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Cornberg M, Sandmann L, Jaroszewicz J, Kennedy P, Lampertico P, Lemoine M, Lens S, Testoni B, Lai-Hung Wong G, Russo FP. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2025:S0168-8278(25)00174-6. [PMID: 40348683 DOI: 10.1016/j.jhep.2025.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.
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Oje MM, Kolawole OJ, Ijarotimi O, Adekanle O, Jegede OS, Ndububa DA. Liver histology pattern of young patients with inactive chronic hepatitis b virus infection from a hospital in South West Nigeria. BMC Gastroenterol 2024; 24:438. [PMID: 39604871 PMCID: PMC11603992 DOI: 10.1186/s12876-024-03501-7] [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: 05/23/2024] [Accepted: 11/07/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Chronic hepatitis B (CHB) infection is the leading cause of chronic liver disease in sub-Saharan Africa. A significant proportion of patients with CHB are inactive carriers, for whom guidelines neither recommend biopsy nor treatment. In sub-Saharan Africa, patients under 30 years old with CHB sometimes develop liver cancer, raising the possibility that significant liver disease may occur early in life in these patients. METHODS A hospital-based cross-sectional study was conducted on patients with inactive CHB. A convenient sampling method was used to recruit patients. All patients underwent a percutaneous liver biopsy to evaluate significant necroinflammation and fibrosis using the Meta-analysis of histological data in viral hepatitis (METAVIR) system, defined as at least METAVIR A2, F2 disease. Tests of association between the histological outcomes, sociodemographic factors, and laboratory findings were performed. The data obtained were entered into the Statistical Package for the Social Sciences (SPSS) version 21 and analysed using descriptive and inferential statistics. A p-value of < 0.05 was considered statistically significant. RESULTS A total of 88 patients-60 males (68.2%) and 28 females (31.8%)-completed the study. The study participants were aged 18 to 29 years, with a mean age of 25.4 ± 3.4 years. Thirty-nine (44.3%) had significant necroinflammation and/or fibrosis on histology, 19 (21.6%) of whom had necroinflammation only, and 13 (14.8%) had both necroinflammation and fibrosis. Males had significant necroinflammation and fibrosis more than the females. A family history of death from liver disease was associated with significant liver fibrosis (p < 0.05). CONCLUSION A portion of young patients with inactive CHB have significant liver disease, particularly those with a family history of liver-related death. Liver biopsy may therefore be beneficial in these categories of patients to detect this.
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Affiliation(s)
- Modupeola Maria Oje
- Department of Medicine, LAUTECH Teaching Hospital, Ogbomoso, Oyo State, Nigeria.
| | - Olawumi Janet Kolawole
- Department of General Medicine, Frimley Health NHS foundation Trust, Wexham Park Hospital, Slough, UK
| | - Oluwasegun Ijarotimi
- Department of Medicine, Faculty of Clinical Sciences, Obafemi Awolowo University and Obafemi Awolowo Teaching Hospital, Ile-Ife, Osun State, Nigeria
| | - Olusegun Adekanle
- Department of Medicine, Faculty of Clinical Sciences, Obafemi Awolowo University and Obafemi Awolowo Teaching Hospital, Ile-Ife, Osun State, Nigeria
| | - Oluwatosin Samson Jegede
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, USA
| | - Dennis Amajuoyi Ndububa
- Department of Medicine, Faculty of Clinical Sciences, Obafemi Awolowo University and Obafemi Awolowo Teaching Hospital, Ile-Ife, Osun State, Nigeria
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Bharadwaj R, Bora A, Sharma K. Liposomal delivery of Annona muricata leaves extract for the treatment of hepatocellular carcinoma. Drug Dev Ind Pharm 2024; 50:968-980. [PMID: 39615035 DOI: 10.1080/03639045.2024.2433618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 03/26/2024] [Accepted: 11/19/2024] [Indexed: 12/25/2024]
Abstract
BACKGROUND Liver in the body plays vital role including digestion, detoxification, metabolism and even production of hormones. Hepatocellular carcinoma is recognized as one of leading cause of death worldwide. Infection with hepatitis B and C virus, nonalcoholic fatty liver disease and excessive consumption of alcohol are among the most common risk factors associated with the development of hepatocellular carcinoma. OBJECTIVE The present research study involves formulation of liposomal delivery of methanolic extract of Annona muricata as an alternative for the treatment of hepatocellular carcinoma. METHODS The methanolic extract of Annona muricata was subjected for both nonvolatile and volatile content analysis by performing phytochemical screening and GCMS. The methanolic extract was entrapped within the liposomes for its effective delivery. The prepared liposomes were characterized in-vitro, and the optimized formulation was further evaluated against hepatocellular carcinoma induced in the animal model. RESULTS The methanolic extract showed the presence of alkaloid, carbohydrate, flavonoid, tannin, proteins and acetogenins, whereas the GMCS analysis depicts presence of 12 different compounds. The optimized in-vitro analysis of prepared liposomes showed a particle size of 107.2 ± 1.7 nm, zeta potential of -30.6 mV and entrapment efficiency of 62.15%. TEM micrograph of the optimized liposome formulation has showed spherical geometry with homogenous distribution and negligible agglomeration. In-vivo anticancer study reveals the potent efficacy of the formulation for the treatment of hepatocellular carcinoma. CONCLUSION The research findings have established the efficacy of the methanolic extract of Annona muricata in the treatment of hepatocellular carcinoma.
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Affiliation(s)
- Rituraj Bharadwaj
- Department of Bioengineering and Technology, Gauhati University, Assam, India
| | - Achyut Bora
- Department of Bioengineering and Technology, Gauhati University, Assam, India
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Hassan MM, Li D, Han Y, Byun J, Hatia RI, Long E, Choi J, Kelley RK, Cleary SP, Lok AS, Bracci P, Permuth JB, Bucur R, Yuan JM, Singal AG, Jalal PK, Ghobrial RM, Santella RM, Kono Y, Shah DP, Nguyen MH, Liu G, Parikh ND, Kim R, Wu HC, El-Serag H, Chang P, Li Y, Chun YS, Lee SS, Gu J, Hawk E, Sun R, Huff C, Rashid A, Amin HM, Beretta L, Wolff RA, Antwi SO, Patt Y, Hwang LY, Klein AP, Zhang K, Schmidt MA, White DL, Goss JA, Khaderi SA, Marrero JA, Cigarroa FG, Shah PK, Kaseb AO, Roberts LR, Amos CI. Genome-wide association study identifies high-impact susceptibility loci for HCC in North America. Hepatology 2024; 80:87-101. [PMID: 38381705 PMCID: PMC11191046 DOI: 10.1097/hep.0000000000000800] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Accepted: 12/18/2023] [Indexed: 02/23/2024]
Abstract
BACKGROUND AND AIMS Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). APPROACH AND RESULTS We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP , rs9842969, (0.51, [0.40-0.65]); 5p15.33, TERT , rs2242652, (0.70, (0.62-0.79]); 19q13.11, TM6SF2 , rs58542926, (1.49, [1.29-1.72]); 19p13.11 MAU2 , rs58489806, (1.53, (1.33-1.75]); and 22q13.31, PNPLA3 , rs738409, (1.66, [1.51-1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74-0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. CONCLUSIONS Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.
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Affiliation(s)
- Manal M Hassan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Donghui Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Younghun Han
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA
| | - Jinyoung Byun
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA
| | - Rikita I Hatia
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Erping Long
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Jiyeon Choi
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Robin Kate Kelley
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA
| | - Sean P Cleary
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, Minnesota, USA
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Paige Bracci
- Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California, USA
| | - Jennifer B Permuth
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida, USA
- Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA
| | - Roxana Bucur
- Princess Margaret Cancer Center and Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
| | - Jian-Min Yuan
- Cancer Epidemiology and Prevention Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Amit G Singal
- Division of Digestive and Liver Diseases, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Prasun K Jalal
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
| | - R Mark Ghobrial
- J.C. Walter Jr. Transplant Center, Houston Methodist Hospital, Houston, Texas, USA
| | - Regina M Santella
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, New York, USA
| | - Yuko Kono
- Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA
| | - Dimpy P Shah
- Mays Cancer Center, The University of Texas Health Science Center San Antonio MD Anderson, San Antonio, Texas, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, California, USA
| | - Geoffrey Liu
- Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | - Neehar D Parikh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Richard Kim
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, Florida, USA
| | - Hui-Chen Wu
- Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, New York, USA
| | - Hashem El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Ping Chang
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Yanan Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Yun Shin Chun
- Division of Surgery, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Sunyoung S Lee
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jian Gu
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ernest Hawk
- Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ryan Sun
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Chad Huff
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Asif Rashid
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Hesham M Amin
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Laura Beretta
- Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Robert A Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Samuel O Antwi
- Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Jacksonville, Florida, USA
| | - Yehuda Patt
- Division of Hematology/Oncology, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Lu-Yu Hwang
- Department of Epidemiology, Human Genetics, and Environment Science, The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Alison P Klein
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA
| | - Karen Zhang
- Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA
| | - Mikayla A Schmidt
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Donna L White
- Sections of Gastroenterology and Hepatology and Health Services Research, Baylor College of Medicine, Houston, Texas, USA
| | - John A Goss
- Division of Abdominal Transplantation, Michael E. DeBakey School of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Saira A Khaderi
- Division of Abdominal Transplantation, Baylor College of Medicine, Houston, Texas, USA
| | - Jorge A Marrero
- Division of Digestive and Liver Diseases, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Francisco G Cigarroa
- Transplant Center, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
| | - Pankil K Shah
- Mays Cancer Center, The University of Texas Health Science Center San Antonio MD Anderson, San Antonio, Texas, USA
| | - Ahmed O Kaseb
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Christopher I Amos
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas, USA
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Peruhova M, Banova-Chakarova S, Miteva DG, Velikova T. Genetic screening of liver cancer: State of the art. World J Hepatol 2024; 16:716-730. [PMID: 38818292 PMCID: PMC11135278 DOI: 10.4254/wjh.v16.i5.716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Revised: 02/14/2024] [Accepted: 04/09/2024] [Indexed: 05/22/2024] Open
Abstract
Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.
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Affiliation(s)
- Milena Peruhova
- Department of Gastroenterology, University Hospital "Heart and Brain", Burgas 8000, Bulgaria
| | - Sonya Banova-Chakarova
- Department of Gastroenterology, University Hospital "Heart and Brain", Burgas 8000, Bulgaria.
| | - Dimitrina Georgieva Miteva
- Department of Genetics, Faculty of Biology, Sofia University" St. Kliment Ohridski, Sofia 1164, Bulgaria
| | - Tsvetelina Velikova
- Medical Faculty, Sofia University St. Kliment Ohridski, Sofia 1407, Bulgaria
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Uwuratuw JA, Lihawa NR, Faruk M, Dani MI, Warsinggih. Left hepatectomy for hepatocellular carcinoma in situs inversus totalis. Int J Surg Case Rep 2024; 118:109650. [PMID: 38653167 PMCID: PMC11063493 DOI: 10.1016/j.ijscr.2024.109650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 04/04/2024] [Accepted: 04/18/2024] [Indexed: 04/25/2024] Open
Abstract
INTRODUCTION One of the most prevalent primary liver cancer, particularly in Eastern Asia, is hepatocellular carcinoma (HCC), which has a poor prognosis. A rare condition known as situs inversus totalis (SIT) causes the abdominal and thoracic organs to be completely inverted. PRESENTATION OF CASE A 51-year-old woman complained of a lump in the abdomen since 4 years ago, slowly enlarging to the suprapubic area, without pain. Laboratory findings showed an alpha-fetoprotein level was 13.24 IU/mL. A three-phase abdominal CT scan showed a left lobe hepatoma with local metastases and situs inversus totalis. The patient was diagnosed with left lobe HCC cT2N0M0, stage II, Barcelona Clinic Liver Cancer (BCLC) A, Child-Pugh A, Karnofsky 80 % and SIT. In this case, segment II, III, and IV left hepatectomy was performed with the crushing clamp technique. The main challenges during surgery were the inverted intra-abdominal organs, where the liver was located on the left and the spleen on the right, and the very large tumor size of approximately 28 cm × 20 cm. DISCUSSION This interesting case creates challenges in clinical practice, particularly in surgery, due to the reversal of the normal anatomy. Thus, accurate imaging is crucial for diagnosis and treatment planning. The surgeon should remain adaptable while performing the procedure for mirrored anatomy in situs inversus. CONCLUSION The unique anatomy may make the liver resection procedure for HCC in patients with SIT challenging. Surgery involving these patients with inverted anatomy can be assisted by the appropriate preoperative imaging and staging using BCLC.
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Affiliation(s)
- Julianus Aboyaman Uwuratuw
- Division of Digestive Surgery, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia; Department of Surgery, Primaya Hospital, Makassar, Indonesia.
| | - Nur Ramadhiany Lihawa
- Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
| | - Muhammad Faruk
- Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
| | - Muhammad Iwan Dani
- Division of Digestive Surgery, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
| | - Warsinggih
- Division of Digestive Surgery, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia; Department of Surgery, Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia.
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Soliman N, Saharia A, Abdelrahim M, Connor AA. Molecular profiling in the management of hepatocellular carcinoma. Curr Opin Organ Transplant 2024; 29:10-22. [PMID: 38038621 DOI: 10.1097/mot.0000000000001124] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2023]
Abstract
PURPOSE OF REVIEW The purpose of this review is to both summarize the current knowledge of hepatocellular carcinoma molecular biology and to suggest a framework in which to prospectively translate this knowledge into patient care. This is timely as recent guidelines recommend increased use of these technologies to advance personalized liver cancer care. RECENT FINDINGS The main themes covered here address germline and somatic genetic alterations recently discovered in hepatocellular carcinoma, largely owing to next generation sequencing technologies, and nascent efforts to translate these into contemporary practice. SUMMARY Early efforts of translating molecular profiling to hepatocellular carcinoma care demonstrate a growing number of potentially actionable alterations. Still lacking are a consensus on what biomarkers and technologies to adopt, at what scale and cost, and how to integrate them most effectively into care.
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Chotiprasidhi P, Sato-Espinoza AK, Wangensteen KJ. Germline Genetic Associations for Hepatobiliary Cancers. Cell Mol Gastroenterol Hepatol 2023; 17:623-638. [PMID: 38163482 PMCID: PMC10899027 DOI: 10.1016/j.jcmgh.2023.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 12/19/2023] [Accepted: 12/20/2023] [Indexed: 01/03/2024]
Abstract
Hepatobiliary cancers (HBCs) include hepatocellular carcinoma, cholangiocarcinoma, and gallbladder carcinoma, which originate from the liver, bile ducts, and gallbladder, respectively. They are responsible for a substantial burden of cancer-related deaths worldwide. Despite knowledge of risk factors and advancements in therapeutics and surgical interventions, the prognosis for most patients with HBC remains bleak. There is evidence from familial aggregation and case-control studies to suggest a familial risk component in HBC susceptibility. Recent progress in genomics research has led to the identification of germline variants including single nucleotide polymorphisms (SNPs) and pathogenic or likely pathogenic (P/LP) variants in cancer-associated genes associated with HBC risk. These findings emerged from genome-wide association studies and next-generation sequencing techniques such as whole-exome sequencing. Patients with other cancer types, including breast, colon, ovarian, prostate, and pancreatic cancer, are recommended by guidelines to undergo germline genetic testing, but similar recommendations are lagging in HBC. This prompts the question of whether multi-gene panel testing should be integrated into clinical guidelines for HBC management. Here, we review the hereditary genetics of HBC, explore studies investigating SNPs and P/LP variants in HBC patients, discuss the clinical implications and potential for personalized treatments and impact on patient's family members, and conclude that additional studies are needed to examine how genetic testing can be applied clinically.
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Affiliation(s)
- Perapa Chotiprasidhi
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | | | - Kirk J Wangensteen
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
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Liu TY, Liao CC, Chang YS, Chen YC, Chen HD, Lai IL, Peng CY, Chung CC, Chou YP, Tsai FJ, Jeng LB, Chang JG. Identification of 13 Novel Loci in a Genome-Wide Association Study on Taiwanese with Hepatocellular Carcinoma. Int J Mol Sci 2023; 24:16417. [PMID: 38003606 PMCID: PMC10671380 DOI: 10.3390/ijms242216417] [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: 10/02/2023] [Revised: 11/09/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
Liver cancer is caused by complex interactions among genetic factors, viral infection, alcohol abuse, and metabolic diseases. We conducted a genome-wide association study and polygenic risk score (PRS) model in Taiwan, employing a nonspecific etiology approach, to identify genetic risk factors for hepatocellular carcinoma (HCC). Our analysis of 2836 HCC cases and 134,549 controls revealed 13 novel associated loci such as the FAM66C gene, noncoding genes, liver-fibrosis-related genes, metabolism-related genes, and HCC-related pathway genes. We incorporated the results from the UK Biobank and Japanese database into our study for meta-analysis to validate our findings. We also identified specific subtypes of the major histocompatibility complex that influence both viral infection and HCC progression. Using this data, we developed a PRS to predict HCC risk in the general population, patients with HCC, and HCC-affected families. The PRS demonstrated higher risk scores in families with multiple HCCs and other cancer cases. This study presents a novel approach to HCC risk analysis, identifies seven new genes associated with HCC development, and introduces a reproducible PRS model for risk assessment.
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Affiliation(s)
- Ting-Yuan Liu
- Center for Precision Medicine and Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan; (T.-Y.L.); (C.-C.L.); (Y.-S.C.); (Y.-C.C.); (H.-D.C.); (I.-L.L.); (C.-C.C.); (Y.-P.C.)
- Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan
| | - Chi-Chou Liao
- Center for Precision Medicine and Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan; (T.-Y.L.); (C.-C.L.); (Y.-S.C.); (Y.-C.C.); (H.-D.C.); (I.-L.L.); (C.-C.C.); (Y.-P.C.)
| | - Ya-Sian Chang
- Center for Precision Medicine and Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan; (T.-Y.L.); (C.-C.L.); (Y.-S.C.); (Y.-C.C.); (H.-D.C.); (I.-L.L.); (C.-C.C.); (Y.-P.C.)
| | - Yu-Chia Chen
- Center for Precision Medicine and Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan; (T.-Y.L.); (C.-C.L.); (Y.-S.C.); (Y.-C.C.); (H.-D.C.); (I.-L.L.); (C.-C.C.); (Y.-P.C.)
- Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan
| | - Hong-Da Chen
- Center for Precision Medicine and Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan; (T.-Y.L.); (C.-C.L.); (Y.-S.C.); (Y.-C.C.); (H.-D.C.); (I.-L.L.); (C.-C.C.); (Y.-P.C.)
- Department of Laboratory Medicine, China Medical University Hospital, Taichung 404, Taiwan
| | - I-Lu Lai
- Center for Precision Medicine and Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan; (T.-Y.L.); (C.-C.L.); (Y.-S.C.); (Y.-C.C.); (H.-D.C.); (I.-L.L.); (C.-C.C.); (Y.-P.C.)
| | - Cheng-Yuan Peng
- Department of Internal Medicine, Section of Hepatobiliary Tract, China Medical University Hospital, Taichung 40447, Taiwan;
| | - Chin-Chun Chung
- Center for Precision Medicine and Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan; (T.-Y.L.); (C.-C.L.); (Y.-S.C.); (Y.-C.C.); (H.-D.C.); (I.-L.L.); (C.-C.C.); (Y.-P.C.)
| | - Yu-Pao Chou
- Center for Precision Medicine and Epigenome Research Center, China Medical University Hospital, Taichung 40447, Taiwan; (T.-Y.L.); (C.-C.L.); (Y.-S.C.); (Y.-C.C.); (H.-D.C.); (I.-L.L.); (C.-C.C.); (Y.-P.C.)
| | - Fuu-Jen Tsai
- Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan
- School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
- Division of Pediatric Genetics, Children’s Hospital of China Medical University, Taichung 40447, Taiwan
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, Taiwan
| | - Long-Bin Jeng
- Department of Surgery, Section of Hepatobiliary Tract, China Medical University Hospital, Taichung 40447, Taiwan;
| | - Jan-Gowth Chang
- Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan
- Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan
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10
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Lampimukhi M, Qassim T, Venu R, Pakhala N, Mylavarapu S, Perera T, Sathar BS, Nair A. A Review of Incidence and Related Risk Factors in the Development of Hepatocellular Carcinoma. Cureus 2023; 15:e49429. [PMID: 38149129 PMCID: PMC10750138 DOI: 10.7759/cureus.49429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/26/2023] [Indexed: 12/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary liver malignancy, ranking as the seventh most common cancer globally and the second leading cause of deaths due to cancer. This review examines the incidence of HCC, its associated risk factors, and constantly changing global trends. Incidence has been noted to be varying worldwide, particularly due to environmental and infectious risk factors. Chronic hepatitis B (HBV) and C (HCV) virus infections, alcohol abuse, aflatoxin exposure, diabetes, obesity, and tobacco consumption are some of the leading risk factors noted. Eastern Asia and sub-Saharan Africa were noted to have the highest disease burden for HCC, with China representing a considerably large majority. On the contrary, the United States reports a lower HCC incidence overall due to improved vaccination programs against HBV; however, with a rising incidence of prominent risk factor in non-alcoholic fatty liver disease (NAFLD), the trend may very well change. Gender disparities were noted to be evident with men experiencing higher rates of HCC compared to women, which may be due to various environmental and biological factors, including alcohol intake, smoking, and androgen hormone levels. Currently, efforts to reduce the overall incidence of HCC include universal HBV vaccinations, antiviral therapies, aflatoxin prevention measures, genetic screening for hereditary hemochromatosis, and early ultrasound evaluation in patients with liver cirrhosis. Understanding these evolving trends and risk factors is essential in combating the rising HCC incidence, especially in Western countries, where risk factors, such as obesity, diabetes, and metabolic disorders, are on the rise.
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Affiliation(s)
| | - Tabarak Qassim
- School of Medicine, Royal College of Surgeons in Ireland - Medical University of Bahrain, Busaiteen, BHR
| | - Rakshaya Venu
- College of Medicine, Saveetha Medical College, Chennai, IND
| | - Nivedita Pakhala
- College of Medicine, Sri Padmavathi Medical College for Women, Tirupati, IND
| | - Suchita Mylavarapu
- College of Medicine, Malla Reddy Medical College for Women, Hyderabad, IND
| | - Tharindu Perera
- General Medicine, Grodno State Medical University, Grodno, BLR
| | - Beeran S Sathar
- College of Medicine, Jagadguru Jayadeva Murugarajendra Medical College, Davanagere, IND
| | - Arun Nair
- Pediatrics, Saint Peter's University Hospital, Somerset, USA
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11
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Legese H, Berhe B, Adhanom G, Kahsay T, Gebrewahd A, Gebremariam G, Mardu F, Tesfay K, Gebremedhin H, Negash H. Trend analysis of hepatitis B and C among patients visiting health facility of Tigrai, Ethiopia, 2014-2019. BMC Gastroenterol 2023; 23:164. [PMID: 37208626 DOI: 10.1186/s12876-023-02807-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 05/09/2023] [Indexed: 05/21/2023] Open
Abstract
BACKGROUND Hepatitis B and C viruses are the major public health concerns of the globe. The two hepatotropic viruses share common modes of transmission and their co-infection is common. Despite the provision of an effective prevention mechanism, the infections caused by these viruses remain a significant problem worldwide, particularly among developing countries like Ethiopia. METHODS This institutional-based retrospective study was conducted between January 2014 December and December 2019 from documented laboratory logbooks of Adigrat general hospital serology laboratory, Tigrai, Ethiopia. data were collected and checked for completeness on a daily based, coded, entered, and cleaned using Epinfo version 7.1, exported and analyzed using SPSS version 23. Binary logistic regression analysis and Chi-square test (X2) assessed the association between dependent and independent variables. The corresponding variables with a P-value (P < 0.05) and 95% confidence interval were considered statistically significant. RESULTS Out of 20,935 clinically suspected individuals, 20,622 were given specimens and tested for hepatitis B and C viruses with total completeness of 98.5%. The overall prevalence of hepatitis B and hepatitis C virus was found to be 3.57% (689/19,273) and 2.13% (30/1,405), respectively. The positivity rate of the hepatitis B virus was 8.0% (106/1317) and 3.24% (583/17,956) among males and females, respectively. Additionally, 2.49%( 12/481) of males and 1.94% (18/924) of females were positive for hepatitis C virus infection. The overall prevalence of co-infection for both hepatitis B and hepatitis C virus was 7.4% (4/54). Sex and age were significantly associated with hepatitis B and C virus infection. CONCLUSIONS The overall prevalence of hepatitis B and C is low intermediate according to the WHO criteria. Although there was a fluctuating trend of hepatitis B and C through the years 2014-2019, the result shows moreover declining trend. Both hepatitis B and C share similar routes of transmission and affect all age categories but males were more highly affected than females. Therefore, awareness creation of the community about the methods of transmission, education about prevention, and control of hepatitis B and C virus infection, and improving coverage of youth-friendly services in health facilities should be strengthened.
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Affiliation(s)
- Haftom Legese
- Department of Medical Laboratory, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia.
| | - Brhane Berhe
- Department of Medical Laboratory, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia
| | - Gebre Adhanom
- Department of Medical Laboratory, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia
| | - Tsega Kahsay
- Department of Medical Laboratory, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia
| | - Aderajew Gebrewahd
- Department of Medical Laboratory, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia
| | - Guesh Gebremariam
- Department of Medical Laboratory, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia
| | - Fitsum Mardu
- Department of Medical Laboratory, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia
| | - Kebede Tesfay
- Department of Medical Laboratory, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia
| | - Haftay Gebremedhin
- Department of Public Health, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia
| | - Hadush Negash
- Department of Medical Laboratory, College of Health Sciences, Adigrat University, Adigrat City, Tigrai, Ethiopia
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12
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Genetic Susceptibility to Hepatocellular Carcinoma in Patients with Chronic Hepatitis Virus Infection. Viruses 2023; 15:v15020559. [PMID: 36851773 PMCID: PMC9964813 DOI: 10.3390/v15020559] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 02/13/2023] [Accepted: 02/14/2023] [Indexed: 02/22/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk factors, individual genetic predisposition is a major determinant of HCC risk. Familial clustering of HCC has been observed, and a hereditary factor likely contributes to the risk of HCC development. The familial aggregation may depend on a shared environment and genetic background as well as the interactions of environmental and genetic factors. Genome-wide association studies (GWASs) are one of the most practical tools for mapping the patterns of inheritance for the most common form of genomic variation, single nucleotide polymorphisms. This approach is practical for investigating genetic variants across the human genome, which is affected by thousands of common genetic variants that do not follow Mendelian inheritance. This review article summarizes the academic knowledge of GWAS-identified genetic loci and their association with HCC. We summarize the GWASs in accordance with various chronic hepatitis virus infection statuses. This genetic profiling could be used to identify candidate biomarkers to refine HCC screening and management by enabling individual risk-based personalization and stratification. A more comprehensive understanding of the genetic mechanisms underlying individual predisposition to HCC may lead to improvements in the prevention and early diagnosis of HCC and the development of effective treatment strategies.
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13
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Tan YW. Risk stratification of primary liver cancer. World J Clin Cases 2022; 10:9545-9549. [PMID: 36159415 PMCID: PMC9477684 DOI: 10.12998/wjcc.v10.i26.9545] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/29/2022] [Accepted: 08/12/2022] [Indexed: 02/05/2023] Open
Abstract
The risk stratification of primary liver cancer (PLC) discussed in a review of viral hepatitis and PLC could lead to misunderstandings by readers. For example, a single study or a small number of studies cannot comprehensively summarize the risk factors of PLC, is not included in the family history of liver cancer, and chronic hepatitis D is listed as a medium risk factor for the development of PLC. Currently, PLC prediction models with good clinical validation values have been applied clinically, such as the Toronto hepatocellular carcinoma risk index, REACH-B model, and PAGE-B model. Therefore, the Chinese, together with several research societies, have formulated the “Guideline for stratified screening and surveillance of primary liver cancer (2020 edition).” This guideline outlines PLC screening in at-risk populations, both in hospitals and communities. It is recommended to stratify the at-risk population into four risk levels: low-, intermediate-, high-, and extremely high-risk. This is highly recommended and applied in clinical practice.
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Affiliation(s)
- You-Wen Tan
- Department of Hepatology, The Third Hospital of Zhenjiang Affiliated Jiangsu University, Zhenjiang 212000, Jiangsu Province, China
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14
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Hemminki K, Sundquist K, Sundquist J, Försti A, Liska V, Hemminki A, Li X. Familial Risks for Liver, Gallbladder and Bile Duct Cancers and for Their Risk Factors in Sweden, a Low-Incidence Country. Cancers (Basel) 2022; 14:1938. [PMID: 35454845 PMCID: PMC9030935 DOI: 10.3390/cancers14081938] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/30/2022] [Accepted: 04/06/2022] [Indexed: 12/11/2022] Open
Abstract
We used the Swedish Cancer Registry data to address familial risks for concordant (same) and discordant (different) hepatobiliary cancers, including their associations with any other cancers and with known risk factors. Risks were also assessed between spouses. The analysis covered Swedish families and their cancers between years 1958 and 2018. Adjusted familial risks were expressed as standardized incidence ratios (SIRs). Familial SIRs for concordant hepatocellular carcinoma (HCC) were 2.60, and for gallbladder cancer they were at the same level (2.76). Familial risk was also found for intrahepatic bile duct cancer and for female extrahepatic bile duct cancer. HCC was associated with lung and cervical cancers; extrahepatic bile duct and ampullary cancers were associated with colon and pancreatic cancers, suggesting Lynch syndrome. Among spouses, hepatobiliary cancer was associated with HCC, stomach, pancreatic, cervical and upper aerodigestive tract cancers. Among risk factors, family members diagnosed with alcohol-related disease showed association with HCC. The observed familial risks for hepatobiliary cancers were relatively high, and considering the poor prognosis of these cancers, prevention is of the utmost importance and should focus on moderation of alcohol consumption, vaccination/treatment of hepatitis viral infections and avoidance of overweight and other risk factors of type 2 diabetes.
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Affiliation(s)
- Kari Hemminki
- Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605 Pilsen, Czech Republic
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120 Heidelberg, Germany
- Center for Primary Health Care Research, Lund University, 205 02 Malmö, Sweden; (K.S.); (J.S.); (A.F.); (X.L.)
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University, 205 02 Malmö, Sweden; (K.S.); (J.S.); (A.F.); (X.L.)
- Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Center for Community-Based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Shimane 693-8501, Japan
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University, 205 02 Malmö, Sweden; (K.S.); (J.S.); (A.F.); (X.L.)
- Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
- Center for Community-Based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Shimane 693-8501, Japan
| | - Asta Försti
- Center for Primary Health Care Research, Lund University, 205 02 Malmö, Sweden; (K.S.); (J.S.); (A.F.); (X.L.)
- Hopp Children’s Cancer Center (KiTZ), D-69120 Heidelberg, Germany
- Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), D-69120 Heidelberg, Germany
| | - Vaclav Liska
- Department of Surgery, School of Medicine in Pilsen, University Hospital, Charles University, 30605 Pilsen, Czech Republic;
- Biomedical Center, Faculty of Medicine and Biomedical Center in Pilsen, Charles University in Prague, 30605 Pilsen, Czech Republic
| | - Akseli Hemminki
- Cancer Gene Therapy Group, Translational Immunology Research Program, University of Helsinki, 00290 Helsinki, Finland;
- Comprehensive Cancer Center, Helsinki University Hospital, 00290 Helsinki, Finland
| | - Xinjun Li
- Center for Primary Health Care Research, Lund University, 205 02 Malmö, Sweden; (K.S.); (J.S.); (A.F.); (X.L.)
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15
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Metabolomics and the Multi-Omics View of Cancer. Metabolites 2022; 12:metabo12020154. [PMID: 35208228 PMCID: PMC8880085 DOI: 10.3390/metabo12020154] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 01/29/2022] [Accepted: 01/31/2022] [Indexed: 11/17/2022] Open
Abstract
Cancer is widely regarded to be a genetic disease. Indeed, over the past five decades, the genomic perspective on cancer has come to almost completely dominate the field. However, this genome-only view is incomplete and tends to portray cancer as a disease that is highly heritable, driven by hundreds of complex genetic interactions and, consequently, difficult to prevent or treat. New evidence suggests that cancer is not as heritable or purely genetic as once thought and that it really is a multi-omics disease. As highlighted in this review, the genome, the exposome, and the metabolome all play roles in cancer’s development and manifestation. The data presented here show that >90% of cancers are initiated by environmental exposures (the exposome) which lead to cancer-inducing genetic changes. The resulting genetic changes are, then, propagated through the altered DNA of the proliferating cancer cells (the genome). Finally, the dividing cancer cells are nourished and sustained by genetically reprogrammed, cancer-specific metabolism (the metabolome). As shown in this review, all three “omes” play roles in initiating cancer. Likewise, all three “omes” interact closely, often providing feedback to each other to sustain or enhance tumor development. Thanks to metabolomics, these multi-omics feedback loops are now much more evident and their roles in explaining the hallmarks of cancer are much better understood. Importantly, this more holistic, multi-omics view portrays cancer as a disease that is much more preventable, easier to understand, and potentially, far more treatable.
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16
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Aruna V, Sneha A, Harshitha DS. Hepatocellular carcinoma—An updated review. THERANOSTICS AND PRECISION MEDICINE FOR THE MANAGEMENT OF HEPATOCELLULAR CARCINOMA 2022:11-31. [DOI: 10.1016/b978-0-323-98806-3.00022-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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17
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Vittal A, Sharma D, Hu A, Majeed NA, Terry N, Auh S, Ghany MG. Systematic review with meta-analysis: the impact of functional cure on clinical outcomes in patients with chronic hepatitis B. Aliment Pharmacol Ther 2022; 55:8-25. [PMID: 34850415 DOI: 10.1111/apt.16659] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 03/17/2021] [Accepted: 10/06/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Although hepatitis B surface antigen (HBsAg) loss is considered the ideal therapeutic endpoint for the treatment of chronic hepatitis B virus (HBV) infection, its impact on clinical outcomes remains uncertain. AIM To assess the impact of HBsAg loss on clinical outcomes following spontaneous and treatment-related HBsAg loss. METHODS We searched PUBMED, Embase, the Cochrane library, and published abstracts through to May 2021 for studies that reported HBsAg loss, had >1 year of follow-up and reported at least one clinical outcome in adults with chronic HBV infection. RESULTS We identified 57 studies (258 744 HBsAg-positive patients, 63 270 with HBsAg loss). Based on 24 studies including 160 598 patients with and without HBsAg loss, HBsAg loss was associated with a non-significant 23% relative risk reduction of developing hepatocellular carcinoma (HCC) compared to those who remained HBsAg-positive (RR = 0.77; 95% CI: 0.38-1.57). In subgroup meta-analysis of 10 studies, treatment-related HBsAg loss was associated with a non-significant higher pooled proportion of HCC (0.94%) compared to spontaneous HBsAg loss (0.45%). HCC development after HBsAg loss was significantly higher in males, those with underlying cirrhosis, and those with a family history of HCC. HBsAg loss was associated with lower pooled proportions of incident cirrhosis, hepatic decompensation, overall and liver-related mortality compared to no HBsAg loss. Substantial heterogeneity was noted across studies for all outcomes. CONCLUSION HBsAg loss is associated with a reduced risk of clinical outcomes. However, several shortcomings in the published studies prevent a more definitive conclusion on the potential benefits of HBsAg loss.
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Affiliation(s)
- Anusha Vittal
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Disha Sharma
- Department of Internal Medicine, Medstar Washington Hospital Center, Washington DC, USA
| | - Alvin Hu
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Nehna A Majeed
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Nancy Terry
- Division of Library Services, National Institutes of Health Library, National Institutes of Health, Bethesda, Maryland, USA
| | - Sungyoung Auh
- Biostatistics Program, Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Marc G Ghany
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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18
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Rios RS, Zheng KI, Zheng MH. Non-alcoholic steatohepatitis and risk of hepatocellular carcinoma. Chin Med J (Engl) 2021; 134:2911-2921. [PMID: 34855640 PMCID: PMC8710331 DOI: 10.1097/cm9.0000000000001888] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Indexed: 12/18/2022] Open
Abstract
The emergence of non-alcoholic fatty liver disease (NAFLD) as the leading chronic liver disease worldwide raises some concerns. In particular, NAFLD is closely tied to sedentary lifestyle habits and associated with other metabolic diseases, such as obesity and diabetes. At the end of the disease spectrum, non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma (HCC), representing a serious health problem to modern society. Recently, an increasing number of HCC cases originating from this progressive disease spectrum have been identified, with different levels of severity and complications. Updating the current guidelines by placing a bigger focus on this emerging cause and highlighting some of its unique features is necessary. Since, the drivers of the disease are complex and multifactorial, in order to improve future outcomes, having a better understanding of NASH progression into HCC may be helpful. The risks that can promote disease progression and currently available management strategies employed to monitor and treat NASH-related HCC make up the bulk of this review.
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Affiliation(s)
- Rafael S. Rios
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Kenneth I. Zheng
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Ming-Hua Zheng
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
- Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, Zhejiang 325000, China
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19
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Roberts SK, Majeed A, Kemp W. Controversies in the Management of Hepatitis B: Hepatocellular Carcinoma. Clin Liver Dis 2021; 25:785-803. [PMID: 34593153 DOI: 10.1016/j.cld.2021.06.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis B is the leading cause of hepatocellular cancer (HCC) worldwide. Untreated, annual HCC incidence rates in chronic hepatitis B subjects are 0.4% in noncirrhotics and 2% to 3% in cirrhotics. Surveillance with ultrasound with/without α-fetoprotein at 6-month intervals is recommended in at-risk persons including children. Antiviral therapy in chronic hepatitis B with entecavir or tenofovir significantly lowers the risk of HCC across all stages of liver disease, and lowers the risk of HCC recurrence following curative therapy. There are insufficient data to recommend use of tenofovir over entecavir in the prevention of de novo or recurrent HCC postcurative therapy.
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Affiliation(s)
- Stuart K Roberts
- The Alfred, 55 Commercial Road, Melbourne 3004, Australia; Monash University, Melbourne, Australia.
| | - Ammar Majeed
- The Alfred, 55 Commercial Road, Melbourne 3004, Australia; Monash University, Melbourne, Australia
| | - William Kemp
- The Alfred, 55 Commercial Road, Melbourne 3004, Australia; Monash University, Melbourne, Australia
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20
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Tang LJ, Rios RS, Zhang H, Byrne CD, Targher G, Zheng MH. Telomerase: a key player in the pathogenesis of non-alcoholic fatty liver disease? Expert Rev Gastroenterol Hepatol 2021; 15:811-819. [PMID: 33709875 DOI: 10.1080/17474124.2021.1903318] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Accepted: 03/10/2021] [Indexed: 10/21/2022]
Abstract
Introduction: Telomerase is a basic nuclear protein reverse transcriptase, which plays a key role in maintaining telomere stability, genome integrity, long-term cell activity, and potential continued proliferation.Area covered: This narrative review discusses key research advances involving telomerase in the development and progression of nonalcoholic fatty liver disease (NAFLD). The review evaluates 9a) whether the assessment of telomerase can be used as a noninvasive diagnostic tool; and (b) whether modification of telomerase function might be a useful potential therapeutic target for treatment of NAFLD. Furthermore, the relationship between telomerase and other chronic metabolic diseases is evaluated.Expert opinion: Several experimental and preclinical studies have suggested that telomerase plays an important role in the development of NAFLD. However, further mechanistic studies are needed to prove a causal relationship and to better elucidate whether the measurement of telomerase has utility as a diagnostic tool or whether pharmacological manipulation of telomerase has therapeutic potential in NAFLD treatment.
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Affiliation(s)
- Liang-Jie Tang
- NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Rafael S Rios
- NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Huai Zhang
- NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Christopher D Byrne
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Ming-Hua Zheng
- NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
- Institute of Hepatology, Wenzhou Medical University, Wenzhou, China
- Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
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21
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Mezina A, Philips N, Bogus Z, Erez N, Xiao R, Fan R, Olthoff KM, Reddy KR, Samadder NJ, Nielsen SM, Hatchell KE, Esplin ED, Rustgi AK, Katona BW, Hoteit MA, Nathanson KL, Wangensteen KJ. Multigene Panel Testing in Individuals With Hepatocellular Carcinoma Identifies Pathogenic Germline Variants. JCO Precis Oncol 2021; 5:PO.21.00079. [PMID: 34250406 DOI: 10.1200/po.21.00079] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 04/16/2021] [Accepted: 04/28/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) has well-defined environmental risk factors. In addition, epidemiologic studies have suggested hereditary risk factors. The goals of this study were to determine the rate of pathogenic and likely pathogenic (P/LP) germline variants in cancer predisposition genes in patients with HCC, possible enrichment of P/LP variants in particular genes, and potential impact on clinical management. MATERIALS AND METHODS A prospective study at a tertiary medical center enrolled 217 patients with a personal history of HCC. Multigene panel testing was performed for 134 cancer predisposition genes in all patients. The rate of P/LP variants was compared with population rates. A separate retrospective cohort included 219 patients with HCC who underwent testing at a commercial laboratory. RESULTS In the prospective cohort, P/LP germline variants were identified in 25 of 217 patients with HCC (11.5%). Four patients (1.8%) had P/LP variants in the highly penetrant cancer genes BRCA2 (n = 2), MSH6 (n = 1), and PMS2 (n = 1). In addition, multiple patients had P/LP variants in FANCA (n = 5) and BRIP1 (n = 4), which were significantly enriched in HCC compared with the general population. Detection of P/LP variants led to changes in clinical management in regard to therapy selection, screening recommendations, and cascade testing of relatives. In a separate retrospective analysis of 219 patients with HCC, 30 (13.7%) were positive for P/LP variants including 13 (5.9%) with highly penetrant genes APC (n = 2), BRCA1 (n = 1), BRCA2 (n = 6), MSH2 (n = 2), or TP53 (n = 2). CONCLUSION P/LP germline variants in cancer predisposition genes were detected in 11%-14% of patients with HCC. Inherited genetics should not be overlooked in HCC as there are important implications for precision treatment, future risk of cancers, and familial cancer risk.
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Affiliation(s)
- Anya Mezina
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Neil Philips
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Zoe Bogus
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.,Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Noam Erez
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Rui Xiao
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Ruoming Fan
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Kim M Olthoff
- Department of Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - K Rajender Reddy
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | | | | | | | | | - Anil K Rustgi
- Division of Digestive and Liver Diseases, Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY
| | - Bryson W Katona
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Maarouf A Hoteit
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Katherine L Nathanson
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.,Abramson Cancer Center, University of Perelman School of Medicine, Philadelphia, PA
| | - Kirk J Wangensteen
- Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.,Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.,Abramson Cancer Center, University of Perelman School of Medicine, Philadelphia, PA
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22
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Yang DH, Wang WP, Zhang Q, Pan HY, Huang YC, Zhang JJ. Hepatocellular carcinoma progression in hepatitis B virus-related cirrhosis patients receiving nucleoside (acid) analogs therapy: A retrospective cross-sectional study. World J Gastroenterol 2021; 27:2025-2038. [PMID: 34007137 PMCID: PMC8108039 DOI: 10.3748/wjg.v27.i17.2025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 03/25/2021] [Accepted: 04/02/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Antiviral therapy cannot completely block the progression of hepatitis B to hepatocellular carcinoma (HCC). Furthermore, there are few predictors of early HCC progression and limited strategies to prevent progression in patients with HBV-related cirrhosis who receive nucleos(t)ide analog (NA) therapy. AIM The study aim was to clarify risk factors and the diagnostic value of alpha-fetoprotein (AFP) for HCC progression in NA-treated hepatitis B virus (HBV)-related cirrhosis patients. METHODS In this retrospective cross-sectional study, we analyzed the clinical data of 266 patients with HBV-related cirrhosis who received NA treatment between February 2014 and April 2020 at Zhejiang Provincial People's Hospital. The patients were divided into two groups, 145 who did not progress to HCC (No-HCC group), and 121 who progressed to HCC during NA treatment (HCC group). The logistic regression analysis was used to analyze the risk factors of HCC progression. The diagnostic value of AFP for HCC was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS Univariate analysis showed that age ≥ 60 years (P = 0.001), hepatitis B and alcoholic etiology (P = 0.007), smoking history (P < 0.001), family history of HBV-related HCC (P = 0.002), lamivudine resistance (P = 0.011), HBV DNA negative (P = 0.023), aspartate aminotransferase > 80 U/L (P = 0.002), gamma-glutamyl transpeptidase > 120 U/L (P = 0.001), alkaline phosphatase > 250 U/L (P = 0.001), fasting blood glucose (FBG) ≥ 6.16 (mmol/L) (P = 0.001) and Child-Pugh class C (P = 0.005) were correlated with HCC progression. In multivariate analysis, age ≥ 60 years [hazard ratio (HR) = 3.089, 95% confidence interval (CI): 1.437-6.631, P = 0.004], smoking history (HR = 4.001, 95%CI: 1.836-8.716, P < 0.01), family history of HBV-related HCC (HR = 6.763, 95%CI: 1.253-36.499, P < 0.05), lamivudine resistance (HR = 2.949, 95%CI: 1.207-7.208, P = 0.018), HBV DNA negative (HR = 0.026, 95%CI: 0.007-0.139, P < 0.01), FBG ≥ 6.16 mmol/L (HR = 7.219, 95%CI: 3.716-14.024, P < 0.01) were independent risk factors of HCC progression. ROC of AFP for diagnosis of HCC was 0.746 (95%CI: 0.674-0.818). A cutoff value of AFP of 9.00 ug/L had a sensitivity of 0.609, and specificity of 0.818 for diagnosing HCC. CONCLUSION Age ≥ 60 years, smoking history, family history of HCC, lamivudine resistance, HBV DNA negative, FBG ≥ 6.16 mmol/L were risk factors of HCC progression. Serum AFP had limited diagnostic value for HCC.
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Affiliation(s)
- Dan-Hong Yang
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Wei-Ping Wang
- Postgraduate Department, Bengbu Medical College, Bengbu 233030, Anhui Province, China
| | - Qiang Zhang
- Postgraduate Department, Bengbu Medical College, Bengbu 233030, Anhui Province, China
| | - Hong-Ying Pan
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Yi-Cheng Huang
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Jia-Jie Zhang
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
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23
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Diallo I, Ndiaye B, Touré M, Sow A, Mbengue A, Diawara PS, Gning SB, Mbaye PS, Fall F, Mbengue M. Hepatocellular carcinoma in Senegal: epidemiological, clinical and etiological aspects about 229 cases at Hôpital Principal de Dakar. Pan Afr Med J 2021; 38:99. [PMID: 33889265 PMCID: PMC8035678 DOI: 10.11604/pamj.2021.38.99.25195] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Accepted: 12/03/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a major public health problem in Senegal, and the third most common cancer in terms of incidence. However, there are no recent data on the characteristics of this pathology in our country. The aim was to describe the epidemiological, clinical, aetiological and therapeutic aspects of HCC at Hôpital Principal de Dakar, Senegal. We did a descriptive retrospective study, including patients hospitalized from January 2012 to December 2017. We included 229 patients. The mean age was 47.4 years (21 - 88 years), and 77 patients (33.6%) were under 40 years of age. The sex ratio was 6.6. Twelve patients (5.2%) had a family history of 1st degree cirrhosis or HCC. Ten patients (4.4%) were previously treated with nucleotide analogues. The most common clinical sign at diagnosis was abdominal pain (91.7%). Alpha-fetoprotein level was normal in 12.2% of patients, and greater than 400 ng/ml in 68.1% of cases. Abdominal ultrasound found nodular HCC in 122 patients (68.2%), infiltrative HCC in 19 patients (10.6%), and was normal in 38 cases (21.2%). Subjacent cirrhosis was detected in 71.3% of cases. Abdominal computed tomography (CT) scan showed compatible HCC lesions in 88.8% of cases. A histological diagnosis was obtained in 2 patients (0.9%). The most common etiological factor was hepatitis B virus (69.4%), characterized mostly by a younger age (p = 0.001). In 20.9% of cases, no aetiology was found. An advanced or terminal stage (BCLC C/D) was found in 217 cases (94.8%). The treatment was curative in 12 patients (5.2%), and palliative in 7 cases (3.1%). The evolution at one year was favourable in 6 patients (2.6%). Hepatocellular carcinoma (HCC) is a disease that mainly affects young male adults in Senegal. The main aetiological factor remains HBV infection. The diagnosis is made at an advanced stage and the prognosis very bad.
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Affiliation(s)
- Ibrahima Diallo
- Department of Internal Medicine and Hepatogastroenterology, Hôpital Principal de Dakar, Dakar, Senegal
| | - Bineta Ndiaye
- Department of Internal Medicine and Hepatogastroenterology, Hôpital Principal de Dakar, Dakar, Senegal
| | - Mouhamed Touré
- Department of Internal Medicine and Hepatogastroenterology, Hôpital Principal de Dakar, Dakar, Senegal
| | - Abdoul Sow
- Department of Internal Medicine and Hepatogastroenterology, Hôpital Principal de Dakar, Dakar, Senegal
| | - Ababacar Mbengue
- Department of Medical Biology, Hôpital Principal de Dakar, Dakar, Senegal
| | | | - Sara Boury Gning
- Department of Internal Medicine and Hepatogastroenterology, Hôpital Principal de Dakar, Dakar, Senegal
| | - Papa Saliou Mbaye
- Department of Internal Medicine and Hepatogastroenterology, Hôpital Principal de Dakar, Dakar, Senegal
| | - Fatou Fall
- Department of Internal Medicine and Hepatogastroenterology, Hôpital Principal de Dakar, Dakar, Senegal
| | - Mouhamadou Mbengue
- Department of Internal Medicine and Hepatogastroenterology, Hôpital Général de Grand-Yoff, Dakar, Senegal
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Zheng C, Yu S. Expression and gene regulatory network of SNHG1 in hepatocellular carcinoma. BMC Med Genomics 2021; 14:28. [PMID: 33499863 PMCID: PMC7836560 DOI: 10.1186/s12920-021-00878-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 01/17/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Small nucleolar RNA host gene 1 (SNHG1), a long noncoding RNA (lncRNA), is a transcript that negatively regulates tumour suppressor genes, such as p53. Abnormal SNHG1 expression is associated with cell proliferation and cancer. We used sequencing data downloaded from Genomic Data Commons to analyse the expression and interaction networks of SNHG1 in hepatocellular carcinoma (HCC). METHODS Expression was examined using the limma package of R and verified by Gene Expression Profiling Interactive Analysis. We also obtained miRNA expression data from StarBase to determine the lncRNA-miRNA-mRNA-related RNA regulatory network in HCC. Kaplan-Meier (KM) analysis was performed using the survival package of R. Gene Ontology annotation of genes was carried out using Metascape. RESULTS We found that SNHG1 was overexpressed and often amplified in HCC patients. In addition, SNHG1 upregulation was associated with the promotion of several primary biological functions, including cell proliferation, transcription and protein binding. Moreover, we found similar trends of small nucleolar RNA host gene 1 (SNHG1), E2F8 (E2F transcription factor 8), FANCE (FA complementation group E) and LMNB2 (encodes lamin B2) expression. In the SNHG1-associated network, high expression levels of SNHG1 (log-rank P value = 0.0643), E2F8 (log-rank P value = 0.000048), FANCE (log-rank P value = 0.00125) and LMNB2 (log-rank P value = 0.0392) were significantly associated with poor survival. Single-cell analysis showed that E2F8 may play an important role in tumorigenesis or cancer development. CONCLUSIONS Our results highlight the benefit of utilizing multiple datasets to understand the functional potential regulatory networks of SNHG1 and the role of SNHG1 in tumours.
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Affiliation(s)
- Chaoran Zheng
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China.
| | - Shicheng Yu
- Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, School of Pharmaceutical Sciences, Wuhan University, Wuhan, 430071, China.
- Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou Science Park, Luogang District, Guangzhou, 510530, China.
- Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Bioland Laboratory, Guangzhou, 510005, China.
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25
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Meng ZW, Cai XR, Lin CZ, Chen YL, Liu S. The Islanding effect - a special method of percutaneous peritumor ethanol injection for hepatocellular carcinoma: 15-year follow-up outcome. Medicine (Baltimore) 2021; 100:e24365. [PMID: 33546073 PMCID: PMC7837841 DOI: 10.1097/md.0000000000024365] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 12/19/2020] [Indexed: 12/28/2022] Open
Abstract
Percutaneous ethanol injection is a well-known ablation therapy for hepatocellular carcinoma and is well-tolerated, inexpensive, and effective with few adverse events. In this study, another type of ethanol injection was introduced in the present study.Sixty two patients with hepatocellular carcinoma received 133 percutaneous peritumor ethanol injection treatments and the 15-year follow-up outcomes were analyzed through a collected database.The technical efficiency was 89.5% (119/133 treatments) after the first percutaneous peritumor ethanol injection procedure. However, after the second repeated percutaneous peritumor ethanol injection procedure, technical efficiency increased to 98.5% (131/133 treatments). The 1 year, 3 years, 5 years, 10 years, and 15 years rates of tumor recurrence were 12.9%, 50.0%, 59.7%, 74.2%, and 74.2%, respectively. Multivariate analysis demonstrated that diabetes, Child-Pugh class B, and tumor size greater than 2 cm were significantly related to tumor recurrence. The 1 year, 3 years, 5 years, 10 years, and 15 years rates of overall survival were 98.4%, 83.6%, 61.3%, 19.4%, and 0%, respectively. Multivariate analysis demonstrated that Child-Pugh class B, tumor size greater than 2 cm, and multiple tumors were significantly related to overall survival.Compared with other ablation methods (including peritumor ethanol injection), percutaneous peritumor ethanol injection can avoid tumor ruptures, reduce tumor proliferation and metastasis, and is suitable for the treatment of small tumors. In addition, when combined with other treatment methods, percutaneous peritumor ethanol injection can form a tumor metastatic isolation zone in advance and improve the comprehensive treatment effect.
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Abstract
Hepatocellular carcinoma (HCC) is one of the five leading causes of cancer death in human. Hepatitis B virus (HBV) is the most common etiologic agent of HCC in the world. Prevention is the best way to control cancer. There are three levels of liver cancer prevention, i.e., primary prevention by HBV vaccination targeting the general population starting from birth dose, secondary prevention by antiviral agent for high-risk subjects with chronic HBV infection, and tertiary prevention by antiviral agent to prevent recurrence for patients who have been successfully treated for liver cancer. Primary prevention by hepatitis B vaccination is most cost effective, the cancer preventive efficacy support it as the first successful example of cancer preventive vaccine in human. Addition of hepatitis B immunoglobulin immediately after birth and antiviral agent during the third trimester of pregnancy to block mother-to-infant transmission of HBV are existing or possible emerging strategies to enhance the prevention efficacy of HBV infection and its related liver cancer. Secondary prevention with current antiviral agents may reduce the risk or delay the onset of HCC development, but could not eradicate HBV infection and HCC. Better antiviral therapeutic agents are needed for better secondary prevention.
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Affiliation(s)
- Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
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27
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Wangensteen KJ, Chang KM. Multiple Roles for Hepatitis B and C Viruses and the Host in the Development of Hepatocellular Carcinoma. Hepatology 2021; 73 Suppl 1:27-37. [PMID: 32737895 PMCID: PMC7855312 DOI: 10.1002/hep.31481] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Revised: 05/21/2020] [Accepted: 07/02/2020] [Indexed: 02/06/2023]
Abstract
Chronic hepatitis B and C viral infections are major risk factors for hepatocellular carcinoma (HCC) in the United States and worldwide. Direct and indirect mechanisms of viral infection lead to the development of HCC. Chronic viral infection leads to inflammation and liver damage, culminating in cirrhosis, the penultimate step in the progression toward HCC. Host, viral, and environmental factors likely interact to promote oncogenesis. Clinical considerations include recommendations for screening for HCC in persons at risk, treatment with antivirals, and an emerging role for immunotherapy in HCC. We pose unanswered questions regarding HCC susceptibility and pathogenesis in the setting of chronic hepatitis B and C.
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Affiliation(s)
- Kirk J Wangensteen
- Gastroenterology Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Kyong-Mi Chang
- The Corporal Michael J. Crescenz VA Medical Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
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Macek Jílková Z, Seigneurin A, Coppard C, Ouaguia L, Aspord C, Marche PN, Leroy V, Decaens T. Circulating IL-13 Is Associated with De Novo Development of HCC in HCV-Infected Patients Responding to Direct-Acting Antivirals. Cancers (Basel) 2020; 12:cancers12123820. [PMID: 33352852 PMCID: PMC7766760 DOI: 10.3390/cancers12123820] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 12/10/2020] [Accepted: 12/16/2020] [Indexed: 12/16/2022] Open
Abstract
Direct-acting antivirals (DAAs) are highly effective in targeting hepatitis C virus (HCV) infections, but the incidence of HCV-related hepatocellular carcinoma (HCC) remains still high. In this study, we investigated a cohort of HCV-infected patients treated with DAAs who were followed up for 4 years after sustained virological response (SVR) achievement. Patients who developed de novo HCC following DAA treatment were compared to matched controls who did not develop HCC. These control patients were selected based on DAA treatment, sex, age, fibrosis status, and platelet counts. We evaluated serum levels of 30 immune mediators before, during, at the end of, and three months after DAA treatment using Luminex technology. We identified the immune factors associated with de novo HCC occurrence following DAA treatment. Specifically, interleukin (IL)-4 and IL-13 levels were significantly higher before start of the DAA treatment in the serum of patients who later developed HCC than in controls and stayed higher at each subsequent time point. Least absolute shrinkage and selection operator (LASSO) regression revealed IL-13 as the only strong factor associated with HCC development in this cohort of HCV patients. The difference was observed already at baseline of DAA treatment, which confirms the existence of a specific immune profile in these patients who later develop HCC.
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Affiliation(s)
- Zuzana Macek Jílková
- Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, 38700 Grenoble, France; (C.C.); (L.O.); (C.A.); (P.N.M.); (V.L.)
- Service d’Hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, 38043 Grenoble, France
- Correspondence: (Z.M.J.); (T.D.); Tel.: +33-4765-49417 (Z.M.J.); +33-4767-65441 (T.D.); Fax: +33-4767-65179 (T.D.)
| | - Arnaud Seigneurin
- University Grenoble Alpes, 38400 Saint-Martin-d’Hères, France;
- Service d’Evaluation Médicale, CHU Grenoble Alpes, 38043 Grenoble, France
- TIMC-IMAG UMR 5525, 38700 La Tronche, France
| | - Celine Coppard
- Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, 38700 Grenoble, France; (C.C.); (L.O.); (C.A.); (P.N.M.); (V.L.)
| | - Laurissa Ouaguia
- Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, 38700 Grenoble, France; (C.C.); (L.O.); (C.A.); (P.N.M.); (V.L.)
- Etablissement Français du Sang, Rhone-Alpes Auvergne, 38043 Grenoble, France
| | - Caroline Aspord
- Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, 38700 Grenoble, France; (C.C.); (L.O.); (C.A.); (P.N.M.); (V.L.)
- Etablissement Français du Sang, Rhone-Alpes Auvergne, 38043 Grenoble, France
| | - Patrice N. Marche
- Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, 38700 Grenoble, France; (C.C.); (L.O.); (C.A.); (P.N.M.); (V.L.)
| | - Vincent Leroy
- Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, 38700 Grenoble, France; (C.C.); (L.O.); (C.A.); (P.N.M.); (V.L.)
- Service d’Hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, 38043 Grenoble, France
- University Grenoble Alpes, 38400 Saint-Martin-d’Hères, France;
| | - Thomas Decaens
- Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309, 38700 Grenoble, France; (C.C.); (L.O.); (C.A.); (P.N.M.); (V.L.)
- Service d’Hépato-gastroentérologie, Pôle Digidune, CHU Grenoble Alpes, 38043 Grenoble, France
- University Grenoble Alpes, 38400 Saint-Martin-d’Hères, France;
- Correspondence: (Z.M.J.); (T.D.); Tel.: +33-4765-49417 (Z.M.J.); +33-4767-65441 (T.D.); Fax: +33-4767-65179 (T.D.)
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Neuman MG, Cohen LB, Malnick S. Familial non-alcoholic steatohepatitis leading to hepatocellular carcinoma. Chem Biol Interact 2020; 323:109054. [PMID: 32217109 DOI: 10.1016/j.cbi.2020.109054] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 02/17/2020] [Accepted: 03/10/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Non-alcoholic steatohepatitis (NASH) has been associated with fibrosis that may progress to cirrhosis. The purpose of this study was to examine hepatocytes and perisinusoidal cells in liver biopsies of 3 families (3 males and 4 females) with non-cirrhotic and cirrhotic NASH to determine unique histological changes during a period of 2-7 years from diagnosis. METHODS In this study, hepatocytes, stellate cells and Kupffer cells were analyzed using light and electron microscopy, and immunohistochemistry with specific anti-macrophage antibody staining of liver biopsies. RESULTS Body mass index of all patients was over 28, and all viral, metabolic markers were negative. Alcohol consumption was insignificant. In all liver biopsies, diffuse, non-zonal macrovesicular steatosis involved 40-70% of liver samples. The lobular hepatocytes showed prominent ballooning hepatocyte degeneration. No Mallory Denk hyaline bodies (MDBs) were observed in three of the patients. MDBs developed in ballooned hepatocytes of four individuals that also presented foci of lobular inflammation. The apoptotic bodies were stained by cytokeratin 18. The trichrome stain revealed portal to portal bridging fibrosis. In one family, there was a three-fold increase in relative numbers of perisinusoidal macrophages in the older sister with NASH compared to livers of the younger siblings. The special finding in livers of patients with NASH was accumulation of groups of perisinusoidal macrophages, which was not associated with focal necrosis. CONCLUSION Perisinusoidal macrophages appear to accumulate in NASH. It is possible that collections of macrophages are a response to chronic portal endotoxemia or lipotoxic activation of immuno-mediators. The persistent activation of these macrophages could lead to the chronic release of pro-inflammatory cytokines and contribute to chronic inflammation, fibrosis and cirrhosis leading to HCC.
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Affiliation(s)
- Manuela G Neuman
- In Vitro Drug Safety and Biotechnology, Canada; Department of Pharmacology & Toxicology, University of Toronto, Canada.
| | - Lawrence B Cohen
- Division of Gastroenterology, Sunnybrook Health Science Centre, Canada; Department of Medicine, University of Toronto, Toronto, Canada.
| | - Stephen Malnick
- Department of Internal Medicine, Kaplan Medical Centre, Affiliated to Hebrew University, Rehovot, Israel.
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Matsubayashi H, Takaori K, Morizane C, Kiyozumi Y. Familial Pancreatic Cancer and Surveillance of High-Risk Individuals. Gut Liver 2020; 13:498-505. [PMID: 30917631 PMCID: PMC6743804 DOI: 10.5009/gnl18449] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 12/04/2018] [Accepted: 12/13/2018] [Indexed: 12/15/2022] Open
Abstract
Family history of pancreatic cancer (PC) is a risk factor for PC development, and the risk level correlates with the number of affected families. A case of PC with ≥1 PC cases in the first-degree relative is broadly defined as familial pancreatic cancer (FPC) and accounts for 5% to 10% of total PC cases. FPC possesses several epidemiological, genetic and clinicopathological aspects that are distinct from those of conventional PCs. In Western countries, FPC registries have been established since the 1990s, and high-risk individuals are screened to detect early PCs. For the pharmacotherapy of FPC, especially in cases with germline pathogenic BRCA mutations, regimens using platinum and poly (ADP-ribose) polymerase inhibitor have recently been studied for their effectiveness. To date, the concept of FPC has prevailed in Western countries, and it has begun to infiltrate into Eastern countries. As the genetic background and environmental conditions vary in association with ethnicity and living area, we need to establish our own FPC registries and accumulate data in Asian countries.
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Affiliation(s)
- Hiroyuki Matsubayashi
- Divisions of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan.,Divisions of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kyoichi Takaori
- Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Chigusa Morizane
- Division of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Yoshimi Kiyozumi
- Divisions of Genetic Medicine Promotion, Shizuoka Cancer Center, Shizuoka, Japan
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Hassanipour S, Vali M, Gaffari-Fam S, Nikbakht HA, Abdzadeh E, Joukar F, Pourshams A, Shafaghi A, Malakoutikhah M, Arab-Zozani M, Salehiniya H, Mansour-Ghanaei F. The survival rate of hepatocellular carcinoma in Asian countries: a systematic review and meta-analysis. EXCLI JOURNAL 2020; 19:108-130. [PMID: 32038120 PMCID: PMC7003639 DOI: 10.17179/excli2019-1842] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Accepted: 11/19/2019] [Indexed: 12/18/2022]
Abstract
Hepatocellular carcinoma or Liver cancer (LC) is the sixth most common cancer and the fourth cause of death worldwide in 2018. There has not been a comprehensive study on the survival rate of patients with LC in Asia yet. Therefore, the present study was conducted to evaluate the survival rate of patients with LC in Asian countries. The methodology of the present study is based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement. The researchers searched five international databases including Medline/PubMed, Scopus, Embase, Web of Knowledge and ProQuest until July 1, 2018. We also searched Google Scholar for detecting grey literature. The Newcastle-Ottawa Quality Assessment Form was used to evaluate the quality of selected papers. A total of 1425 titles were retrieved. 63 studies met the inclusion criteria. Based on the random-effect model one-year, three-year and five-year survival rate of LC were 34.8 % (95 % CI; 30.3-39.3), 19 % (95 % CI ; 18.2-21.8) and 18.1 % (95 % CI ;16.1-20.1) respectively. According to the results of our study, the LC survival rate in Asian countries is relatively lower than in Europe and North America.
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Affiliation(s)
- Soheil Hassanipour
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Mouhebat Vali
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saber Gaffari-Fam
- Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein-Ali Nikbakht
- Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Elham Abdzadeh
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Farahnaz Joukar
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Akram Pourshams
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Afshin Shafaghi
- Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Mahdi Malakoutikhah
- Department of Occupational Health, Kashan University of Medical Sciences, Kashan, Iran
| | - Morteza Arab-Zozani
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, Iran.,Iranian Center of Excellence in Health Management, School of Management and Medical Informatics, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamid Salehiniya
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Fariborz Mansour-Ghanaei
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.,Caspian Digestive Disease Research Center, Guilan University of Medical Sciences, Rasht, Iran
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Pennisi G, Celsa C, Giammanco A, Spatola F, Petta S. The Burden of Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: Screening Issue and Future Perspectives. Int J Mol Sci 2019; 20:ijms20225613. [PMID: 31717576 PMCID: PMC6887792 DOI: 10.3390/ijms20225613] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/04/2019] [Accepted: 11/06/2019] [Indexed: 02/07/2023] Open
Abstract
In recent decades, non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease in the Western world, and the occurrence of its complications, such as hepatocellular carcinoma (HCC), has rapidly increased. Obesity and diabetes are considered not only the main triggers for the development of the disease, but also two independent risk factors for HCC. Single nucleotide polymorphisms (such as PNPLA3, TM6SF2 and MBOAT7) are related to the susceptibility to the development of HCC and its progression. Therefore, an appropriate follow-up of these patients is needed for the early diagnosis and treatment of HCC. To date, international guidelines recommend the use of ultrasonography with or without alpha-fetoprotein (AFP) in patients with advanced fibrosis. Furthermore, the use of non-invasive tools could represent a strategy to implement surveillance performance. In this review, we analyzed the main risk factors of NAFLD-related HCC, the validated screening methods and the future perspectives.
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Affiliation(s)
- Grazia Pennisi
- Sezione di Gastroenterologia e Epatologia, PROMISE, University of Palermo, 90127 Palermo, Italy; (C.C.); (F.S.)
- Correspondence: (G.P.); (S.P.); Tel.: +39-0916552170 (G.P.); +39-0916552170 (S.P.)
| | - Ciro Celsa
- Sezione di Gastroenterologia e Epatologia, PROMISE, University of Palermo, 90127 Palermo, Italy; (C.C.); (F.S.)
| | - Antonina Giammanco
- Sezione di Astanteria e MCAU, PROMISE, University of Palermo, 90127 Palermo, Italy;
| | - Federica Spatola
- Sezione di Gastroenterologia e Epatologia, PROMISE, University of Palermo, 90127 Palermo, Italy; (C.C.); (F.S.)
| | - Salvatore Petta
- Sezione di Gastroenterologia e Epatologia, PROMISE, University of Palermo, 90127 Palermo, Italy; (C.C.); (F.S.)
- Correspondence: (G.P.); (S.P.); Tel.: +39-0916552170 (G.P.); +39-0916552170 (S.P.)
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An J, Chang S, Kim HI, Song GW, Shim JH. The clinical behavior and survival of patients with hepatocellular carcinoma and a family history of the disease. Cancer Med 2019; 8:6624-6633. [PMID: 31532075 PMCID: PMC6825981 DOI: 10.1002/cam4.2543] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 08/19/2019] [Accepted: 08/20/2019] [Indexed: 12/14/2022] Open
Abstract
Purpose Familial clustering is a common feature of hepatocellular carcinoma (HCC) as well as a risk factor for the disease. We aimed to assess whether such a family history affected prognostic outcomes in patients with HCC diagnosed at different stages of the disease. Materials/Methods This hospital registry‐based cohort study included 5484 patients initially diagnosed with HCC. Individual family histories of cancer were obtained by interview and reported by trained nurses who constructed three‐generation pedigrees. Overall survival data were compared between cases with and without first‐degree relatives affected by HCC, with adjustment for other potential predictors. Results Of 5484 patients, 845 (15.4%) had first‐degree relatives with a history of HCC. Family history was associated with longer survival in the entire cohort (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80‐0.98, P = .025). A significant trend for reduced risk of death with increasing number of affected family members was also observed (P for trend = 0.018). The stage‐stratified analysis showed that the presence of family history was especially associated with a reduced risk of death in the subset of patients with HCC at a (very) early stage (adjusted HR 0.83, 95% CI 0.69‐0.99; P = .042). The proportion of cases receiving curative treatment was also higher in early‐stage patients with a family history (72.6% vs 63.3%; P < .001). Conclusions A first‐degree family history of the disease is a prognostic factor for improved survival in patients with HCC, especially in those whose tumors can be cured by radical treatments.
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Affiliation(s)
- Jihyun An
- Gastroenterology and Hepatology, Hanyang University College of Medicine, Guri, Korea
| | - Seheon Chang
- Internal Medicine, Myongji Saint Mary's Hospital, Seoul, Korea
| | - Ha Il Kim
- Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ju Hyun Shim
- Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.,Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Hassanipour S, Mohammadzadeh M, Mansour-Ghanaei F, Fathalipour M, Joukar F, Salehiniya H, Abdzadeh E, Samadani AA, Nikbakht HA, Arab-Zozani M. The Incidence of Hepatocellular Carcinoma in Iran from 1996 to 2016: a Systematic Review and Meta-analysis. J Gastrointest Cancer 2019; 50:193-200. [PMID: 30725358 DOI: 10.1007/s12029-019-00207-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE Hepatocellular carcinoma or liver cancer (LC) is one of most important cancer around the world. There are several reports about LC incidence from various Iranian locations with conflicting results. The present study aimed to accomplish a systematic review to estimate the accurate incidence rate of LC among Iranian people. METHODS This systematic review was performed based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist in 2018. A literature search was conducted using international databases (Medline/PubMed, Scopus, ScienceDirect, and Google Scholar) for English papers and national databases (Scientific Information Database, MagIran, IranMedex, and IranDoc) for Persian papers which estimated incidence rate of LC in any geographical area of Iran. The incidence rate of LC was calculated using random effect model. RESULTS Of 171 papers in the primary searches, 15 studies were included by advanced screening and refinement. The age-standardized rate (ASR) of LC was 1.66 (95% CI 1.49-1.83) for males and 1.25 (95% CI 1.12-1.38) for females. CONCLUSIONS The incidence rate of LC in Iran was lower in comparison to other countries. Afterwards, more studies are necessary to outline the accurate incidence rate and the trend of LC among Iranian population.
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Affiliation(s)
- Soheil Hassanipour
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Majid Mohammadzadeh
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fariborz Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.
| | - Mohammad Fathalipour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Farahnaz Joukar
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Hamid Salehiniya
- Zabol University of Medical Sciences, Zabol, Iran.,Department of Epidemiology and Biostatistics, Tehran University of medical sciences, Tehran, Iran
| | - Elham Abdzadeh
- Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran
| | - Ali Akbar Samadani
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Hossein-Ali Nikbakht
- Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Morteza Arab-Zozani
- Iranian Center of Excellence in Health Management, School of Management and Medical Informatics, Tabriz University of Medical Sciences, Tabriz, Iran
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Liu X, Baecker A, Wu M, Zhou JY, Yang J, Han RQ, Wang PH, Jin ZY, Liu AM, Gu X, Zhang XF, Wang XS, Su M, Hu X, Sun Z, Li G, Fu A, Jung SY, Mu L, He N, Li L, Zhao JK, Zhang ZF. Family history of liver cancer may modify the association between HBV infection and liver cancer in a Chinese population. Liver Int 2019; 39:1490-1503. [PMID: 31228882 PMCID: PMC6705127 DOI: 10.1111/liv.14182] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 06/07/2019] [Accepted: 06/08/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The potential interaction between family history of liver cancer and HBV infection on liver cancer has not been fully examined. METHODS We conducted a population-based case-control study composed of 2011 liver cancer cases and 7933 controls in Jiangsu province, China from 2003 to 2010. Data on major risk or protective factors were collected and HBV/HCV sero-markers were assayed using blood samples. Semi-Bayes (SB) adjustments were applied to provide posterior estimates. RESULTS Both family history of liver cancer (adjusted odds ratios [OR]: 4.32, 95% confidence intervals [CI]: 3.25-5.73) and hepatitis B surface antigen (HBsAg) positivity (adjusted OR: 9.94, 95% CI: 8.33-11.87) were strongly associated with liver cancer development. For individuals with different combinations of serological markers, the adjusted ORs were 8.45 (95% CI: 5.16-13.82) for HBsAg- and HBcAb-positive; 7.57 (95% CI: 4.87-11.77) for HBsAg-, HBeAg- and HBcAb-positive; and 3.62 (95% CI: 2.47-5.31) for HBsAg-, HBeAb- and HBcAb-positive, compared to all negatives in HBV serological markers. One log increase in HBV DNA level was associated with 17% increased risk (adjusted OR: 1.17, 95% CI: 1.03-1.32). The SB-adjusted OR of HBV-positive individuals with family history of liver cancer was 41.34 (95% posterior interval [PI]: 23.69-72.12) compared with those HBV-negative without family history. Relative excess risk due to additive interaction, the attributable proportion and synergy index were 73.13, 0.87 and 8.04 respectively. Adjusted ratio of OR for multiplicative interaction was 2.84 (95% CI: 1.41-5.75). CONCLUSIONS Super-additive and super-multiplicative interactions may exist between family history of liver cancer and HBV infection on the development of liver cancer.
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Affiliation(s)
- Xing Liu
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, California
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Aileen Baecker
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, California
| | - Ming Wu
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China
| | - Jin-Yi Zhou
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China
| | - Jie Yang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China
| | - Ren-Qiang Han
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China
| | - Pei-Hua Wang
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China
| | - Zi-Yi Jin
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Ai-Min Liu
- Dafeng Center for Disease Control and Prevention, Dafeng, Jiangsu, China
| | - Xiaoping Gu
- Dafeng Center for Disease Control and Prevention, Dafeng, Jiangsu, China
| | - Xiao-Feng Zhang
- Ganyu Center for Disease Control and Prevention, Ganyu, Jiangsu, China
| | - Xu-Shan Wang
- Ganyu Center for Disease Control and Prevention, Ganyu, Jiangsu, China
| | - Ming Su
- Chuzhou County Center for Disease Control and Prevention, Chuzhou, Jiangsu, China
| | - Xu Hu
- Chuzhou County Center for Disease Control and Prevention, Chuzhou, Jiangsu, China
| | - Zheng Sun
- Tongshan County Center for Disease control and Prevention, Tongshan, Jiangsu, China
| | - Gang Li
- Tongshan County Center for Disease control and Prevention, Tongshan, Jiangsu, China
| | - Alan Fu
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, California
| | - Su Yon Jung
- Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
- School of Nursing, UCLA, Los Angeles, California
| | - Lina Mu
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, New York
| | - Na He
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Liming Li
- Department of Epidemiology, School of Public Health, Peking University, Beijing, China
| | - Jin-Kou Zhao
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, Jiangsu, China
| | - Zuo-Feng Zhang
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, California
- Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California
- Center for Human Nutrition, David Geffen School of Medicine, UCLA, Los Angeles, California
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Abdelmoez FAB, Imam HM, Idriss NK, Wahid LA, Abbas WA, Abozaid MAA, Abdelwahab HM. The Role of Hepatitis C virus and Possible Risk factors in development of Hepatocellular carcinoma: 400 Patients based study. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2019. [DOI: 10.4103/ejim.ejim_50_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Li ZL, Han J, Liu K, Xing H, Wu H, Lau WY, Pawlik TM, Li C, Wang MD, Yu JJ, Wu MC, Shen F, Yang T. Association of family history with long-term prognosis in patients undergoing liver resection of HBV-related hepatocellular carcinoma. Hepatobiliary Surg Nutr 2019; 8:88-100. [PMID: 31098356 DOI: 10.21037/hbsn.2018.11.20] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Background Family history is a risk factor for the development of hepatocellular carcinoma (HCC). The aim of the current study was to investigate the association between family history of HCC and long-term oncologic prognosis among patients undergoing curative liver resection for hepatitis B virus (HBV)-related HCC. Methods Patients who underwent curative liver resection of HBV-related HCC between 2003 and 2013 were consecutively enrolled. Family history was defined as a self-reported history of HCC in a first-degree relative. Propensity score matching (PSM) and multivariable Cox-regression analyses were performed to compare overall survival (OS) and recurrence-free survival (RFS) among patients with and without a family history. Results Among 1,112 patients, 183 (16.5%) patients had a family history of HCC. Using PSM, 179 pairs of patients with and without a family history were created that had no differences in the baseline characteristics and operative variables. On matched analysis, family history was associated with decreased OS and RFS after curative-intent resection of HBV-related HCC in the propensity matching cohort (P=0.042 and 0.006, respectively). On multivariable Cox-regression analyses, a family history of HCC was associated with decreased OS (HR: 1.574; 95% CI: 1.171-2.116; P=0.003) and RFS (HR: 1.534; 95% CI: 1.176-2.002; P=0.002) after adjusting for other prognostic risk factors. Conclusions Family history was associated with decreased OS and RFS rates among patients undergoing curative liver resection of HBV-related HCC.
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Affiliation(s)
- Zhen-Li Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Jun Han
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Kai Liu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Hao Xing
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Han Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Wan Yee Lau
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.,Faculty of Medicine, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
| | - Timothy M Pawlik
- Department of Surgery, Ohio State University, Wexner Medical Center, Columbus, OH, USA
| | - Chao Li
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Ming-Da Wang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Jiong-Jie Yu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Meng-Chao Wu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Feng Shen
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
| | - Tian Yang
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
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Li S, Xue F, Zheng Y, Yang P, Lin S, Deng Y, Xu P, Zhou L, Hao Q, Zhai Z, Wu Y, Dai Z, Chen S. GSTM1 and GSTT1 null genotype increase the risk of hepatocellular carcinoma: evidence based on 46 studies. Cancer Cell Int 2019; 19:76. [PMID: 30976200 PMCID: PMC6441207 DOI: 10.1186/s12935-019-0792-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Accepted: 03/20/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND It is well known that hepatocellular carcinoma (HCC) has been one of the most life-threatening diseases all over the world. Plenty of internal and extrinsic factors have been proven to be related to HCC, such as gene mutation, viral hepatitis, and Nitrosamines. Though previous studies demonstrated that glutathione S-transferase (GST) genotypes are associated with HCC, the conclusions are inconsistent. Therefore, we carried on a renewed meta-analysis to expound the connection between the null GSTM1, GSTT1 polymorphisms and the risk of HCC. METHODS We searched PubMed, Web of Science, Embase, and CNKI databases to select qualified researches which satisfied the inclusion criteria up to July 31, 2018. Finally, we selected 41 articles with 6124 cases and 9781 controls in this meta-analysis. We use ORs and 95% confidence interval (CI) to evaluate the correlation intension between the GSTM1 and GSTT1 null genes and the risk of HCC. All the statistical processes were executed by Stata (version 12.0). RESULTS The pooled analysis showed that both GSTM1 null genotypes (OR = 1.37, 95% CI = 1.18-1.59) and GSTT1 null genotypes (OR = 1.43, 95% CI = 1.23-1.66) increased the risk of HCC. And GSTM1-GSTT1 dual-null genotypes also increased the risk of HCC (OR = 1.58, 95% CI = 1.22-2.05). In the subgroup analysis, we obtained significant results among Asians when stratified by race, and the results are GSTM1 null OR = 1.44, 95% CI = (1.22-1.71), GSTT1 null OR = 1.48, 95% CI = (1.25-1.77), GSTM1-GSTT1 null OR = 1.58, 95% CI = (1.19-2.09), while we didn't obtain significant results among Caucasians or Africans. Stratified analyses on the type of control indicated a higher risk of HCC associated with GSTM1, GSTT1 single null genotypes and GSTM1-GSTT1 dual-null genotypes in healthy people. No evidence of significant connection was discovered in chronic liver disease (CLD) except in GSTT1 single null. CONCLUSIONS Our study indicated that an individual who carries the GSTM1, GSTT1 single null genotypes and GSTT1-GSTM1 dual-null genotypes is more likely to develop HCC.
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Affiliation(s)
- Shanli Li
- Department of Interventional Vascular Surgery, The Affiliated Bao ji Central Hospital of Xi’an Jiaotong University College of Medicine, Bao ji, 721008 Shaan xi China
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Feng Xue
- Department of Hepatobiliary Surgery, The 3rd Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Tumor Hospital), Urumqi, 830000 China
| | - Yi Zheng
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Pengtao Yang
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Shuai Lin
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Yujiao Deng
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Peng Xu
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Linghui Zhou
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Qian Hao
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Zhen Zhai
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Ying Wu
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Zhijun Dai
- Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004 China
| | - Shu Chen
- Department of Interventional Vascular Surgery, The Affiliated Bao ji Central Hospital of Xi’an Jiaotong University College of Medicine, Bao ji, 721008 Shaan xi China
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Pelusi S, Baselli G, Pietrelli A, Dongiovanni P, Donati B, McCain MV, Meroni M, Fracanzani AL, Romagnoli R, Petta S, Grieco A, Miele L, Soardo G, Bugianesi E, Fargion S, Aghemo A, D'Ambrosio R, Xing C, Romeo S, De Francesco R, Reeves HL, Valenti LVC. Rare Pathogenic Variants Predispose to Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease. Sci Rep 2019; 9:3682. [PMID: 30842500 PMCID: PMC6403344 DOI: 10.1038/s41598-019-39998-2] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 01/23/2019] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a rising cause of hepatocellular carcinoma (HCC). We examined whether inherited pathogenic variants in candidate genes (n = 181) were enriched in patients with NAFLD-HCC. To this end, we resequenced peripheral blood DNA of 142 NAFLD-HCC, 59 NAFLD with advanced fibrosis, and 50 controls, and considered 404 healthy individuals from 1000 G. Pathogenic variants were defined according to ClinVar, likely pathogenic as rare variants predicted to alter protein activity. In NAFLD-HCC patients, we detected an enrichment in pathogenic (p = 0.024), and likely pathogenic variants (p = 1.9*10-6), particularly in APOB (p = 0.047). APOB variants were associated with lower circulating triglycerides and higher HDL cholesterol (p < 0.01). A genetic risk score predicted NAFLD-HCC (OR 4.96, 3.29-7.55; p = 5.1*10-16), outperforming the diagnostic accuracy of common genetic risk variants, and of clinical risk factors (p < 0.05). In conclusion, rare pathogenic variants in genes involved in liver disease and cancer predisposition are associated with NAFLD-HCC development.
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Affiliation(s)
- Serena Pelusi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Translational Medicine, Department of Transfusion Medicine and Hepatology, Milan, Italy
| | - Guido Baselli
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Alessandro Pietrelli
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Paola Dongiovanni
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Benedetta Donati
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Misti Vanette McCain
- Northern Institute for Cancer Research, The Medical School, Newcastle University, Newcastle upon Tyne, UK
| | - Marica Meroni
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Anna Ludovica Fracanzani
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Renato Romagnoli
- Department of Surgical Sciences, Liver Transplantation Center, University of Turin, Turin, Italy
| | - Salvatore Petta
- Section of Gastroenterology, DIBIMIS, University of Palermo, 90127, Palermo, Italy
| | - Antonio Grieco
- Internal Medicine and Gastroenterology Area, Fondazione Policlinico Universitario A. Gemelli, Catholic University of Rome, 00168, Rome, Italy
| | - Luca Miele
- Internal Medicine and Gastroenterology Area, Fondazione Policlinico Universitario A. Gemelli, Catholic University of Rome, 00168, Rome, Italy
| | - Giorgio Soardo
- Clinic of Internal Medicine-Liver Unit, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
| | - Elisabetta Bugianesi
- Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy
| | - Silvia Fargion
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Alessio Aghemo
- Division of Gastroenterology and Hepatology Unit, Humanitas Research Hospital and Humanitas University, Rozzano (MI), Italy
| | - Roberta D'Ambrosio
- "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano, Italy
| | - Chao Xing
- McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Stefano Romeo
- Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Cardiology Department, University of Gothenburg, Gothenburg, Sweden
- Clinical Nutrition Unit, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy
| | - Raffaele De Francesco
- Istituto Nazionale di Genetica Molecolare (INGM), Romeo ed Enrica Invernizzi, Bioinformatic group, Milan, Italy
| | - Helen Louise Reeves
- Northern Institute for Cancer Research, The Medical School, Newcastle University, Newcastle upon Tyne, UK
- Newcastle upon Tyne NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Luca Vittorio Carlo Valenti
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
- Internal Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
- Translational Medicine, Department of Transfusion Medicine and Hepatology, Milan, Italy.
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Yang J, Trépo E, Nahon P, Cao Q, Moreno C, Letouzé E, Imbeaud S, Gustot T, Deviere J, Debette S, Amouyel P, Bioulac-Sage P, Calderaro J, Ganne-Carrié N, Laurent A, Blanc JF, Guyot E, Sutton A, Ziol M, Zucman-Rossi J, Nault JC. PNPLA3 and TM6SF2 variants as risk factors of hepatocellular carcinoma across various etiologies and severity of underlying liver diseases. Int J Cancer 2019; 144:533-544. [PMID: 30289982 DOI: 10.1002/ijc.31910] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2018] [Revised: 08/30/2018] [Accepted: 09/10/2018] [Indexed: 01/10/2023]
Abstract
Few single nucleotide polymorphisms (SNPs) have been reproducibly associated with hepatocellular carcinoma (HCC). Our aim was to test the association between nine SNPs and HCC occurrence. SNPs in genes linked to HCC (DEPDC5, GRIK1, KIF1B, STAT4, MICA, DLC1, DDX18) or to liver damage (PNPLA3-rs738409, TM6SF2-rs58542926) in GWAS were genotyped in discovery cohorts including 1,020 HCC, 2,021 controls with chronic liver disease and 2,484 healthy individuals and replication was performed in prospective cohorts of cirrhotic patients with alcoholic liver disease (ALD, n = 249) and hepatitis C (n = 268). In the discovery cohort, PNPLA3 and TM6SF2 SNPs were associated with HCC (OR = 1.67 [CI95%:1.16-2.40], p = 0.005; OR = 1.45 [CI95%:1.08-1.94], p = 0.01) after adjustment for fibrosis, age, gender and etiology. In contrast, STAT4-rs7574865 was associated with HCC only in HBV infected patients (p = 0.03) and the other tested SNP were not linked with HCC risk. PNPLA3 and TM6SF2 variants were independently associated with HCC in patients with ALD (OR = 3.91 [CI95%:2.52-6.06], p = 1.14E-09; OR = 1.79 [CI95%:1.25-2.56], p = 0.001) but not with other etiologies. PNPLA3 SNP was also significantly associated with HCC developed on a nonfibrotic liver (OR = 2.19 [CI95%:1.22-3.92], p = 0.007). The association of PNPLA3 and TM6SF2 with HCC risk was confirmed in the prospective cohort with ALD. A genetic score including PNPLA3 and TM6SF2 minor alleles showed a progressive significant increased risk of HCC in ALD patients. In conclusion, PNPLA3-rs738409 and TM6SF2-rs58542926 are inherited risk variants of HCC development in patients with ALD in a dose dependent manner. The link between PNPLA3 and HCC on nonfibrotic liver suggests a direct role in liver carcinogenesis.
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Affiliation(s)
- Jie Yang
- Inserm UMR-1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
| | - Eric Trépo
- Inserm UMR-1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Cliniques Universitaires de Bruxelles Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Pierre Nahon
- Inserm UMR-1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Liver unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Qian Cao
- Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Christophe Moreno
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Cliniques Universitaires de Bruxelles Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Eric Letouzé
- Inserm UMR-1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
| | - Sandrine Imbeaud
- Inserm UMR-1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
| | - Thierry Gustot
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Cliniques Universitaires de Bruxelles Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Jacques Deviere
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Cliniques Universitaires de Bruxelles Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium
| | - Stéphanie Debette
- Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, Bordeaux, France
- CHU de Bordeaux, Department of Neurology, Bordeaux, France
| | - Philippe Amouyel
- University of Lille, Institut National de la Santé et de la Recherche Médicale, CHU Lille, Institut Pasteur de Lille, Lille, France
| | - Paulette Bioulac-Sage
- Univ. Bordeaux, UMR1053 Bordeaux Research in Translational Oncology, Bordeaux, France
- Service de Pathologie, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France
| | - Julien Calderaro
- Service d'anatomopathologie, Hôpital Henri Mondor, Créteil
- Université Paris Est Créteil, Inserm U955, Team 18, Institut Mondor de Recherche Biomédicale, France
| | - Nathalie Ganne-Carrié
- Inserm UMR-1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Liver unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France
| | - Alexis Laurent
- Service de chirurgie digestive, Hôpital Henri Mondor, Créteil
- Université Paris Est Créteil, Institut Mondor de Recherche Biomédicale, France
| | - Jean Frédéric Blanc
- Service Hépato-Gastroentérologie et oncologie digestive, Centre Medico-Chirurgical Magellan, Hôpital Haut-Lévêque, CHU de Bordeaux, Bordeaux, France
| | - Erwan Guyot
- Laboratoire de biochimie, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France
- INSERM U1148 LVTS, UFR SMBH, Université Paris 13, PRES Paris Sorbonne Cité, Bobigny, France
| | - Angela Sutton
- Laboratoire de biochimie, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France
- INSERM U1148 LVTS, UFR SMBH, Université Paris 13, PRES Paris Sorbonne Cité, Bobigny, France
| | - Marianne Ziol
- Inserm UMR-1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France
- Centre de Ressources Biologiques (BB-0033-00027) Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France
| | - Jessica Zucman-Rossi
- Inserm UMR-1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Hôpital Europeen Georges Pompidou, Paris, France
| | - Jean-Charles Nault
- Inserm UMR-1162, Génomique fonctionnelle des Tumeurs solides, Université Paris Descartes, Université Paris Diderot, Université Paris 13, Labex Immuno-Oncology, Paris, France
- Liver unit, Hôpital Jean Verdier, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance-Publique Hôpitaux de Paris, Bondy, France
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France
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Abstract
Amongst the primary tumors of the liver, hepatocellular carcinoma (HCC) is the most common. It is also one of the most prevalent types of cancers in Asia. Mostly, HCC occurs on a background of chronic liver disease and liver cirrhosis; however, de novo HCCs can also arise in apparently normal looking livers on imaging. There are multiple risk factors for HCC, including hepatitis B and C infections, diabetes mellitus, alcohol, and nonalcoholic steatohepatitis. Other common risk factors which are known to be involved in the pathogenesis of HCC are obesity, food contaminated with aflatoxin and hemochromatosis. Many of these factors are commonly found in this part of the world, hence the high burden of disease. Besides these, smoking and familial predisposition to HCC also seem to have an important role to play in its development. Majority of HCC are missed at an early stage despite the emphasis on adequate screening and surveillance strategies. Therefore, most of the time these tumors are diagnosed at a fairly advanced stage, when palliative treatment is the only therapeutic option left. Hence, prevention of HCC by controlling and minimizing the possible risk factors is the need of the hour. How to cite this article: Jafri W, Kamran M. Hepatocellular Carcinoma in Asia: A Challenging Situation. Euroasian J Hepatogastroenterol 2019; 9(1):27-33.
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Affiliation(s)
- Wasim Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - Muhammad Kamran
- Department of Medicine, Baqai Medical University, Karachi, Pakistan
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Familial hepatocellular carcinoma: 'A model for studying preventive and therapeutic measures'. Ann Med Surg (Lond) 2018; 35:129-132. [PMID: 30305894 PMCID: PMC6172566 DOI: 10.1016/j.amsu.2018.09.035] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2018] [Revised: 07/18/2018] [Accepted: 09/21/2018] [Indexed: 12/12/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with more than 80% of cases found in endemic areas of hepatitis B such as Africa or East Asia. A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk and poor prognosis. Only limited attention has been given to the role of primary genetic factors in HCC, but scattered anecdotal reports have identified familial aggregations of HCC. This article reviewed the literature on familial hepatocellular carcinoma and suggest that familial HCC may be a good model for studying preventive and therapeutic measures.
Highest risk for HCC occur when a hereditary component acts in concert with hepatitis B virus. Different single nucleotide polymorphisms affect various biological pathways predisposing other risk factors. More extensive investigation of the genetic hypothesis of HCC and its fibrolamellar variant required. Prevention with neonatal vaccination is better than cure.
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Qin YL, Li B, Zhou YS, Zhang X, Li L, Song B, Liu P, Yuan Y, Zhao ZP, Jiao J, Li J, Sun Y, Sevalie S, Kanu JE, Song YJ, Jiang JF, Sahr F, Jiang TJ. Prevalence and associated knowledge of hepatitis B infection among healthcare workers in Freetown, Sierra Leone. BMC Infect Dis 2018; 18:315. [PMID: 29986658 PMCID: PMC6038231 DOI: 10.1186/s12879-018-3235-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2018] [Accepted: 07/03/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) is considered highly prevalent in West Africa. However, major gaps in surveillance exist in Sierra Leone. Although healthcare workers (HCWs) are at high risk for HBV infection, little is known about the prevalence and knowledge of hepatitis B among HCWs in Sierra Leone. METHODS A cross-sectional study of all HCWs at the No. 34 Military Hospital located in Freetown, Sierra Leone, was conducted from March 20 to April 10, 2017. Whole blood was collected and screened for HBV markers using a one-step rapid immunochromatographic test with positive samples tested for HBV DNA. Additionally, questionnaires assessing self-reported knowledge of HBV infections were administered to all participants. Data were processed and analyzed using SPSS (version 17.0) software. RESULTS A total of 211 HCWs were included in this study with a median age of 39.0 years (range: 18-59). Of the participating HCWs, 172 (81.5%) participants were susceptible (all markers negative), 21(10.0%) were current HBV (HBsAg positive) and nine (4.3%) were considered immune because of past infection (HBsAg negative and anti-HBc positive; anti-HBs positive). Additionally, nine (4.3%) participants displayed immunity to the virus as a result of prior hepatitis B vaccination (only anti-HBs positive). Of the 21 HCWs with positive HBsAg, 13 (61.9%) had detectable HBV DNA. There was a significantly lower risk for current HBV infection among HCWs older than 39 years (OR 0.337, p = 0.046). In addition, only 14 (6.6%), 73 (34.6%) and 82 (38.9%) participants in this survey had adequate knowledge about the clinical outcome, routes of transmission, and correct preventive measures of HBV infection, respectively. CONCLUSIONS HCWs in Sierra Leone lacked adequate knowledge of the hepatitis B virus. Additionally, the low coverage rate of hepatitis B vaccination among HCWs fails to meet WHO recommendations, leaving many of the sampled HCWs susceptible to infection. This study reaffirms the need for more intensive training for HCWs in addition to strengthening vaccination programmes to protect HCWs against HBV in Sierra Leone.
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Affiliation(s)
| | - Bo Li
- Beijing 302 Hospital, Beijing, China
| | | | - Xin Zhang
- Beijing 302 Hospital, Beijing, China
| | - Lei Li
- Beijing 302 Hospital, Beijing, China
| | - Bing Song
- Beijing 302 Hospital, Beijing, China
| | - Peng Liu
- Beijing 302 Hospital, Beijing, China
| | - Yue Yuan
- Beijing 302 Hospital, Beijing, China
| | - Zhong-Peng Zhao
- Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Jun Jiao
- Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Jing Li
- Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Yi Sun
- Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Stephen Sevalie
- No. 34 Military Hospital, Wilberforce, Freetown, Sierra Leone
| | - Joseph E Kanu
- No. 34 Military Hospital, Wilberforce, Freetown, Sierra Leone
| | - Ya-Jun Song
- Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Jia-Fu Jiang
- Beijing Institute of Microbiology and Epidemiology, Beijing, China.
| | - Foday Sahr
- No. 34 Military Hospital, Wilberforce, Freetown, Sierra Leone. .,College of Medicine and Allied Health Sciences, Freetown, Sierra Leone.
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Li RD, Tang YH, Wang HL, Yang D, Sun LJ, Li W. The SMYD3 VNTR 3/3 polymorphism confers an increased risk and poor prognosis of hepatocellular carcinoma in a Chinese population. Pathol Res Pract 2018; 214:625-630. [PMID: 29691085 DOI: 10.1016/j.prp.2018.04.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Revised: 03/27/2018] [Accepted: 04/13/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies in China, and the genetic link of hepatocarcinogenesis remains to be defined. Thus, we explored the role of SET and myeloid translocation protein 8, Nervy, and DEAF1 (MYND) domain containing protein 3 (SMYD3) gene polymorphism on risk and prognosis of HCC. METHODS A total of 236 patients with HCC who received treatment in Affiliated Hospital of Jining Medical University for the first time and 230 healthy individuals were enrolled in the study. After DNA extraction for all the subjects, polymerase chain reaction (PCR) was used to amplify and sequence variable numbers of tandem repeat (VNTR) loci of SMYD3 gene. SMYD3 gene was genotyped and its frequency distribution was calculated. Age, education level, income, smoking and drinking history, HCC family history, tumor node metastasis (TNM) staging, maximum tumor diameter, lymph node metastasis (LNM) etc. were investigated. Correlation of SMYD3 gene polymorphism and other risk factors with the occurrence and prognosis of HCC was analyzed. RESULTS The family history of HCC, drinking history, cirrhosis, and HBV or/and HCV infection, SMYD3 VNTR 3/3 were more frequently observed in subjects with HCC. Patients with SMYD3 VNTR 3/3 genotype, drinking-history, family history of HCC, cirrhosis and hepatitis B virus (HBV), TNM staging, maximum tumor diameter, LNM were more vulnerable to HCC. Besides, patients with SMYD3 VNTR 3/3 genotype had lower 2- and 3-year survival rate. The COX regression analysis revealed that drinking history, family history of HCC, SMYD3 VNTR 3/3 genotype, TNM staging, and LNM were all related to the prognosis of HCC. CONCLUSION This study indicates that drinking history, family history of HCC and SMYD3 VNTR 3/3, TNM staging, maximum tumor diameter, LNM might be risk factors for HCC, and SMYD3 VNTR 3/3 might contribute to a lower 2- and 3-year survival rate of patients with HCC.
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Affiliation(s)
- Rui-Dong Li
- Department of Oncology, Affiliated Hospital of Jining Medical University, Jining 272009, PR China
| | - Yan-Hua Tang
- Department of Oncology, Affiliated Hospital of Jining Medical University, Jining 272009, PR China
| | - Hui-Li Wang
- Department of Oncology, Affiliated Hospital of Jining Medical University, Jining 272009, PR China.
| | - Dong Yang
- Department of Oncology, Affiliated Hospital of Jining Medical University, Jining 272009, PR China
| | - Li-Jun Sun
- Department of Oncology, Affiliated Hospital of Jining Medical University, Jining 272009, PR China
| | - Wei Li
- Department of Oncology, Affiliated Hospital of Jining Medical University, Jining 272009, PR China
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Shi Y, Zhai W, Wang B, Zhao D, Jin H, Wang Y, Zhang J, An H, Fu Z, Zhao K, Lu C. Genetic susceptibility of eight nonsynonymous polymorphisms in HLA-DRB1 gene to hepatocellular carcinoma in Han Chinese. Oncotarget 2018; 7:80935-80942. [PMID: 27821814 PMCID: PMC5348366 DOI: 10.18632/oncotarget.13111] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Accepted: 10/28/2016] [Indexed: 01/17/2023] Open
Abstract
Backgrounds and Objective Mounting evidence suggests that human leukocyte antigen (HLA) plays a central role in anti-virus and tumor defense. To test whether genetic variation in HLA-DRB1 gene, a key component of HLA system, can predict its predisposition to hepatocellular carcinoma (HCC), we thereby conducted an association study by genotyping 8 nonsynonymous polymorphisms in HLA-DRB1 gene among 257 HCC patients and 264 controls. Results All polymorphisms respected the Hardy-Weinberg equilibrium. The genotypes and alleles of rs17879599 differed significantly between patients and controls after Bonferroni correction (both P < 0.001), and the power to detect this significance was 94.4%. After adjusting for age, gender, smoking, drinking and hepatitis infection, the mutant allele of rs17879702 was significantly associated with an increased risk for HCC under additive (odds ratio [OR] = 2.12, 95% confidence interval [CI]: 1.20-4.02, P = 0.004) and dominant (OR = 2.51, 95% CI: 1.39–2.96, P = 0.004) models. Haplotype analysis indicated that haplotype A-T-C-T-G-C-T-A (alleles ordered by rs199514452, rs201540428, rs201614260, rs17879702, rs17880292, rs17879599, rs17424145 and rs35445101) was overrepresented in patients and enhanced predisposition to HCC (adjusted OR = 2.72, 95% CI: 1.24–5.78, P = 0.004). In cumulative analysis, carriers of 7–9 unfavorable alleles had a 2.41-fold (95% CI: 1.18–4.92, P = 0.016) increased risk for HCC after adjusting for confounding factors relative to those possessing 4 or less unfavorable alleles. Materials and Methods Genotypes were determined by ligase detection reaction. HCC patients were newly diagnosed, histopathologically confirmed or previously untreated and controls were cancer-free. Conclusions Our findings suggest an independent leading contribution of rs17879599 in the 2nd exon of HLA-DRB1 gene to HCC risk in Han Chinese.
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Affiliation(s)
- Yanhui Shi
- Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - Weiyu Zhai
- Department of Pharmacy, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Bin Wang
- Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Dongmei Zhao
- Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - He Jin
- Department of Cardiology, Hospital of Traditional Chinese Medicine of Qiqihar, Qiqihar, Heilongjiang, China
| | - Yuefei Wang
- Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Jidong Zhang
- Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - Hongjun An
- Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - Zhongze Fu
- Department of Gastroenterology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, China
| | - Kun Zhao
- Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China
| | - Changzhu Lu
- Department of Physiology, Qiqihar Medical University, Qiqihar, Heilongjiang, China
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Lui KY, Zhao H, Qiu C, Li C, Zhang Z, Peng H, Fu R, Chen HA, Lu MQ. Integrator complex subunit 6 (INTS6) inhibits hepatocellular carcinoma growth by Wnt pathway and serve as a prognostic marker. BMC Cancer 2017; 17:644. [PMID: 28899352 PMCID: PMC5596937 DOI: 10.1186/s12885-017-3628-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2016] [Accepted: 08/28/2017] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Integrator complex subunit 6 (INTS6) was found to play a tumour suppressing role in certain types of solid tumours. In this study, we wanted to determine the expression level of INTS6 in hepatocellular carcinoma (HCC) and evaluate its clinical characteristics and mechanisms in HCC patients (Lui and Lu, European Journal of Cancer, 51:S94, 2015). METHODS First, we used a microarray analysis to explore the mRNA expression levels in HCC and paired normal liver tissues; second, we used qRT-PCR to measure the INTS6 mRNA levels in a cohort of 50 HCC tissues and adjacent normal liver tissues; third, we used Western blot analyses to detect the INTS6 protein levels in 20 paired HCC and normal liver tissues; fourth, we used immunohistochemistry to determine the INTS6 expression levels in 70 archived paraffin-embedded HCC samples. Finally, we investigated the suppressive function of INTS6 in the Wnt pathway. RESULTS Herein, according to the microarray data analysis, the expression levels of INTS6 were dramatically down-regulated in HCC tissues vs. those in normal liver tissues (p<0.05). qRT-PCR and Western blot analyses showed that the INTS6 mRNA and protein expression was significantly down-regulated in tumour tissues compared to the adjacent normal liver tissues (p<0.05). Immunohistochemical assays revealed that decreased INTS6 expression was present in 62.9% (44/70) of HCC patients. Correlation analyses showed that INTS6 expression was significantly correlated with serum alpha-fetoprotein levels (AFP, p =0.004), pathology grade (p =0.005), and tumour recurrence (p =0.04). Kaplan-Meier analysis revealed that patients with low INTS6 expression levels had shorter overall and disease-free survival rates than patients with high INTS6 expression levels (p =0.001 and p =0.001). Multivariate regression analysis indicated that INTS6 was an independent predictor of overall survival and disease-free survival rates. Mechanistically, INTS6 increased WIF-1 expression and then inhibited the Wnt/β-catenin signalling pathway. CONCLUSION The results of our study show that down-regulated INTS6 expression is associated with a poorer prognosis in HCC patients. This newly identified INTS6/WIF-1 axis indicates the molecular mechanism of HCC and may represent a therapeutic target in HCC patients.
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Affiliation(s)
- Ka Yin Lui
- Department of Critical Care Medicine, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China
| | - Hui Zhao
- Department of Hepatic Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Chunhui Qiu
- Department of Hepatic Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Chuo Li
- Obstetric Laboratory, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Zhigang Zhang
- Department of Pathology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Haoran Peng
- Transitional Year, Gwinnentt Medical Center, Lawrenceville, GA, USA
| | - Rongdang Fu
- Department of Hepatic Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China
| | - Hu-An Chen
- Department of Hepatic Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
| | - Min-Qiang Lu
- Department of Hepatobiliary Surgery, Guangzhou First People's Hospital, Guangzhou, 510180, China.
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Donati B, Pietrelli A, Pingitore P, Dongiovanni P, Caddeo A, Walker L, Baselli G, Pelusi S, Rosso C, Vanni E, Daly A, Mancina RM, Grieco A, Miele L, Grimaudo S, Craxi A, Petta S, De Luca L, Maier S, Soardo G, Bugianesi E, Colli F, Romagnoli R, Anstee QM, Reeves HL, Fracanzani AL, Fargion S, Romeo S, Valenti L. Telomerase reverse transcriptase germline mutations and hepatocellular carcinoma in patients with nonalcoholic fatty liver disease. Cancer Med 2017; 6:1930-1940. [PMID: 28677271 PMCID: PMC5548883 DOI: 10.1002/cam4.1078] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2016] [Revised: 03/25/2017] [Accepted: 03/27/2017] [Indexed: 12/18/2022] Open
Abstract
In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD-HCC. In 40 patients with NAFLD-HCC, 45 with NAFLD-cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT-PCR and hTERT coding regions and intron-exon boundaries sequenced. We further analyzed 78 patients affected by primary liver cancer (NAFLD-PLC, 76 with HCC). Enrichment of rare coding mutations (allelic frequency <0.001) was evaluated by Burden test. Functional consequences were estimated in silico and by over-expressing protein variants in HEK-293 cells. We found that telomere length was reduced in individuals with NAFLD-HCC versus those with cirrhosis (P = 0.048) and healthy controls (P = 0.0006), independently of age and sex. We detected an enrichment of hTERT mutations in NAFLD-HCC, that was confirmed when we further considered a larger cohort of NAFLD-PLC, and was more marked in female patients (P = 0.03). No mutations were found in cirrhosis and local controls, and only one in 503 healthy Europeans from the 1000 Genomes Project (allelic frequency = 0.025 vs. <0.001; P = 0.0005). Mutations with predicted functional impact, including the frameshift Glu113Argfs*79 and missense Glu668Asp, cosegregated with liver disease in two families. Three patients carried missense mutations (Ala67Val in homozygosity, Pro193Leu and His296Pro in heterozygosity) in the N-terminal template-binding domain (P = 0.037 for specific enrichment). Besides Glu668Asp, the Ala67Val variant resulted in reduced intracellular protein levels. In conclusion, we detected an association between shorter telomeres in peripheral blood and rare germline hTERT mutations and NAFLD-HCC.
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Donati B, Dongiovanni P, Romeo S, Meroni M, McCain M, Miele L, Petta S, Maier S, Rosso C, De Luca L, Vanni E, Grimaudo S, Romagnoli R, Colli F, Ferri F, Mancina RM, Iruzubieta P, Craxi A, Fracanzani AL, Grieco A, Corradini SG, Aghemo A, Colombo M, Soardo G, Bugianesi E, Reeves H, Anstee QM, Fargion S, Valenti L. MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals. Sci Rep 2017; 7:4492. [PMID: 28674415 PMCID: PMC5495751 DOI: 10.1038/s41598-017-04991-0] [Citation(s) in RCA: 193] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 05/23/2017] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) represents an emerging cause of hepatocellular carcinoma (HCC), especially in non-cirrhotic individuals. The rs641738 C > T MBOAT7/TMC4 variant predisposes to progressive NAFLD, but the impact on hepatic carcinogenesis is unknown. In Italian NAFLD patients, the rs641738 T allele was associated with NAFLD-HCC (OR 1.65, 1.08-2.55; n = 765), particularly in those without advanced fibrosis (p < 0.001). The risk T allele was linked to 3'-UTR variation in MBOAT7 and to reduced MBOAT7 expression in patients without severe fibrosis. The number of PNPLA3, TM6SF2, and MBOAT7 risk variants was associated with NAFLD-HCC independently of clinical factors (p < 0.001), but did not significantly improve their predictive accuracy. When combining data from an independent UK NAFLD cohort, in the overall cohort of non-cirrhotic patients (n = 913, 41 with HCC) the T allele remained associated with HCC (OR 2.10, 1.33-3.31). Finally, in a combined cohort of non-cirrhotic patients with chronic hepatitis C or alcoholic liver disease (n = 1121), the T allele was independently associated with HCC risk (OR 1.93, 1.07-3.58). In conclusion, the MBOAT7 rs641738 T allele is associated with reduced MBOAT7 expression and may predispose to HCC in patients without cirrhosis, suggesting it should be evaluated in future prospective studies aimed at stratifying NAFLD-HCC risk.
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Affiliation(s)
- Benedetta Donati
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy
| | - Paola Dongiovanni
- Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy
| | - Stefano Romeo
- Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Department of Cardiology, University of Gothenburg, Gothenburg, Sweden
- Clinical Nutrition Unit, Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy
| | - Marica Meroni
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy
| | - Misti McCain
- Northern Institute of Cancer Research, The Medical School, Newcastle University, Newcastle-upon-Tyne, UK
- Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Luca Miele
- Internal Medicine, Policlinico Gemelli, Roma, Italy
| | - Salvatore Petta
- Department of Gastroenterology, Università di Palermo, Palermo, Italy
| | - Silvia Maier
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
| | - Chiara Rosso
- Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Laura De Luca
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
| | - Ester Vanni
- Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Stefania Grimaudo
- Department of Gastroenterology, Università di Palermo, Palermo, Italy
| | - Renato Romagnoli
- General Surgery and Liver Transplantation Center, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Fabio Colli
- General Surgery and Liver Transplantation Center, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Flaminia Ferri
- Department of Clinical Medicine, Gastroenterology division, Sapienza University, Rome, Italy
| | - Rosellina Margherita Mancina
- Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Department of Cardiology, University of Gothenburg, Gothenburg, Sweden
| | - Paula Iruzubieta
- Liver Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle-upon-Tyne, UK
| | - Antonio Craxi
- Department of Gastroenterology, Università di Palermo, Palermo, Italy
| | - Anna Ludovica Fracanzani
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy
- Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy
| | | | | | - Alessio Aghemo
- Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy
| | - Massimo Colombo
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy
- Hepatology, Humanitas Clinical and Research Center, Rozzano, Italy
| | - Giorgio Soardo
- Internal Medicine and Liver Unit, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy
| | - Elisabetta Bugianesi
- Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Helen Reeves
- Northern Institute of Cancer Research, The Medical School, Newcastle University, Newcastle-upon-Tyne, UK
- Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Quentin M Anstee
- Hepatology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Liver Research Group, Institute of Cellular Medicine, The Medical School, Newcastle University, Newcastle-upon-Tyne, UK
| | - Silvia Fargion
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy
- Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy
| | - Luca Valenti
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122, Milano, Italy.
- Internal Medicine, Fondazione IRCCS Ca' Granda Ospedale Policlinico Milano, Milano, Italy.
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Zhang EL, Gu J, Zhang ZY, Dong KS, Liang BY, Huang ZY. MicroRNA expression profiling in patients with hepatocellular carcinoma of familial aggregation and hepatitis B virus infection. Oncol Lett 2017; 14:971-976. [PMID: 28693260 PMCID: PMC5494791 DOI: 10.3892/ol.2017.6178] [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: 09/18/2015] [Accepted: 02/23/2017] [Indexed: 12/15/2022] Open
Abstract
Numerous studies have suggested that microRNAs (miRNAs) potently affect hepatocarcinogenesis. However, the miRNA expression profiling in patients with hepatocellular carcinoma (HCC) of familial aggregation and hepatitis B virus (HBV) infection has not been elucidated. In the present study, the plasma miRNA expression profiles of 3 patients with HCC with familial aggregation of HCC and HBV infection and 1 healthy volunteer were examined by microarray analysis, in order to identify relevant miRNAs involved in the pathogenesis of HCC with familial aggregation and HBV infection. The results indicated that 26 miRNAs exhibited a ≥20-fold increase or decrease in the plasma of patients with HCC, compared with the healthy control (24 upregulated and 2 downregulated). Among these altered miRNAs, 15 of them have been reported in HCC. The other 11 miRNAs have never been reported in HCC. These differentially-expressed miRNAs may be potential molecular markers for HCC pathogenesis and development.
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Affiliation(s)
- Er-Lei Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Jin Gu
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Zun-Yi Zhang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Ke-Shuai Dong
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Bin-Yong Liang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
| | - Zhi-Yong Huang
- Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
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50
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Liu F, Li F, Luo L, Yang H, Wei Y, Wang W, Yan L, Wen T, Yang J, Li B. Genetic variants in cell death pathway genes and HBV-related hepatocellular carcinoma among a Chinese Han population. Apoptosis 2017. [DOI: 10.1007/s10495-017-1385-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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