy Cheng
- Department of Gastroenterology & Hepatology, Royal Perth Hospital, WA, Australia
| | - Stephen Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital and University of New South Wales, Sydney, NSW, Australia
| | - Janett Fischer
- Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany
| | - Manuel Romero-Gomez
- Unit for the Clinical Management of Digestive Diseases and CIBERehd, Hospital Universitario de Valme, Sevilla, Spain
| | - Ulrich Spengler
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Jacob Nattermann
- Department of Internal Medicine I, University of Bonn, Bonn, Germany
| | - Antony Rahme
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
| | - David Sheridan
- Institute of Translational and Stratified Medicine, Plymouth University, UK
| | - David R Booth
- Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, NSW, Australia
| | - Duncan McLeod
- Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia
| | - Elizabeth Powell
- The University of Queensland, School of Medicine, Princess Alexandra Hospital, Woolloongabba, QLD, Australia
| | - Christopher Liddle
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
| | - Mark W Douglas
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
- Centre for Infectious Diseases and Microbiology, Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney at Westmead Hospital, Westmead, NSW, Australia
| | - David van der Poorten
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
| | - Jacob George
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia
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Kuo YH, Tsai MC, Kee KM, Chang KC, Wang JH, Lin CY, Lin SC, Lu SN. Associated Factors for Metabolic Syndrome in the Older Adults with Chronic Virus Hepatitis in the Community. PLoS One 2016; 11:e0155544. [PMID: 27177024 PMCID: PMC4866736 DOI: 10.1371/journal.pone.0155544] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Accepted: 04/30/2016] [Indexed: 12/21/2022] Open
Abstract
This study was to evaluate the association between metabolic syndrome (MetS) and chronic virus hepatitis elders in the community. Those subjects with positive hepatitis B surface antigen (HBsAg) and/or anti-hepatitis C virus (anti-HCV) screened in the community before were invited to this study and 451 responded. All participants underwent anthropometric measurements, blood tests, ultrasound and fibroscan examinations. The cut-off of liver stiffness measurement-liver cirrhosis (LSM-LC) was 10 kPa for chronic hepatitis B (CHB) patients and 12 kPa for chronic hepatitis C (CHC) patients, respectively. Among 451 responders, 56 were excluded due to negative HBsAg or anti-HCV. Three hundreds and ninety-five subjects included 228 CHB patients, 156 CHC patients and 11 dual hepatitis patients, had a mean age of 62±12.6 years. Fifty-four (23.7%) CHB patients coexisted with MetS whereas 40 (25.6%) CHC patients also had MetS. Those patients with MetS had more LSM-LC cases than those without (20.4% vs 9.8%, p = 0.04 in CHB patients; 28.2% vs 13.5%, p = 0.037 in CHC patients, respectively). In multivariate logistic analysis, detectable viremia was reversely associated with MetS in CHB patients after adjustment for age, gender and body mass index (odds ratio (OR): 0.42; 95% confidence interval (CI): 0.18-0.99; p = 0.047). Regarding CHC patients, higher LSM level was the only factor contributed to MetS (OR: 1.1; 95% CI: 1.02-1.19; p = 0.012). In conclusion, elder CHB patients coexisted with MetS might experience an inactive virus replication but have an advanced liver fibrosis. In elder CHC patients, only higher LSM level was associated with MetS.
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Affiliation(s)
- Yuan-Hung Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College Medicine, Taoyuan, Taiwan
| | - Ming-Chao Tsai
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College Medicine, Taoyuan, Taiwan
| | - Kwong-Ming Kee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College Medicine, Taoyuan, Taiwan
| | - Kuo-Chin Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College Medicine, Taoyuan, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College Medicine, Taoyuan, Taiwan
| | - Chun-Yin Lin
- Health Center of Yujing district, Tainan, Taiwan
| | - Sheng-Che Lin
- Department of Health, Tainan City Government, Tainan, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Chang Gung University College Medicine, Taoyuan, Taiwan
- * E-mail:
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Hu JH, Chen MY, Yeh CT, Lin HS, Lin MS, Huang TJ, Chang ML. Sexual Dimorphic Metabolic Alterations in Hepatitis C Virus-infected Patients: A Community-Based Study in a Hepatitis B/Hepatitis C Virus Hyperendemic Area. Medicine (Baltimore) 2016; 95:e3546. [PMID: 27149466 PMCID: PMC4863783 DOI: 10.1097/md.0000000000003546] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
The impact of sex on metabolic alterations in individuals with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection remains elusive.A community-based study was performed to assess sex, age, body mass index, the lipid profile, blood pressure, glucose, alanine aminotransferase, HBV surface antigen (HBsAg), and HCV antibody levels, smoking and alcohol drinking habits, and cardiometabolic diseases, including diabetes, hypertension, cardiovascular events, and renal diseases. The HCV-RNA level and genotype were further assessed in HCV antibody-positive subjects, and the hepatitis B e antigen and HBV-DNA levels were further examined in HBsAg-positive subjects.Among the 10,959 adults enrolled, 1949 (17.8%) and 1536 (14.0%) were HBV and HCV-infected, respectively. Univariate and multivariate analyses showed that the lipid profile and hypertension were independently associated with HCV infection (95% confidence intervals of odds ratios [OR 95% CI]: total cholesterol [TC] = 0.508-0.677; triglycerides = 0.496-0.728; hypertension = 0.669-0.937), but not with HBV infection. Consistently, HCV, but not HBV infection, was negatively associated with the TC and triglyceride levels (OR 95% CI for TC: 0.450-0.601; triglycerides: 0.443-0.671). Generalized linear models revealed that HCV infection, sex, and age interactively affected the lipid profile (OR 95% CI TC = 1.189-1.385; triglycerides = 1.172-5.289). Age-stratification analysis showed that the lipid levels were lower in both the HCV-positive females aged ≥49 years (TC, P < 0.001; triglycerides, P = 0.001) and males of all ages (TC, P < 0.001; triglycerides, P < 0.001) compared with their sex and age-matched HCV-negative counterparts. HCV infection was associated with a higher body mass index (≥49 years, β = 0.405, P = 0.002) and increased rates of cardiovascular events (<49 years, OR 95% CI 1.23-9.566), diabetes (≥49 years, OR 95% CI 1.114-1.932), and renal diseases (≥49 years, OR 95% CI 1.23-9.55), and with a lower rate of hypertension (≥49 years, OR 95% CI 0.616-0.964) in the females, but not in the males, as determined by multivariate analyses.Only HCV infection was associated with metabolic alterations in this HBV/HCV-hyperendemic area. Females aged ≥49 years and males of all ages exhibited HCV-associated hypolipidemia. HCV-associated cardiometabolic diseases were evident only in the females. Sex dimorphism in HCV-associated metabolic complications warrants personalized follow-up of HCV-positive patients.
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Affiliation(s)
- Jing-Hong Hu
- From the Department of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan (J-HH); College of Nursing, Chang Gung University of Science and Technology, Putz City, Chiayi County, Taiwan (M-YC); Liver Research Center and Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan (C-TY, M-LC); Division of Infection Disease, Department of Medicine, Chang Gung Memory Hospital, Chia-yi, Taiwan (H-SL); Division of Cardiology, Chang-Gung Memorial Hospital, Yunlin, Taiwan (M-SL); Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan (T-JH); and Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, (M-LC)
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Şahin Y. PREVALENCE OF MALNUTRITION IN CHILDREN WITH CHRONIC HEPATITIS B INFECTION. ARQUIVOS DE GASTROENTEROLOGIA 2016; 53:89-93. [PMID: 27305414 DOI: 10.1590/s0004-28032016000200007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 01/15/2016] [Indexed: 11/21/2022]
Abstract
BACKGROUND There have been limited studies investigating the impact of chronic hepatitis B virus infection on the growth of children. OBJECTIVE Our objective was to investigate the prevalence of malnutrition in children with chronic hepatitis B infection. METHODS The nutritional status of patients was retrospectively evaluated in the outpatient Clinic of Pediatric Gastroenterology between February and November 2014. During the study, biochemical laboratory parameters, duration of disease, liver biopsy scores, and medication were evaluated. Additionally body mass index and body mass index centiles were calculated. RESULTS Of the 96 patients in this study, 68 were male and 28 were female, and the mean age was 144.7±43.9 months and 146.1±47.3 months, respectively. According to body mass index centiles five (5.2%) patients were underweight, seven (7.3%) patients were overweight, and seven (7.3%) patients were obese. CONCLUSIONS Moderate rates of malnutrition (including obesity) were found in chronic hepatitis B infection. Additional nutritional status information of healthy and sick children should be assessed in the infection's early period, and timely interventions should be initiated.
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Affiliation(s)
- Yasin Şahin
- Department of Pediatric Gastroenterology-Hepatology and Nutrition, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey, Istanbul University, Department of Pediatric Gastroenterology-Hepatology and Nutrition, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul , Turkey
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Huang CY, Lu CW, Liu YL, Chiang CH, Lee LT, Huang KC. Relationship between chronic hepatitis B and metabolic syndrome: A structural equation modeling approach. Obesity (Silver Spring) 2016; 24:483-9. [PMID: 26719030 DOI: 10.1002/oby.21333] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 08/18/2015] [Accepted: 08/18/2015] [Indexed: 12/17/2022]
Abstract
OBJECTIVE Investigate the nature of the relationship between chronic hepatitis B virus (HBV) infection and metabolic syndrome among nondiabetic adults. METHODS This was a cross-sectional analysis of 17,030 nondiabetic adults (7437 males and 9593 females; mean age, 36.0 ± 3.9 years) in northern Taiwan from 2008 to 2009. The associations of hepatitis B surface antigen (HBsAg) seropositivity with metabolic syndrome and cardio-metabolic parameters were assessed. A structural equation model was constructed to elucidate the pathways between chronic HBV infection and individual cardiometabolic risk factors. RESULTS A total of 2982 (17.5%) participants were HBsAg-seropositive. Of the seropositive and seronegative subjects, 15.5 and 16.9% had metabolic syndrome, respectively. The HBsAg-seropositive subjects had a lower odds of having metabolic syndrome compared with the seronegative subjects irrespective of gender and age (OR: 0.76, 95% CI: 0.68-0.85). The inverse associations remained significant after adjusting for body mass index and serum alanine aminotransferase levels. HBsAg seropositivity was inversely associated with hypertriglyceridemia (OR: 0.59, 95% CI: 0.52-0.66), and low serum levels of high-density lipoprotein cholesterol (OR: 0.86, 95% CI: 0.79-0.93) after adjustments. The structural equation model revealed chronic HBV infection had a significant negative effect on dyslipidemia both in males (B = -0.054) and females (B = -0.064). CONCLUSIONS The inverse relationship between chronic HBV infection and metabolic syndrome may be attributable to the net beneficial effects on lipid profiles.
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Affiliation(s)
- Chiao-Yu Huang
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Wen Lu
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Yi-Lien Liu
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Min-Sheng General Hospital, Taoyuan, Taiwan
| | - Chien-Hsieh Chiang
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Community and Family Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan
| | - Long-Teng Lee
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Kuo-Chin Huang
- Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Family Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Office of Superintendent, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
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Chiang CH, Lu CW, Han HC, Hung SH, Lee YH, Yang KC, Huang KC. The Relationship of Diabetes and Smoking Status to Hepatocellular Carcinoma Mortality. Medicine (Baltimore) 2016; 95:e2699. [PMID: 26871803 PMCID: PMC4753898 DOI: 10.1097/md.0000000000002699] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
The relationship of diabetes and smoking status to hepatocellular carcinoma (HCC) mortality is not clear. We aimed to investigate the association of smoking cessation relative to diabetes status with subsequent deaths from HCC.We followed up 51,164 participants (aged 44-94 years) without chronic hepatitis B or C from 1 January 1998 to 31 December 2008 enrolled from nationwide health screening units in a prospective cohort study. The primary outcomes were deaths from HCC.During the study period, there were 253 deaths from HCC. History of diabetes was associated with deaths from HCC for both total participants (adjusted hazard ratio [HR], 2.97; 95% confidence interval [CI], 2.08-4.23) and ever smokers with current or past smoking habits (HR, 1.92; 95% CI, 1.10-3.34). Both never smokers (HR, 0.46; 95% CI, 0.32-0.65) and quitters (HR, 0.62; 95% CI, 0.39-0.97) had a lower adjusted risk of HCC deaths compared with current smokers. Among all ever smokers with current or past smoking habits, as compared with diabetic smokers, only quitters without diabetes had a lower adjusted risk of HCC deaths (HR, 0.37; 95% CI, 0.18-0.78). However, quitters with diabetes were observed to have a similar risk of deaths from HCC when compared with smokers with diabetes. Regarding the interaction between diabetes and smoking status on adjusted HCC-related deaths, with the exception of quitters without history of diabetes, all groups had significantly higher HRs than nondiabetic never smokers. There was also a significant multiplicative interaction between diabetes and smoking status on risk of dying from HCC (P = 0.033). We suggest clinicians should promote diabetes prevention and never smoking to associate with reduced subsequent HCC mortality even in adults without chronic viral hepatitis.
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Affiliation(s)
- Chien-Hsieh Chiang
- From the Department of Family Medicine, National Taiwan University College of Medicine, Taipei (C-HC, S-HH, K-CH); Department of Community and Family Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin (C-HC, S-HH); Department of Family Medicine, National Taiwan University Hospital (C-HC, C-WL, S-HH, K-CH); Research Center for Applied Sciences, Academia Sinica (H-CH); Community and Geriatric Medicine Research Center, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan (Y-HL, K-CH); Department of Global Health and Population, Harvard T. H. Chan School of Public Health, Boston, MA (Y-HL); Department of Community and Family Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu (K-CY); Institute of Epidemiology and Preventive Medicine, National Taiwan University (K-CY); and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan (K-CH)
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Jarcuska P, Drazilova S, Fedacko J, Pella D, Janicko M. Association between hepatitis B and metabolic syndrome: Current state of the art. World J Gastroenterol 2016; 22:155-164. [PMID: 26755867 PMCID: PMC4698482 DOI: 10.3748/wjg.v22.i1.155] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 07/22/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) is a global health issue that increases the risk of liver cirrhosis and hepatocellular carcinoma in infected patients. Metabolic syndrome (MetS) is a disease endemic mostly to the developed countries. It is associated with high cardiovascular mortality and morbidity, diabetes mellitus as well as cancer. In this manuscript, we systematically review the published data on the relationship between MetS and CHB infection. Multiple studies have described highly variable correlations between CHB on one hand and MetS, non-alcoholic fatty liver disease and dyslipidemia on the other. No association between CHB and diabetes mellitus or atherosclerosis has been described as of now. The presence of MetS in patients infected with hepatitis B virus increases the risk of fibrosis, cirrhosis and hepatocellular carcinoma. Appropriate lifestyle, but also pharmacological interventions are needed to prevent the development of these complications.
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Jarcuska P, Drazilova S, Fedacko J, Pella D, Janicko M. Association between hepatitis B and metabolic syndrome: Current state of the art. World J Gastroenterol 2016. [PMID: 26755867 DOI: 110.3748/wjg.v3722.i3741.3155] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) is a global health issue that increases the risk of liver cirrhosis and hepatocellular carcinoma in infected patients. Metabolic syndrome (MetS) is a disease endemic mostly to the developed countries. It is associated with high cardiovascular mortality and morbidity, diabetes mellitus as well as cancer. In this manuscript, we systematically review the published data on the relationship between MetS and CHB infection. Multiple studies have described highly variable correlations between CHB on one hand and MetS, non-alcoholic fatty liver disease and dyslipidemia on the other. No association between CHB and diabetes mellitus or atherosclerosis has been described as of now. The presence of MetS in patients infected with hepatitis B virus increases the risk of fibrosis, cirrhosis and hepatocellular carcinoma. Appropriate lifestyle, but also pharmacological interventions are needed to prevent the development of these complications.
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Affiliation(s)
- Peter Jarcuska
- Peter Jarcuska, Jan Fedacko, Daniel Pella, Martin Janicko, 1 Department of Internal Medicine, University Hospital and Pavol Jozef Šafárik University in Kosice, 04001 Košice, Slovakia
| | - Sylvia Drazilova
- Peter Jarcuska, Jan Fedacko, Daniel Pella, Martin Janicko, 1 Department of Internal Medicine, University Hospital and Pavol Jozef Šafárik University in Kosice, 04001 Košice, Slovakia
| | - Jan Fedacko
- Peter Jarcuska, Jan Fedacko, Daniel Pella, Martin Janicko, 1 Department of Internal Medicine, University Hospital and Pavol Jozef Šafárik University in Kosice, 04001 Košice, Slovakia
| | - Daniel Pella
- Peter Jarcuska, Jan Fedacko, Daniel Pella, Martin Janicko, 1 Department of Internal Medicine, University Hospital and Pavol Jozef Šafárik University in Kosice, 04001 Košice, Slovakia
| | - Martin Janicko
- Peter Jarcuska, Jan Fedacko, Daniel Pella, Martin Janicko, 1 Department of Internal Medicine, University Hospital and Pavol Jozef Šafárik University in Kosice, 04001 Košice, Slovakia
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Geier A. Hepatitis B virus: the "metabolovirus" highjacks cholesterol and bile acid metabolism. Hepatology 2014; 60:1458-60. [PMID: 24829054 DOI: 10.1002/hep.27224] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Accepted: 05/13/2014] [Indexed: 12/23/2022]
Affiliation(s)
- Andreas Geier
- Division of Hepatology, Department of Internal Medicine II, University Hospital Wuerzburg, Wuerzburg, Germany
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Chiang CH, Huang KC. Association between metabolic factors and chronic hepatitis B virus infection. World J Gastroenterol 2014; 20:7213-7216. [PMID: 24966591 PMCID: PMC4064066 DOI: 10.3748/wjg.v20.i23.7213] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2013] [Revised: 11/28/2013] [Accepted: 02/27/2014] [Indexed: 02/06/2023] Open
Abstract
There are limited data regarding the relationship between chronic hepatitis B virus (HBV) infection and metabolic factors. This article aims to highlight the link of metabolic factors with hepatitis B surface antigen (HBsAg) serostatus, HBV load, and HBV-related hepatocellular carcinoma (HCC). Although HBsAg-positive serostatus was positively correlated with a high risk of metabolic syndrome in students, chronic HBV-infected individuals have high serum adiponectin levels. The androgen pathway in HBV carriers with a low body mass index is more triggered which leads to enhanced HBV replication. High HBV load was inversely associated with obesity in hepatitis B e antigen (HBeAg)-seropositive HBV carriers; while in HBeAg-seronegative HBV carriers, high HBV load was inversely related to hypertriglyceridemia rather than obesity. For overweight and obese HBV-infected patients, high HBV load was positively associated with serum adiponectin levels. Several large cohort studies have revealed a positive link of diabetes with incidence of HBV-related HCC. However, the association between incidence of HCC and metabolic factors other than diabetes is still inconclusive. More long-term prospective studies should elucidate the association of chronic HBV infection and its outcomes with metabolic factors in clinical practice.
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Chiang CH, Lee LT, Hung SH, Lin WY, Hung HF, Yang WS, Sung PK, Huang KC. Opposite association between diabetes, dyslipidemia, and hepatocellular carcinoma mortality in the middle-aged and elderly. Hepatology 2014; 59:2207-15. [PMID: 24425422 DOI: 10.1002/hep.27014] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Accepted: 01/10/2014] [Indexed: 12/20/2022]
Abstract
UNLABELLED Limited data exist regarding metabolic risk factors for deaths from hepatocellular carcinoma (HCC) in aging individuals. We investigated the association between diabetes, dyslipidemia, and HCC mortality in those aged 40 years or more (middle-aged and elderly). In this prospective cohort study based on nationwide health screening units, we consecutively followed middle-aged and elderly participants who had no chronic hepatitis B or C virus infection and received health screening from January 1 1998 to December 31 2008. There were 235 deaths from HCC among 50,080 individuals, ascertained by validated death certificates and the national death registry. Diabetes (adjusted hazard ratio [HR], 3.38; 95% confidence interval [CI], 2.35 to 4.86) was positively associated with deaths from HCC. However, hypertriglyceridemia (HR, 0.38; 95% CI, 0.26 to 0.55) and hypercholesterolemia (HR, 0.50; 95% CI, 0.37 to 0.67) were inversely associated with HCC mortality. The above significant associations remained in the lag time analyses, applied to check for reverse causation. Metabolic syndrome, as defined by the American Heart Association / National Heart Lung Blood Institute criteria (HR, 0.63; 95% CI, 0.46 to 0.86) or by the International Diabetes Federation criteria (HR, 0.62; 95% CI, 0.43 to 0.89), was inversely associated with deaths from HCC, especially in men. CONCLUSION Middle-aged and elderly individuals, once having diabetes, deserve HCC surveillance to reduce HCC mortality. More research is needed to elucidate why having baseline dyslipidemia relates to lower future HCC mortality.
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Affiliation(s)
- Chien-Hsieh Chiang
- Department of Family Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Department of Community and Family Medicine, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan
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Jarčuška P, Janičko M, Kružliak P, Novák M, Veselíny E, Fedačko J, Senajová G, Dražilová S, Madarasová-Gecková A, Mareková M, Pella D, Siegfried L, Kristián P, Kolesárová E. Hepatitis B virus infection in patients with metabolic syndrome: a complicated relationship. Results of a population based study. Eur J Intern Med 2014; 25:286-291. [PMID: 24445023 DOI: 10.1016/j.ejim.2014.01.006] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Revised: 11/29/2013] [Accepted: 01/03/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND The presence of hepatitis B infection (HBI) and metabolic syndrome (MS) at the same time constitutes a high risk for liver cirrhosis and potentially hepatocellular carcinoma. AIM In this study we aim to explore the relationship between MS and HBI. METHODS We used data from the cross-sectional HepaMeta study conducted in 2011 in Slovakia. Patients were tested for presence of MS, while lipid levels (total cholesterol, HDL, LDL, TG, apolipoprotein B100 and HBI (HBsAg and antiHBcIgG)) were also monitored. Viral load was measured in HBsAg positive patients. RESULTS Altogether 855 patients were screened, MS was diagnosed in 25.1% of patients and 7.9% of patients presented with HBI. AntiHBcIgG antibodies were present in 34.6% patients. HBI patients had lower levels of total and LDL cholesterol along with a decreased apolipoprotein B100 (4.54 ± 0.84 vs. 5.0 ± 0.99 mmol/l, P=0.001; 2.29 ± 0.58 vs. 2.6 ± 0.68 mmol/l, P=0.001 and 0.71 ± 0.21 vs. 0.77 ± 0.23 mmol/l, P=0.013 respectively). Patients diagnosed with MS had higher HBV DNA load than patients without MS - 1300.2 (95% CI 506.06-3440.41) vs. 7661.3 (95% CI 2008.17-29,228.06) IU/ml; P=0.011. HBI patients with TC and apolipoprotein B100 in the reference range had lower HBV DNA load than patients with high or low values of TC or apolipoprotein B100. CONCLUSION Hepatitis B patients had lower levels of total and LDL cholesterol along with a decreased apolipoprotein B100. Viral load of chronic hepatitis B patients with MS was higher than that in patients without MS.
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Affiliation(s)
- Peter Jarčuška
- 1st Department of Internal Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Martin Janičko
- 1st Department of Internal Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Peter Kružliak
- Department of Cardiovascular Diseases, International Clinical Research Center, St. Anne's University Hospital, Masaryk University, Pekarska 53, 656 91 Brno, Czech Republic; Division of Cardiovascular Diseases, Mayo Clinic and Mayo College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
| | - Miroslav Novák
- Department of Cardiovascular Diseases, International Clinical Research Center, St. Anne's University Hospital, Masaryk University, Pekarska 53, 656 91 Brno, Czech Republic; Division of Cardiovascular Diseases, Mayo Clinic and Mayo College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
| | - Eduard Veselíny
- 1st Department of Internal Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Ján Fedačko
- 1st Department of Internal Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Gabriela Senajová
- 1st Department of Internal Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Sylvia Dražilová
- Internal Department, Poprad Hospital, Banícka 803/28, 05845 Poprad, Slovakia.
| | - Andrea Madarasová-Gecková
- Department of Public Health, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Mária Mareková
- Department of Medical Biochemistry, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Daniel Pella
- 1st Department of Internal Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Leonard Siegfried
- Department of Medical Microbiology, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Pavol Kristián
- Department of Infectious Diseases, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia.
| | - Eva Kolesárová
- 1st Department of Internal Medicine, Pavol Jozef Šafárik University in Košice, Trieda SNP 1, 04001 Košice, Slovakia
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Inverse association between hepatitis B virus infection and fatty liver disease: a large-scale study in populations seeking for check-up. PLoS One 2013; 8:e72049. [PMID: 23991037 PMCID: PMC3750031 DOI: 10.1371/journal.pone.0072049] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2013] [Accepted: 07/05/2013] [Indexed: 02/06/2023] Open
Abstract
Background Although many studies have attempted to clarify the association between hepatitis B virus (HBV) infection and fatty liver disease, no prior studies have emphasized the relationship of HBV and fatty liver regarding different demographics of age and body mass index (BMI). Aim To investigate the correlation of HBV and fatty liver in the different demographics of age and BMI. Methods We enrolled consecutive subjects who had received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009 and ultrasonography was used to diagnose fatty liver according to the practice guidelines of the American Gastroenterological Association. Results Among the 33,439 subjects enrolled in this study, fatty liver was diagnosed in 43.9% of the population and 38.9% of patients with chronic HBV infection. Multivariate analysis showed that BMI, age, waist circumference, systolic blood pressure, fasting glucose, cholesterol, alanine aminotransferase (ALT) levels, and platelet counts were positively associated, while hepatitis B surface antigen (HBsAg) positivity was inversely associated with fatty liver, especially for subjects with BMI>22.4 kg/m2 and age>50 years. On the contrary, HBV infection was positively correlated with the presence of elevated serum ALT levels in subjects with fatty liver disease regardless of their age and BMI. Conclusions Metabolic factors are important determinants for the prevalence of fatty liver. Patients with HBV infection were inversely associated with fatty liver disease than the general population, especially in older and obese patients. Furthermore, metabolic factors and HBV infection were associated with elevated serum ALT levels in fatty liver disease.
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Liu PT, Hwang AC, Chen JD. Combined effects of hepatitis B virus infection and elevated alanine aminotransferase levels on dyslipidemia. Metabolism 2013; 62:220-5. [PMID: 22938729 DOI: 10.1016/j.metabol.2012.07.022] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2012] [Revised: 07/27/2012] [Accepted: 07/27/2012] [Indexed: 02/09/2023]
Abstract
OBJECTIVE Although elevated alanine aminotransferase (ALT) levels are associated with lipid profiles, most studies do not consider the role of hepatitis B virus (HBV) infection. This study investigated the combined effects of HBV infection and elevated ALT levels on the lipid profiles of Taiwanese adults. MATERIALS/METHODS A total of 7695 subjects were enrolled after an annual health examination. Dyslipidemia was defined as serum total cholesterol≥200 mg/dL, serum triglyceride≥150 mg/dL, high-density lipoprotein cholesterol<40 mg/dL in men or <50 mg/dL in women, or low-density lipoprotein cholesterol≥130 mg/dL. Multiple logistic regression analysis was performed to assess the associations between dyslipidemia, HBV infection, and elevated ALT levels. RESULTS Hepatitis B surface antigen positivity (HBV[+]) and elevated ALT levels (ALT[+], ≥50 U/L) were observed in 13.5% and 12.2% of the subjects, respectively. Multiple logistic analysis revealed that the HBV(+) group had a significantly lower odds ratios (ORs) for hypercholesterolemia (OR, 0.8), hypertriglyceridemia (OR, 0.7), and high low-density lipoprotein cholesterol levels (OR, 0.8); whereas, the subjects with elevated ALT levels had significantly higher ORs for all of the dyslipidemia criteria. The interaction between HBV(+) and ALT(+) had a significantly lower OR for hypertriglyceridemia (OR, 0.7). The subjects with HBV infections had a significantly lower OR for hypertriglyceridemia regardless of the ALT levels. CONCLUSIONS HBV infection and elevated ALT levels have opposite effects on dyslipidemia, whereas their combined effects result in a significantly lower OR for hypertriglyceridemia.
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Affiliation(s)
- Peng-Tzu Liu
- Department of Family Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
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