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Ramier C, Protopopescu C, Di Beo V, Parlati L, Marcellin F, Carrat F, Asselah T, Bourlière M, Carrieri P. Behaviour-Based Predictive Scores of Hepatocellular Carcinoma in People With Chronic Hepatitis B (ANRS CO22 HEPATHER). Liver Int 2025; 45:e70065. [PMID: 40087922 PMCID: PMC11909585 DOI: 10.1111/liv.70065] [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: 07/15/2024] [Revised: 01/21/2025] [Accepted: 03/05/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND AND AIMS Early assessment of hepatocellular carcinoma (HCC) risk could improve long-term outcomes in people with chronic hepatitis B virus (HBV) infection. Some existing HCC predictive scores are not easily implementable. We developed easy-to-use HCC predictive scores based on behavioural and routine bio-clinical data in people with chronic HBV infection. METHODS Eight-year follow-up data was analysed from people with chronic HBV infection enrolled in the French ANRS CO22 HEPATHER cohort. Patients were randomly split into two samples (training/testing). A multivariable Cox model for time to HCC was estimated on the training sample. The HCC predictive score was computed by summing the points assigned to model predictors, normalising their coefficients over a 10-year age increment, and rounding to the nearest integer. The Youden index identified the score's optimal risk threshold. Comparisons with existing predictive scores were performed on the testing sample. RESULTS In the study population (N = 4370; 63% of men; 65% of < 50 years old), 56 HCC cases occurred during 25,900 follow-up person-years. Two HCC predictive scores were defined: SADAPTT (daily soft drink consumption, age, hepatitis Delta infection, unhealthy alcohol use, platelet count, heavy tobacco smoking, and HBV treatment) and ADAPTT (the same predictors except for daily soft drink consumption), with ranges 0-13 and 0-14, respectively, and values ≥ 3 indicating a high HCC risk. Their performances were similar to existing scores. CONCLUSIONS We developed two effective behaviour-based HCC predictive scores, implementable in many settings, including primary care and decentralised areas. Further studies are needed to validate these scores in other datasets.
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Affiliation(s)
- Clémence Ramier
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
| | - Camelia Protopopescu
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
| | - Vincent Di Beo
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
| | - Lucia Parlati
- Département d'Hépatologie/AddictologieUniversité de Paris Cité; INSERM U1016, AP‐HP, Hôpital CochinParisFrance
| | - Fabienne Marcellin
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
| | - Fabrice Carrat
- Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne UniversitéParisFrance
- Hôpital Saint‐Antoine, Unité de Santé Publique, Assistance Publique‐Hôpitaux de Paris (AP‐HP)ParisFrance
| | - Tarik Asselah
- Department of HepatologyCentre de Recherche Sur l'Inflammation, INSERM UMR 1149, Hôpital Beaujon, Université de Paris‐CitéClichyFrance
| | - Marc Bourlière
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
- Département d'hépatologie et GastroentérologieHôpital Saint JosephMarseilleFrance
| | - Patrizia Carrieri
- Aix Marseille Univ, INSERM, IRD, SESSTIM, Sciences Économiques and Sociales de la Santé and Traitement de l'Information MédicaleMarseilleFrance
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Wu YP, Yang XY, Tian YX, Feng J, Yeo YH, Ji FP, Zheng MH, Fan YC. Dose-dependent Relationship between Alcohol Consumption and the Risks of Hepatitis B Virus-associated Cirrhosis and Hepatocellular Carcinoma: A Meta-analysis and Systematic Review. J Clin Transl Hepatol 2025; 13:179-188. [PMID: 40078198 PMCID: PMC11894389 DOI: 10.14218/jcth.2024.00379] [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: 10/15/2024] [Revised: 11/18/2024] [Accepted: 11/20/2024] [Indexed: 03/14/2025] Open
Abstract
Background and Aims The quantitative effects of alcohol consumption on cirrhosis and hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) infection are unknown. This study aimed to establish a dose-dependent model of alcohol consumption on the risks of cirrhosis and HCC. Methods PubMed, Embase, the Cochrane Library, Web of Science, and four Chinese databases were searched for studies published from their inception to 15 May 2024. A random-effects model was used to pool the data on the incidence of cirrhosis and HCC, and a dose-dependent model of alcohol's effect on cirrhosis and HCC was established. Results A total of 33,272 HBV patients from 45 studies were included. Compared with non-drinkers, the overall pooled odds ratio (OR) for cirrhosis was 2.61 (95% confidence interval [CI]: 1.46-4.66; I2 = 94%, p < 0.001), and the OR for HCC was 2.27 (95% CI: 1.50-3.43; I2 = 90%, p < 0.001) among drinkers. Compared with low-level drinkers, the estimated pooled OR for cirrhosis was 2.34 (95% CI: 1.59-3.44; I2 = 87%, p < 0.001), and the OR for HCC was 2.42 (95% CI: 1.90-3.09; I2 = 80%, p < 0.001) among high-level drinkers. Furthermore, a linear dose-dependent analysis showed that each daily consumption of 12 g of alcohol increased the risk of cirrhosis by 6.2% and the risk of HCC by 11.5%. Conclusions Alcohol dose-dependently increases the risks of cirrhosis and HCC in patients with HBV infection, and patients with daily alcohol consumption of more than 12 g should be strictly monitored.
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Affiliation(s)
- Yin-Ping Wu
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China
- Institute of Hepatology, Shandong University, Jinan, Shandong, China
| | - Xue-Yan Yang
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China
- Institute of Hepatology, Shandong University, Jinan, Shandong, China
| | - Yu-Xin Tian
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China
- Institute of Hepatology, Shandong University, Jinan, Shandong, China
| | - Jin Feng
- Department of Epidemiology, Public Health School of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yee Hui Yeo
- Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Fan-Pu Ji
- Department of Infectious Diseases, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Ming-Hua Zheng
- MAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yu-Chen Fan
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, Shandong, China
- Institute of Hepatology, Shandong University, Jinan, Shandong, China
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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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Fu Y, Maccioni L, Wang XW, Greten TF, Gao B. Alcohol-associated liver cancer. Hepatology 2024; 80:1462-1479. [PMID: 38607725 DOI: 10.1097/hep.0000000000000890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 03/28/2024] [Indexed: 04/14/2024]
Abstract
Heavy alcohol intake induces a wide spectrum of liver diseases ranging from steatosis, steatohepatitis, cirrhosis, and HCC. Although alcohol consumption is a well-known risk factor for the development, morbidity, and mortality of HCC globally, alcohol-associated hepatocellular carcinoma (A-HCC) is poorly characterized compared to viral hepatitis-associated HCC. Most A-HCCs develop after alcohol-associated cirrhosis (AC), but the direct carcinogenesis from ethanol and its metabolites to A-HCC remains obscure. The differences between A-HCC and HCCs caused by other etiologies have not been well investigated in terms of clinical prognosis, genetic or epigenetic landscape, molecular mechanisms, and heterogeneity. Moreover, there is a huge gap between basic research and clinical practice due to the lack of preclinical models of A-HCC. In the current review, we discuss the pathogenesis, heterogeneity, preclinical approaches, epigenetic, and genetic profiles of A-HCC, and discuss the current insights into and the prospects for future research on A-HCC. The potential effect of alcohol on cholangiocarcinoma and liver metastasis is also discussed.
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Affiliation(s)
- Yaojie Fu
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Luca Maccioni
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
| | - Xin Wei Wang
- Liver Carcinogenesis Section, Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Tim F Greten
- Liver Cancer Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA
- Gastrointestinal Malignancies Section, Thoracic and Gastrointestinal Malignancies Branch, National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Bin Gao
- Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA
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Tseng YA, Ou YL, Geng JH, Wang CW, Wu DW, Chen SC, Lu PL. The association between alcohol, betel nut, and cigarette use with hepatitis C virus infection in Taiwan. Sci Rep 2023; 13:23082. [PMID: 38155257 PMCID: PMC10754914 DOI: 10.1038/s41598-023-50588-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 12/21/2023] [Indexed: 12/30/2023] Open
Abstract
Hepatitis C virus (HCV) infection may cause chronic liver disease, liver cirrhosis, and liver cancer. It has been reported to associate with habits including alcohol, betel nut and cigarette use. We aimed to investigate the association between alcohol, betel nut, and cigarette use with HCV infection in Taiwan and to explore their effects. A total of 121,421 participants were enrolled from the Taiwan Biobank. They were stratified into two groups according to whether they had (n = 2750; 2.3%) or did not have (n = 118,671; 97.7%) HCV infection. All participants were also classified into four groups according to the number of habits, including a history of alcohol drinking, betel nut chewing, and cigarette smoking. There were 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits) participants in the four groups, respectively. Multivariable analysis showed that the participants who had an alcohol drinking history (odds ratio [OR] 1.568; 95% confidence interval [CI] 1.388-1.773; p < 0.001), betel nut chewing history (OR 1.664; 95% CI 1.445-1.917; p < 0.001), cigarette smoking history (OR 1.387; 95% CI 1.254-1.535; p < 0.001), were significantly associated with HCV infection. Furthermore, the participants were classified into four groups according to the number of habits as follows: 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits). The HCV infection rates in these four groups were 2.11%, 2.14%, 3.23%, and 4.78%, respectively. Compared to the participants with no or one habit, those with two habits had a higher HCV infection rate (all p < 0.001). In addition, compared to the participants who had no, one or two habits, those who had three habits also had higher HCV infection rates (all p < 0.001). The participants who had three habits had the highest prevalence of HCV infection. In an era when most HCV can be cured, understanding the epidemiology link between habits and HCV may help the case finding.
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Affiliation(s)
- Yuan-Ai Tseng
- Department of Post Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC
| | - Yu-Lun Ou
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 482, Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung, 812, Taiwan, ROC
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Jiun-Hung Geng
- Department of Urology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 812, Taiwan, ROC
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC
| | - Chih-Wen Wang
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 482, Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung, 812, Taiwan, ROC
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC
| | - Da-Wei Wu
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 482, Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung, 812, Taiwan, ROC
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC
| | - Szu-Chia Chen
- Department of Post Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC.
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 482, Shan-Ming Rd., Hsiao-Kang Dist., Kaohsiung, 812, Taiwan, ROC.
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC.
- Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC.
| | - Po-Liang Lu
- Department of Post Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan, ROC.
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, No.100, Tzyou 1st Rd., Sanmin Dist., Kaohsiung City, 80756, Taiwan, ROC.
- Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
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Chandrababu G, Sah SK, Kumar AR, M S, Nath LR. Green Synthesized Nanoparticles as a Plausible Therapeutic Strategy Against Hepatocellular Carcinoma: An Update on its Preclinical and Clinical Relevance. Recent Pat Anticancer Drug Discov 2023; 18:268-291. [PMID: 35616675 DOI: 10.2174/1574892817666220523124437] [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: 10/13/2021] [Revised: 01/29/2022] [Accepted: 02/18/2022] [Indexed: 11/22/2022]
Abstract
Green nanotechnology can offer notable advantages over the conventional drug delivery methods in terms of improved drug stability, drug-carrying capacity, site-specificity, and feasibility to apply different routes of administration with less systemic toxicities. Metal nanoparticles bio fabricated with phytoconstituents and microbial extracts have gained significant interest for the treatment of various solid tumors including hepatocellular carcinoma. Hepatocellular carcinoma (HCC) is an aggressive cancer with a very poor prognosis. The current treatments of HCC fails to provide tumor specificity, causing many systemic toxicities and poor overall survival benefits especially for patients in advanced and terminal stages. A novel therapeutic approach with maximal therapeutic effect and minimum adverse effects are urgently required for HCC patients. Green synthesized metal nanoparticles offer significant anticancer effects along with minimal systemic toxicities because of their site-specific delivery into the tumor microenvironment (TME). Green synthesized metal nanoparticles can therefore be a highly beneficial strategy for the treatment of HCC if properly validated with preclinical and clinical studies. This review focuses on the preclinical evidence of the most widely studied green metal nanoparticles such as green synthesized silver nanoparticles, gold nanoparticles and selenium nanoparticles. We have also summarised the clinical studies and the patents approved for nanoparticles against HCC.
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Affiliation(s)
- Gopika Chandrababu
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi-682041, Kerala, India
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi-682041, Kerala, India
| | - Sunil Kumar Sah
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi-682041, Kerala, India
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi-682041, Kerala, India
| | - Ayana R Kumar
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi-682041, Kerala, India
- Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi-682041, Kerala, India
| | - Sabitha M
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi-682041, Kerala, India
| | - Lekshmi R Nath
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi-682041, Kerala, India
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Abassa KK, Wu XY, Xiao XP, Zhou HX, Guo YW, Wu B. Effect of alcohol on clinical complications of hepatitis virus-induced liver cirrhosis: a consecutive ten-year study. BMC Gastroenterol 2022; 22:130. [PMID: 35305565 PMCID: PMC8934474 DOI: 10.1186/s12876-022-02198-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 03/04/2022] [Indexed: 12/12/2022] Open
Abstract
Background and aims Although coexisting alcohol-induced liver disease and hepatitis B or C virus-induced liver cirrhosis (ALD + HBV or ALD + HCV) has been the center of recent hepatology researches, numerous controversies still persist. This study aimed to showcase the influence of alcohol on the laboratory values and on the clinical outcomes of patients with hepatitis B and C virus-induced liver cirrhosis. Methods Patients diagnosed with liver cirrhosis (n = 22,287) from January 2010 to December 2019 were enrolled, and divided into five groups according to the etiology: alcohol-induced liver disease (ALD, 1652 cases), hepatitis B virus (HBV, 18,079 cases), hepatitis C virus (HCV, 682 cases), ALD + HBV (1594 cases) and ALD + HCV (280 cases). Laboratory results and proportion of different liver cirrhosis complications were contrasted between groups. Results The proportions of patients with Child Pugh grade C (28.0% vs 18.8%, P < 0.001) or MELD greater than 18 (24.1% vs 18.5%, P < 0.001) in the ALD + HBV group exceeded significantly those in the HBV group. Multivariate logistic regression revealed that the risk of hepatocellular carcinoma (HCC) and that of esophageal gastric variceal bleeding (EGVB) in the ALD + HBV group was respectively 2.01-fold and 1.74-fold that in the HBV group (HCC: OR = 2.01, 95% CI [1.58–2.55]; EGVB: OR = 1.74, 95% CI [1.30–2.33]) after adjusting for potential confounders. Furthermore, a linear-by-linear analysis test showed a decrease in the risk of HCC and EGVB with the duration of alcohol abstinence. Moreover, patients with both antiviral treatment and alcohol abstinence had the lowest risk of HCC and EGVB (HCC: OR = 0.10, 95% CI [0.05–0.20], P < 0.001; EGVB: OR = 0.17, 95% CI [0.06–0.45], P < 0.001) compared to those without any treatment, those with abstinence alone and those with antiviral therapy alone. Similar pattern was noticed while comparing the ALD + HCV group to the HCV group. Conclusion Heavy alcohol use increased the severity of liver function impairment and the prevalence of HCC and EGVB in hepatitis virus-induced liver cirrhosis patients. Remarkably, long-term alcohol abstinence coupled with antiviral treatment effectively decreased the risk of HCC and EGVB in these populations. Supplementary Information The online version contains supplementary material available at 10.1186/s12876-022-02198-w.
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Xu HQ, Wang CG, Zhou Q, Gao YH. Effects of alcohol consumption on viral hepatitis B and C. World J Clin Cases 2021; 9:10052-10063. [PMID: 34904075 PMCID: PMC8638036 DOI: 10.12998/wjcc.v9.i33.10052] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/15/2021] [Accepted: 08/25/2021] [Indexed: 02/06/2023] Open
Abstract
The liver is the main target organ for hepatitis viruses and the vital organ for alcohol metabolism. These two factors of viral hepatitis and alcohol abuse in combination can exert dual harmful actions, leading to enhanced damage to the liver. Epidemiological studies have revealed a higher prevalence of hepatitis C virus (HCV) infection among alcoholics than the general population. The interaction of alcohol with viral hepatitis [e.g., hepatitis B virus (HBV), HCV] and the underlying mechanisms are not fully understood. The effects of alcohol on viral hepatitis include promoted viral replication, weakened immune response, and increased oxidative stress. Clinically, alcohol abuse is correlated with an increased risk of developing end-stage liver cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B and C, suggesting that the combination of alcohol and HBV/HCV lead to more severe liver damage. The influence of mild to moderate alcohol drinking on the HBV-induced liver fibrosis, cirrhosis, and hepatocellular carcinoma among patients infected with HBV remains unclear. Unlike HBV infected patients, no safe level of alcohol intake has been established for patients with HCV. Even light to moderate alcohol use can exert a synergistic effect with viral hepatitis, leading to the rapid progression of liver disease. Furthermore, interferon-based therapy is less effective in alcohol drinkers than in control patients, even after abstinence from alcohol for a period of time. Therefore, abstaining from alcohol is highly recommended to protect the liver, especially in individuals with HBV/HCV infection, to improve the clinical efficacy of antiviral treatment and prevent the rapid progression of chronic viral hepatitis.
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Affiliation(s)
- Hong-Qin Xu
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Chun-Guang Wang
- Department of Surgery, The Second Hospital of Jilin University, Jilin University, Changchun 130041, Jilin Province, China
| | - Qiang Zhou
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
| | - Yan-Hang Gao
- Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
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Huang Y, Tu WL, Yao YQ, Cai YL, Ma LP. Construction of a Novel Gene-Based Model for Survival Prediction of Hepatitis B Virus Carriers With HCC Development. Front Genet 2021; 12:720888. [PMID: 34531900 PMCID: PMC8439286 DOI: 10.3389/fgene.2021.720888] [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: 06/09/2021] [Accepted: 07/30/2021] [Indexed: 11/14/2022] Open
Abstract
Despite the effectiveness of hepatitis B virus (HBV) vaccination in reducing the prevalence of chronic HBV infection as well as the incidence of acute hepatitis B, fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC), there was still a large crowd of chronically infected populations at risk of developing cirrhosis or HCC. In this study, we established a comprehensive prognostic system covering multiple signatures to elevate the predictive accuracy for overall survival (OS) of hepatitis B virus carriers with HCC development. Weighted Gene Co-Expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine Recursive Feature Elimination (SVM-RFE), and multivariate COX analysis, along with a suite of other online analyses were successfully applied to filtrate a three-gene signature model (TP53, CFL1, and UBA1). Afterward, the gene-based risk score was calculated based on the Cox coefficient of the individual gene, and the prognostic power was assessed by time-dependent receiver operating characteristic (tROC) and Kaplan–Meier (KM) survival analysis. Furthermore, the predictive power of the nomogram, integrated with the risk score and clinical parameters (age at diagnosis and TNM stage), was revealed by the calibration plot and tROC curves, which was verified in the validation set. Taken together, our study may be more effective in guiding the clinical decision-making of personalized treatment for HBV carriers.
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Affiliation(s)
- Yuan Huang
- Department of Biochemistry and Molecular Biology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, China
| | - Wen-Ling Tu
- Department of Genetics, School of Bioscience and Technology, Chengdu Medical College, Chengdu, China.,The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, China
| | - Yan-Qiu Yao
- Department of Biochemistry and Molecular Biology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, China
| | - Ye-Ling Cai
- Department of Biochemistry and Molecular Biology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, China
| | - Li-Ping Ma
- Department of Biochemistry and Molecular Biology, School of Bioscience and Technology, Chengdu Medical College, Chengdu, China
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Donato F, Moneda M, Portolani N, Rossini A, Molfino S, Ministrini S, Contessi GB, Pesenti S, De Palma G, Gaia A, Zanardini E, Sileo CV, Magoni M. Polychlorinated biphenyls and risk of hepatocellular carcinoma in the population living in a highly polluted area in Italy. Sci Rep 2021; 11:3064. [PMID: 33542320 PMCID: PMC7862237 DOI: 10.1038/s41598-021-82657-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2020] [Accepted: 01/08/2021] [Indexed: 01/23/2023] Open
Abstract
Polychlorinated biphenyls (PCBs) are human carcinogens, based on sufficient evidence for melanoma and limited evidence for non-Hodgkin lymphoma and breast cancer. Few data are available for liver cancer, although PCBs cause it in rats and determined liver damage in poisoned people. We investigated the association between PCB serum levels and hepatocellular carcinoma (HCC) with a case-control study in a PCB-polluted area in North Italy. We enrolled prospectively 102 HCC incident cases and 102 age and gender-matched hospital controls. Serum concentrations of 33 PCB congeners were determined by a gas chromatograph coupled to mass spectrometry. Of 102 HCC cases, 62 who had lost < 3 kg of body weight in past 3 years were included in the analysis (67.7% males, mean age 68 years). The odds ratio (OR) for HCC for 3rd compared to 1st tertile of PCB distribution was 1.76 (95% confidence interval 0.62-5.03) for total PCB, adjusting for socio-demographic variables and risk factors for HCC by logistic regression. For most PCB congeners, ORs > 1.5 or 2 were found, although the 95% CIs included the null value for almost all of them. This preliminary study suggests that PCBs might play a role in HCC development.
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Affiliation(s)
- Francesco Donato
- Unit of Hygiene, Epidemiology and Public Health, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
| | - Marco Moneda
- Post-Graduate School of Public Health, University of Brescia, Brescia, Italy
| | - Nazario Portolani
- Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, Brescia, Italy
| | - Angelo Rossini
- Hepatology Unit, Spedali Civili General Hospital, ASST (Territorial Socio-Sanitary Agency) Spedali Civili Di Brescia, Brescia, Italy
| | - Sarah Molfino
- Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, Brescia, Italy
| | - Silvia Ministrini
- Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, Brescia, Italy
| | - Giovanni Battista Contessi
- Hepatology Unit, Spedali Civili General Hospital, ASST (Territorial Socio-Sanitary Agency) Spedali Civili Di Brescia, Brescia, Italy
| | - Silvia Pesenti
- Hepatology Unit, Spedali Civili General Hospital, ASST (Territorial Socio-Sanitary Agency) Spedali Civili Di Brescia, Brescia, Italy
| | - Giuseppe De Palma
- Unit of Occupational Health and Industrial Hygiene, University of Brescia, Brescia, Italy
- Unit of Occupational Health, Hygiene, Toxicology and Prevention, ASST (Territorial Socio-Sanitary Agency) Spedali Civili Di Brescia, Brescia, Italy
| | - Alice Gaia
- Unit of Occupational Health, Hygiene, Toxicology and Prevention, ASST (Territorial Socio-Sanitary Agency) Spedali Civili Di Brescia, Brescia, Italy
| | - Elena Zanardini
- Post-Graduate School of Public Health, University of Brescia, Brescia, Italy
| | | | - Michele Magoni
- ATS Brescia (Brescia Health Protection Agency), Brescia, Italy
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11
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Abstract
Liver cancer is a global problem and hepatocellular carcinoma (HCC) accounts for about 85% of this cancer. In the USA, etiologies and risk factors for HCC include chronic hepatitis C virus (HCV) infection, diabetes, non-alcoholic steatohepatitis (NASH), obesity, excessive alcohol drinking, exposure to tobacco smoke, and genetic factors. Chronic HCV infection appears to be associated with about 30% of HCC. Chronic HCV infection induces multistep changes in liver, involving metabolic disorders, steatosis, cirrhosis and HCC. Liver carcinogenesis requires initiation of neoplastic clones, and progression to clinically diagnose malignancy. Tumor progression associates with profound exhaustion of tumor-antigen-specific CD8+T cells, and accumulation of PD-1hi CD8+T cells and Tregs. In this chapter, we provide a brief description of HCV and environmental/genetic factors, immune regulation, and highlight mechanisms of HCV associated HCC. We also underscore HCV treatment and recent paradigm of HCC progression, highlighted the current treatment and potential future therapeutic opportunities.
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12
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Esmaeili A, Yu W, Cucciare MA, Combs AS, Joshi G, Humphreys K. Budget Impact Analysis of a Computer-Delivered Brief Alcohol Intervention in Veterans Affairs (VA) Liver Clinics: A Randomized Controlled Trial. ALCOHOLISM TREATMENT QUARTERLY 2020. [DOI: 10.1080/07347324.2020.1760755] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Aryan Esmaeili
- U.S. Department of Veterans Affairs, Health Economics Resource Center, Menlo Park, California, USA
| | - Wei Yu
- U.S. Department of Veterans Affairs, Health Economics Resource Center, Menlo Park, California, USA
| | - Michael A. Cucciare
- Center for Mental Healthcare and Outcomes Research, Central Arkansas Veterans Affairs Healthcare System, North Little Rock, Arkansas, USA
- Veterans Affairs South Central Mental Illness Research, Education and Clinical Center, Central Arkansas Veterans Healthcare System, North Little Rock, Arkansas, USA
- Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
| | - Ann S. Combs
- Center for Innovation to Implementation, Veterans Affairs Palo Alto Health Care System, Menlo Park, California, USA
| | - Gauri Joshi
- Center for Innovation to Implementation, Veterans Affairs Palo Alto Health Care System, Menlo Park, California, USA
| | - Keith Humphreys
- Center for Innovation to Implementation, Veterans Affairs Palo Alto Health Care System, Menlo Park, California, USA
- Department of Psychiatry, Stanford University, Stanford, California, USA
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13
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Shawon MAA, Yousuf MAK, Raheem E, Ahmed S, Dipti TT, Hoque MR, Taniguchi H, Karim MR. Epidemiology, clinical features, and impact of food habits on the risk of hepatocellular carcinoma: A case-control study in Bangladesh. PLoS One 2020; 15:e0232121. [PMID: 32339207 PMCID: PMC7185601 DOI: 10.1371/journal.pone.0232121] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 04/07/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most common cause of cancer mortality worldwide. Infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) is the most predominant cause of HCC. Concerns arise for the presence of additional risk factors, as there is still a large proportion of patients without HBV or HCV infection. Previous studies have reported that higher intake of fruits and vegetables and reduced consumption of red/processed meat might play a protective role in HCC etiology, though the nationwide proof is limited. Hence, we studied multiple risk factors including food habit, lifestyle, and clinical implications of HCC patients in Bangladeshi. Demographic, clinical, and biochemical data, as well as data on food habits, were collected in this study. Our results indicated that a high intake of rice (AOR 4.28, 95% CI 1.48 to 14.07, p = 0.011), low intake of fruits (AOR = 4.41 95% CI 1.48-15.46; p = 0.012), leafy vegetables (AOR = 2.80, 95% CI 1.32-6.08; p = 0.008), and fish (AOR = 4.64 95% CI 2.18-10.23; p<0.001) increased the HCC risk. Moreover, a high intake of eggs (AOR = 2.07 95% CI 0.98-4.43; p = 0.058) also showed an increased risk. Roti, non-leafy vegetables, red meat, and tea were found to have no association with HCC risk. This study revealed that food habit patterns and lifestyle may have a profound effect on HCC development among Bangladeshi patients in addition to well established risk factors.
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Affiliation(s)
- M. Al-Amin Shawon
- Laboratory for Cancer Biology, Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka, Bangladesh
| | - M. Abul Khair Yousuf
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | | | - Sium Ahmed
- Laboratory for Cancer Biology, Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka, Bangladesh
| | - Tyeaba Tasnim Dipti
- Laboratory for Cancer Biology, Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka, Bangladesh
| | - Mohammad Razuanul Hoque
- Department of Biochemistry and Molecular Biology, University of Chittagong, Chittagong, Bangladesh
| | - Hiroaki Taniguchi
- Institute of Genetics and Animal Breeding of the Polish Academy of Sciences, Jastrzebiec, Magdalenka, Poland
| | - M. Rezaul Karim
- Laboratory for Cancer Biology, Department of Biotechnology and Genetic Engineering, Jahangirnagar University, Savar, Dhaka, Bangladesh
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14
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Ganesan M, Eikenberry A, Poluektova LY, Kharbanda KK, Osna NA. Role of alcohol in pathogenesis of hepatitis B virus infection. World J Gastroenterol 2020; 26:883-903. [PMID: 32206001 PMCID: PMC7081008 DOI: 10.3748/wjg.v26.i9.883] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 02/09/2020] [Accepted: 02/15/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) and alcohol abuse often contribute to the development of end-stage liver disease. Alcohol abuse not only causes rapid progression of liver disease in HBV infected patients but also allows HBV to persist chronically. Importantly, the mechanism by which alcohol promotes the progression of HBV-associated liver disease are not completely understood. Potential mechanisms include a suppressed immune response, oxidative stress, endoplasmic reticulum and Golgi apparatus stresses, and increased HBV replication. Certainly, more research is necessary to gain a better understanding of these mechanisms such that treatment(s) to prevent rapid liver disease progression in alcohol-abusing HBV patients could be developed. In this review, we discuss the aforementioned factors for the higher risk of liver diseases in alcohol-induced HBV pathogenies and suggest the areas for future studies in this field.
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Affiliation(s)
- Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Allison Eikenberry
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Larisa Y Poluektova
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
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15
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Kumar A, Acharya SK, Singh SP, Arora A, Dhiman RK, Aggarwal R, Anand AC, Bhangui P, Chawla YK, Datta Gupta S, Dixit VK, Duseja A, Kalra N, Kar P, Kulkarni SS, Kumar R, Kumar M, Madhavan R, Mohan Prasad V, Mukund A, Nagral A, Panda D, Paul SB, Rao PN, Rela M, Sahu MK, Saraswat VA, Shah SR, Shalimar, Sharma P, Taneja S, Wadhawan M. 2019 Update of Indian National Association for Study of the Liver Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri II Recommendations. J Clin Exp Hepatol 2020; 10:43-80. [PMID: 32025166 PMCID: PMC6995891 DOI: 10.1016/j.jceh.2019.09.007] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/15/2019] [Indexed: 01/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations.
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Key Words
- AFP, alpha-fetoprotein
- AIH, autoimmune hepatitis
- ALT, alanine aminotransferase
- DAA, direct-acting antiviral
- DALY, disability-adjusted life-year
- DNA, deoxyribonucleic acid
- GRADE, Grading of Recommendations Assessment Development and Evaluation
- Gd-BOPTA, gadolinium benzyloxypropionictetraacetate
- Gd-EOB-DTPA, gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid
- HBV, hepatitis B virus
- HBeAg, hepatitis B envelope antigen
- HCC, hepatocellular carcinoma
- HIV, human immunodeficiency virus
- IARC, International Agency for Research on Cancer
- IFN, interferon
- INASL, Indian National Association for Study of the Liver
- MiRNA, micro-RNA
- NAFLD, non-alcoholic fatty liver disease
- NASH, non-alcoholic steatohepatitis
- PIVKA, protein induced by vitamin K absence
- RFA
- RNA, ribonucleic acid
- SVR, sustained virological response
- TACE
- TACE, trans-arterial chemoembolization
- TARE, transarterial radioembolization
- TNF, tumor necrosis factor
- WHO, World Health Organization
- liver cancer
- targeted therapy
- transplant
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Affiliation(s)
- Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Subrat K. Acharya
- Department of Gastroenterology and Hepatology, KIIT University, Patia, Bhubaneswar, Odisha, 751 024, India
| | - Shivaram P. Singh
- Department of Gastroenterology, SCB Medical College, Cuttack, Dock Road, Manglabag, Cuttack, Odisha, 753 007, India
| | - Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Anil C. Anand
- Department of Gastroenterology, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110 076, India
| | - Prashant Bhangui
- Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta the Medicity, CH Baktawar Singh Road, Sector 38, Gurugram, Haryana, 122 001, India
| | - Yogesh K. Chawla
- Department of Gastroenterology, Kalinga Institute of Medical Sciences (KIMS), Kushabhadra Campus (KIIT Campus-5), Patia, Bhubaneswar, Odisha, 751 024, India
| | - Siddhartha Datta Gupta
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221 005, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Naveen Kalra
- Department of Radio Diagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Premashish Kar
- Department of Gastroenterology and Hepatology, Max Super Speciality Hospital, Vaishali, Ghaziabad, Uttar Pradesh, 201 012, India
| | - Suyash S. Kulkarni
- Division of Interventional Radiology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, Maharashtra, 400 012, India
| | - Rakesh Kumar
- Department of Nuclear Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver & Biliary Sciences, Sector D-1, Vasant Kunj, New Delhi, 110 070, India
| | - Ram Madhavan
- Department of Radiation Oncology, Amrita Institute of Medical Sciences, Amrita University, Peeliyadu Road, Ponekkara, Edappally, Kochi, Kerala, 682 041, India
| | - V.G. Mohan Prasad
- Department of Gastroenterology, VGM Gastro Centre, 2100, Trichy Road, Rajalakshmi Mills Stop, Singanallur, Coimbatore, Tamil Nadu, 641 005, India
| | - Amar Mukund
- Department of Radiology, Institute of Liver & Biliary Sciences, Sector D-1, Vasant Kunj, New Delhi, 110 070, India
| | - Aabha Nagral
- Department of Gastroenterology, Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Dipanjan Panda
- Department of Oncology, Institutes of Cancer, Indraprastha Apollo Hospital, Sarita Vihar, New Delhi, 110 076, India
| | - Shashi B. Paul
- Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Padaki N. Rao
- Department of Medical Gastroenterology, Asian Institute of Gastroenterology, No. 6-3-661, Punjagutta Road, Somajiguda, Hyderabad, Telangana, 500 082, India
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Gleneagles Global Health City, 439, Cheran Nagar, Perumbakkam, Chennai, Tamil Nadu, 600 100, India
| | - Manoj K. Sahu
- Department of Medical Gastroenterology, IMS & SUM Hospital, K8 Kalinga Nagar, Shampur, Bhubaneswar, Odisha 751 003, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, 226 014, India
| | - Samir R. Shah
- Department of Gastroenterology, Jaslok Hospital & Research Centre, 15, Dr Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, 400 026, India
| | - Shalimar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110 060, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160 012, India
| | - Manav Wadhawan
- Liver & Digestive Diseases Institute, Institute of Liver & Digestive Diseases, BLK Super Specialty Hospital, Delhi, 110 005, India
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16
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Ling C, Khalid S, Martin D, Hanson J, Castresana D, McCarthy D. HCCs and HCAs in Non-cirrhotic Patients: What You See May Not Be Enough. Dig Dis Sci 2019; 64:3440-3445. [PMID: 31673903 DOI: 10.1007/s10620-019-05920-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Christina Ling
- Division of Gastroenterology and Hepatology, University of New Mexico School of Medicine, Albuquerque, NM, USA.
| | - Sameen Khalid
- Division of Gastroenterology and Hepatology, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - David Martin
- Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Joshua Hanson
- Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Daniel Castresana
- Division of Gastroenterology and Hepatology, University of New Mexico School of Medicine, Albuquerque, NM, USA
| | - Denis McCarthy
- Division of Gastroenterology and Hepatology, University of New Mexico School of Medicine, Albuquerque, NM, USA
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17
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Heo MJ, Yun J, Kim SG. Role of non-coding RNAs in liver disease progression to hepatocellular carcinoma. Arch Pharm Res 2019; 42:48-62. [PMID: 30610616 DOI: 10.1007/s12272-018-01104-x] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 12/23/2018] [Indexed: 12/17/2022]
Abstract
Hepatocellular carcinoma (HCC) is a tumor with poor prognosis and frequently aggressive. The development of HCC is associated with fibrosis and cirrhosis, which mainly results from nonalcoholic fatty liver disease, excessive alcohol consumption, and viral infections. Non-coding RNAs (ncRNAs) are RNAs transcribed from the genome, but are not translated into proteins. Recently, ncRNAs emerged as key contributors to tumor development and progression because of their abilities to regulate various targets and modulate cell proliferation, differentiation, apoptosis, and development. In this review, we summarize the frequently activated pathways in HCC and discuss the pathological implications of ncRNAs in the context of human liver disease progression, in particular HCC development and progression. This review aims to summarize the role of ncRNA dysregulation in the diseases and discuss the diagnostic and therapeutic potentials of ncRNAs.
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Affiliation(s)
- Mi Jeong Heo
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanakro, Seoul, 08826, South Korea
| | - Jessica Yun
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanakro, Seoul, 08826, South Korea
| | - Sang Geon Kim
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 1 Gwanakro, Seoul, 08826, South Korea.
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18
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Evaluation of hepatitis A, B, and C serology in patients with cirrhosis and intensive alcohol consumption. North Clin Istanb 2018; 5:109-113. [PMID: 30374475 PMCID: PMC6191551 DOI: 10.14744/nci.2018.50570] [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: 02/06/2018] [Accepted: 04/25/2018] [Indexed: 11/20/2022] Open
Abstract
OBJECTIVE The objective of this study was to evaluate the serology of hepatitis A, B, and C in patients with cirrhosis and intensive alcohol consumption. METHODS We retrospectively reviewed the viral serology results of 817 patients with cirrhosis and intensive alcohol consumption who presented to the Gastroenterology Clinic of Atatürk Training and Research Hospital of Izmir Katip Çelebi University between April 2008 and December 2017. The diagnosis of cirrhosis was based on clinical and biochemical evaluations and imaging results. Patients consuming absolute alcohol 40 g/day for >10 years were included and those who quit drinking ≥15 years ago were excluded. RESULTS Of all the patients, 806 (98.7%) were positive for anti-HAV IgG, 159 (19.5%) for HBsAg, and 32 (3.9%) for anti-HCV. Genotyping was performed in 13 patients. Genotype 1 was detected in 10 patients (1a, one patient; 1b, nine patients) and genotype 3 in three patients. Of the patients with HBV, 10.0% had HBeAg and 7.6% had anti-delta. One-hundred and two (12.5%) patients had HCC, and of these, six (5.9%) were HCV-positive and 53 (52.0%) were HBsAg-positive. CONCLUSION Patients with cirrhosis and intensive alcohol consumption have an increased hepatitis B and C prevalence. Patients with chronic viral hepatitis with alcohol habit are at a higher risk for HCC. Therefore, patients with cirrhosis and intensive alcohol consumption should be screened for hepatitis B and C.
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19
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Proeschold-Bell RJ, Evon DM, Makarushka C, Wong JB, Datta SK, Yao J, Patkar AA, Mannelli P, Hodge T, Naggie S, Wilder JM, Fried MW, Niedzwiecki D, Muir AJ. The Hepatitis C-Alcohol Reduction Treatment (Hep ART) intervention: Study protocol of a multi-center randomized controlled trial. Contemp Clin Trials 2018; 72:73-85. [PMID: 30006024 PMCID: PMC6711183 DOI: 10.1016/j.cct.2018.07.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Revised: 05/25/2018] [Accepted: 07/09/2018] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Among patients with hepatitis C virus (HCV) infection, alcohol synergistically increases the risk of cirrhosis, hepatocellular carcinoma, and death. Randomized controlled trials of integrated models of HCV-alcohol treatment have been recommended but only performed in patients with severe alcohol use disorders. OBJECTIVES This pragmatic randomized controlled trial seeks to compare clinical effectiveness and cost-effectiveness of integrated alcohol treatment compared to enhanced treatment as usual (TAU) on alcohol consumption and economic outcomes among patients ever infected with HCV. METHODS Patients recruited from three liver centers who had current or prior chronic HCV and qualifying alcohol screener scores were randomly assigned to enhanced TAU or the Hepatitis C-Alcohol Reduction Treatment (Hep ART) intervention. All patients received enhanced TAU, consisting of a patient-administered alcohol screener and care from medical providers who were trained in Screening, Brief Intervention and Referral to Treatment (SBIRT), including brief motivational interviewing counseling. The Hep ART intervention combined enhanced TAU with up to six months of integrated co-located individual and/or group therapy that provided motivational, cognitive, and behavioral strategies to reduce alcohol consumption. The Timeline Followback (TLFB) Method was used to evaluate alcohol use at baseline, 3, 6, and 12 months. Primary outcomes are alcohol abstinence and fewer heavy drinking days, and for the cost-effectiveness analysis, measures included grams of alcohol consumed. DISCUSSION This study will determine whether Hep ART, a six-month integrated alcohol treatment, compared to enhanced TAU, is both clinically effective and cost-effective in patients with a history of comorbid HCV and alcohol use.
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Affiliation(s)
- Rae Jean Proeschold-Bell
- Duke Global Health Institute, Duke University, Box 90392, Durham, NC 27708-0392, USA; Duke Center for Health Policy & Inequalities Research, Duke University, Box 90392, Durham, NC 27708-0392, USA.
| | - Donna M Evon
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, CB# 7584, Chapel Hill, NC 27599-7584, United States.
| | - Christina Makarushka
- Duke Center for Health Policy & Inequalities Research, Duke University, Box 90392, Durham, NC 27708-0392, USA.
| | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, 800 Washington St #302, Boston, MA 02111, USA.
| | - Santanu K Datta
- Department of Medicine, Duke University, 411 West Chapel Hill St, Suite 500, Durham, NC 27701, USA.
| | - Jia Yao
- Duke Center for Health Policy & Inequalities Research, Duke University, Box 90392, Durham, NC 27708-0392, USA.
| | - Ashwin A Patkar
- Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 2213 Elba Street, Suite 165, Durham, NC 27705, United States; Department of Community and Family Medicine, Duke University Medical Center, 2213 Elba Street, Suite 165, Durham, NC 27705, United States.
| | - Paolo Mannelli
- Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 2213 Elba Street, Suite 165, Durham, NC 27705, United States.
| | - Terra Hodge
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, DUMC 3913, Durham, NC 27710, USA.
| | - Susanna Naggie
- Duke University School of Medicine, Infectious Diseases, Durham, NC 27710, USA; Duke Clinical Research Institute, 2400 Pratt Street, Rm. 0311, Terrace Level, Durham, NC 27705, USA; Durham VA Medical Center, Durham, NC 27705, USA.
| | - Julius M Wilder
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, DUMC 3913, Durham, NC 27710, USA; Duke Clinical Research Institute, 2400 Pratt Street, Rm. 0311, Terrace Level, Durham, NC 27705, USA.
| | - Michael W Fried
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina, CB# 7584, Chapel Hill, NC 27599-7584, United States.
| | - Donna Niedzwiecki
- Department of Biostatistics and Bioinformatics, Duke University, Box 2721, Durham, NC 27710, United States.
| | - Andrew J Muir
- Division of Gastroenterology, Department of Medicine, Duke University School of Medicine, DUMC 3913, Durham, NC 27710, USA; Duke Clinical Research Institute, 2400 Pratt Street, Rm. 0311, Terrace Level, Durham, NC 27705, USA.
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20
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Kim H, Chung YK, Kim I. Recognition criteria for occupational cancers in relation to hepatitis B virus and hepatitis C virus in Korea. Ann Occup Environ Med 2018; 30:6. [PMID: 29423229 PMCID: PMC5791172 DOI: 10.1186/s40557-018-0217-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Accepted: 01/17/2018] [Indexed: 01/05/2023] Open
Abstract
The goal of this study was to review the scientific basis for the recognition of occupational cancer, in relation to hepatitis viral infections in Korea. Most Hepatitis B virus (HBV) infections in Korea occur as vertical infections, but these are decreasing rapidly due to vaccination. Hepatitis C virus (HCV) is known to be transmitted through parenteral routes, but the transmission route is often unclear. Most occupational infections of hepatitis virus involve accidental injuries of medical institution workers while using virus-contaminated medical devices. Many cohort studies and case-control studies have consistently reported that HBV and HCV infection increases the risk of hepatocellular carcinoma (HCC) and the strength of this association is high. Non-Hodgkin’s lymphoma appears to be associated with HCV. Cholangiocarcinoma, pancreatic cancer, leukemia, and thyroid cancer are considered to be less related or unrelated to epidemiological causation. There are no uniform international specific criteria for occupational cancer caused through occupational exposure to a hepatitis virus. In establishing appropriate standards applicable to Korea, there should be sufficient consideration of latency, virus exposure levels and frequency, and other cancers, apart from HCC. In conclusion, we recommend keeping the current specific criteria. However, if a worker is injured at work when using a sharp medical device, and HBV and HCV viral infections are confirmed through serologic tests; if the worker is diagnosed as having a chronic HBV or HCV infection, a subsequent HCC (or Non-Hodgkin’s lymphoma following chronic HCV infection) can then be considered highly related to the worker’s occupation.
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Affiliation(s)
- Hogil Kim
- 1Department of Occupational and Environmental Medicine, Hanyang University College of Medicine, 222-1, Wansimniro, Seongdonggu, Seoul, 04763 South Korea
| | | | - Inah Kim
- 1Department of Occupational and Environmental Medicine, Hanyang University College of Medicine, 222-1, Wansimniro, Seongdonggu, Seoul, 04763 South Korea
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21
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Burra P, Zanetto A, Germani G. Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma. Cancers (Basel) 2018; 10:E46. [PMID: 29425151 PMCID: PMC5836078 DOI: 10.3390/cancers10020046] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2017] [Revised: 02/01/2018] [Accepted: 02/07/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128 Padua, Italy.
| | - Alberto Zanetto
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128 Padua, Italy.
| | - Giacomo Germani
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Via Giustiniani 2, 35128 Padua, Italy.
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22
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Ren B, Zou G, Xu F, Huang Y, Xu G, He J, Li Y, Zhu H, Yu P. Serum levels of anti-sperm-associated antigen 9 antibody are elevated in patients with hepatocellular carcinoma. Oncol Lett 2017; 14:7608-7614. [PMID: 29344208 DOI: 10.3892/ol.2017.7152] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Accepted: 01/19/2017] [Indexed: 02/06/2023] Open
Abstract
At present, there is a high incidence of viral hepatitis and high mortality rates due to hepatocellular carcinoma (HCC) in China. In the current study, the quantification of antibodies against the cancer-testis antigen sperm-associated antigen 9 (SPAG9), alone and combined with α-fetoprotein (AFP), were evaluated as biomarkers for the diagnosis of HCC. The levels of anti-SPAG9 antibody and AFP were quantified in serum samples from patients with HCC and hepatitis or cirrhosis, as well as healthy volunteers. The results revealed that the serum levels of anti-SPAG9 immunoglobulin G antibody in patients with HCC were significantly higher compared with those in patients with hepatitis/cirrhosis and healthy controls. Using receiver operator characteristic curves, the area under the curve (AUC, 0.870) of SPAG9 as a diagnostic marker of HCC was significant [P<0.001; 95% confidence interval (CI), 0.793-0.947], whereas the AUC of AFP was 0.832 (P<0.001; 95% CI, 0.736-0.928). Serum anti-SPAG9 antibody levels exhibited significant potential for the differential diagnosis of HCC, with an AUC value of 0.729, (P=0.008; 95% CI, 0.559-0.899). Similarly, serum AFP levels exhibited significant value for the differential diagnosis of HCC, with an AUC value of 0.842 (P<0.001; 95% CI, 0.732-0.953). When combined with quantification of AFP, the diagnostic sensitivity and specificity of anti-SPAG9 levels were increased. In summary, the results suggested that anti-SPAG9 antibody is a potential early diagnostic marker of HCC.
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Affiliation(s)
- Biqiong Ren
- Clinical Laboratory, Hunan Provincial Second People's Hospital, Changsha, Hunan 410007, P.R. China.,Clinical Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.,Department of Immunology, School of Basic Medicine, Central South University, Changsha, Hunan 410078, P.R. China
| | - Guoying Zou
- Clinical Laboratory, Hunan Provincial Second People's Hospital, Changsha, Hunan 410007, P.R. China.,Clinical Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.,Department of Immunology, School of Basic Medicine, Central South University, Changsha, Hunan 410078, P.R. China
| | - Fei Xu
- Clinical Laboratory, Hunan Provincial Second People's Hospital, Changsha, Hunan 410007, P.R. China.,Clinical Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China
| | - Yiran Huang
- Clinical Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China
| | - Guofeng Xu
- Clinical Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.,Department of Immunology, School of Basic Medicine, Central South University, Changsha, Hunan 410078, P.R. China
| | - Junyu He
- Clinical Laboratory, Hunan Provincial Second People's Hospital, Changsha, Hunan 410007, P.R. China.,Clinical Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.,Department of Immunology, School of Basic Medicine, Central South University, Changsha, Hunan 410078, P.R. China
| | - Yong Li
- Clinical Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.,Department of Immunology, School of Basic Medicine, Central South University, Changsha, Hunan 410078, P.R. China
| | - Haowen Zhu
- Clinical Medical School, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.,Department of Immunology, School of Basic Medicine, Central South University, Changsha, Hunan 410078, P.R. China
| | - Ping Yu
- Department of Immunology, School of Basic Medicine, Central South University, Changsha, Hunan 410078, P.R. China
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23
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Singh S, Osna NA, Kharbanda KK. Treatment options for alcoholic and non-alcoholic fatty liver disease: A review. World J Gastroenterol 2017; 23:6549-6570. [PMID: 29085205 PMCID: PMC5643281 DOI: 10.3748/wjg.v23.i36.6549] [Citation(s) in RCA: 164] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Revised: 07/25/2017] [Accepted: 09/05/2017] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma. Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver (simple steatosis), a small percentage develops progressive liver disease. Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available. The treatment for ALD remains as it was 50 years ago: abstinence, nutritional support and corticosteroids (or pentoxifylline as an alternative if steroids are contraindicated). As for NAFLD, the treatment modality is mainly directed toward weight loss and co-morbidity management. Therefore, new pathophysiology directed therapies are urgently needed. However, the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy. Hence, a combination therapy towards multiple targets would eventually be required. In this review, we delineate the treatment options in ALD and NAFLD, including various new targeted therapies that are currently under investigation. We hope that soon we will be having an effective multi-therapeutic regimen for each disease.
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Affiliation(s)
- Sukhpreet Singh
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
| | - Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Nebraska Medical Center, Omaha, NE 68198, United States
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Nebraska Medical Center, Omaha, NE 68198, United States
- Department of Biochemistry and Molecular Biology, Nebraska Medical Center, Omaha, NE 68198, United States
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24
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Zheng H, Zou AE, Saad MA, Wang XQ, Kwok JG, Korrapati A, Li P, Kisseleva T, Wang-Rodriguez J, Ongkeko WM. Alcohol-dysregulated microRNAs in hepatitis B virus-related hepatocellular carcinoma. PLoS One 2017; 12:e0178547. [PMID: 28562643 PMCID: PMC5451132 DOI: 10.1371/journal.pone.0178547] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 05/15/2017] [Indexed: 12/17/2022] Open
Abstract
Alcohol consumption and chronic hepatitis B virus (HBV) infection are two well-established risk factors for Hepatocellular carcinoma (HCC); however, there remains a limited understanding of the molecular pathway behind the pathogenesis and progression behind HCC, and how alcohol promotes carcinogenesis in the context of HBV+ HCC. Using next-generation sequencing data from 130 HCC patients and 50 normal liver tissues, we identified a panel of microRNAs that are significantly dysregulated by alcohol consumption in HBV+ patients. In particular, two microRNAs, miR-944 and miR-223-3p, showed remarkable correlation with clinical indication and genomic alterations. We confirmed the dysregulation of these two microRNAs in liver cell lines treated by alcohol and acetaldehyde, and showed that manipulation of miR-223-3p and miR-944 expression induces significant changes in cellular proliferation, sensitivity to doxorubicin, and the expression of both direct-binding and downstream mRNA targets. Together, the results of this study suggest that alcohol consumption in HBV+ HCCs regulates microRNAs that likely play previously uncharacterized roles in the alcohol-associated carcinogenesis of HCC, and future studies of these microRNAs may be valuable for furthering the understanding and treatment of alcohol and HBV-associated HCC.
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Affiliation(s)
- Hao Zheng
- Department of Surgery, University of California, San Diego, La Jolla, California, United States of America
| | - Angela E. Zou
- Department of Surgery, University of California, San Diego, La Jolla, California, United States of America
| | - Maarouf A. Saad
- School of medicine, Yale University, New Haven, Connecticut, United States of America
| | - Xiao Qi Wang
- Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - James G. Kwok
- Department of Surgery, University of California, San Diego, La Jolla, California, United States of America
| | - Avinaash Korrapati
- Department of Surgery, University of California, San Diego, La Jolla, California, United States of America
| | - Pinxue Li
- Department of Surgery, University of California, San Diego, La Jolla, California, United States of America
| | - Tatiana Kisseleva
- Department of Surgery, University of California, San Diego, La Jolla, California, United States of America
| | - Jessica Wang-Rodriguez
- Department of Pathology, Veterans Administration Medical Center, San Diego, La Jolla, California, United States of America
- Department of Pathology, University of California, San Diego, La Jolla, California, United States of America
| | - Weg M. Ongkeko
- Department of Surgery, University of California, San Diego, La Jolla, California, United States of America
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25
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Elsayed HM, Nabiel Y, Sheta T. IL12 Gene Polymorphism in Association with Hepatocellular Carcinoma in HCV-infected Egyptian Patients. Immunol Invest 2016; 46:123-133. [DOI: 10.1080/08820139.2016.1229789] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Heba Mosaad Elsayed
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Yasmin Nabiel
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Tarek Sheta
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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26
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Abraham JA, Golubnitschaja O. Time for paradigm change in management of hepatocellular carcinoma: is a personalized approach on the horizon? Per Med 2016; 13:455-467. [PMID: 29767598 DOI: 10.2217/pme-2016-0013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most frequent cancer form but the second leading cause of all cancer-related deaths. There are several reasons for high mortality in the HCC cohort: lack of effective screening programs and consequently late diagnosis, multifactorial origin with cumulative risk factors, complex carcinogenesis, tumor heterogeneity, unpredictable impacts of individual microenvironment on tumor development and progression, and, as the consequence, frequently untargeted therapy and cancer resistance toward currently applied treatment approaches. The currently applied 'treat and wait' approach is inappropriate in the overall HCC management. Urgent need in paradigm change toward predictive, preventive and personalized medicine is discussed in this review article. Innovative strategies for an advanced predictive, preventive and personalized medicine approach in the overall HCC management benefiting the patient are presented.
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Affiliation(s)
- Jella-Andrea Abraham
- Department of Radiology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany
| | - Olga Golubnitschaja
- Department of Radiology, University of Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany
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27
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Kwak HW, Park JW, Koh YH, Lee JH, Yu A, Nam BH. Clinical Characteristics of Patients with Cryptogenic Hepatocellular Carcinoma in a Hepatitis B Virus-Endemic Area. Liver Cancer 2016; 5:21-36. [PMID: 26989657 PMCID: PMC4789902 DOI: 10.1159/000367756] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES Chronic hepatitis B virus (HBV) infection is the most common cause of hepatocellular carcinoma (HCC) in South Korea, but a high prevalence of metabolic diseases may result in increases in the incidence of cryptogenic HCC (cHCC). We studied characteristics of the cHCC in a single-center cohort. METHODS A cohort of 1,784 HCC patients newly diagnosed and treated at the National Cancer Center, Korea, between 2004 and 2009 was reviewed and analyzed. RESULTS The cause of HCC was categorized as cHCC, HBV, hepatitis C virus (HCV), or alcohol. Overall, 162 (9.1%) patients of the HCC cohort had cHCC, and their mean age was 61.9 years. The median survival of cHCC patients was 24.7 months, which was the second shortest among the four groups after HBV HCC. cHCC patients had the largest tumor size (mean 7.4 cm) and the second highest proportion of poor prognostic factors such as the proportion of poorly defined tumors and extrahepatic spread in imaging studies. cHCC patients had better survival than HBV HCC patients according to multivariate analysis. Among cHCC patients, 137 (84.6%) had anti-HBc IgG antibodies, but this sub-group had different clinical features to those of HBV HCC patients. The body mass index (BMI) and hyperglycemia and hypercholesterolemia levels in cHCC patients were similar to those in HCV and alcoholic HCC patients. CONCLUSIONS Anti-HBc IgG antibodies were present in most cHCC patients, but cHCC patients had better survival than HBV HCC patients on multivariate analysis. However, cHCC patients had a larger mean tumor size and more aggressive tumor characteristics than HCV HCC or alcoholic HCC patients did. It is hoped that this study will contribute to a better understanding of cHCC in HBV-endemic areas.
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Affiliation(s)
- Hee-Won Kwak
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Joong-Won Park
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea,*Joong-Won Park, MD, PhD, Center for Liver Cancer, National Cancer Center, 323 Ilsan-ro, Ilsan dong-gu, Goyang, Gyeonggi 411-769 (Republic of Korea), Tel. +82 31 920 1605, E-Mail
| | - Young Hwan Koh
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Ju Hee Lee
- Center for Liver Cancer, National Cancer Center, Goyang, Republic of Korea
| | - Ami Yu
- Cancer Biostatistics Branch, National Cancer Center, Goyang, Republic of Korea
| | - Byung-Ho Nam
- Cancer Biostatistics Branch, National Cancer Center, Goyang, Republic of Korea
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28
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Novo-Veleiro I, Alvela-Suárez L, Chamorro AJ, González-Sarmiento R, Laso FJ, Marcos M. Alcoholic liver disease and hepatitis C virus infection. World J Gastroenterol 2016. [PMID: 26819510 DOI: 10.3748/wjg.v22.i4.141] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Alcohol consumption and hepatitis C virus (HCV) infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. The main mechanisms of this effect are increased viral replication and altered immune response, although genetic predisposition may also play an important role. Traditionally, HCV prevalence has been considered to be higher (up to 50%) in alcoholic patients than in the general population. However, the presence of advanced alcoholic liver disease (ALD) or intravenous drug use (IDU) may have confounded the results of previous studies, and the real prevalence of HCV infection in alcoholic patients without ALD or prior IDU has been shown to be lower. Due to the toxic combined effect of HCV and alcohol, patients with HCV infection should be screened for excessive ethanol intake. Patients starting treatment for HCV infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefit from additional support during antiviral therapy. This recommendation might be extended to all currently recommended drugs for HCV treatment. Patients with alcohol dependence and HCV infection, can be treated with acamprosate, nalmefene, topiramate, and disulfiram, although baclofen is the only drug specifically tested for this purpose in patients with ALD and/or HCV infection.
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Affiliation(s)
- Ignacio Novo-Veleiro
- Ignacio Novo-Veleiro, Lucía Alvela-Suárez, Department of Internal Medicine, University Hospital of Santiago de Compostela, 37007 Salamanca, Spain
| | - Lucía Alvela-Suárez
- Ignacio Novo-Veleiro, Lucía Alvela-Suárez, Department of Internal Medicine, University Hospital of Santiago de Compostela, 37007 Salamanca, Spain
| | - Antonio-Javier Chamorro
- Ignacio Novo-Veleiro, Lucía Alvela-Suárez, Department of Internal Medicine, University Hospital of Santiago de Compostela, 37007 Salamanca, Spain
| | - Rogelio González-Sarmiento
- Ignacio Novo-Veleiro, Lucía Alvela-Suárez, Department of Internal Medicine, University Hospital of Santiago de Compostela, 37007 Salamanca, Spain
| | - Francisco-Javier Laso
- Ignacio Novo-Veleiro, Lucía Alvela-Suárez, Department of Internal Medicine, University Hospital of Santiago de Compostela, 37007 Salamanca, Spain
| | - Miguel Marcos
- Ignacio Novo-Veleiro, Lucía Alvela-Suárez, Department of Internal Medicine, University Hospital of Santiago de Compostela, 37007 Salamanca, Spain
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29
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Novo-Veleiro I, Alvela-Suárez L, Chamorro AJ, González-Sarmiento R, Laso FJ, Marcos M. Alcoholic liver disease and hepatitis C virus infection. World J Gastroenterol 2016; 22:1411-1420. [PMID: 26819510 PMCID: PMC4721976 DOI: 10.3748/wjg.v22.i4.1411] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 10/01/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
Alcohol consumption and hepatitis C virus (HCV) infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. The main mechanisms of this effect are increased viral replication and altered immune response, although genetic predisposition may also play an important role. Traditionally, HCV prevalence has been considered to be higher (up to 50%) in alcoholic patients than in the general population. However, the presence of advanced alcoholic liver disease (ALD) or intravenous drug use (IDU) may have confounded the results of previous studies, and the real prevalence of HCV infection in alcoholic patients without ALD or prior IDU has been shown to be lower. Due to the toxic combined effect of HCV and alcohol, patients with HCV infection should be screened for excessive ethanol intake. Patients starting treatment for HCV infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefit from additional support during antiviral therapy. This recommendation might be extended to all currently recommended drugs for HCV treatment. Patients with alcohol dependence and HCV infection, can be treated with acamprosate, nalmefene, topiramate, and disulfiram, although baclofen is the only drug specifically tested for this purpose in patients with ALD and/or HCV infection.
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30
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Li Y, Luo HB, Zhang HY, Guo Q, Yao HC, Li JQ, Chang Q, Yang JG, Wang F, Wang CD, Yang X, Liu ZG, Ye X. Potential hepatoprotective effects of fullerenol nanoparticles on alcohol-induced oxidative stress by ROS. RSC Adv 2016. [DOI: 10.1039/c5ra25750f] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The free radical scavenging ability of fullerenols is their most exploited property in biomedical studies.
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31
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Di Nuzzo S, Boccaletti V, Fantini C, Cortelazzi C, Missale G, Fabrizi G, Lotti T, Hercogová J, Pagliarello C. Are Anti-TNF-α Agents Safe for Treating Psoriasis in Hepatitis C Virus Patients with Advanced Liver Disease? Case Reports and Review of the Literature. Dermatology 2015; 232:102-6. [PMID: 26444967 DOI: 10.1159/000439587] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Accepted: 08/20/2015] [Indexed: 12/14/2022] Open
Abstract
Tumor necrosis factor-alpha (TNF-α) inhibitors represent an effective treatment for severe psoriasis in hepatitis C virus (HCV) patients. The literature reports mainly on short-term treatment in patients with chronic hepatitis with minimum-to-moderate activity with an acceptable safety profile. We report the first 2 cases of hepatocellular carcinoma (HCC) arising in HCV psoriatic patients with advanced liver disease during long-term treatment with etanercept. Our first patient, known to have had HCV infection for 41 years, developed an HCC after 21 months of therapy with etanercept (50 mg/week). The second patient, HCV+ for 20 years, was treated for 58 months with the same therapy, and despite no signs of liver function impairment was diagnosed with HCC. Both of them presented with cirrhosis, which was diagnosed 9 and 5 years earlier, respectively. It remains to be clarified whether there is any connection between psoriasis treatment with anti-TNF-α agents and the development of HCC in HCV-infected patients. Further long-term, follow-up studies and registries of HCV patients with mild/moderate activity may contribute to clarify this issue.
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Affiliation(s)
- Sergio Di Nuzzo
- Section of Dermatology, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy
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32
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Chitapanarux T, Phornphutkul K. Risk Factors for the Development of Hepatocellular Carcinoma in Thailand. J Clin Transl Hepatol 2015; 3:182-8. [PMID: 26623264 PMCID: PMC4663199 DOI: 10.14218/jcth.2015.00025] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 08/25/2015] [Accepted: 08/28/2015] [Indexed: 01/25/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. The incidence of HCC is on the rise in Thailand, where it has become the most common malignancy in males and the third most common in females. Here, we review some of the risk factors that have contributed to this increase in HCC incidence in the Thai population. Hepatitis B virus (HBV) is the main etiologic risk factor for HCC, followed by hepatitis C virus (HCV). Patients with HBV genotype C have a higher positive rate of hepatitis B early antigen (HBeAg) and progress to cirrhosis and HCC earlier than genotype B. For HCV patients, 16% developed HCC associated cirrhosis by year 5 after diagnosis, and the cumulative risk for death from HCC at year 10 was 60%. Dietary exposure to the fungal hepatocarcinogen aflatoxin B1 has been shown to interact synergistically with HBV infection to increase the risk of early onset HCC. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. In recent years, obesity and metabolic syndrome have markedly increased the incidence of HCC and are important causes of HCC in some resource-rich regions.
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Affiliation(s)
- Taned Chitapanarux
- Division of Gastrohepatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Correspondence to: Taned Chitapanarux, Division of Gastrohepatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand. Tel: +66-53-945482, Fax: +66-53-945481, E-mail:
| | - Kannika Phornphutkul
- Division of Gastrohepatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Gastrohepatology unit, Rajavej Chiang Mai Hospital, Chiang Mai, Thailand
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Alcohol consumption and liver cancer risk: a meta-analysis. Cancer Causes Control 2015; 26:1205-31. [PMID: 26134046 DOI: 10.1007/s10552-015-0615-3] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2014] [Accepted: 06/09/2015] [Indexed: 02/07/2023]
Abstract
PURPOSE Alcohol is a confirmed risk factor of liver cancer. Yet, its dose-response function and synergistic effects with other risk factors remain unclear. METHODS We performed a meta-analysis on publications up to May 2014. A total of 112 publications were identified. The meta-relative risk (mRR) and the dose-response trend were calculated. Tests for heterogeneity, publication bias, and sensitivity analyses were performed. The synergy index (SI) was recorded or calculated, whenever possible. RESULTS Compared to individuals who never drank or drank at very low frequencies, the mRR for ever drinkers was 1.29 (95% confidence interval, CI 1.16-1.42) and 1.46 (95% CI 1.27-1.65) for case-control studies, and 1.07 (95% CI 0.87-1.27) for cohort studies. Being a current drinker was associated with an increased liver cancer risk in case-control studies (mRR = 1.55, 95% CI 0.38-2.73), but not in cohort studies (mRR = 0.86, 95% CI 0.74-0.97). The dose-response relation between alcohol and liver cancer was apparent with RR = 1.08 (95% CI 1.04-1.11) for 12 g/day (~1 drink), 1.54 (95% CI 1.36-1.74) for 50 g/day, 2.14 (95% CI 1.74-2.62) for 75 g/day, 3.21 (95% CI 2.34-4.40) for 100 g/day, and 5.20 (95% CI 3.25-8.29) for 125 g/day of alcohol consumption. There were synergistic effects of alcohol consumption with hepatitis (S = 2.14, 95% CI 1.31-2.98) and with diabetes (S = 3.57, 95% CI 2.29-4.84) on the risk of liver cancer, although this may be subject to publication bias. CONCLUSION Overall, one alcoholic drink per day (~12 g/day) may be associated with a 1.1 times higher liver cancer risk. Further studies on the synergistic effects of alcohol consumption and other major risk factors are warranted.
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Ashtari S, Pourhoseingholi MA, Sharifian A, Zali MR. Hepatocellular carcinoma in Asia: Prevention strategy and planning. World J Hepatol 2015; 7:1708-1717. [PMID: 26140091 PMCID: PMC4483553 DOI: 10.4254/wjh.v7.i12.1708] [Citation(s) in RCA: 84] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Revised: 12/31/2014] [Accepted: 05/26/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To review all of epidemiological and etiological aspects of hepatocellular carcinoma (HCC) and examined the prevention of this disease in Asia. METHODS We conducted a systematic review according to the PRISMA guidelines. We were chosen articles that published previously, from PubMed (MEDLINE), the Cochrane database and Scopus. The key words used in this research were as follows: HCC in Asia and the way of prevention of this disease, with no language limitations. We selected those papers published before 2014 that we considered to be most important and appropriate. All relevant articles were accessed in full text and all relevant materials was evaluated and reviewed. RESULTS More than 70% of all new cases of liver cancer were diagnosed in Asia, a region that 75% of all those chronically infected with hepatitis B virus (HBV) in the world. Chronic HBV infection is the main cause of HCC in Asia, where the virus is endemic and vertical transmission is common. Japan, Saudi Arabia, Egypt and Pakistan are exception because of high prevalence of HCV infection in these regions. The prevalence of this cancer is high in Eastern and South-Eastern Asia, But Middle Eastern countries are characterized as moderate prevalence rate of HCC region and Central Asia and some part of Middle Eastern countries are known as low prevalence rate of HCC. In addition of HBV and HCV the other factors such as aflatoxin, alcohol, obesity, diabetes and non-alcoholic fatty liver disease (NAFLD) might be responsible for a low prevalence of HCC in Asian countries. Currently available HCC therapies, chemotherapy, surgical are inefficient, mainly due to usually late diagnosis and high recurrence rates after surgical resection, and usually end with treatment failure. Liver transplantation also remains as a difficult strategy in patients with HCC. Thus prevention of HCC by treating and prevention HBV and HCV infection, the major causative agents of HCC, and the other risk factors such as aflatoxin, alcohol, obesity, diabetes and NAFLD is of a great medical importance. CONCLUSION The main challenge which still present in Asia, is the high prevalence of chronic hepatitis. So, prevention of HBV and HCV is the key strategy to reduce the incidence of HCC in Asia.
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Affiliation(s)
- Sara Ashtari
- Sara Ashtari, Mohamad Amin Pourhoseingholi, Afsaneh Sharifian, Mohamad Reza Zali, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran
| | - Mohamad Amin Pourhoseingholi
- Sara Ashtari, Mohamad Amin Pourhoseingholi, Afsaneh Sharifian, Mohamad Reza Zali, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran
| | - Afsaneh Sharifian
- Sara Ashtari, Mohamad Amin Pourhoseingholi, Afsaneh Sharifian, Mohamad Reza Zali, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran
| | - Mohamad Reza Zali
- Sara Ashtari, Mohamad Amin Pourhoseingholi, Afsaneh Sharifian, Mohamad Reza Zali, Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran
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Lin JN, Chang LL, Lai CH, Lin KJ, Lin MF, Yang CH, Lin HH, Chen YH. Development of an Animal Model for Alcoholic Liver Disease in Zebrafish. Zebrafish 2015; 12:271-80. [PMID: 25923904 DOI: 10.1089/zeb.2014.1054] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Alcoholic liver disease (ALD) continues to be a major cause of liver-related morbidity and mortality worldwide. To date, no zebrafish animal model has demonstrated the characteristic manifestations of ALD in the setting of chronic alcohol exposure. The aim of this study was to develop a zebrafish animal model for ALD. Male adult zebrafish were housed in a 1% (v/v) ethanol solution up to 3 months. A histopathological study showed the characteristic features of alcoholic liver steatosis and steatohepatitis in the early stages of alcohol exposure, including fat droplet accumulation, ballooning degeneration of the hepatocytes, and Mallory body formation. As the exposure time increased, collagen deposition in the extracellular matrix was observed by Sirius red staining and immunofluorescence staining. Finally, anaplastic hepatocytes with pleomorphic nuclei were arranged in trabecular patterns and formed nodules in the zebrafish liver. Over the time course of 1% ethanol exposure, upregulations of lipogenesis, fibrosis, and tumor-related genes were also revealed by semiquantitative and quantitative real-time reverse transcription-polymerase chain reaction. As these data reflect characteristic liver damage by alcohol in humans, this zebrafish animal model may serve as a powerful tool to study the pathogenesis and treatment of ALD and its related disorders in humans.
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Affiliation(s)
- Jiun-Nong Lin
- 1 Department of Critical Care Medicine, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan .,2 School of Medicine, College of Medicine, I-Shou University , Kaohsiung, Taiwan .,3 Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan
| | - Lin-Li Chang
- 4 Department of Microbiology, Faculty of Medicine, Kaohsiung Medical University , Kaohsiung, Taiwan
| | - Chung-Hsu Lai
- 3 Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan
| | - Kai-Jen Lin
- 5 Department of Pathology, I-Shou University , Kaohsiung, Taiwan
| | - Mei-Fang Lin
- 6 Department of Pharmacy, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan
| | - Chih-Hui Yang
- 7 General Education Center, Meiho University , Pingtung, Taiwan
| | - Hsi-Hsun Lin
- 3 Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan
| | - Yen-Hsu Chen
- 8 School of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung, Taiwan .,9 Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital , Kaohsiung, Taiwan .,10 Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan
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Wang F, Yang JL, Yu KK, Xu M, Xu YZ, Chen L, Lu YM, Fang HS, Wang XY, Hu ZQ, Li FF, Kan L, Luo J, Wang SY. Activation of the NF-κB pathway as a mechanism of alcohol enhanced progression and metastasis of human hepatocellular carcinoma. Mol Cancer 2015; 14:10. [PMID: 25622857 PMCID: PMC4320626 DOI: 10.1186/s12943-014-0274-0] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Accepted: 12/22/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is the third leading cause of cancer-related death in human. Alcohol is a known risk factor for HCC. However it is still unclear whether and how alcohol enhances the progression and metastasis of existing HCC. METHODS AND RESULTS We first retrospectively investigated 52 HCC patients (24 alcohol-drinkers and 28 non-drinkers), and found a positive correlation between alcohol consumption and advanced Tumor-Node-Metastasis (TNM) stages, higher vessel invasion and poorer prognosis. In vitro and in vivo experiments further indicated that alcohol promoted the progression and migration/invasion of HCC. Specifically, in a 3-D tumor/endothelial co-culture system, we found that alcohol enhanced the migration/invasion of HepG2 cells and increased tumor angiogenesis. Consistently, higher expression of VEGF, MCP-1 and NF-κB was observed in HCC tissues of alcohol-drinkers. Alcohol induced the accumulation of intracellular reactive oxygen species (ROS) and the activation of NF-κB signaling in HepG2 cells. Conversely, blockage of alcohol-mediated ROS accumulation and NF-κB signaling inhibited alcohol-induced expression of VEGF and MCP-1, the tumor growth, angiogenesis and metastasis. CONCLUSION This study suggested that chronic moderate alcohol consumption may promote the progression and metastasis of HCC; the oncogenic effect may be at least partially mediated by the ROS accumulation and NF-ĸB-dependent VEGF and MCP-1 up-regulation.
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Affiliation(s)
- Fei Wang
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China. .,Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, P.R. China.
| | - Jin-Lian Yang
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
| | - Ke-ke Yu
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
| | - Mei Xu
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China. .,Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA.
| | - You-zhi Xu
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
| | - Li Chen
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
| | - Yan-min Lu
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
| | - Hao-shu Fang
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
| | - Xin-yi Wang
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China. .,Department of Clinical Medicine, Anhui Medical University, Hefei, Anhui, 230032, P.R. China.
| | - Zhong-qian Hu
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
| | - Fei-fei Li
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
| | - Lixin Kan
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
| | - Jia Luo
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China. .,Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, Kentucky, 40536, USA.
| | - Si-Ying Wang
- Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, P.R. China.
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Shao YY, Shau WY, Chan SY, Lu LC, Hsu CH, Cheng AL. Treatment efficacy differences of sorafenib for advanced hepatocellular carcinoma: a meta-analysis of randomized clinical trials. Oncology 2015; 88:345-52. [PMID: 25572912 DOI: 10.1159/000369559] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Accepted: 11/03/2014] [Indexed: 01/17/2023]
Abstract
OBJECTIVES Hepatocellular carcinoma (HCC) is a heterogeneous disease. We explored whether any specific subgroups of patients may gain more survival benefits from sorafenib as the first-line therapy for advanced HCC. METHODS PubMed and the Cochrane library were searched for phase III clinical trials that compared sorafenib with other treatments as first-line therapy for advanced HCC. We retrieved data from the published articles and then calculated synthesized hazard ratios (HRs) of overall mortality for patients of different subgroups, using patients who received other treatments as the reference. RESULTS Four phase III clinical trials comparing sorafenib with other treatments were included in this study. The HRs were not significantly different between patients from various geographic regions (p = 0.183), patients with different Eastern Cooperative Oncology Group performance statuses (p = 0.699), or patients with different tumor involvement (p = 0.221). By contrast, the synthesized HR for hepatitis C virus (HCV)+ patients was 0.65 [95% confidence interval (CI) 0.53-0.80], which was significantly lower than that for HCV- patients (0.87, 95% CI 0.79-0.96, p = 0.013). CONCLUSIONS As the first-line therapy for advanced HCC, sorafenib might provide more survival benefits to HCV+ patients than to HCV- patients.
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Affiliation(s)
- Yu-Yun Shao
- Department of Oncology, National Taiwan University Hospital, New Taipei City, Taiwan, ROC
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Chou CT, Wu WP, Chen CB, Su WW, Chen RC, Chen YL. The utility of gadoxetic acid-enhanced MR imaging to characterize atypical cirrhotic nodules detected on dynamic CT images. PLoS One 2014; 9:e107869. [PMID: 25310817 PMCID: PMC4195587 DOI: 10.1371/journal.pone.0107869] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2014] [Accepted: 08/22/2014] [Indexed: 02/06/2023] Open
Abstract
Purpose To evaluate whether gadoxetic acid (Gd-EOB-DTPA)-enhanced MR images of tumors taken during the hepatocyte-specific phase can aid in the differentiation between hepatocellular carcinoma (HCC) and dysplastic nodules (DNs) in patients with atypical cirrhotic nodules detected on dynamic CT images. Materials and Methods Seventy-one patients with 112 nodules showing atypical dynamic enhancement on CT images underwent gadoxetic acid-enhanced MR imaging (MRI) studies. Using a reference standard, we determined that 33 of the nodules were DNs and that 79 were true HCCs. Tumor size, signal intensity on precontrast T1-weighted images (T1WI) and T2WI, and the pattern of dynamic enhancement on MR images taken in the hepatocyte-phase were determined. Results There were significant differences in tumor size, hyperintensity on T2WI, hypointensity on T1WI, typical HCC enhancement pattern on dynamic MR images, or hypointensity on hepatocyte-phase images between DNs and HCC. The sensitivity and specificity were 60.8% and 87.9% for T2WI, 38.0% and 87.9% for T1WI, 17.7% and 100% for dynamic MR imaging, 83.5% and 84.9% for hepatocyte-phase imaging, and 60.8% and 87.9% for tumor size (threshold of 1.7 cm). Conclusion Gd-EOB-DTPA-enhanced hepatocyte-phase imaging is recommended for patients at high risk of HCC who present with atypical lesions on dynamic CT images.
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Affiliation(s)
- Chen-Te Chou
- Department of Biomedical Imaging and Radiological Science, National Yang-Ming Medical University, Taipei, Taiwan; Department of Radiology, Chang-Hua Christian Hospital, Changhua, Taiwan
| | - Wen-Pei Wu
- Department of Biomedical Imaging and Radiological Science, National Yang-Ming Medical University, Taipei, Taiwan
| | - Chia-Bang Chen
- Department of Radiology, Chang-Hua Christian Hospital, Changhua, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology, Chang-Hua Christian Hospital, Changhua, Taiwan
| | - Ran-Chou Chen
- Department of Biomedical Imaging and Radiological Science, National Yang-Ming Medical University, Taipei, Taiwan; Department of Radiology, Taipei City Hospital, Taipei, Taiwan
| | - Yao-Li Chen
- Transplantation Medicine and Surgery Research Centre, Chang-Hua Christian Hospital, Changhua, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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Abstract
Hepatocellular carcinoma is one of the major malignant tumors in the world today. The number of new cases of the tumor increases year by year, and hepatocellular carcinoma almost always runs a fulminant course and carries an especially grave prognosis. It has a low resectability rate and a high recurrence rate after surgical intervention, and responds poorly to anticancer drugs and radiotherapy. Hepatocellular carcinoma does not have a uniform geographical distribution: rather, very high incidences occur in Eastern and Southeastern Asia and in sub-Saharan Black Africans. In these regions and populations, the tumor shows a distinct shift in age distribution toward the younger ages, seen to greatest extent in sub-Saharan Black Africans. In all populations, males are more commonly affected. The most common risk factors for hepatocellular carcinoma in resource-poor populations with a high incidence of the tumor are chronic hepatitis B virus infection and dietary exposure to the fungal hepatocarcinogen aflatoxin B1. These two causative agents act either singly or synergistically. Both the viral infection and exposure to the fungus occur from early childhood, and the tumor typically presents at an early age. Chronic hepatitis C virus infection is an important cause of hepatocellular carcinoma in resource-rich countries with a low incidence of the tumor. The infection is acquired in adulthood and hepatocellular carcinoma occurs later than it does with hepatitis B virus-induced tumors. In recent years, obesity and the metabolic syndrome have increased markedly in incidence and importance as a cause of hepatocellular carcinoma in some resource-rich regions. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. Excessive iron accumulation in hereditary hemochromatosis and dietary iron overload in the Black African population and membranous obstruction of the inferior cava cause the tumor in a few countries.
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Affiliation(s)
- Michael C Kew
- Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa
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Alcohol induced hepatic degeneration in a hepatitis C virus core protein transgenic mouse model. Int J Mol Sci 2014; 15:4126-41. [PMID: 24608925 PMCID: PMC3975388 DOI: 10.3390/ijms15034126] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Revised: 02/08/2014] [Accepted: 02/26/2014] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) has become a major public health issue. It is prevalent in most countries. HCV infection frequently begins without clinical symptoms, before progressing to persistent viremia, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) in the majority of patients (70% to 80%). Alcohol is an independent cofactor that accelerates the development of HCC in chronic hepatitis C patients. The purpose of the current study was to evaluate ethanol-induced hepatic changes in HCV core-Tg mice and mutant core Tg mice. Wild type (NTG), core wild-Tg mice (TG-K), mutant core 116-Tg mice (TG-116) and mutant core 99-Tg mice (TG-99) were used in this investigation. All groups were given drinking water with 10% ethanol and 5% sucrose for 13 weeks. To observe liver morphological changes, we performed histopathological and immunohistochemical examinations. Histopathologically, NTG, TG-K and TG-116 mice showed moderate centrilobular necrosis, while severe centrilobular necrosis and hepatocyte dissociation were observed in TG-99 mice with increasing lymphocyte infiltration and piecemeal necrosis. In all groups, a small amount of collagen fiber was found, principally in portal areas. None of the mice were found to have myofibroblasts based on immunohistochemical staining specific for α-SMA. CYP2E1-positive cells were clearly detected in the centrilobular area in all groups. In the TG-99 mice, we also observed cells positive for CK8/18, TGF-β1 and phosphorylated (p)-Smad2/3 and p21 around the necrotic hepatocytes in the centrilobular area (p < 0.01). Based on our data, alcohol intake induced piecemeal necrosis and hepatocyte dissociation in the TG-99 mice. These phenomena involved activation of the TGF-β1/p-Smad2/3/p21 signaling pathway in hepatocytes. Data from this study will be useful for elucidating the association between alcohol intake and HCV infection.
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Chou CT, Chou JM, Chang TA, Huang SF, Chen CB, Chen YL, Chen RC. Differentiation between dysplastic nodule and early-stage hepatocellular carcinoma: The utility of conventional MR imaging. World J Gastroenterol 2013; 19:7433-7439. [PMID: 24259975 PMCID: PMC3831226 DOI: 10.3748/wjg.v19.i42.7433] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2013] [Revised: 09/03/2013] [Accepted: 09/17/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To elucidate the variety of ways early-stage hepatocellular carcinoma (HCC) can appear on magnetic resonance (MR) imaging by analyzing T1-weighted, T2-weighted, and gadolinium-enhanced dynamic studies.
METHODS: Seventy-three patients with well-differentiated HCC (wHCC) or dysplastic nodules were retrospectively identified from medical records, and new histological sections were prepared and reviewed. The tumor nodules were categorized into three groups: dysplastic nodule (DN), wHCC compatible with Edmondson-Steiner grade I HCC (w1-HCC), and wHCC compatible with Edmondson-Steiner grade II HCC (w2-HCC). The signal intensity on pre-contrast MR imaging and the enhancing pattern for each tumor were recorded and compared between the three tumor groups.
RESULTS: Among the 73 patients, 14 were diagnosed as having DN, 40 were diagnosed as having w1-HCC, and 19 were diagnosed as having w2-HCC. Hyperintensity measurements on T2-weighted axial images (T2WI) were statistically significant between DNs and wHCC (P = 0.006) and between DN and w1-HCC (P = 0.02). The other imaging features revealed no significant differences between DN and wHCC or between DN and w1-HCC. Hyperintensity on both T1W out-phase imaging (P = 0.007) and arterial enhancement on dynamic study (P = 0.005) showed statistically significant differences between w1-HCC and w2-HCC. The other imaging features revealed no significant differences between w1-HCC and w2-HCC.
CONCLUSION: In the follow-up for a cirrhotic nodule, increased signal intensity on T2WI may be a sign of malignant transformation. Furthermore, a noted loss of hyperintensity on T1WI and the detection of arterial enhancement might indicate further progression of the histological grade.
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Welzel TM, Graubard BI, Quraishi S, Zeuzem S, Davila JA, El-Serag HB, McGlynn KA. Population-attributable fractions of risk factors for hepatocellular carcinoma in the United States. Am J Gastroenterol 2013; 108:1314-21. [PMID: 23752878 PMCID: PMC4105976 DOI: 10.1038/ajg.2013.160] [Citation(s) in RCA: 241] [Impact Index Per Article: 20.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2013] [Revised: 04/22/2013] [Accepted: 04/28/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Risk factors for hepatocellular carcinoma (HCC) include hepatitis B and C viruses (HBV, HCV), excessive alcohol consumption, rare genetic disorders and diabetes/obesity. The population attributable fractions (PAF) of these factors, however, have not been investigated in population-based studies in the United States. METHODS Persons ≥68 years diagnosed with HCC (n=6,991) between 1994 and 2007 were identified in the SEER-Medicare database. A 5% random sample (n=255,702) of persons residing in SEER locations were selected for comparison. For each risk factor, odds ratios (ORs), 95% confidence intervals (95% CI) and PAFs were calculated. RESULTS As anticipated, the risk of HCC was increased in relationship to each factor: HCV (OR 39.89, 95% CI: 36.29-43.84), HBV (OR 11.17, 95% CI: 9.18-13.59), alcohol-related disorders (OR 4.06, 95% CI: 3.82-4.32), rare metabolic disorders (OR 3.45, 95% CI: 2.97-4.02), and diabetes and/or obesity (OR 2.47, 95% CI: 2.34-2.61). The PAF of all factors combined was 64.5% (males 65.6%; females 62.2%). The PAF was highest among Asians (70.1%) and lowest among black persons (52.4%). Among individual factors, diabetes/obesity had the greatest PAF (36.6%), followed by alcohol-related disorders (23.5%), HCV (22.4%), HBV (6.3%) and rare genetic disorders (3.2%). While diabetes/obesity had the greatest PAF among both males (36.4%) and females (36.7%), alcohol-related disorders had the second greatest PAF among males (27.8%) and HCV the second greatest among females (28.1%). Diabetes/obesity had the greatest PAF among whites (38.9%) and Hispanics (38.1%), while HCV had the greatest PAF among Asians (35.4%) and blacks (34.9%). The second greatest PAF was alcohol-related disorders in whites (25.6%), Hispanics (30.1%) and blacks (and 18.5%) and HBV in Asians (28.5%). CONCLUSIONS The dominant risk factors for HCC in the United States among persons ≥68 years differ by sex and race/ethnicity. Overall, eliminating diabetes/obesity could reduce the incidence of HCC more than the elimination of any other factor.
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Affiliation(s)
- Tania M. Welzel
- Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany
| | - Barry I. Graubard
- Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland, USA
| | - Sabah Quraishi
- Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland, USA
| | - Stefan Zeuzem
- Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany
| | - Jessica A. Davila
- Houston Veterans Affairs Medical Center, Houston, Texas, USA,Baylor College of Medicine, Houston, Texas, USA
| | - Hashem B. El-Serag
- Houston Veterans Affairs Medical Center, Houston, Texas, USA,Baylor College of Medicine, Houston, Texas, USA
| | - Katherine A. McGlynn
- Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland, USA
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Bruno S, Saibeni S, Bagnardi V, Vandelli C, De Luca M, Felder M, Fracanzani AL, Prisco C, Vitaliani G, Simone L, Gaeta GB, Stanzione M, Persico M, Furlan C, Stroffolini T, Salerno F, Maisonneuve P, Almasio PL. Mortality risk according to different clinical characteristics of first episode of liver decompensation in cirrhotic patients: a nationwide, prospective, 3-year follow-up study in Italy. Am J Gastroenterol 2013; 108:1112-22. [PMID: 23732467 DOI: 10.1038/ajg.2013.110] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2012] [Accepted: 03/19/2013] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The occurrence of decompensation marks a crucial turning point in the course of cirrhosis. The purpose of this study was to assess the risk of mortality according to the clinical characteristics of first decompensation, considering also the impact of acute-on-chronic liver failure (AoCLF). METHODS We conducted a prospective nationwide inception cohort study in Italy. Decompensation was defined by the presence of ascites, either overt or detected by ultrasonography (UD), gastroesophageal variceal bleeding (GEVB), and hepatic encephalopathy (HE). AoCLF was defined according to the Asian Pacific Association for the Study of the Liver criteria. Multivariable Cox proportional hazards regression was used to analyze the risk of failure (death or orthotopic liver transplantation (OLT)). RESULTS A total of 490 consecutive cirrhotic patients (314 males, mean age 60.9±12.6 years) fulfilled the study criteria. AoCLF was identified in 59 patients (12.0%). Among the remaining 431 patients, ascites were found in 330 patients (76.6%): in 257 (77.8%) as overt ascites and in 73 (22.2%) as UD ascites. GEVB was observed in 77 patients (17.9%) and HE in 30 patients (7.0%). After a median follow-up of 33 months, 24 patients underwent OLT and 125 died. The cumulative incidence of failure (death or OLT) after 1, 2, and 3 years was, respectively, 28, 53, and 62% in patients with AoCLF; 10, 18, and 25% in patients with UD ascites; 17, 31, and 41% in patients with overt ascites; and 8, 12, and 24% in patients with GEVB (P<0.0001). CONCLUSIONS AoCLF is responsible for a relevant proportion of first decompensation in cirrhotic patients and is associated with the poorest outcome. Patients with UD ascites do not have a negligible mortality rate and require clinical monitoring similar to that of patients with overt ascites.
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Affiliation(s)
- Savino Bruno
- Dipartimento di Medicina Interna, A.O. Fatebenefratelli e Oftalmico, Milano, Italy
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Novo-Veleiro I, Calle CDL, Domínguez-Quibén S, Pastor I, Marcos M, Laso FJ. Prevalence of Hepatitis C Virus Infection in Alcoholic Patients: Cohort Study and Systematic Review. Alcohol Alcohol 2013; 48:564-9. [DOI: 10.1093/alcalc/agt044] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Singal AK, Salameh H, Singal A, Jampana SC, Freeman DH, Anderson KE, Brunder D. Management practices of hepatitis C virus infected alcoholic hepatitis patients: A survey of physicians. World J Gastrointest Pharmacol Ther 2013; 4:16-22. [PMID: 23667769 PMCID: PMC3644613 DOI: 10.4292/wjgpt.v4.i2.16] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2013] [Revised: 03/27/2013] [Accepted: 04/11/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To survey gastroenterologists and hepatologists regarding their current views on treating hepatitis C virus (HCV) infected alcoholic hepatitis (AH) patients.
METHODS: A sixteen item questionnaire was electronically mailed to gastroenterologists and hepatologists. A reminder was sent after 2 mo to increase the response rate. Participation of respondents was confidential. Accessing secured web site to respond to the questionnaire was considered as informed consent. Responses received on the secured website were downloaded in an excel sheet for data analysis.
RESULTS: Analyzing 416 responses to 1556 (27% response rate) emails, 57% respondents (56% gastroenterologists) reported HCV prevalence > 20% amongst AH patients. Sixty nine percent often treated AH and 46% preferred corticosteroids (CS). Proportion of respondents with consensus (75% or more respondents agreeing on question) on specific management of HCV infected AH were: routine HCV testing (94%), HCV not changing response to CS (80%) or pentoxifylline (91%), no change in approach to treating HCV infected AH (75%). None of respondent variables: age, specialty, annual number of patients seen, and HCV prevalence could predict respondent to be in consensus on any of or all 4 questions. Further, only 4% would choose CS for treating HCV infected AH as opposed to 47% while treating HCV negative AH.
CONCLUSION: Gastroenterologists and hepatologists believe that AH patients be routinely checked for HCV. However, there is lack of consensus on choice of drug for treatment and outcome of HCV positive AH patients. Studies are needed to develop guidelines for management of HCV infected AH patients.
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Stephens DB, Havens JR. Predictors of alcohol use among rural drug users after disclosure of hepatitis C virus status. J Stud Alcohol Drugs 2013; 74:386-95. [PMID: 23490567 PMCID: PMC3602359 DOI: 10.15288/jsad.2013.74.386] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Accepted: 10/29/2012] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Alcohol consumption dramatically increases the risk of liver damage among those with hepatitis C virus (HCV) infection, yet the impact of HCV status disclosure and standard informational counseling on alcohol use among rural drug users remains poorly understood. METHOD In this prospective study, 503 rural Appalachian drug users were recruited using respondent-driven sampling. Participants were tested for HCV antibodies, and data on sociodemographic characteristics, lifetime and past-30-day drug and alcohol use, and psychiatric disorders were collected by interviewer-administered questionnaires. A total of 470 participants returned after 6 months for follow-up; however,4 of those had no history of alcohol use, thus leaving a final sample size of 466. Multivariate negative binomial regression was used to determine the effect of disclosure of HCV status and posttest counseling on alcohol consumption at follow-up. RESULTS Despite an overall decrease in drinking frequency in the cohort, those who were HCV-positive were drinking at a frequency similar to their HCV-negative counterparts at follow-up, despite posttest counseling informing them of the risks of alcohol use with an HCV diagnosis (adjusted incidence rate ratio = 1.07, 95% CI [0.72, 1.61]). Significant predictors of increased days of alcohol use after 6 months included baseline alcohol use, baseline marijuana use, and meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for antisocial personality disorder. Those using OxyContin at baseline had significantly fewer days of alcohol use at follow-up. CONCLUSIONS HCV status disclosure and standard informational counseling alone do not curtail drinking among HCV-positive drug users in the rural setting. Targeted interventions with regard to alcohol use are warranted in order to mitigate the damage of the HCV epidemic.
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Affiliation(s)
- Dustin B. Stephens
- Center on Drug and Alcohol Research, Department of
Behavioral Science, University of Kentucky College of Medicine,
Lexington,Kentucky
| | - Jennifer R. Havens
- Center on Drug and Alcohol Research, Department of
Behavioral Science, University of Kentucky College of Medicine,
Lexington,Kentucky
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48
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Lin CW, Lin CC, Mo LR, Chang CY, Perng DS, Hsu CC, Lo GH, Chen YS, Yen YC, Hu JT, Yu ML, Lee PH, Lin JT, Yang SS. Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis. J Hepatol 2013; 58:730-5. [PMID: 23220252 DOI: 10.1016/j.jhep.2012.11.045] [Citation(s) in RCA: 111] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2012] [Revised: 11/21/2012] [Accepted: 11/29/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Taiwan has a high prevalence of hepatitis B viral (HBV) infection and hepatocellular carcinoma (HCC) with increasing consumption of alcohol. We investigated the impact of heavy alcohol consumption and HBV infection on HCC in cirrhotic patients. METHODS 966 cirrhotic patients (132 with HBV infection and alcoholism, 632 with HBV infection, and 202 patients with alcoholism) were enrolled between 2000 and 2009 and followed until 2011. The primary end point was newly developed HCC. RESULTS Within the three patient groups (cirrhotic patients with HBV infection and alcoholism, HBV infection alone, and alcoholism alone) 38 (28.8%), 100 (15.8%), and 21 (10.4%) showed newly developed HCC, respectively. The 10-year cumulative (52.8% vs. 39.8% vs. 25.6%, p <0.001) and annual incidences (9.9%, 4.1%, and 2.1%) of HCC were significantly higher in cirrhotic patients with HBV infection and alcoholism than those in patients with HBV infection or alcoholism alone. For patients with HBV infection and alcoholism, baseline serum HBV DNA (OR=16.8, p=0.025), antiviral nucleos(t)ides analogues (NUCs) therapy (OR=0.01, p=0.035), and serum α-fetoprotein (OR=1.18, p=0.045) were risk predictors of HCC by multivariate logistic regression models. The cumulative incidence of HCC was higher in patients with higher baseline serum HBV DNA. Antiviral NUCs therapy reduced the incidence of HCC. CONCLUSIONS Heavy alcohol consumption significantly increased the risk of HCC in HBV-related cirrhotic patients. Elevated baseline serum HBV DNA was a strong risk predictor of HCC and antiviral NUCs therapy reduced the incidence of HCC in cirrhotic patients with HBV infection and alcoholism.
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Affiliation(s)
- Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan
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Persson EC, Schwartz LM, Park Y, Trabert B, Hollenbeck AR, Graubard BI, Freedman ND, McGlynn KA. Alcohol consumption, folate intake, hepatocellular carcinoma, and liver disease mortality. Cancer Epidemiol Biomarkers Prev 2013; 22:415-21. [PMID: 23307533 PMCID: PMC3596467 DOI: 10.1158/1055-9965.epi-12-1169] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Excessive alcohol consumption is a well-established risk factor for liver disease and hepatocellular carcinoma (HCC). Previous studies have found that increased alcohol consumption can lead to lower absorption of folate. Conversely, higher folate intake has been inversely associated with liver damage and HCC. In the current study, we investigate the effect of alcohol consumption and folate intake on HCC incidence and liver disease mortality in the NIH-American Association of Retired Persons Diet and Health Study. METHODS The study population included 494,743 participants who reported at baseline their dietary intake for the previous year. Alcohol and folate were analyzed with hazards ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards regression models adjusted for age, sex, race, education, smoking, body mass index, and diabetes. HCC incidence (n = 435) was determined through 2006 via linkage with cancer registries, and liver disease mortality (n = 789) was determined through 2008 via linkage to the U.S. Social Security Administration Death Master File and the National Death Index Plus by the National Center for Health Statistics. RESULTS Consumption of more than three drinks per day was positively associated with both HCC incidence (HR: 1.92; 95%CI: 1.42-2.60) and liver disease mortality (HR: 5.84; 95%CI: 4.81-7.10), whereas folate intake was associated with neither outcome. Folate, however, modified the relationship between alcohol and HCC incidence (Pinteraction = 0.03), but had no effect on the relationship between alcohol and liver disease mortality (Pinteraction = 0.54). CONCLUSIONS These results suggest that higher folate intake may ameliorate the effect of alcohol consumption on the development of HCC. IMPACT Folate intake may be beneficial in the prevention of alcohol-associated HCC.
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Affiliation(s)
- E Christina Persson
- Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, EPS/Suite 550/Room 5008, Bethesda, MD 20852, USA.
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50
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Persson EC, Schwartz LM, Park Y, Trabert B, Hollenbeck AR, Graubard BI, Freedman ND, McGlynn KA. Alcohol consumption, folate intake, hepatocellular carcinoma, and liver disease mortality. Cancer Epidemiol Biomarkers Prev 2013. [PMID: 23307533 DOI: 10.1158/1055-9965-9965.epi-12-1169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Excessive alcohol consumption is a well-established risk factor for liver disease and hepatocellular carcinoma (HCC). Previous studies have found that increased alcohol consumption can lead to lower absorption of folate. Conversely, higher folate intake has been inversely associated with liver damage and HCC. In the current study, we investigate the effect of alcohol consumption and folate intake on HCC incidence and liver disease mortality in the NIH-American Association of Retired Persons Diet and Health Study. METHODS The study population included 494,743 participants who reported at baseline their dietary intake for the previous year. Alcohol and folate were analyzed with hazards ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards regression models adjusted for age, sex, race, education, smoking, body mass index, and diabetes. HCC incidence (n = 435) was determined through 2006 via linkage with cancer registries, and liver disease mortality (n = 789) was determined through 2008 via linkage to the U.S. Social Security Administration Death Master File and the National Death Index Plus by the National Center for Health Statistics. RESULTS Consumption of more than three drinks per day was positively associated with both HCC incidence (HR: 1.92; 95%CI: 1.42-2.60) and liver disease mortality (HR: 5.84; 95%CI: 4.81-7.10), whereas folate intake was associated with neither outcome. Folate, however, modified the relationship between alcohol and HCC incidence (Pinteraction = 0.03), but had no effect on the relationship between alcohol and liver disease mortality (Pinteraction = 0.54). CONCLUSIONS These results suggest that higher folate intake may ameliorate the effect of alcohol consumption on the development of HCC. IMPACT Folate intake may be beneficial in the prevention of alcohol-associated HCC.
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Affiliation(s)
- E Christina Persson
- Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, 6120 Executive Blvd, EPS/Suite 550/Room 5008, Bethesda, MD 20852, USA.
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