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Kim M, Jun BG, Shin HS, Yi JJ, Kim SG, Yi SW. Impact of high body mass index on hepatocellular carcinoma risk in chronic liver disease: A population-based prospective cohort study. PLoS One 2025; 20:e0316175. [PMID: 39841714 PMCID: PMC11753674 DOI: 10.1371/journal.pone.0316175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 12/08/2024] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND AND AIMS We investigated associations between body mass index (BMI) and hepatocellular carcinoma (HCC) in patients with hepatitis B (HBV) C (HCV) virus infection, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and liver cirrhosis (LC). METHODS We followed 350,608 Korean patients with liver disease who underwent routine health examinations from 2003-2006 until December 2018 via national hospital discharge records. Multivariable adjusted hazard ratios (HRs) per 5-kg/m2 BMI increase (BMI ≥25 kg/m2) for HCC risk were calculated using Cox models. HCC developed in 17,752 patients. RESULTS The HRs (95% CI) were 1.17 (1.06-1.28), 1.08 (0.87-1.34), 1.34 (1.14-1.58), 1.51 (1.17-1.94), and 1.11 (1.00-1.23) for HBV, HCV, ALD, NAFLD, and LC, respectively. The HRs for HBV were 1.45 (1.23-1.70) and 1.06 (0.95-1.19) in women and men, respectively; the corresponding HRs for LC were 1.27 (1.07-1.50) and 1.02 (0.90-1.16), respectively. In patients <65 years old with HBV, HCV, and NAFLD, the HRs were 1.17 (1.07-1.29), 1.33 (1.03-1.73), and 1.20 (0.87-1.64), respectively; the corresponding HRs were 1.05 (0.70-1.59), 0.74 (0.50-1.10), and 2.40 (1.62-3.54), respectively, in patients ≥65 years old. A BMI of 27.5-29.9 kg/m2 showed significantly higher HCC risks in patients with HBV, ALD, NAFLD, and LC. CONCLUSIONS Higher BMIs were associated with increased HCC risks in patients with HBV, ALD, NAFLD, and LC. Overweight status increased HCC risk. Women with HBV and LC had stronger BMI-HCC associations than men. The effect of high BMI was stronger in older patients with NAFLD and younger patients with viral hepatitis.
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Affiliation(s)
- Moonho Kim
- Department of Hematology and Oncology, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea
| | - Baek Gyu Jun
- Department of Internal Medicine, Asanseoul Internal Medicine Clinic, Seoul, South Korea
| | - Hwang Sik Shin
- Department of Family Medicine, Soonchunhyang University Hospital Cheonan, Soonchunhyang University College of Medicine, Cheonan, South Korea
| | - Jee-Jeon Yi
- Institute for Occupational and Environmental Health, Catholic Kwandong University, Gangneung, South Korea
| | - Sang Gyune Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine Bucheon Hospital, Bucheon, South Korea
| | - Sang-Wook Yi
- Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Gangneung, South Korea
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Poorolajal J, Shadi Y, Heshmati B. Interaction Between Hepatitis B, Hepatitis C and Alcohol in the Development of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. J Viral Hepat 2025; 32:e14042. [PMID: 39716779 DOI: 10.1111/jvh.14042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 11/26/2024] [Indexed: 12/25/2024]
Abstract
The objective of this report is to provide clarification on the interaction among hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol in the development of hepatocellular carcinoma (HCC). A systematic search was performed in PubMed, Web of Science and Scopus databases up to July 18, 2023. The inclusion criteria involved observational studies that examined the relationship between HBV, HCV, alcohol use and the development of HCC. To assess between-study heterogeneity, the I2 statistics were employed. Publication bias was evaluated using the Begg and Egger tests. The effect sizes were estimated as odds ratios (ORs) with 95% confidence intervals (CIs) utilising a random-effects model. Among the initial pool of 31,021 studies identified, 28 studies involving 42,406 participants met the inclusion criteria. Through our meta-analysis, we found that the combined effect of HBV and alcohol was associated with an OR of 14.56 (95% CI: 9.80, 21.65). The combined impact of HCV and alcohol showed an OR of 42.44 (95% CI: 20.11, 89.56). Coinfection with both HBV and HCV was associated with an OR of 32.58 (95% CI: 20.57, 51.60). These results emphasising the importance of reducing alcohol consumption and implementing effective viral hepatitis prevention and treatment.
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Affiliation(s)
- Jalal Poorolajal
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
- Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Yahya Shadi
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Bahram Heshmati
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan, Iran
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Gavilán P, Gavilán JC, Arnedo R, Clavijo E, Viciana I, González-Correa JA. Prediction model of hepatocellular carcinoma development in chronic hepatitis B virus infection in a Spanish cohort. Med Clin (Barc) 2024; 163:609-616. [PMID: 39424472 DOI: 10.1016/j.medcli.2024.07.022] [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: 03/11/2024] [Revised: 07/20/2024] [Accepted: 07/27/2024] [Indexed: 10/21/2024]
Abstract
INTRODUCTION AND OBJECTIVES To identify risk factors associated with the development of hepatocellular carcinoma (HCC) in an unselected cohort of patients with chronic B virus infection (CHB) in Spain. A predictive model was developed to assess the risk of HCC. MATERIAL AND METHODS A prospective open-cohort study recruited 446 unselected patients with chronic hepatitis B infection from two hospitals in Málaga (Spain). The follow-up time ranged from 0.5 to 31.5 years (mean: 13.8; SD: 9.5; median: 11.4 years). We used a Cox proportional hazard model to estimate the multivariable-adjusted hazard ratios of risk factors associated with the development of liver cancer and developed a clinical score, (HCCB score) to determine the risk of liver cancer, that categories patients into two risk levels for the development of HCC. We compared the diagnostic accuracy of our model with other previously published. RESULTS During the follow-up period, 4.80% of the patients developed liver cancer (21 out of 437), 0.33 cases per 100 patient-years. Multivariate Cox regression analysis revealed that age >45 years, male gender, hepatitis C coinfection, alkaline phosphatase >147IU/L, Child score >5 points, glucose >126mg/dL, and a viral load >4.3 log10 IU/mL were independent risk factors. A risk score has been developed with a high predictive capacity for identifying patients at high risk of developing hepatocellular carcinoma. AUROC 0.87 (95% CI: 0.79-0.95). CONCLUSIONS An HCCB score greater than 5.42 points identifies a subgroup of chronic hepatitis B patients at high risk of developing liver cancer, who could benefit from screening measures for the early diagnosis of HCC.
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Affiliation(s)
- Paula Gavilán
- Universidad de Málaga, IBIMA-Plataforma BIONAND, Departamento de Farmacología y Pediatría, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain
| | - Juan-Carlos Gavilán
- Departamento de Medicina Interna, Hospital Universitario Virgen de la Victoria, Málaga, Spain; Hospital Internacional Vithas Xanit, Benalmádena, Spain.
| | - Rocío Arnedo
- Departamento de Medicina Interna, Hospital Universitario Virgen de la Victoria, Málaga, Spain; Hospital Internacional Vithas Xanit, Benalmádena, Spain
| | - Encarnación Clavijo
- Universidad de Málaga, IBIMA-Plataforma BIONAND, Departamento de Microbiología, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain
| | - Isabel Viciana
- Departamento de Microbiología, Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - José-Antonio González-Correa
- Universidad de Málaga, IBIMA-Plataforma BIONAND, Departamento de Farmacología y Pediatría, Facultad de Medicina, Campus de Teatinos s/n, 29071 Málaga, Spain
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Chang SH, Su TH, Ling ZM, Lee MH, Liu CJ, Chen PJ, Yang HC, Liu CH, Chen CL, Tseng TC, Chen CH, Lee HS, Chen CJ, Kao JH. Fibrosis-4 index stratifies risks of hepatocellular carcinoma in patients with chronic hepatitis C. J Formos Med Assoc 2024; 123:1154-1160. [PMID: 38944614 DOI: 10.1016/j.jfma.2024.06.008] [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: 01/04/2024] [Revised: 04/17/2024] [Accepted: 06/12/2024] [Indexed: 07/01/2024] Open
Abstract
BACKGROUND AND AIMS Risk stratification for patients with a higher risk of hepatocellular carcinoma (HCC) is crucial. We aimed to investigate the role of the Fibrosis-4 (FIB-4) index in predicting chronic hepatitis C (CHC)-related HCC. METHODS A retrospective cohort study consecutively included treatment-naive CHC patients receiving longitudinal follow-up at the National Taiwan University Hospital from 1986 to 2014. The clinical data were collected and traced for HCC development. Multivariable Cox proportional hazard regression analysis was used to investigate the predictors for HCC. RESULTS A total of 1285 patients in the ERADICATE-C cohort were included. The median age was 54, 56% were females, and 933 had HCV viremia. There were 33%, 38%, and 29% of patients having FIB-4 index <1.45, 1.45-3.25, and ≥3.25, respectively. After a median of 9-year follow-up, 186 patients developed HCC. Multivariable analysis revealed that older age, AFP≥20 ng/mL, cirrhosis, and a higher FIB-4 index were independent predictors for HCC. Compared with patients with FIB-4 index <1.45, those with FIB-4 1.45-3.25 had a 5.51-fold risk (95% confidence interval [CI]: 2.65-11.46), and those with FIB-4 ≥ 3.25 had 7.45-fold risk (95% CI: 3.46-16.05) of HCC. In CHC patients without viremia, FIB-4 index 1.45-3.25 and FIB-4 ≥ 3.25 increased 6.78-fold and 16.77-fold risk of HCC, respectively, compared with those with FIB-4 < 1.45. CONCLUSION The baseline FIB-4 index can stratify the risks of HCC in untreated CHC patients, even those without viremia. The FIB-4 index should thus be included in the management of CHC.
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Affiliation(s)
- Shan-Han Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Ze-Min Ling
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | | | - Hsuan-Shu Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
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Qadri O, Bashir S, Banday M, Hilal N, Majeed Y, Fatima NI, Pal D, Fazili KM. Tumour suppressor protein sMEK1 links to IRE1 signalling pathway to modulate its activity during ER stress. BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH 2024; 1871:119774. [PMID: 38838857 DOI: 10.1016/j.bbamcr.2024.119774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 05/27/2024] [Accepted: 05/28/2024] [Indexed: 06/07/2024]
Abstract
The Endoplasmic Reticulum is a pervasive, dynamic cellular organelle that performs a wide range of functions in the eukaryotic cell, including protein folding and maturation. Upon stress, ER activates an adaptive cellular pathway, namely Unfolded Protein Response, that transduces information from ER to nucleus, restoring homeostasis in the ER milieu. UPR consists of three membrane-tethered sensors; IRE1, PERK and ATF6. Among all the UPR sensors, the IRE1 branch acts as a central pathway that orchestrates several pathways to determine cell fate. However, the detailed knowledge underlying the whole process is not understood yet. Previously, we determined the sMEK1 as one of the interacting partners of IRE1. sMEK1 is a protein phosphatase, which has been indicated in a number of critical cellular functions like apoptosis, cell proliferation, and tumour suppression. In this study, we evaluated the role of sMEK1 on the IRE1 signalling pathway. Our data indicate that sMEK1 can inhibit IRE1 phosphorylation under ER stress. This inhibitory effect of sMEK1 could be reflected in its downstream effectors, Xbp1 and RIDD, which are downregulated in the presence of sMEK1. We also found that the repressing effect of sMEK1 was specific to the IRE1 signalling pathway and could be preserved even under prolonged ER stress. Our findings also indicate that sMEK1 can inhibit IRE1 and its downstream molecules under ER stress irrespective of other UPR sensors. These results help to draw the mechanistic details giving insights into different molecular connections of UPR with other pathways.
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Affiliation(s)
- Ozaira Qadri
- Department of Biotechnology, University of Kashmir, Hazratbal J&K, India
| | - Samirul Bashir
- Department of Biotechnology, University of Kashmir, Hazratbal J&K, India
| | - Mariam Banday
- Department of Biotechnology, University of Kashmir, Hazratbal J&K, India
| | - Nazia Hilal
- Department of Biotechnology, University of Kashmir, Hazratbal J&K, India
| | - Younis Majeed
- Department of Biotechnology, University of Kashmir, Hazratbal J&K, India
| | - Nida I Fatima
- Department of Biotechnology, University of Kashmir, Hazratbal J&K, India
| | - Debnath Pal
- Department of Computational and Data Science (CDS), Indian Institute of Science (IISc), Bengaluru, India
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Mak LY. Disease modifiers and novel markers in hepatitis B virus-related hepatocellular carcinoma. JOURNAL OF LIVER CANCER 2024; 24:145-154. [PMID: 39099070 PMCID: PMC11449577 DOI: 10.17998/jlc.2024.08.03] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 07/25/2024] [Accepted: 08/03/2024] [Indexed: 08/06/2024]
Abstract
Chronic hepatitis B (CHB) infection is responsible for 40% of the global burden of hepatocellular carcinoma (HCC) with a high case fatality rate. The risk of HCC differs among CHB subjects owing to differences in host and viral factors. Modifiable risk factors include viral load, use of antiviral therapy, co-infection with other hepatotropic viruses, concomitant metabolic dysfunctionassociated steatotic liver disease or diabetes mellitus, environmental exposure, and medication use. Detecting HCC at early stage improves survival, and current practice recommends HCC surveillance among individuals with cirrhosis, family history of HCC, or above an age cut-off. Ultrasonography with or without serum alpha feto-protein (AFP) every 6 months is widely accepted strategy for HCC surveillance. Novel tumor-specific markers, when combined with AFP, improve diagnostic accuracy than AFP alone to detect HCC at an early stage. To predict the risk of HCC, a number of clinical risk scores have been developed but none of them are clinically implemented nor endorsed by clinical practice guidelines. Biomarkers that reflect viral transcriptional activity and degree of liver fibrosis can potentially stratify the risk of HCC, especially among subjects who are already on antiviral therapy. Ongoing exploration of these novel biomarkers is required to confirm their performance characteristics, replicability and practicability.
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Affiliation(s)
- Lung-Yi Mak
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China
- State Key Laboratory of Liver Research, The Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
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Huang JH, Wei Y, Fang Z, Yu C, Zhang R, Feng ZB, Zeng LP. Clinical pathological significance and biological function of PLIN1 in hepatocellular carcinoma: bioinformatics analysis and in vitro experiments. BMC Cancer 2024; 24:1073. [PMID: 39215210 PMCID: PMC11363539 DOI: 10.1186/s12885-024-12842-1] [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] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND & AIMS Perilipin 1 (PLIN1) is an essential lipid droplet surface protein that participates in cell life activities by regulating energy balance and lipid metabolism. PLIN1 has been shown to be closely related to the development of numerous tumor types. The purpose of this work was to elucidate the clinicopathologic significance of PLIN1 in hepatocellular carcinoma (HCC), as well as its impact on the biological functions of HCC cells, and to investigate the underlying mechanisms involved. METHODS Public high-throughput RNA microarray and RNA sequencing data were collected to examine PLIN1 levels and clinical significance in patients with HCC. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (RT‒qPCR) were conducted to assess the expression levels and the clinicopathological relevance of PLIN1 in HCC. Then, SK and Huh7 cells were transfected with a lentivirus overexpressing PLIN1. CCK8 assay, wound healing assay, transwell assay, and flow cytometric analysis were conducted to explore the effects of PLIN1 overexpression on HCC cell proliferation, migration, invasion, and cell cycle distribution. Ultimately, Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the underlying mechanisms of PLIN1 in HCC progression based on HCC differentially expressed genes and PLIN1 co-expressed genes. RESULTS PLIN1 was markedly downregulated in HCC tissues, which correlated with a noticeably worse prognosis for HCC patients. Additionally, PLIN1 overexpression inhibited the proliferation, migration, and invasion of SK and Huh7 cells in vitro, as well as arresting the HCC cell cycle at the G0/G1 phase. More significantly, energy conversion-related biological processes, lipid metabolism, and cell cycle signalling pathways were the three most enriched molecular mechanisms. CONCLUSION The present study revealed that PLIN1 downregulation is associated with poor prognosis in HCC patients and accelerated HCC progression by promoting cellular proliferation, migration, and metastasis, as well as the mechanisms underlying the regulation of lipid metabolism-related pathways in HCC.
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Affiliation(s)
- Jiang-Hua Huang
- Department of Pathology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou Worker's Hospital, Liuzhou, Guangxi Zhuang Autonomous Region, 545000, People's Republic of China
| | - Yan Wei
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People's Republic of China
| | - Zhen Fang
- Department of Pathology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou Worker's Hospital, Liuzhou, Guangxi Zhuang Autonomous Region, 545000, People's Republic of China
| | - Cong Yu
- Department of Pathology, Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region , 530000, China
| | - Rui Zhang
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People's Republic of China
| | - Zhen-Bo Feng
- Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, 530021, People's Republic of China.
| | - Li-Ping Zeng
- Department of Pathology, Hunan University of Medicine, 492 Jinxinan RD, Huaihua, Hunan, 418000, People's Republic of China.
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Lee MH, Chen YT, Huang YH, Lu SN, Yang TH, Huang JF, Yin SC, Yeh ML, Huang CF, Dai CY, Chuang WL, Yu ML, Yang HI, Chen HY, Chen CJ. Chronic Viral Hepatitis B and C Outweigh MASLD in the Associated Risk of Cirrhosis and HCC. Clin Gastroenterol Hepatol 2024; 22:1275-1285.e2. [PMID: 38365094 DOI: 10.1016/j.cgh.2024.01.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/24/2024] [Accepted: 01/29/2024] [Indexed: 02/18/2024]
Abstract
BACKGROUND & AIMS The impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on the development of cirrhosis and hepatocellular carcinoma (HCC) by chronic hepatitis B (CHB) or C infection and antiviral treatment statuses is not well-known. METHODS A total of 336,866 adults aged ≥30 years were prospectively enrolled in a health screening program between 1997-2013. MASLD was identified by abdominal ultrasonography and cardiometabolic profiles. Data linkage was performed using 3 nationwide databases-National Health Insurance, Cancer Registry, and Death Certification System-to obtain information on antiviral treatment, vital status, and newly diagnosed cirrhosis and HCC. Follow-up was conducted until December 31, 2019. RESULTS In the total population, 122,669 (36.4%) had MASLD. Over a mean follow-up of 15 years, 5562 new cases of cirrhosis and 2273 new cases of HCC were diagnosed. Although MASLD significantly increased the cumulative risks of cirrhosis or HCC (P < .0001), the associated risk was more pronounced when comparing CHB or C infection with the presence of MASLD. Stratifying the participants based on their MASLD and CHB or C statuses, hazard ratios (HRadj) with 95% confidence intervals for HCC were 8.81 (7.83-9.92) for non-steatotic liver disease (SLD) with CHB or C, 1.52 (1.32-1.74) for MASLD without CHB or C, and 8.86 (7.76-10.12) for MASLD with CHB or C, compared with non-SLD without CHB or C (all P < .0001). Among CHB or C patients who received antivirals during follow-up, MASLD was associated with increased risks of cirrhosis and HCC, with HRadj of 1.23 (1.01-1.49) and 1.32 (1.05-1.65), respectively. CONCLUSIONS These findings underscore the need to prioritize treatment of chronic viral hepatitis before addressing MASLD.
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Affiliation(s)
- Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan; Advanced Therapeutics Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; Master of Public Health Program, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Yi-Ting Chen
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yu-Han Huang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Sheng-Nan Lu
- Department of Gastroenterology, Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Tsai-Hsuan Yang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Szu-Ching Yin
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan; Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Hwai-I Yang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Hsuan-Yu Chen
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
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Meroni M, Longo M, Dongiovanni P. Cardiometabolic risk factors in MASLD patients with HCC: the other side of the coin. Front Endocrinol (Lausanne) 2024; 15:1411706. [PMID: 38846491 PMCID: PMC11153718 DOI: 10.3389/fendo.2024.1411706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 05/10/2024] [Indexed: 06/09/2024] Open
Abstract
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) constitutes the commonest cause of chronic liver disorder worldwide, whereby affecting around one third of the global population. This clinical condition may evolve into Metabolic Dysfunction-Associated Steatohepatitis (MASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC), in a predisposed subgroup of patients. The complex pathogenesis of MASLD is severely entangled with obesity, dyslipidemia and type 2 diabetes (T2D), so far so nutritional and lifestyle recommendations may be crucial in influencing the risk of HCC and modifying its prognosis. However, the causative association between HCC onset and the presence of metabolic comorbidities is not completely clarified. Therefore, the present review aimed to summarize the main literature findings that correlate the presence of inherited or acquired hyperlipidemia and metabolic risk factors with the increased predisposition towards liver cancer in MASLD patients. Here, we gathered the evidence underlining the relationship between circulating/hepatic lipids, cardiovascular events, metabolic comorbidities and hepatocarcinogenesis. In addition, we reported previous studies supporting the impact of triglyceride and/or cholesterol accumulation in generating aberrancies in the intracellular membranes of organelles, oxidative stress, ATP depletion and hepatocyte degeneration, influencing the risk of HCC and its response to therapeutic approaches. Finally, our pursuit was to emphasize the link between HCC and the presence of cardiometabolic abnormalities in our large cohort of histologically-characterized patients affected by MASLD (n=1538), of whom 86 had MASLD-HCC by including unpublished data.
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Ghazanfar H, Javed N, Qasim A, Zacharia GS, Ghazanfar A, Jyala A, Shehi E, Patel H. Metabolic Dysfunction-Associated Steatohepatitis and Progression to Hepatocellular Carcinoma: A Literature Review. Cancers (Basel) 2024; 16:1214. [PMID: 38539547 PMCID: PMC10969013 DOI: 10.3390/cancers16061214] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Revised: 03/12/2024] [Accepted: 03/19/2024] [Indexed: 11/26/2024] Open
Abstract
The prevalence of metabolic-associated fatty liver disease (MAFLD) is increasing globally due to factors such as urbanization, obesity, poor nutrition, sedentary lifestyles, healthcare accessibility, diagnostic advancements, and genetic influences. Research on MAFLD and HCC risk factors, pathogenesis, and biomarkers has been conducted through a narrative review of relevant studies, with a focus on PubMed and Web of Science databases and exclusion criteria based on article availability and language. Steatosis marks the early stage of MASH advancement, commonly associated with factors of metabolic syndrome such as obesity and type 2 diabetes. Various mechanisms, including heightened lipolysis, hepatic lipogenesis, and consumption of high-calorie diets, contribute to the accumulation of lipids in the liver. Insulin resistance is pivotal in the development of steatosis, as it leads to the release of free fatty acids from adipose tissue. Natural compounds hold promise in regulating lipid metabolism and inflammation to combat these conditions. Liver fibrosis serves as a significant predictor of MASH progression and HCC development, underscoring the need to target fibrosis in treatment approaches. Risk factors for MASH-associated HCC encompass advanced liver fibrosis, older age, male gender, metabolic syndrome, genetic predispositions, and dietary habits, emphasizing the requirement for efficient surveillance and diagnostic measures. Considering these factors, it is important for further studies to determine the biochemical impact of these risk factors in order to establish targeted therapies that can prevent the development of HCC or reduce progression of MASH, indirectly decreasing the risk of HCC.
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Affiliation(s)
- Haider Ghazanfar
- Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (A.J.); (E.S.)
| | - Nismat Javed
- Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (G.S.Z.)
| | - Abeer Qasim
- Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (G.S.Z.)
| | - George Sarin Zacharia
- Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (G.S.Z.)
| | - Ali Ghazanfar
- Department of Internal Medicine, Fauji Foundation Hospital, Rawalpindi 45000, Pakistan
| | - Abhilasha Jyala
- Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (A.J.); (E.S.)
| | - Elona Shehi
- Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (A.J.); (E.S.)
| | - Harish Patel
- Division of Gastroenterology, Department of Internal Medicine, BronxCare Health System, Bronx, NY 10457, USA (A.J.); (E.S.)
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11
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Li M, Sun J, Wang Y, Ma J, Hao X, Liu Y, Zhou C, Zhou H. Construction of a hepatocellular carcinoma high-risk population rating scale and independent predictors' assessment. Am J Med Sci 2024; 367:181-189. [PMID: 37989441 DOI: 10.1016/j.amjms.2023.11.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 08/28/2023] [Accepted: 11/17/2023] [Indexed: 11/23/2023]
Abstract
BACKGROUND With increasing mortality and incidence, hepatocellular carcinoma (HCC) has become a major public health problem. The early diagnosis of HCC can improve its prognosis. The aim of this study was to identify potential risk factors related to HCC development and to establish a high-risk population rating scale. METHODS A total of 853 patients with chronic hepatitis B (CHB) were enrolled in this study, including 403 patients with HCC as the case group and others as the control group. Their demographic and clinical characteristics were compared and the independent risk factors for HCC were assessed. Then, the optimal cutoff levels of these factors were analyzed by the receiver operating characteristic (ROC) method. A high-risk population rating scale was constructed based on the factors and then evaluated in the modeling population. RESULTS The factors that presented statistically significant differences between the two groups included age, smoking, alcohol abuse, body mass index, triglyceride, high‒density lipoprotein cholesterol, aspartate transaminase, alanine transaminase, fasting plasma glucose, creatinine and uric acid. The ROC curve showed that the cutoff score for the HCC high risk population was 5 (AUC=0.74, P<0.001) and the Hosmer‒Lemeshow analysis showed that the fitting effect of this rating scale was good (P = 0.294). CONCLUSIONS The integration of these factors can contribute to a prognostic score for the risk of HCC development, which offered certain clinical practicability.
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Affiliation(s)
- Manyu Li
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing, China.
| | - Jing Sun
- Department of Physiology, Collaborative Innovation Center for Aging Mechanism Research and Transformation, Center for Healthy Aging, Changzhi Medical College, Changzhi, China
| | - Yan Wang
- Department of Hepatobiliary and Pancreatic Surgery, First Hospital/First Clinical College of Shanxi Medical University, Taiyuan, China
| | - Jun Ma
- Department of Thoracic Surgery, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Xiaotian Hao
- Department of Thoracic Surgery, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Yan Liu
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing, China
| | - Cheng Zhou
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing, China
| | - Haiwei Zhou
- Division I of In Vitro Diagnostics for Infectious Diseases, Institute for In Vitro Diagnostics Control, National Institutes for Food and Drug Control, Beijing, China
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12
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Shadi Y, Heshmati B, Poorolajal J. Interaction between hepatitis B, hepatitis C and smoking in the development of hepatocellular carcinoma: a systematic review and meta-analysis. J Public Health (Oxf) 2024; 46:51-60. [PMID: 37934962 DOI: 10.1093/pubmed/fdad214] [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: 07/26/2023] [Revised: 10/06/2023] [Accepted: 10/16/2023] [Indexed: 11/09/2023] Open
Abstract
BACKGROUND This meta-analysis reports the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), smoking and their combined impact on the development of hepatocellular carcinoma (HCC). METHODS We conducted a systematic search of PubMed, Web of Science and Scopus databases up to 15 July 2023. Observational studies investigating the association between HBV, HCV and smoking in the development of HCC were included. We assessed between-study heterogeneity using the I2 statistics. The effect sizes were estimated as odds ratio (OR) with 95% confidence intervals (CIs) using a random-effects model. RESULTS Out of 20 794 studies identified in the initial search, 32 observational studies involving 22 282 participants met the inclusion criteria. Our meta-analysis showed that the combined impact of HBV and smoking was associated with an OR of 19.81 (95% CI: 14.77, 26.58), HCV and smoking was associated with an OR of 24.86 (95% CI: 12.41, 49.79), and coinfection of HBV and HCV was associated with an OR of 32.58 (95% CI: 20.57, 51.60). CONCLUSIONS Our findings indicate a significant interaction between HBV, HCV and smoking in the development of HCC and highlight the importance of addressing smoking cessation and viral hepatitis prevention and treatment as potential strategies for reducing HCC.
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Affiliation(s)
- Yahya Shadi
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan 6517838695, Iran
| | - Bahram Heshmati
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan 6517838695, Iran
| | - Jalal Poorolajal
- Department of Epidemiology, School of Public Health, Hamadan University of Medical Sciences, Hamadan 6517838695, Iran
- Modeling of Noncommunicable Diseases Research Center, Hamadan University of Medical Sciences, Hamadan 6517838695, Iran
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13
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Tai AS, Lin SH. Multiply robust estimation of natural indirect effects with multiple ordered mediators. Stat Med 2024; 43:656-673. [PMID: 38081593 DOI: 10.1002/sim.9977] [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: 05/25/2022] [Revised: 08/06/2023] [Accepted: 11/20/2023] [Indexed: 01/13/2024]
Abstract
Multiple mediation analysis is a powerful methodology to assess causal effects in the presence of multiple mediators. Several methodologies, such as G-computation and inverse-probability-weighting, have been widely used to draw inferences about natural indirect effects (NIEs). However, a limitation of these methods is their potential for model misspecification. Although powerful semiparametric methods with high robustness and consistency have been developed for inferring average causal effects and for analyzing the effects of a single mediator, a comparably robust method for multiple mediation analysis is still lacking. Therefore, this theoretical study proposes a method of using multiply robust estimators of NIEs in the presence of multiple ordered mediators. We show that the proposed estimators not only enjoy the multiply robustness to model misspecification, they are also consistent and asymptotically normal under regular conditions. We also performed simulations for empirical comparisons of the finite-sample properties between our multiply robust estimators and existing methods. In an illustrative example, a dataset for liver disease patients in Taiwan is used to examine the mediating roles of liver damage and liver cancer in the pathway from hepatitis B/C virus infection to mortality. The model is implemented in the open-source R package "MedMR."
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Affiliation(s)
- An-Shun Tai
- Department of Statistics, National Cheng Kung University, Tainan, Taiwan
| | - Sheng-Hsuan Lin
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
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Varghese N, Majeed A, Nyalakonda S, Boortalary T, Halegoua-DeMarzio D, Hann HW. Review of Related Factors for Persistent Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:777. [PMID: 38398168 PMCID: PMC10887172 DOI: 10.3390/cancers16040777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 01/30/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV's covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies. Some studies suggest that HBV undergoes compartmentalization in peripheral blood mononuclear cells that serve as a sanctuary for replication during antiviral therapy. The aim of this review is to expand on how patients with HBV may develop HCC despite years of HBV viral suppression and carry worse prognosis than treatment-naive HBV patients who develop HCC. Furthermore, HCC recurrence after initial surgical or locoregional treatment in this setting may cause carcinogenic cells to behave more aggressively during treatment. Curative novel therapies which target the life cycle of HBV, modulate host immune response, and inhibit HBV RNA translation are being investigated.
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Affiliation(s)
- Nevin Varghese
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
| | - Amry Majeed
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
| | - Suraj Nyalakonda
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
| | - Tina Boortalary
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Hie-Won Hann
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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15
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Lu TY, Wu CD, Huang YT, Chen YC, Chen CJ, Yang HI, Pan WC. Exposure to PM 2.5 Metal Constituents and Liver Cancer Risk in REVEAL-HBV. J Epidemiol 2024; 34:87-93. [PMID: 36908115 PMCID: PMC10751193 DOI: 10.2188/jea.je20220262] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 02/05/2023] [Indexed: 03/13/2023] Open
Abstract
BACKGROUND Ambient particulate matter is classified as a human Class 1 carcinogen, and recent studies found a positive relationship between fine particulate matter (PM2.5) and liver cancer. Nevertheless, little is known about which specific metal constituent contributes to the development of liver cancer. OBJECTIVE To evaluate the association of long-term exposure to metal constituents in PM2.5 with the risk of liver cancer using a Taiwanese cohort study. METHODS A total of 13,511 Taiwanese participants were recruited from the REVEAL-HBV in 1991-1992. Participants' long-term exposure to eight metal constituents (Ba, Cu, Mn, Sb, Zn, Pb, Ni, and Cd) in PM2.5 was based on ambient measurement in 2002-2006 followed by a land-use regression model for spatial interpolation. We ascertained newly developed liver cancer (ie, hepatocellular carcinoma [HCC]) through data linkage with the Taiwan Cancer Registry and national health death certification in 1991-2014. A Cox proportional hazards model was utilized to assess the association between exposure to PM2.5 metal component and HCC. RESULTS We identified 322 newly developed HCC with a median follow-up of 23.1 years. Long-term exposure to PM2.5 Cu was positively associated with a risk of liver cancer. The adjusted hazard ratio (HR) was 1.13 (95% confidence interval [CI], 1.02-1.25; P = 0.023) with one unit increment on Cu normalized by PM2.5 mass concentration in the logarithmic scale. The PM2.5 Cu-HCC association remained statistically significant with adjustment for co-exposures to other metal constituents in PM2.5. CONCLUSION Our findings suggest PM2.5 containing Cu may attribute to the association of PM2.5 exposure with liver cancer.
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Affiliation(s)
- Tzu-Yi Lu
- Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chih-Da Wu
- Department of Geomatics, National Cheng Kung University, Chiayi, Taiwan
- Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA
| | - Yen-Tsung Huang
- Institue of Statistical Science, Academia Sinica, Taipei, Taiwan
| | - Yu-Cheng Chen
- National Institution of Environmental Health Sciences, National Health Research Institute, Mioli, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wen-Chi Pan
- Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
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16
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Chu PY, Hsu CL, Lin YA, Pan YC, Dai YH, Yu YC, Yang JC, Ma WL, Chen YJL, Lee CL, Wu YC. Effects of Citrus depressa Hayata juice on high-fat diet-induced obesity in HBV transgenic mice. Heliyon 2024; 10:e24438. [PMID: 38312542 PMCID: PMC10835261 DOI: 10.1016/j.heliyon.2024.e24438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 12/20/2023] [Accepted: 01/09/2024] [Indexed: 02/06/2024] Open
Abstract
The present study investigated the potential anti-obesity properties of Citrus depressa Hayata (CDH) juice in HBV transgenic mice, as well as the impact of fermentation on the effectiveness of the juice. The results revealed that fermentation increased the levels of polyphenols and hesperidin in CDH juice. The animal study demonstrated that both juices were effective in mitigating the weight gain induced by a high-fat diet by correcting metabolic parameter imbalances, reducing hepatic lipid accumulation, and reversing hepatic immune suppression. Furthermore, fermented juice exhibited superior efficacy in managing body weight and inhibiting the expansion of white adipose tissue (WAT). Fermented juice significantly enhanced adiponectin production and PPARγ expression in WAT, while also reducing hypertrophy. This study offers valuable insights into the potential role of CDH juices in combating obesity associated with high fat consumption and underscores the promise of CDH juice as a functional beverage.
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Affiliation(s)
- Pei-Yi Chu
- Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
| | - Chang-Lu Hsu
- Department of Business Administration, National Chiayi University, Chiayi, Taiwan
| | - Yen-An Lin
- Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
| | - Yi-Cheng Pan
- Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
- .Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, Taiwan
| | - Yun-Hao Dai
- Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
- School of Pharmacy, China Medical University, Taichung, Taiwan
| | - Ying-Chun Yu
- Department of Medical Research, and Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | - Juan-Cheng Yang
- Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
- School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Wen-Lung Ma
- Department of Medical Research, and Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | | | - Chia-Lin Lee
- Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
- Department of Cosmeceutics, China Medical University, Taichung 40604, Taiwan
| | - Yang-Chang Wu
- Chinese Medicine Research and Development Center, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan
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17
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Ribback S, Peters K, Yasser M, Prey J, Wilhelmi P, Su Q, Dombrowski F, Bannasch P. Hepatocellular Ballooning is Due to Highly Pronounced Glycogenosis Potentially Associated with Steatosis and Metabolic Reprogramming. J Clin Transl Hepatol 2024; 12:52-61. [PMID: 38250461 PMCID: PMC10794273 DOI: 10.14218/jcth.2023.00242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 08/22/2023] [Accepted: 09/05/2023] [Indexed: 01/23/2024] Open
Abstract
Background and Aims Hepatocellular ballooning is a common finding in chronic liver disease, mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies (MDB). Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes (BH) are damaged cells on the path to death or rather viable cells, possibly involved in neoplastic development. Methods Using specimens from 96 cirrhotic human livers, BH characteristics were assessed for their glycogen/lipid stores, enzyme activities, and proto-oncogenic signaling cascades by enzyme- and immunohistochemical approaches with serial paraffin and cryostat sections. Results BH were present in 43.8% of cirrhotic livers. Particularly pronounced excess glycogen storage of (glycogenosis) and/or lipids (steatosis) were characteristic, ground glass features and MDB were often observed. Decreased glucose-6-phosphatase, increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis, lipid metabolism, and cholesterol biosynthesis were discovered. Furthermore, components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with de novo lipogenesis. Conclusions BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis, many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver diseases. Hence, BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming, indicative of a preneoplastic nature.
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Affiliation(s)
- Silvia Ribback
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Kristin Peters
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Mohd Yasser
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Jessica Prey
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Paula Wilhelmi
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Qin Su
- Cell Marque, Millipore-Sigma, Rocklin, CA, USA
| | - Frank Dombrowski
- Institut für Pathologie, Universitaetsmedizin Greifswald, Greifswald, Germany
| | - Peter Bannasch
- German Cancer Research Center (DKFZ), Heidelberg, Germany
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18
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Mezzacappa C, Mahmud N, Serper M, John BV, Taddei TH, Kaplan DE. HCC is associated with diabetes and longitudinal blood glucose control in a national cohort with cirrhosis. Hepatol Commun 2023; 7:e0344. [PMID: 38055642 PMCID: PMC10984661 DOI: 10.1097/hc9.0000000000000344] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 11/05/2023] [Indexed: 12/08/2023] Open
Abstract
BACKGROUND Diabetes is associated with HCC; however, the impact of longitudinal blood glucose (BG) control on HCC risk in cirrhosis is not well known. We investigated this knowledge gap in a cohort of United States Veterans with cirrhosis from 2015 to 2021. METHODS We used repeated hemoglobin A1c measurements to categorize follow-up time according to BG control (defined as hemoglobin A1c < 7%) state over time: uncontrolled, nonsustained control (≤2 y), or sustained control (>2 y). We performed a sensitivity analysis using hemoglobin A1c < 8% to define BG control. We used Fine and Gray Cox proportional hazards regression with death and transplant as competing events to compare rates of incident HCC. RESULTS Our study included 81,907 individuals, 56.2% of whom had diabetes at baseline. There were 8,002 incident HCCs. The rate of HCC was 18% higher in diabetes (95% CI: 13% - 24%), and the relative increase in the rate of HCC varied by etiology of cirrhosis from nonsignificant (HCV) to an increase of 120% (HBV). Uncontrolled and nonsustained BG control was associated with 1.80 (95% CI: 1.70-1.91) and 2.34 (95% CI: 2.21-2.48) times the rate of HCC compared to sustained BG control, respectively. Using Hgb A1c < 8% to define BG control, HCC rates in uncontrolled and nonsustained BG control were 2.43 (2.28-2.58) and 2.23 (2.11-2.36) times that observed in sustained BG control. CONCLUSIONS Associations between diabetes and HCC in cirrhosis vary according to the longitudinal BG control state. Inadequate BG control is consistently associated with a higher risk of HCC, and long-term BG control should be considered in comprehensive cirrhosis care.
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Affiliation(s)
- Catherine Mezzacappa
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
- VA Connecticut Healthcare System, Department of Internal Medicine West Haven, Connecticut, USA
| | - Nadim Mahmud
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Marina Serper
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
| | - Binu V. John
- University of Miami School of Medicine, Miami, Florida, USA
- Bruce W Carter VA Medical Center, Miami, Florida, USA
| | - Tamar H. Taddei
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut, USA
- VA Connecticut Healthcare System, Department of Internal Medicine West Haven, Connecticut, USA
| | - David E. Kaplan
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA
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Yang Z, Cheung RC, Chitnis AS, Zhang W, Gish RG, Wong RJ. On-treatment risks of cirrhosis and hepatocellular carcinoma among a large cohort of predominantly non-Asian patients with non-cirrhotic chronic hepatitis B. JHEP Rep 2023; 5:100852. [PMID: 37701335 PMCID: PMC10494462 DOI: 10.1016/j.jhepr.2023.100852] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 09/14/2023] Open
Abstract
Background & Aims The vast majority of studies evaluating differences in on-treatment risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) have been conducted in Asia. Data on the course of CHB on antiviral therapy among predominantly non-Asian populations is less well described. We aimed to evaluate overall risks of cirrhosis and HCC and the influence of baseline factors on this risk among a predominantly non-Asian cohort of patients with CHB in the US. Methods Using longitudinal data from the national Veterans Affairs database, we evaluated the incidence of cirrhosis or HCC among adults with non-cirrhotic CHB on continuous antiviral therapy. Cumulative incidence functions and adjusted Cox proportional hazards models employed competing risks methods and evaluated overall risk and predictors of developing cirrhosis or HCC while on treatment. Results Among 2,496 patients with non-cirrhotic CHB (39.1% African American, 38.4% non-Hispanic White, 18.8% Asian, mean age 58.0 ± 13.4 years), the overall incidences of cirrhosis and HCC were 3.99 per 100 person-years (95% CI 3.66-4.35) and 0.43 per 100 person-years (95% CI 0.33-0.54), respectively. The highest incidences of cirrhosis and HCC were observed in non-Hispanic White patients (5.74 and 0.52 per 100 person-years, respectively), which were significantly higher than in Asian patients (1.93 and 0.17 per 100 person-years, respectively, p <0.0001). On multivariate regression, only baseline FIB-4 score was consistently associated with long-term risk of cirrhosis or HCC. Conclusions Using a longitudinal cohort of predominantly non-Asian Veterans with non-cirrhotic CHB on antiviral therapy (an understudied population), we provide important epidemiological data to describe long-term risks of cirrhosis and HCC. Impact and implications In one of the largest studies to date of a predominantly non-Asian cohort of patients with non-cirrhotic chronic hepatitis B, we provide important epidemiological data describing the long-term risks of cirrhosis and hepatocellular carcinoma among patients on antiviral therapies. Among this understudied population, the overall incidence of cirrhosis was 3.99 per 100-person-years (95% CI 3.66-4.35) and of HCC was 0.43 per 100-person-years (95% CI 0.33-0.54). These data also emphasize the importance of continued monitoring and HCC surveillance among CHB patients who are maintained on antiviral therapies.
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Affiliation(s)
- Zeyuan Yang
- Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA
| | - Ramsey C. Cheung
- Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Amit S. Chitnis
- Tuberculosis Control Section, Division of Communicable Disease Control and Prevention, Alameda County Public Health Department, San Leandro, CA, USA
| | - Wei Zhang
- Division of Gastroenterology and Hepatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | | | - Robert J. Wong
- Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA, USA
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20
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Scherübl H. [Metabolic syndrome and gastrointestinal cancer screening]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1394-1400. [PMID: 36379464 DOI: 10.1055/a-1959-3829] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Cancer has become a leading cause of death among patients with metabolic syndrome (MetS). The more components of MetS a patient has, the higher his cancer risk is. MetS is causally associated with colorectal, pancreatic, gallbladder, biliary, hepatocellular, gastric and esophageal adenocarcinomas. MetS increases cancer mortality up to 2.4-fold. Intentional long-term weight loss reduces the excess cancer risk of obese MetS-patients. Preventing and treating the MetS together with GI cancer screening is effective and decreases the burden of GI cancer mortality significantly.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin; Gastroenterol., GI Onkol. u. Infektiol., Vivantes Klinikum Am Urban, Berlin, Germany
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21
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Huang SC, Su TH, Tseng TC, Chen CL, Hsu SJ, Liao SH, Hong CM, Liu CH, Lan TY, Yang HC, Liu CJ, Chen PJ, Kao JH. Distinct effects of hepatic steatosis and metabolic dysfunction on the risk of hepatocellular carcinoma in chronic hepatitis B. Hepatol Int 2023; 17:1139-1149. [PMID: 37247045 DOI: 10.1007/s12072-023-10545-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2023] [Accepted: 04/29/2023] [Indexed: 05/30/2023]
Abstract
OBJECTIVE Chronic hepatitis B (CHB) and metabolic dysfunction-associated fatty liver disease (MAFLD) are the leading causes of hepatocellular carcinoma (HCC). We aim to explore the impact of concurrent MAFLD on the risk of HCC in CHB. METHODS Patients with CHB were consecutively recruited from 2006 to 2021. MAFLD was defined by steatosis and either obesity, diabetes mellitus, or other metabolic abnormalities. The cumulative incidence of HCC and associated factors were compared between the MAFLD and non-MAFLD groups. RESULTS 10,546 treatment-naïve CHB patients were included with a median follow-up of 5.1 years. CHB patients with MAFLD (n = 2212) had fewer hepatitis B e antigen (HBeAg)-positivity, lower HBV DNA levels, and Fibrosis-4 index compared with the non-MAFLD group (n = 8334). MAFLD was independently associated with a 58% reduced risk of HCC (adjusted hazard ratio [aHR] 0.42, 95% confidence interval [CI] 0.25-0.68, p < 0.001). Furthermore, steatosis and metabolic dysfunction had distinct effects on HCC. Steatosis was protective against HCC (aHR 0.45, 95% CI 0.30-0.67, p < 0.001), while a greater burden of metabolic dysfunction increased the risk (aHR 1.40 per dysfunction increase, 95% CI 1.19-1.66, p < 0.001). The protective effect of MAFLD was further confirmed in analysis with inverse probability of treatment weighting (IPTW), patients who had undergone antiviral therapy, those with probable MAFLD, and after multiple imputation for missing data. CONCLUSIONS Concurrent hepatic steatosis is independently associated with a lower risk of HCC, whereas the increasing burden of metabolic dysfunction aggravates the risk of HCC in untreated CHB patients.
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Affiliation(s)
- Shang-Chin Huang
- Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
| | - Tai-Chung Tseng
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Ling Chen
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Sih-Han Liao
- National Taiwan University Cancer Center, Taipei, Taiwan
| | - Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Yuan Lan
- Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
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Masaoka R, Gyotoku Y, Shirahashi R, Suda T, Tamano M. Combining the age-male-albumin-bilirubin-platelets score and shear wave elastography stratifies carcinogenic risk in hepatitis C patients after viral clearance. World J Clin Cases 2023; 11:5204-5214. [PMID: 37621583 PMCID: PMC10445062 DOI: 10.12998/wjcc.v11.i22.5204] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/23/2023] [Accepted: 07/07/2023] [Indexed: 08/04/2023] Open
Abstract
BACKGROUND The treatment of hepatitis C with direct-acting antiviral agents (DAAs) produces a high rate of sustained virological response (SVR) with fewer adverse events than interferon (IFN) therapy with a similar effect in inhibiting carcinogenesis as IFN therapy. The age-male-albumin-bilirubin-platelets (aMAP) score is useful for stratifying the risk of hepatocellular carcinoma in chronic hepatitis patients, and the velocity of shear waves (Vs) measured by shear wave elastography has also been shown to be useful for diagnosing the level of fibrotic progression in hepatitis C and predicting carcinogenic risk. Combining these two may improve the prediction of carcinogenic risk. AIM To determine whether combining the aMAP score with Vs improves carcinogenic risk stratification in medium-to-high-risk hepatitis C patients. METHODS This retrospective, observational study involved hepatitis C patients treated with DAAs who achieved SVR. Vs was measured before treatment (baseline), at the end of treatment (EOT), and 12 wk (follow-up 12) and 24 wk (follow-up 24) after treatment. The patients were followed for at least six months after EOT to determine whether cancer developed. Multiple regression analysis was used to identify factors contributing to hepatic carcinogenesis. The diagnostic performances of clinical parameters for predicting the presence of hepatocellular carcinoma were evaluated using receiver-operating characteristic (ROC) curve analyses. RESULTS A total of 279 patients (mean age 65.9 years, 118 males, 161 females) were included in the analysis. Multiple regression analysis was performed with carcinogenesis as the target variable and alanine aminotransferase, platelets, α-fetoprotein, Vs, and the Fib-4 index as explanatory variables; only Vs was found to be significant (P = 0.0296). The cut-off value for Vs for liver carcinogenesis calculated using the ROC curve was 1.53 m/s. Carcinoma developed in 2.0% (3/151) of those with Vs < 1.53 m/s and in 10.5% (9/86) of those with Vs ≥ 1.53 m/s. CONCLUSION In hepatitis C patients after SVR, combining the aMAP score and Vs to stratify the risk of carcinogenesis is more efficient than uniform surveillance of all patients.
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Affiliation(s)
- Rion Masaoka
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Yoshinori Gyotoku
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Ryosaku Shirahashi
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Toshikuni Suda
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
| | - Masaya Tamano
- Department of Gastroenterology, Dokkyo Medical University Saitama Medical Center, Koshigaya 343-8555, Saitama, Japan
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23
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You Y, Yang T, Wei S, Liu Z, Liu C, Shen Z, Yang Y, Feng Y, Yao P, Zhu Q. Survival of Patients with Hepatitis B-Related Hepatocellular Carcinoma with Concomitant Metabolic Associated Fatty Liver Disease. Diabetes Metab Syndr Obes 2023; 16:2283-2293. [PMID: 37551338 PMCID: PMC10404410 DOI: 10.2147/dmso.s416280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Accepted: 07/24/2023] [Indexed: 08/09/2023] Open
Abstract
Purpose Metabolic associated fatty liver disease is a novel concept defined as fatty liver associated with metabolic disorders. We investigated the effect of metabolic associated fatty liver disease on hepatocellular carcinoma patient mortality. Patients and Methods A total of 624 patients with hepatocellular carcinoma between 2012 and 2020 were enrolled in this retrospective study. Hepatic steatosis was diagnosed using computed tomography or magnetic resonance imaging. Metabolic associated fatty liver disease was defined based on the proposed criteria in 2020. Propensity score matching was performed for patients with metabolic associated fatty liver disease and those without the condition. A Cox proportional hazards regression model was used to evaluate the association between metabolic associated fatty liver disease and hepatocellular carcinoma patient outcomes. Results Patients with hepatocellular carcinoma and metabolic associated fatty liver disease tended to achieve better outcomes than did those without metabolic associated fatty liver disease after matching (p<0.001). Metabolic associated fatty liver disease was significantly associated with better prognosis in patients with concurrent hepatitis B infection (p<0.001). Moreover, high levels of hepatitis B viral DNA in serum samples was associated with a significantly increased risk of death in patients without non-metabolic associated fatty liver disease (p=0.045). Additionally, the association between metabolic associated fatty liver disease and survival in hepatitis B virus-related hepatocellular carcinoma was similar in all subgroups based on metabolic traits. Conclusion Metabolic associated fatty liver disease increases the survival rate of patients with hepatocellular carcinoma and hepatitis B virus infection. The potential interaction of steatosis and virus replication should be considered for future research and clinical treatment strategies.
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Affiliation(s)
- Yajing You
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Tao Yang
- Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China
| | - Shuhang Wei
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Zongxin Liu
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Chenxi Liu
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Zijian Shen
- Department of Radiology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yinuo Yang
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Yuemin Feng
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
| | - Ping Yao
- Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021, People’s Republic of China
- Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, 830000, People’s Republic of China
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Abdalla MMI. Serum resistin and the risk for hepatocellular carcinoma in diabetic patients. World J Gastroenterol 2023; 29:4271-4288. [PMID: 37545641 PMCID: PMC10401662 DOI: 10.3748/wjg.v29.i27.4271] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/11/2023] [Accepted: 06/27/2023] [Indexed: 07/13/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the predominant type of liver cancer, is a major contributor to cancer-related fatalities across the globe. Diabetes has been identified as a significant risk factor for HCC, with recent research indicating that the hormone resistin could be involved in the onset and advancement of HCC in diabetic individuals. Resistin is a hormone that is known to be involved in inflammation and insulin resistance. Patients with HCC have been observed to exhibit increased resistin levels, which could be correlated with more severe disease stages and unfavourable prognoses. Nevertheless, the exact processes through which resistin influences the development and progression of HCC in diabetic patients remain unclear. This article aims to examine the existing literature on the possible use of resistin levels as a biomarker for HCC development and monitoring. Furthermore, it reviews the possible pathways of HCC initiation due to elevated resistin and offers new perspectives on comprehending the fundamental mechanisms of HCC in diabetic patients. Gaining a better understanding of these processes may yield valuable insights into HCC’s development and progression, as well as identify possible avenues for prevention and therapy.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
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25
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Scherübl H. [Type-2-diabetes and gastrointestinal cancer screening]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:683-689. [PMID: 35697066 DOI: 10.1055/a-1821-9108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
More than 8000000 Germans suffer from diabetes. People with type-2-diabetes (T2D) are at increased risk of gastrointestinal adenocarcinomas. They often develop cancer at younger age and their tumor-specific 5-year-survival is generally shorter. Cancer has become the leading cause of death of T2D-patients. Both chronic hyperglycemia and insulin resistance can stimulate gastrointestinal (GI) tumor growth. T2D can cause colorectal, pancreatic, hepatocellular, biliary and gastric cancer as well as esophageal adenocarcinoma. Both low-risk lifestyle and gastrointestinal cancer screening are effective and reduce GI cancer risk and GI cancer mortality of T2D-patients.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin; Gastroenterol., GI Onkol. u. Infektiol., Vivantes Klinikum Am Urban, Berlin, Germany
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26
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Yan LJ, Yang LS, Yan YC, Tan SY, Ding ZN, Liu H, Wang DX, Dong ZR, Li T. Anthropometric indicators of adiposity and risk of primary liver cancer: A systematic review and dose-response meta-analysis. Eur J Cancer 2023; 185:150-163. [PMID: 36996625 DOI: 10.1016/j.ejca.2023.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 01/29/2023] [Accepted: 03/01/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND AND AIMS Adiposity is associated with an increased risk of primary liver cancer (PLC). As the most commonly used indicator of adiposity, the body mass index (BMI) has been questioned for its limitations in reflecting visceral fat. This study aimed to investigate the role of different anthropometric indicators in identifying the risk of PLC by accounting for potential non-linear associations. METHODS Systematic searches were conducted in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, and CNKI databases. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship was assessed using a restricted cubic spline model. RESULTS Sixty-nine studies involving more than 30 million participants were included in the final analysis. Regardless of the indicator used, adiposity was strongly associated with an increased risk of PLC. When comparing the HRs per 1-standard deviation increment across indicators of adiposity, the association was strongest for waist-to-height ratio (WHtR) (HR = 1.39), followed by waist-to-hip ratio (WHR) (HR = 1.22), BMI (HR = 1.13), waist circumference (WC) (HR = 1.12), and hip circumference (HC) (HR = 1.12). A strong non-linear association was observed between each anthropometric parameter and the risk of PLC, regardless of whether the original or decentralised value was used. The positive association between WC and PLC risk remained substantial after adjusting for BMI. The incidence of PLC was higher with central adiposity (52.89 per 100,000 person-years, 95% CI = 50.33-55.44) than general adiposity (39.01 per 100,000 person-years, 95% CI = 37.26-40.75). CONCLUSION Central adiposity seems to contribute more to the development of PLC than general adiposity. A larger WC, independent of BMI, was strongly associated with the risk of PLC and might be a more promising predictive indicator than BMI.
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Affiliation(s)
- Lun-Jie Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Long-Shan Yang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Yu-Chuan Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Si-Yu Tan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China.
| | - Tao Li
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China; Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan 250012, PR China.
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Tai J, Harrison AP, Chen HM, Hsu CY, Hsu TH, Chen CJ, Jeng WJ, Chang ML, Lu L, Tai DI. Acoustic radiation force impulse predicts long-term outcomes in a large-scale cohort: High liver cancer, low comorbidity in hepatitis B virus. World J Gastroenterol 2023; 29:2188-2201. [PMID: 37122600 PMCID: PMC10130974 DOI: 10.3748/wjg.v29.i14.2188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/15/2023] [Accepted: 03/23/2023] [Indexed: 04/13/2023] Open
Abstract
BACKGROUND Acoustic radiation force impulse (ARFI) is used to measure liver fibrosis and predict outcomes. The performance of elastography in assessment of fibrosis is poorer in hepatitis B virus (HBV) than in other etiologies of chronic liver disease.
AIM To evaluate the performance of ARFI in long-term outcome prediction among different etiologies of chronic liver disease.
METHODS Consecutive patients who received an ARFI study between 2011 and 2018 were enrolled. After excluding dual infection, alcoholism, autoimmune hepatitis, and others with incomplete data, this retrospective cohort were divided into hepatitis B (HBV, n = 1064), hepatitis C (HCV, n = 507), and non-HBV, non-HCV (NBNC, n = 391) groups. The indexed cases were linked to cancer registration (1987-2020) and national mortality databases. The differences in morbidity and mortality among the groups were analyzed.
RESULTS At the enrollment, the HBV group showed more males (77.5%), a higher prevalence of pre-diagnosed hepatocellular carcinoma (HCC), and a lower prevalence of comorbidities than the other groups (P < 0.001). The HCV group was older and had a lower platelet count and higher ARFI score than the other groups (P < 0.001). The NBNC group showed a higher body mass index and platelet count, a higher prevalence of pre-diagnosed non-HCC cancers (P < 0.001), especially breast cancer, and a lower prevalence of cirrhosis. Male gender, ARFI score, and HBV were independent predictors of HCC. The 5-year risk of HCC was 5.9% and 9.8% for those ARFI-graded with severe fibrosis and cirrhosis. ARFI alone had an area under the receiver operating characteristic curve (AUROC) of 0.742 for prediction of HCC in 5 years. AUROC increased to 0.828 after adding etiology, gender, age, and platelet score. No difference was found in mortality rate among the groups.
CONCLUSION The HBV group showed a higher prevalence of HCC but lower comorbidity that made mortality similar among the groups. Those patients with ARFI-graded severe fibrosis or cirrhosis should receive regular surveillance.
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Affiliation(s)
- Jennifer Tai
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | | | - Hui-Ming Chen
- Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Chiu-Yi Hsu
- Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Tse-Hwa Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Cheng-Jen Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Ming-Ling Chang
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
| | - Le Lu
- DAMO Academy, Alibaba Group, New York, NY 94085, United States
| | - Dar-In Tai
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
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Ding Y, Feng M, Ma D, Zhao G, Wang X, An B, Xu Y, Lou S, Lin L, Xie Q, Liu K, Bao S, Wang H. The 20 years transition of clinical characteristics and metabolic risk factors in primary liver cancer patients from China. Front Oncol 2023; 13:1109980. [PMID: 36998463 PMCID: PMC10043326 DOI: 10.3389/fonc.2023.1109980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 03/02/2023] [Indexed: 03/15/2023] Open
Abstract
BackgroundThe clinical characteristics of primary liver cancer (PLC) patients are changing, maybe due to hepatitis viral vaccination and lifestyle changes, etc. The linkage between these changes and outcomes among these PLCs has not yet been fully elucidated.MethodsIt was identified total of 1691 PLC cases diagnosed between 2000 ~ 2020. Cox proportional hazards models were utilized to determine the connections between the clinical presentations and their close risk factor(s) from PLC patients.ResultsThe average age of PLC patients increased gradually from 52.74 ± 0.5 years in 2000 ~ 2004 to 58.63 ± 0.44 years in 2017 ~ 2020, accompanied by an increased proportion of females from 11.11% to 22.46%, and non-viral hepatitis-related PLC was raised from 1.5% to 22.35%. 840 (49.67%) PLC patients with alpha-fetoprotein (AFP) < 20ng/mL (AFP-negative). The mortality was 285 (16.85%) or 532 (31.46%) PLC patients with alanine transaminase (ALT) between 40 ~ 60 IU/L or ALT > 60 IU/L. The PLC patients with pre-diabetes/diabetes or dyslipidemia also increased from 4.29% or 11.1% in 2000 ~ 2004 to 22.34% or 46.83% in 2017 ~ 2020. The survival period of the PLC patients with normoglycemia or normolipidemic was 2.18 or 3.14 folds longer than those patients with pre-diabetes/diabetes or hyperlipidemia (P<0.05).ConclusionsIt was gradually increased that age, the proportion of females, non-viral hepatitis-related causes, AFP-negative, and abnormal glucose/lipids among PLC patients. Proper control of glucose/lipids or ALT may improve the prognosis of PLCs.
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Affiliation(s)
- Yezhou Ding
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mingyang Feng
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Di Ma
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gangde Zhao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaolin Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Baoyan An
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yumin Xu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shike Lou
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lanyi Lin
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Kehui Liu
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Hui Wang, ; Shisan Bao, ; Kehui Liu,
| | - Shisan Bao
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Hui Wang, ; Shisan Bao, ; Kehui Liu,
| | - Hui Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- *Correspondence: Hui Wang, ; Shisan Bao, ; Kehui Liu,
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Cramer T. Impact of dietary carbohydrate restriction on the pathobiology of Hepatocellular Carcinoma: The gut-liver axis and beyond. Semin Immunol 2023; 66:101736. [PMID: 36857893 DOI: 10.1016/j.smim.2023.101736] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 02/02/2023] [Accepted: 02/09/2023] [Indexed: 03/01/2023]
Abstract
Despite decades of fiercely competitive research and colossal financial investments, the majority of patients with advanced solid cancers cannot be treated with curative intent. To improve this situation, conceptually novel treatment approaches are urgently needed. Cancer is increasingly appreciated as a systemic disease and numerous organismal factors are functionally linked to neoplastic growth, e.g. systemic metabolic dysregulation, chronic inflammation, intestinal dysbiosis and disrupted circadian rhythms. It is tempting to hypothesize that interventions targeting these processes could be of significant account for cancer patients. One important driver of tumor-supporting systemic derangements is inordinate consumption of simple and highly processed carbohydrates. This dietary pattern is causally linked to hyperinsulinemia, insulin resistance, chronic inflammation and intestinal dysbiosis, begging the pertinent question whether the adoption of dietary carbohydrate restriction can be beneficial for patients with cancer. This review summarizes the published data on the role of dietary carbohydrate restriction in the pathogenesis of Hepatocellular Carcinoma (HCC), the most frequent type of primary liver cancer. In addition to outlining the functional interplay between diet, the intestinal microbiome and immunity, the review underscores the importance of bile acids as interconnectors between the intestinal microbiota and immune cells.
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Affiliation(s)
- Thorsten Cramer
- Department of General, Visceral and Transplantation Surgery, RWTH University Hospital, 52074 Aachen, Germany; Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands; NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
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Yu ML, Wang CY, Lee MH, Ou HY, Cheng PN, Tu ST, Huang JF, Chen JF, Hu TH, Hsu CC, Kao JH, Chen CJ, Lin HC, Huang CN. TASL, TADE, and DAROC consensus for the screening and management of hepatitis C in patients with diabetes. J Formos Med Assoc 2023; 122:202-220. [PMID: 36750398 DOI: 10.1016/j.jfma.2023.01.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/19/2023] [Accepted: 01/21/2023] [Indexed: 02/09/2023] Open
Abstract
Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Chih-Yuan Wang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Horng-Yih Ou
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng-Kung University Medical College and Hospital, Tainan, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Te Tu
- Department of Endocrinology and Metabolism, Changhua Christian Hospital, Changhua, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jung-Fu Chen
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Department of Internal Medicine, Kaohsiung, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
| | - Chien-Ning Huang
- Department of Internal Medicine, Chung Shan Medical University Hospital, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
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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: 1] [Impact Index Per Article: 0.5] [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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Genetic Susceptibility to Hepatocellular Carcinoma in Patients with Chronic Hepatitis Virus Infection. Viruses 2023; 15:v15020559. [PMID: 36851773 PMCID: PMC9964813 DOI: 10.3390/v15020559] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk factors, individual genetic predisposition is a major determinant of HCC risk. Familial clustering of HCC has been observed, and a hereditary factor likely contributes to the risk of HCC development. The familial aggregation may depend on a shared environment and genetic background as well as the interactions of environmental and genetic factors. Genome-wide association studies (GWASs) are one of the most practical tools for mapping the patterns of inheritance for the most common form of genomic variation, single nucleotide polymorphisms. This approach is practical for investigating genetic variants across the human genome, which is affected by thousands of common genetic variants that do not follow Mendelian inheritance. This review article summarizes the academic knowledge of GWAS-identified genetic loci and their association with HCC. We summarize the GWASs in accordance with various chronic hepatitis virus infection statuses. This genetic profiling could be used to identify candidate biomarkers to refine HCC screening and management by enabling individual risk-based personalization and stratification. A more comprehensive understanding of the genetic mechanisms underlying individual predisposition to HCC may lead to improvements in the prevention and early diagnosis of HCC and the development of effective treatment strategies.
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33
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Tai AS, Lin SH. Complete effect decomposition for an arbitrary number of multiple ordered mediators with time-varying confounders: A method for generalized causal multi-mediation analysis. Stat Methods Med Res 2023; 32:100-117. [PMID: 36321187 DOI: 10.1177/09622802221130580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Causal mediation analysis is advantageous for mechanism investigation. In settings with multiple causally ordered mediators, path-specific effects have been introduced to specify the effects of certain combinations of mediators. However, most path-specific effects are unidentifiable. An interventional analog of path-specific effects is adapted to address the non-identifiability problem. Moreover, previous studies only focused on cases with two or three mediators due to the complexity of the mediation formula in a large number of mediators. In this study, we provide a generalized definition of traditional path-specific effects and interventional path-specific effects with a recursive formula, along with the required assumptions for nonparametric identification. Subsequently, a general approach is developed with an arbitrary number of multiple ordered mediators and with time-varying confounders. All methods and software proposed in this study contribute to comprehensively decomposing a causal effect confirmed by data science and help disentangling causal mechanisms in the presence of complicated causal structures among multiple mediators.
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Affiliation(s)
- An-Shun Tai
- Department of Statistics, 34912National Cheng Kung University, Tainan
| | - Sheng-Hsuan Lin
- Institute of Statistics, 34914National Yang Ming Chiao Tung University, Hsinchu
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Yang F, Ni B, Lian Q, Qiu X, He Y, Zhang Q, Zou X, He F, Chen W. Key genes associated with non-alcoholic fatty liver disease and hepatocellular carcinoma with metabolic risk factors. Front Genet 2023; 14:1066410. [PMID: 36950134 PMCID: PMC10025510 DOI: 10.3389/fgene.2023.1066410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 02/21/2023] [Indexed: 03/08/2023] Open
Abstract
Background: Hepatocellular carcinoma (HCC) has become the world's primary cause of cancer death. Obesity, hyperglycemia, and dyslipidemia are all illnesses that are part of the metabolic syndrome. In recent years, this risk factor has become increasingly recognized as a contributing factor to HCC. Around the world, non-alcoholic fatty liver disease (NAFLD) is on the rise, especially in western countries. In the past, the exact pathogenesis of NAFLD that progressed to metabolic risk factors (MFRs)-associated HCC has not been fully understood. Methods: Two groups of the GEO dataset (including normal/NAFLD and HCC with MFRs) were used to analyze differential expression. Differentially expressed genes of HCC were verified by overlapping in TCGA. In addition, functional enrichment analysis, modular analysis, Receiver Operating Characteristic (ROC) analysis, LASSO analysis, and Genes with key survival characteristics were analyzed. Results: We identified six hub genes (FABP5, SCD, CCL20, AGPAT9(GPAT3), PLIN1, and IL1RN) that may be closely related to NAFLD and HCC with MFRs. We constructed survival and prognosis gene markers based on FABP5, CCL20, AGPAT9(GPAT3), PLIN1, and IL1RN.This gene signature has shown good diagnostic accuracy in both NAFLD and HCC and in predicting HCC overall survival rates. Conclusion: As a result of the findings of this study, there is some guiding significance for the diagnosis and treatment of liver disease associated with NAFLD progression.
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Affiliation(s)
- Fan Yang
- Department of Infectious Diseases, The First People’s Hospital of Kashi, The Kashi Affiliated Hospital, Sun Yat-Sen University, Kashi, China
- Biotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
- Postdoctoral Research Station, Xinjiang Medical University, Ürümqi, China
| | - Beibei Ni
- Cell-Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Qinghai Lian
- Cell-Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xiusheng Qiu
- Cell-Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Yizhan He
- Biotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Qi Zhang
- Department of Infectious Diseases, The First People’s Hospital of Kashi, The Kashi Affiliated Hospital, Sun Yat-Sen University, Kashi, China
- Biotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Xiaoguang Zou
- Department of Infectious Diseases, The First People’s Hospital of Kashi, The Kashi Affiliated Hospital, Sun Yat-Sen University, Kashi, China
- *Correspondence: Xiaoguang Zou, ; Fangping He, ; Wenjie Chen,
| | - Fangping He
- Department of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, China
- *Correspondence: Xiaoguang Zou, ; Fangping He, ; Wenjie Chen,
| | - Wenjie Chen
- Biotherapy Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
- Cell-Gene Therapy Translational Medicine Research Centre, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
- *Correspondence: Xiaoguang Zou, ; Fangping He, ; Wenjie Chen,
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Wang MD, Tang SC, Li C, Sun LY, Xu X, Liang YJ, Liu FB, Gu WM, Wang XM, Zhou YH, Lau WY, Zhang CW, Yao LQ, Diao YK, Gu LH, Shen F, Zeng YY, Yang T. Association of Concurrent Metabolic Syndrome with Long-term Oncological Prognosis Following Liver Resection for Hepatocellular Carcinoma Among Patients with Chronic Hepatitis B Virus Infection: A Multicenter Study of 1753 Patients. Ann Surg Oncol 2023; 30:346-358. [PMID: 36114441 DOI: 10.1245/s10434-022-12529-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 08/22/2022] [Indexed: 02/20/2025]
Abstract
BACKGROUND Although hepatitis B virus (HBV) infection remains the main cause of hepatocellular carcinoma (HCC) worldwide, metabolic syndrome, with its increase in prevalence, has become an important and significant risk factor for HCC. This study was designed to investigate the association of concurrent metabolic syndrome with long-term prognosis following liver resection for patients with HBV-related HCC. METHODS From a Chinese, multicenter database, HBV-infected patients who underwent curative resection for HCC between 2010 and 2020 were identified. Long-term oncological prognosis, including overall survival (OS), recurrence-free survival (RFS), and early (≤2 years of surgery) and late (>2 years) recurrences were compared between patients with versus those without concurrent metabolic syndrome. RESULTS Of 1753 patients, 163 (9.3%) patients had concurrent metabolic syndrome. Compared with patients without metabolic syndrome, patients with metabolic syndrome had poorer 5-year OS (47.5% vs. 61.0%; P = 0.010) and RFS (28.3% vs. 44.2%; P = 0.003) rates and a higher 5-year overall recurrence rate (67.3% vs. 53.3%; P = 0.024). Multivariate analysis revealed that concurrent metabolic syndrome was independently associated with poorer OS (hazard ratio: 1.300; 95% confidence interval: 1.018-1.660; P = 0.036) and RFS (1.314; 1.062-1.627; P = 0.012) rates, and increased rates of late recurrence (hazard ratio: 1.470; 95% confidence interval: 1.004-2.151; P = 0.047). CONCLUSIONS In HBV-infected patients with HCC, concurrent metabolic syndrome was associated with poorer postoperative long-term oncologic survival outcomes. These results suggested that patients with metabolic syndrome should undergo enhanced surveillance for tumor recurrence even after 2 years of surgery to early detect late HCC recurrence. Whether improving metabolic syndrome can reduce postoperative recurrence of HCC deserves further exploration.
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Affiliation(s)
- Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Shi-Chuan Tang
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Li-Yang Sun
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Xiao Xu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Ying-Jian Liang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Harbin Medical University, Heilongjiang, China
| | - Fu-Bao Liu
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China
| | - Wei-Min Gu
- The First Department of General Surgery, Fourth Hospital of Harbin, Heilongjiang, China
| | - Xian-Ming Wang
- Department of General Surgery, First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong, China
| | - Ya-Hao Zhou
- Department of Hepatobiliary Surgery, Pu'er People's Hospital, Pu'er, Yunnan, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
| | - Cheng-Wu Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, Cancer Center, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
| | - Lan-Qing Yao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Yong-Kang Diao
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Li-Hui Gu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China.
- Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China.
| | - Yong-Yi Zeng
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China.
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China.
- Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, China.
- Eastern Hepatobiliary Clinical Research Institute, Third Affiliated Hospital of Navy Medical University, Shanghai, China.
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Cavalcante LN, Dezan MGF, Paz CLDSL, Lyra AC. RISK FACTORS FOR HEPATOCELLULAR CARCINOMA IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE. ARQUIVOS DE GASTROENTEROLOGIA 2022; 59:540-548. [PMID: 36515349 DOI: 10.1590/s0004-2803.202204000-93] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 08/29/2022] [Indexed: 11/16/2022]
Abstract
Non-alcoholic fatty liver disease is growing in worldwide prevalence and thus, is expected to have a higher number of NAFLD-related hepatocellular carcinoma (HCC) in the following years. This review describes the risk factors associated with HCC in NAFLD-patients. The presence of liver cirrhosis is the preponderant one. Male gender, PNPLA3 variants, diabetes, and obesity also appear to predispose to the development of HCC, even in non-cirrhotic subjects. Thus far, intensive lifestyle modifications, including glycemic control, and obesity treatment, are effective therapies for NAFLD/ non-alcoholic steatohepatitis and, therefore, probably, also for HCC. Some drugs that aimed at decreasing inflammatory activity and fibrosis, as well as obesity, were studied. Other data have suggested the possibility of HCC chemoprevention. So far, however, there is no definitive evidence for the routine utilization of these drugs. We hope, in the future, to be able to profile patients at higher risk of NAFLD-HCC and outline strategies for early diagnosis and prevention.
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Affiliation(s)
- Lourianne Nascimento Cavalcante
- Universidade Federal da Bahia, Salvador, BA, Brasil.,Hospital São Rafael, Serviço de Gastro-Hepatologia, Salvador, BA, Brasil
| | | | | | - André Castro Lyra
- Universidade Federal da Bahia, Salvador, BA, Brasil.,Hospital São Rafael, Serviço de Gastro-Hepatologia, Salvador, BA, Brasil
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Chang SS, Hu HY, Chen YC, Yen YF, Huang N. Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case–control study. BMC Gastroenterol 2022; 22:425. [PMID: 36115934 PMCID: PMC9482748 DOI: 10.1186/s12876-022-02504-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 09/13/2022] [Indexed: 12/09/2022] Open
Abstract
Abstract
Background
New direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan.
Methods
We conducted a population-based unmatched case–control study. 2008–2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis.
Results
A decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis.
Conclusions
Elderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.
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Liu Y, Liu L. Changes in the Epidemiology of Hepatocellular Carcinoma in Asia. Cancers (Basel) 2022; 14:cancers14184473. [PMID: 36139633 PMCID: PMC9496757 DOI: 10.3390/cancers14184473] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/09/2022] [Accepted: 09/13/2022] [Indexed: 11/23/2022] Open
Abstract
Simple Summary The incidence and mortality of hepatocellular carcinoma (HCC) in Asia are among the world leaders. By understanding the changes in prevalence and influencing factors of HCC, we can better understand the current situation in Asia and take measures to reduce the incidence. Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with high morbidity and mortality, and the incidence is on the rise. HCC imposes a heavy healthcare burden on Asian countries due to the presence of multiple HCC risk factors in this area. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, non-alcoholic liver disease (NAFLD), aflatoxin and alcohol intake are the causes of HCC that cannot be ignored. Compared with the pre-vaccination era, universal vaccination of newborns reduces the incidence of HCC. Anti-viral therapy with nucleos(t)ide analogues also causes a decline in HCC incidence. Early screening and direct-acting antiviral agent are beneficial to the prevention and treatment of HCV. For HCC caused by NAFLD and other reasons, lifestyle changes are imperative. This paper introduces the epidemiological trends of HCC in Asia and highlight future efforts. Focusing on prevention may be the most effective way to improve the prognosis of this hard-to-treat cancer.
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Affiliation(s)
- Yao Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China
- Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China
| | - Lianxin Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
- Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei 230001, China
- Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei 230001, China
- Correspondence:
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Lin JH, Tai AS, Lin SH. Population attributable fraction based on marginal sufficient component cause model for mediation settings. Ann Epidemiol 2022; 75:57-66. [PMID: 36084802 DOI: 10.1016/j.annepidem.2022.08.050] [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: 08/12/2021] [Revised: 07/28/2022] [Accepted: 08/24/2022] [Indexed: 11/19/2022]
Abstract
PURPOSE Population attributable fraction (PAF), defined as the proportion of the occurrence of a disease which will be reduced by eliminating risk factors in a population, is one of the most common measurements for evaluating the benefit of a health-related policy in epidemiologic study. In this article, we propose an alternative PAF defined based on sufficient cause framework, which decompose the occurrence of a disease into several pathways including mediation and mechanistic interaction. METHODS We propose a formal statistical definition and regression-based estimator for PAF based on sufficient cause framework within mediation settings. Under monotonicity assumption, the proposed method can decompose the occurrence of a disease into nine PAFs corresponding to all types of mechanisms attributing to exposure and the mediator, including the portion attributing to exposure directly, to mediator, to indirect effect through mediator, to the mechanistic interaction, to both of mediation and interaction, and to none of exposure or mediator. RESULTS We apply the proposed method to explore the mechanism of a hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) mediated by and/or interacted with alanine aminotransferase (ALT) and hepatitis B virus (HBV). When treating ALT as mediator, 56.77% of diseased subjects can be attributable to either HCV or abnormal ALT. When treating HBV as mediator, HCC is mainly induced by an exogenous high HBV viral load directly. CONCLUSIONS The proposed method can identify the impact of exposure and pathway effects, and benefit to allocate the resources on intervention strategies.
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Affiliation(s)
- Jui-Hsiang Lin
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
| | - An-Shun Tai
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan; Department of Statistics, National Cheng Kung University, Tainan
| | - Sheng-Hsuan Lin
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
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Hsu WF, Lai HC, Chuang PH, Su WP, Chen SH, Chen HY, Wang HW, Huang GT, Peng CY. Posttreatment nonalcoholic fatty liver disease fibrosis scores for predicting liver-related complications in patients with chronic hepatitis C receiving direct-acting antiviral agents. J Viral Hepat 2022; 29:785-794. [PMID: 35657121 DOI: 10.1111/jvh.13715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 05/10/2022] [Accepted: 05/25/2022] [Indexed: 12/09/2022]
Abstract
Patients with chronic hepatitis C (CHC) have a higher prevalence of hepatic steatosis and dyslipidaemia than healthy individuals. We analysed noninvasive fibrosis assessments, especially nonalcoholic fatty liver disease (NAFLD)-related noninvasive fibrosis tests, for predicting liver-related complications and hepatocellular carcinoma (HCC) occurrence in patients with CHC. This retrospective study enrolled 590 consecutive patients with CHC having a sustained virologic response (SVR) to direct-acting antiviral agent (DAA) therapy. The NAFLD fibrosis score (NFS) exhibiting the highest value of area under the receiver operating characteristic curve (AUROC) was selected for comparison with the fibrosis-4 index (FIB-4). Of the 590 patients, 188 had metabolic syndrome. A multivariate Cox regression analysis identified total bilirubin at 3 or 6 months after DAA therapy (PW12), NFS at PW12 (hazard ratio [HR]: 2.125, 95% confidence interval [CI]: 1.058-4.267, p = .034) and alpha-fetoprotein (AFP) at PW12 (HR: 1.071, 95% CI: 1.005-1.142, p = .034) as the independent predictors of liver-related complications in all patients. In patients with metabolic syndrome, NFS and AFP values at PW12 were independent predictors of liver-related complications and HCC occurrence. Time-dependent NFS AUROC values at PW12 for 1-, 2- and 3-year liver-related complications were higher than NFS values at baseline in patients with metabolic syndrome. NFS at baseline or PW12 is a more effective predictor of liver-related complications than FIB-4 values in all patients. NFS at PW12 may be a useful predictor of liver-related complications and HCC development in patients with CHC with an SVR to DAA therapy, especially in those with metabolic syndrome.
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Affiliation(s)
- Wei-Fan Hsu
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.,School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Hsueh-Chou Lai
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Chinese Medicine, China Medical University, Taichung, Taiwan
| | - Po-Heng Chuang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wen-Pang Su
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Sheng-Hung Chen
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
| | - Hung-Yao Chen
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Hung-Wei Wang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
| | - Guan-Tarn Huang
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.,School of Medicine, China Medical University, Taichung, Taiwan
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Abstract
Cancer has become a leading cause of death among patients with metabolic syndrome (MetS). The more components of MetS a patient has, the higher his risk of cancer. MetS is causally associated with colorectal, pancreatic, gallbladder, biliary, hepatocellular, gastric, esophageal, thyroid, breast, endometrial and renal cell cancers. MetS increases cancer mortality up to 2,4-fold. Intentional long-term weight loss reduces the excess cancer risk of obese MetS-patients. Both a low-risk lifestyle and cancer screening are effective and decrease the burden of cancer.
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Xue J, Wang QX, Xiao HM, Shi MJ, Xie YB, Li S, Lin M, Chi XL. Impact of Metabolic Dysfunction Associated Fatty Liver Disease on the Prognosis of Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma Based on Propensity Score Matching Analysis. Cancer Manag Res 2022; 14:2193-2202. [PMID: 35859711 PMCID: PMC9293246 DOI: 10.2147/cmar.s368366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Accepted: 06/25/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Both metabolic dysfunction-associated fatty liver disease (MAFLD) and hepatitis B virus (HBV) are risk factors for hepatocellular carcinoma (HCC). Although concurrent MAFLD is common in patients with HBV-related HCC, whether MAFLD increases the risk of poor prognosis in patients with HBV-related HCC remains unclear. This study aimed to investigate the impact of MAFLD on prognosis in patients with HBV-related HCC. Patients and Methods In this retrospective cohort study, 549 patients with HBV-related HCC were enrolled from January 2010 to April 2020 in Guangdong Provincial Hospital of Chinese Medicine, including 169 patients with MAFLD (MAFLD group) and 380 patients without MAFLD (Non-MAFLD group). Propensity score matching (PSM) analysis was performed to balance the baseline characteristics. Kaplan–Meier survival curves were performed to compare the prognosis between the two matched groups. A multivariate Cox proportional hazards model was used to determine the risk factors for poor prognosis. Results The median follow-up time for all patients was 20 (interquartile range 8–40) months. We found concurrent MAFLD was associated with a significantly decreased PFS rate before and after PSM analysis. The 1-year, 2-year, and 3-year PFS rates for the MAFLD and Non-MAFLD groups after PSM were 61.3% and 70.8%, 43.9% and 54.5%, 31.1% and 41.8%, respectively. Cox multivariable analysis showed that concurrent MAFLD was an independent risk factor for poor prognosis (death or progression) (HR = 1.49, P = 0.001). More interestingly, the risk of poor prognosis was significantly higher in the MAFLD subtype with metabolic components ≥2 compared to those with metabolic components <2 (HR = 1.97, P < 0.001). Conclusion Concurrent MAFLD was associated with a higher risk of poor prognosis in patients with HBV-related HCC, especially MAFLD with metabolic components ≥2.
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Affiliation(s)
- Jiao Xue
- The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People's Republic of China
| | - Qing-Xia Wang
- The Second School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People's Republic of China
| | - Huan-Ming Xiao
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Mei-Jie Shi
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Yu-Bao Xie
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Sheng Li
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Ming Lin
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
| | - Xiao-Ling Chi
- Department of Hepatology, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, People's Republic of China
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Jun BG, Kim M, Shin HS, Yi JJ, Yi SW. Impact of overweight and obesity on the risk of hepatocellular carcinoma: a prospective cohort study in 14.3 million Koreans. Br J Cancer 2022; 127:109-115. [PMID: 35249102 PMCID: PMC9276765 DOI: 10.1038/s41416-022-01771-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 02/08/2022] [Accepted: 02/17/2022] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Whether obesity and being overweight, defined by body mass index (BMI), increase hepatocellular carcinoma (HCC) has been less apparent in Asian populations. METHODS Overall, 14,265,822 Korean adults who underwent routine health examinations during 2003-2006 were followed up for HCC. Multivariable-adjusted hazard ratios (HRs) associated with BMI were calculated. RESULTS During 13.7 years (mean) of follow-up, 47,308 individuals developed HCC. HRs of HCC associated with BMIs of 25.0-26.4, 26.5-27.9, 28.0-29.4, 29.5-30.9 and ≥31 kg/m² compared to those for 23.5-24.9 kg/m² were 1.05, 1.20, 1.39, 1.59 and 2.13, respectively. For BMI < 25 kg/m², linear associations were not apparent. For BMI ≥ 25 kg/m2, the HR per 5 kg/m2 increase in BMI was 1.60 (total), 1.60 (men), and 1.59 (women). The corresponding HRs were 1.56, 1.61 and 1.60 for individuals aged <45, 45-64 and ≥65 years, respectively. Further adjustment for alanine transaminase (ALT) levels substantially reduced the HRs for high BMI, especially in men and younger adults. CONCLUSIONS Overweight and obesity clearly increase HCC risk in Koreans. ALT levels are a mediator of the impact of obesity, but it may not accurately predict high BMI-induced liver damage that can potentially progress to HCC, especially in women and older adults.
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Affiliation(s)
- Baek Gyu Jun
- grid.411627.70000 0004 0647 4151Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, 01757 Republic of Korea
| | - Moonho Kim
- grid.267370.70000 0004 0533 4667Department of Hematology and Oncology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung-si, Gangwon-do 25440 Republic of Korea
| | - Hwang Sik Shin
- grid.412677.10000 0004 1798 4157Department of Family Medicine, Soonchunhyang University College of Medicine, Cheonan Hospital, Cheonan, 31151 Republic of Korea
| | - Jee-Jeon Yi
- grid.411199.50000 0004 0470 5702Institute for Occupational and Environmental Health, Catholic Kwandong University, Gangneung, 25601 Republic of Korea
| | - Sang-Wook Yi
- Department of Preventive Medicine and Public Health, Catholic Kwandong University College of Medicine, Gangneung, 25601, Republic of Korea.
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Huang Y, Chen L, Huang R, Zhu C, Shang J, Qian Y, Lian J, Liu L, Jiang J, Liu C, Gui H, Xie Q. Tenofovir is superior to entecavir in reducing HCC for patients with HBV-related compensated cirrhosis at high HCC risk scores. Ther Adv Chronic Dis 2022; 13:20406223221102791. [PMID: 35757781 PMCID: PMC9218453 DOI: 10.1177/20406223221102791] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 04/28/2022] [Indexed: 12/25/2022] Open
Abstract
Background: Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are known to reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to compare the difference in HCC risk reduction between TDF and ETV in treatment-naïve patients with CHB-related compensated cirrhosis. Methods: Patients with compensated cirrhosis initially treated with TDF or ETV at nine Chinese hospitals between June 2014 and March 2021 were enrolled in this retrospective study. The cumulative HCC incidence rates for the two drugs were compared for the entire cohort, and a subgroup analysis was performed according to the HCC risk scores. Propensity score matching (PSM) was used to control confounding biases. Results: The analysis included 1453 patients (TDF group, n = 188; ETV group, n = 1265). Ninety-five patients developed HCC, with a median follow-up period of 26.1 months. The 3-year HCC incidence was 2.0% in the TDF group and 7.5% in the ETV group (log-rank p = 0.005). TDF treatment was associated with a lower risk of HCC than ETV treatment [hazard ratio (HR) = 0.222, 95% confidence interval (CI), 0.070–0.702, p = 0.010] but was similar after PSM (HR = 0.483, 95% CI, 0.144–1.626, p = 0.240; log-rank p = 0.230). However, subgroup analysis showed that the cumulative HCC incidence was lower in the TDF group than in the ETV group among patients with a modified PAGE-B score (mPAGE-B) ⩾9, either before or after PSM (log-rank p = 0.048 and p = 0.023, respectively). Conclusion: Among patients with an mPAGE-B score ⩾9, TDF is associated with a lower HCC incidence than ETV in patients with CHB-related compensated cirrhosis.
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Affiliation(s)
- Yan Huang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lichang Chen
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Rui Huang
- Department of Infectious Disease, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou, China
| | - Yunsong Qian
- Department of Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
| | - Jianqi Lian
- Department of Infectious Diseases, Tangdu Hospital, The Fourth Military Medical University, Xian, China
| | - Longgen Liu
- Department of Infectious Diseases, The Third People's Hospital of Changzhou, Changzhou, China
| | - Jianning Jiang
- Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Chenghai Liu
- Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Honglian Gui
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Tarao K, Nozaki A, Komatsu H, Ideno N, Komatsu T, Ikeda T, Taguri M, Maeda S. Difference in incidence of developing hepatocellular carcinoma between hepatitis B virus-and hepatitis C virus-infected patients. World J Meta-Anal 2022; 10:186-194. [DOI: 10.13105/wjma.v10.i3.186] [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: 04/13/2022] [Revised: 06/14/2022] [Accepted: 06/27/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND It is generally accepted that the incidence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-associated patients is higher than that in hepatitis B virus (HBV)-associated patients. The reason why this difference in the incidence of HCC occurs in patients with HBV and HCV infections remains unclear. We report the possibility that the contributing power of inflammation, which is the main risk factor for developing HCC, may be different with HBV and HCV infections.
AIM To investigate this, we surveyed the hazard ratio of inflammation for HCC development which was identified by serum alanine aminotransferase (ALT) levels between patients with HBV and HCV infections.
METHODS The PubMed database was searched (2001-2021) for studies published in English regarding the incidence of HCC identifying 8924 HBV-and 7376 HCV- infected patients. From these studies, interferon-treated patients with both HBV and HCV infections were excluded. Furthermore, in HBV patients, those administered nucleos(t)ide analogues were excluded, and in HCV patients, those administered direct acting antivirals were also excluded. Studies citing hazard ratios of HCC regarding inflammation (serum elevated alanine aminotransferase levels) were selected. Finally, there were 14 studies of HBV- infected patients and 8 studies of HCV-infected patients. We calculated the hazard ratio in patients in an inflammatory state (serum ALT levels were above the normal range).
RESULTS In the 14 studies of HBV patients, the average hazard ratio (HR) of elevated ALT for developing HCC was 2.74 [1.98-3.77] and that in the 8 studies of HCV-infected patients was 5.51 [3.08-9.83]. The HR of inflammation for HCC development in HCV-associated liver diseases is about twice that in HBV-associated liver diseases. HR in HCV-infected patients was significantly (P = 0.0391) higher than that in HBV-infected patients. In hepatitis B patients, the abnormal range adopted was 28-45 IU/L, and in hepatitis C patients, it was 20-50 IU/L. It was demonstrated that the abnormal ALT levels adopted in hepatitis B and C patients were very similar in this series.
CONCLUSION The difference in the incidence of HCC development between HBV and HCV patients may depend on the difference in the hazard risk of ALT between HBV and HCV infections.
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Affiliation(s)
- Kazuo Tarao
- Department of Gastroenterology, Tarao's Gastroenterological Clinic, Yokohama City 241-0821, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama City 232-0024, Japan
| | - Hirokazu Komatsu
- Department of Gastroenterology, Yokohama Municipal Citizen’s Hospital, Yokohama City 2211-0855, Japan
| | - Naomi Ideno
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama City 232-0024, Japan
| | - Tatsuji Komatsu
- Department of Clinical Research, National Hospital Organization, Yokohama Medical Center, Yokohama City 2458575, Japan
| | - Takaaki Ikeda
- Department of Gastroenterology, Yokosuka General Hospital Uwamachi, Yokosuka City 238-8567, Japan
| | - Masataka Taguri
- Department of Data Science, Yokohama City University, Yokohama, Yokohama City 236-0004, Japan
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama City 236-0004, Japan
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Scherübl H. Tobacco Smoking and Gastrointestinal Cancer Risk. Visc Med 2022; 38:217-222. [PMID: 35814979 PMCID: PMC9209969 DOI: 10.1159/000523668] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 02/14/2022] [Indexed: 08/14/2023] Open
Abstract
Background Smoking tobacco is the most preventable cause of gastrointestinal (GI) cancer disease in Germany. The more and the longer you smoke, the higher your risk of GI cancer. About 28% of 18-64 year-old Germans are current smokers; in addition, 11% of the population is regularly exposed to secondhand tobacco smoke. Summary Tobacco use is causally associated with esophageal, gastric, pancreatic, biliary, hepatocellular, colorectal, and anal cancers. Combining smoking with alcohol use, excess body weight, diabetes, or chronic infections synergistically enhances GI cancer risk. Smoking cessation effectively reduces tobacco-associated GI cancer risk. Key Messages Smokers should be encouraged to stop smoking tobacco and join programs of risk-adaptive cancer screening.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin II, Gastroenterologie, GI Onkologie, Diabetologie und Infektiologie, Klinikum Am Urban, Vivantes Netzwerk für Gesundheit, Berlin, Germany
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Scherübl H. Krebsrisiko bei Prädiabetes und Typ-2-Diabetes mellitus. DIABETOL STOFFWECHS 2022. [DOI: 10.1055/a-1837-2035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
ZusammenfassungKrebs ist nun die führende Todesursache bei Typ-2-Diabetes mellitus (T2D). Prädiabetes und T2D erhöhen das Risiko für bestimmte Tumoren. Zu den Prädiabetes- bzw. T2D-assoziierten Malignomen zählen gastrointestinale, gynäkologische, urologische und endokrine Karzinome aber auch Leukämien. Prädiabetes und T2D bedingen eine 1,2- bis 2,7-fach erhöhte Krebssterblichkeit. Zugrundeliegende Mechanismen der Assoziation zwischen T2D und Krebs beinhalten die chronische Hyperglykämie, einen chronischen systemischen Entzündungszustand, oxidativen Stress, Dyslipidämie, die Insulinresistenz sowie chronisch erhöhte Spiegel von insulin-like growth factor 1 (IGF-1) und von Insulin. Eine dauerhafte Gewichtsreduktion kann das Krebsrisiko adipöser T2D-Patienten signifikant senken. Ein gesunder Lebensstil und die regelmäßige Teilnahme an Vorsorgeuntersuchungen sind wichtig und können die Krebsmortalität von Diabetespatienten erheblich verringern.
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Affiliation(s)
- Hans Scherübl
- Klinik für Innere Medizin, Gastroenterologie, GI Onkologie, Diabetologie und Infektiologie, Vivantes Netzwerk für Gesundheit GmbH, Berlin, Germany
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Chang TS, Hsu NT, Chen SC, Hsu IL, Lee MH, Lu SN. Non-B, Non-C Hepatocellular Carcinoma in an HBV- and HCV-Endemic Area: A Community-Based Prospective Longitudinal Study. Viruses 2022; 14:v14050984. [PMID: 35632726 PMCID: PMC9145519 DOI: 10.3390/v14050984] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 04/30/2022] [Accepted: 05/04/2022] [Indexed: 02/04/2023] Open
Abstract
A large community cohort of adults who participated in a health screening program from 2003 to 2013 were prospectively analyzed for the risk factors of non-B, non-C (NBNC) hepatocellular carcinoma (HCC). The serostatus of hepatitis B and C of 52,642 participants was linked to the mortality and cancer registration data of the Health and Welfare Data Science Center, Ministry of Health and Welfare, Taiwan. During a median follow-up of 6 years, 35 of the 43,545 participants who were negative for both HBsAg and anti-HCV antibody developed HCC. Multivariate Cox regression analysis revealed that old age (hazard ratio, 95% CI: 1.058, 1.019−1.098, p = 0.003); male sex (2.446, 1.200−4.985, p = 0.014); high aspartate aminotransferase levels (6.816, 2.945−15.779, p < 0.001); fibrosis index based on four factor score (1.262, 1.154−1.381, p < 0.001); blood sugar (1.009, 1.002−1.015, p = 0.006); and alpha-fetoprotein ≥15 ng/mL (143.938, 43.094−480.760, p < 0.001) were independent risk factors for HCC. By contrast, triglyceride >150 mg/dL was associated with a decreased risk of HCC (0.216, 0.074−0.625, p = 0.005). This prospective community-based study provided insights into the potential HCC risk factors which may shed some light in HCC prevention and screening.
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Affiliation(s)
- Te-Sheng Chang
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
| | - Nien-Tzu Hsu
- Biostatistics Center of Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833253, Taiwan;
| | - Shu-Chuan Chen
- Public Health Bureau, Tainan City Government, Tainan 701017, Taiwan; (S.-C.C.); (I.-L.H.)
| | - I-Lin Hsu
- Public Health Bureau, Tainan City Government, Tainan 701017, Taiwan; (S.-C.C.); (I.-L.H.)
| | - Mei-Hsuan Lee
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Correspondence: (M.-H.L.); (S.-N.L.); Tel.: +886-2-28267248 (M.-H.L.); +886-7-7317123 (ext.6156) (S.-N.L.)
| | - Sheng-Nan Lu
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan
- Department of Gastroenterology and Hepatology, Division of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan
- Correspondence: (M.-H.L.); (S.-N.L.); Tel.: +886-2-28267248 (M.-H.L.); +886-7-7317123 (ext.6156) (S.-N.L.)
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Tai AS, Huang YT, Yang HI, Lan LV, Lin SH. G-Computation to Causal Mediation Analysis With Sequential Multiple Mediators-Investigating the Vulnerable Time Window of HBV Activity for the Mechanism of HCV Induced Hepatocellular Carcinoma. Front Public Health 2022; 9:757942. [PMID: 35071157 PMCID: PMC8779208 DOI: 10.3389/fpubh.2021.757942] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 11/30/2021] [Indexed: 12/09/2022] Open
Abstract
Regression-based approaches are widely used in causal mediation analysis. The presence of multiple mediators, however, increases the complexity and difficulty of mediation analysis. In such cases, regression-based approaches cannot efficiently address estimation issues. Hence, a flexible approach to mediation analysis is needed. Therefore, we developed a method for using g-computation algorithm to conduct causal mediation analysis in the presence of multiple ordered mediators. Compared to regression-based approaches, the proposed simulation-based approach increases flexibility in the choice of models and increases the range of the outcome scale. The Taiwanese Cohort Study dataset was used to evaluate the efficacy of the proposed approach for investigating the mediating role of early and late HBV viral load in the effect of HCV infection on hepatocellular carcinoma (HCC) in HBV seropositive patients (n = 2,878; HCV carrier n = 123). Our results indicated that early HBV viral load had a negative mediating role in HCV-induced HCC. Additionally, early exposure to a low HBV viral load affected HCC through a lag effect on HCC incidence [OR = 0.873, 95% CI = (0.853, 0.893)], and the effect of early exposure to a low HBV viral load on HCC incidence was slightly larger than that of a persistently low viral load on HCC incidence [OR = 0.918, 95% CI = (0.896, 0.941)].
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Affiliation(s)
- An-Shun Tai
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Yen-Tsung Huang
- Institute of Statistical Science, Academia Sinica, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Lauren V Lan
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.,Department of Biostatistics, Johns Hopkins University, Baltimore, MD, United States
| | - Sheng-Hsuan Lin
- Institute of Statistics, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
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50
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Chen L, Dai J, Xie Q, Wang X, Cai W. Metabolic Risk Factors Are Associated with the Disease Severity and Prognosis of Hepatitis B Virus-Related Acute on Chronic Liver Failure. Gut Liver 2022; 16:456-464. [PMID: 35321957 PMCID: PMC9099392 DOI: 10.5009/gnl210449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 12/12/2021] [Accepted: 12/27/2021] [Indexed: 11/23/2022] Open
Abstract
Background/Aims Metabolic risk factors could accelerate hepatitis B virus (HBV)-related mortality; however, their impacts on disease severity in HBV-related acute on chronic liver failure (HBV-ACLF) patients remain unexplored. In this study, we assessed the effects of metabolic risk factors on the outcome of HBV-ACLF patients. Methods This study retrospectively enrolled antiviral therapy naïve HBV-ACLF patients from a single center in China. Patients were evaluated according to Child-Turcotte-Pugh score, Model for End-Stage Liver Disease (MELD) score, 30-day, 90-day mortality and survival rate to estimate the prognosis of HBV-ACLF. The impacts of different metabolic risk factors were further analyzed. Results A total of 233 patients, including 158 (67.8%) with metabolic risk factors and 75 (32.2%) without metabolic risk factors, were finally analyzed. Patients with metabolic risk factors had significantly higher MELD score (22.6±6.1 vs 19.8±3.8, p<0.001), 90-day mortality rate (56.3% vs 38.7%, p=0.017), and shorter median survival time (58 days vs 75 days hazard ratio, 1.553; 95% confidence interval, 1.061 to 2.274; p=0.036) than patients without them. Moreover, metabolic risk factors were independently associated with patients’ 90-day mortality (hazard ratio, 1.621; 95% confidence interval, 1.016 to 2.585; p=0.043). Prediabetes/diabetes and hypertension were related to higher rates of infection and worse renal function in HBV-ACLF patients. Conclusions HBV-ACLF patients with metabolic risk factors, especially prediabetes/diabetes or hypertension, could have more severe disease and lower survival rates. In addition, the existence of metabolic disorder is an independent risk factor for HBV-ACLF patients’ 90-day mortality.
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Affiliation(s)
- Lu Chen
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jinjin Dai
- Department of Infectious Disease, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui Province), Suzhou, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaolin Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Cai
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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