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Bahojb Mahdavi SZ, Jebelli A, Aghbash PS, Baradaran B, Amini M, Oroojalian F, Pouladi N, Baghi HB, de la Guardia M, Mokhtarzadeh AA. A comprehensive overview on the crosstalk between microRNAs and viral pathogenesis and infection. Med Res Rev 2025; 45:349-425. [PMID: 39185567 PMCID: PMC11796338 DOI: 10.1002/med.22073] [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: 11/06/2021] [Revised: 04/11/2023] [Accepted: 08/04/2024] [Indexed: 08/27/2024]
Abstract
Infections caused by viruses as the smallest infectious agents, pose a major threat to global public health. Viral infections utilize different host mechanisms to facilitate their own propagation and pathogenesis. MicroRNAs (miRNAs), as small noncoding RNA molecules, play important regulatory roles in different diseases, including viral infections. They can promote or inhibit viral infection and have a pro-viral or antiviral role. Also, viral infections can modulate the expression of host miRNAs. Furthermore, viruses from different families evade the host immune response by producing their own miRNAs called viral miRNAs (v-miRNAs). Understanding the replication cycle of viruses and their relation with host miRNAs and v-miRNAs can help to find new treatments against viral infections. In this review, we aim to outline the structure, genome, and replication cycle of various viruses including hepatitis B, hepatitis C, influenza A virus, coronavirus, human immunodeficiency virus, human papillomavirus, herpes simplex virus, Epstein-Barr virus, Dengue virus, Zika virus, and Ebola virus. We also discuss the role of different host miRNAs and v-miRNAs and their role in the pathogenesis of these viral infections.
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Affiliation(s)
- Seyedeh Zahra Bahojb Mahdavi
- Department of Biology, Faculty of Basic SciencesAzarbaijan Shahid Madani UniversityTabrizIran
- Immunology Research CenterTabriz University of Medical SciencesTabrizIran
| | - Asiyeh Jebelli
- Department of Biological Science, Faculty of Basic ScienceHigher Education Institute of Rab‐RashidTabrizIran
- Tuberculosis and Lung Diseases Research CenterTabriz University of Medical SciencesTabrizIran
| | | | - Behzad Baradaran
- Immunology Research CenterTabriz University of Medical SciencesTabrizIran
| | - Mohammad Amini
- Immunology Research CenterTabriz University of Medical SciencesTabrizIran
| | - Fatemeh Oroojalian
- Department of Advanced Sciences and Technologies in Medicine, School of MedicineNorth Khorasan University of Medical SciencesBojnurdIran
| | - Nasser Pouladi
- Department of Biology, Faculty of Basic SciencesAzarbaijan Shahid Madani UniversityTabrizIran
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Shi J, Wei X, Jiang F, Zhu J, Shen J, Sun Y. Construction and validation of transcription‑factor‑based prognostic signature for TACE non‑response and characterization of tumor microenvironment infiltration in hepatocellular carcinoma. Oncol Lett 2025; 29:42. [PMID: 39554534 PMCID: PMC11565272 DOI: 10.3892/ol.2024.14788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Accepted: 10/08/2024] [Indexed: 11/19/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Despite continuous development of treatment methods, overall survival rate of liver cancer is low. Transcatheter arterial chemoembolization (TACE) is a first-choice treatment for advanced liver cancer. Although it is generally effective, a number of patients do not benefit from it. Therefore, the present study was conducted to assess the response of patients following TACE. RNA-sequencing data and corresponding clinical information were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. Models were constructed using weighted gene co-expression network analysis and least absolute shrinkage and selection operator-Cox regression analysis based on TCGA-LIHC and GSE104580 cohorts. The receiver operating characteristic curve was used for evaluation. Immunoassay, half-maximal inhibitory concentration analysis of risk groups, genomic enrichment analysis and nomogram construction were also performed. The predictive models were validated at the single-cell level using single-cell databases. Finally, the present study examined the expression of TACE refractoriness-related TFs (TRTs) in TACE-resistant and non-resistant cell lines in vitro. A risk categorization approach was created based on screening of four TRTs. The patients were split into high- and low-risk groups. There were significant variations in immune cell infiltration, medication sensitivity and overall survival (OS) between patients in the high-risk and low-risk groups. Multivariate Cox regression analysis showed that the risk score was an independent prognostic factor for OS. In the single-cell gene set, risk score was a good indicator of tumor microenvironment (TME). Reverse transcription-quantitative PCR revealed that three high-risk TRTs were upregulated in TACE-resistant cells. Prognosis and TME status of liver cancer patients following TACE could be assessed using a predictive model based on transcription factor correlation. This predictive model provided a reliable and simplified method to guide the clinical treatment of HCC.
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Affiliation(s)
- Jiapeng Shi
- Department of Interventional Medicine, Nantong Traditional Chinese Medicine Hospital, Nantong, Jiangsu 226001, P.R. China
| | - Xintong Wei
- Department of Medical Imaging, Nantong Traditional Chinese Medicine Hospital, Nantong, Jiangsu 226001, P.R. China
| | - Fangmei Jiang
- Department of Oncology, Yancheng Tinghu District People's Hospital, Yancheng, Jiangsu 224000, P.R. China
| | - Jianjun Zhu
- Department of Oncology, Yancheng Tinghu District People's Hospital, Yancheng, Jiangsu 224000, P.R. China
| | - Jiandong Shen
- Department of Invasive Technology, Affiliated Nantong Hospital 3 of Nantong University, Nantong, Jiangsu 226001, P.R. China
| | - Yanjun Sun
- Department of Oncology, Yancheng Tinghu District People's Hospital, Yancheng, Jiangsu 224000, P.R. China
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Lam AM, Mani N, Ardzinski A, Stever K, Cuconati A, Micolochick Steuer H, Thi EP, Graves IE, Espiritu CL, Mesaros E, Kultgen SG, Fan K, Cole AG, Harasym TO, Rijnbrand R, Brown J, Eley T, Varughese T, Gane E, Picchio G, Sims KD, Sofia MJ. Preclinical and clinical antiviral characterization of AB-836, a potent capsid assembly modulator against hepatitis B virus. Antiviral Res 2024; 231:106010. [PMID: 39326502 DOI: 10.1016/j.antiviral.2024.106010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/11/2024] [Accepted: 09/23/2024] [Indexed: 09/28/2024]
Abstract
HBV capsid assembly modulators (CAMs) target the core protein and inhibit pregenomic RNA encapsidation and viral replication. HBV CAMs also interfere with cccDNA formation during de novo infection, which in turn suppresses transcription and production of HBV antigens. In this report, we describe the antiviral activities of AB-836, a potent and highly selective HBV CAM. AB-836 inhibited viral replication (EC50 = 0.010 μM) in HepDE19 cells, and cccDNA formation (EC50 = 0.18 μM) and HBsAg production (EC50 = 0.20 μM) in HepG2-NTCP cells during de novo infection. AB-836 showed broad genotype coverage, remained active against variants resistant to nucleos(t)ide analogs, and demonstrated improved antiviral potency against core variants resistant to other CAMs. AB-836 also mediated potent inhibition of HBV replication in a hydrodynamic injection mouse model, reducing both serum and liver HBV DNA. In a Phase 1 clinical study, 28 days of once-daily AB-836 oral dosing at 50, 100, and 200 mg resulted in mean serum HBV DNA declines of 2.57, 3.04, and 3.55 log10 IU/mL from baseline, respectively. Neither on-treatment viral rebound nor the emergence of viral resistance was observed during the 28-day treatment period. Furthermore, HBV DNA sequence analysis of baseline samples from the Phase 1 study revealed that 51.4% of the chronic hepatitis B participants contained at least one core polymorphism within the CAM-binding pocket, suggesting that genetic variations exist at this site. While AB-836 was discontinued due to clinical safety findings, data from the preclinical and clinical studies could help inform future optimization of HBV CAMs.
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Affiliation(s)
| | | | | | - Kim Stever
- Arbutus Biopharma Inc., Warminster, PA, USA
| | | | | | | | | | | | | | | | - Kristi Fan
- Arbutus Biopharma Inc., Warminster, PA, USA
| | | | | | | | | | | | | | - Edward Gane
- Auckland Clinical Studies, Grafton, Auckland, New Zealand
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Jiang J, Shiels MS, Rivera D, Ghany MG, Engels EA, O’Brien TR. Trends in hepatocellular carcinoma and viral hepatitis treatment in older Americans. PLoS One 2024; 19:e0307746. [PMID: 39485782 PMCID: PMC11530004 DOI: 10.1371/journal.pone.0307746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 07/10/2024] [Indexed: 11/03/2024] Open
Abstract
BACKGROUND Incidence of hepatocellular carcinoma (HCC) had been increasing steadily among older Americans but plateaued in 2015-2017. Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) are important causes of HCC. The impact of improved treatments for these infections on recent trends in HCC incidence is unclear. AIMS To examine the relationship between use of antiviral therapy for chronic viral hepatis and HCC incidence in older Americans. METHODS We used 2007-2017 data from the Surveillance, Epidemiology, and End Results-Medicare database to estimate age-standardized incidence rates and average annual percent changes (AAPCs) for viral hepatitis-attributable HCC among individuals ≥66 years. We analyzed data from Medicare Part D to determine the frequency of HBV and HCV treatment utilization in this population. RESULTS Overall HCC incidence increased 10.5%, from 22.2/100,000 in 2007 to 24.5/100,000 in 2017 (AAPC, 1.3%). During that time, HBV-attributable HCC rates decreased from 2.5 to 2.0/100,000 (AAPC, -1.6%), while HCV-attributable HCC rose from 6.6 to 8.0/100,000 (AAPC, 2.0%). HBV treatment among patients with HBV infection increased by 66% (2007, 7.4%; 2015, 12.3%). Treatment for HCV was stable at <2% during 2006-2013 but rose to 6.9% in 2014 and 12.7% in 2015, coinciding with the introduction of direct acting antiviral agents for HCV. CONCLUSIONS A decreased incidence of HBV-attributable HCC corresponded with an increased uptake in treatment for that infection. Despite a marked increase in the effectiveness and frequency of HCV treatment in 2014 and 2015, HCV-attributable HCC had not begun to fall as of 2017.
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Affiliation(s)
- Joy Jiang
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
| | - Meredith S. Shiels
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
| | - Donna Rivera
- Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, Maryland, United States of America
| | - Marc G. Ghany
- Clinical Research Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States of America
| | - Eric A. Engels
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
| | - Thomas R. O’Brien
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, United States of America
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Adra S, Alabrach Y, Hashem A, Mahmoud A, Khalouf A, El-Khapery A, Abdelhay A, Mansour M, Aldaher B, Barqawi H, Abu-Gharbieh E. Trends of primary liver cancer incidence and mortality in the United States: A population-based study over the last four decades. PLoS One 2024; 19:e0309465. [PMID: 39236039 PMCID: PMC11376511 DOI: 10.1371/journal.pone.0309465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 08/12/2024] [Indexed: 09/07/2024] Open
Abstract
BACKGROUND Primary liver cancer is the third leading cause of cancer deaths worldwide and has one of the worst 5-year survival rates. This study examines US primary liver cancer incidence and incidence-based mortality trends over four decades. RESEARCH DESIGN AND METHODS The SEER-9 registry was used to study primary liver cancer cases from 1978 to 2018. The incidence and mortality rates were calculated based on gender, age, race, and stage of diagnosis. Joinpoint regression software was used to calculate the annual percent change. RESULTS The overall incidence rate of primary liver cancer from 1978 to 2018 increased by 2.71%/year (p<0.001). Rates in patients <50 years old began to fall in 2002 at a rate of -3.62%/year (p<0.001). Similarly, the incidence-based mortality rates for primary liver cancer increased by 2.15%/year (p<0.001). Whereas Whites incidence-based mortality rates began to plateau in 2012 (0.18%/year; p = 0.84), Blacks rates have declined since 2010 (-2.93%/year; p = 0.03), and Asian rates have declined since 1999 (-1.30%/year; p<0.001). CONCLUSION While the overall primary liver cancer incidence and incidence-based mortality have been increasing over the last four decades, there was an observed decline in incidence and incidence-based mortality in recent years, especially among at-risk subgroups.
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Affiliation(s)
- Saryia Adra
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Yousef Alabrach
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates
| | - Anas Hashem
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Rochester General Hospital, Rochester, New York, United States of America
| | - Amir Mahmoud
- Rochester General Hospital, Rochester, New York, United States of America
| | - Amani Khalouf
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Rochester General Hospital, Rochester, New York, United States of America
| | - Ahmed El-Khapery
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Rochester General Hospital, Rochester, New York, United States of America
| | - Ali Abdelhay
- Rochester General Hospital, Rochester, New York, United States of America
| | - Mohamad Mansour
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Tawam Hospital, Abu Dhabi, United Arab Emirates
| | - Batool Aldaher
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - Hiba Barqawi
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Eman Abu-Gharbieh
- College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
- Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
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Cheng H, Ouyang Y, Li C. Impact of IRGM gene promoter polymorphisms on susceptibility to chronic HBV infection. Int J Immunogenet 2024; 51:149-156. [PMID: 38514898 DOI: 10.1111/iji.12661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 02/03/2024] [Accepted: 02/16/2024] [Indexed: 03/23/2024]
Abstract
The autophagy gene immunity-related GTPase M (IRGM) can affect the immune response against intracellular pathogens. The study was performed to determine any possible association between three IRGM single-nucleotide polymorphisms (SNPs) (rs4958842, rs4958843 and rs4958846) and chronic hepatitis B virus (HBV) infection. A total of 171 chronic HBV-infected individuals and 171 healthy controls were collected. Peripheral blood cells and Sanger sequencing were used to extract genomic DNA and determine the SNP genotypes, respectively. The C allele of rs4958843 is a risk factor for chronic HBV infection in various genetic models, including allelic, codominant and dominant models, with the following respective statistical data: allelic (T vs. C: OR = 1.371, 95% CI = 1.009-1.863, p = .043), codominant (TT vs. CC: OR = 2.137, 95% CI = 1.104-4.138, p = .024) and dominant (TT + TC vs. CC: OR = 1.976, 95% CI = 1.106-3.533, p = .021) models. The genotype and allele distributions of rs4958842 and rs4958846 showed no significant differences between chronic HBV infection patients and healthy controls. IRGM rs4958843 CC genotype carriers had significantly elevated values of alanine transaminase, aspartate transaminase alpha-fetoprotein and total bilirubin (OR = 3.467, 95%CI = 1.167-10.298), which was positively associated with the disease progression of HBV infection. Mutant allele C of IRGM rs4958843 polymorphism is associated with the risk of chronic HBV infection in the Han people in central China and contributes to the disease progression.
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Affiliation(s)
- Hai Cheng
- School of Medicine & Health Sciences, Jingzhou University, Jingzhou, China
| | - Yaoling Ouyang
- Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
| | - Chengbin Li
- Department of Laboratory Medicine, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China
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Abdelhamed W, El-Kassas M. Hepatitis B virus as a risk factor for hepatocellular carcinoma: There is still much work to do. LIVER RESEARCH (BEIJING, CHINA) 2024; 8:83-90. [PMID: 39959873 PMCID: PMC11771266 DOI: 10.1016/j.livres.2024.05.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 03/23/2024] [Accepted: 05/30/2024] [Indexed: 04/03/2025]
Abstract
Hepatitis B virus (HBV) infection is a significant health problem that can result in progression to liver cirrhosis, decompensation, and the development of hepatocellular carcinoma (HCC). On a country level, the prevalence of chronic HBV infection varies between 0.1% and 35.0%, depending on the locality and the population being investigated. One-third of all liver cancer fatalities worldwide are attributable to HBV. The adoption of standard birth-dose immunization exerted the most significant impact on the decline of HBV prevalence. HCC incidence ranges from 0.01% to 1.40% in noncirrhotic patients and from 0.9% to 5.4% annually, in the settings of liver cirrhosis. Although antiviral therapy significantly reduces the risk of developing HBV-related HCC, studies have demonstrated that the risk persists, and that HCC screening is still essential. This review discusses the complex relationship between HBV infection and HCC, recent epidemiological data, different aspects of clinical disease characteristics, and the impact of antiviral therapy in this context.
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Affiliation(s)
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt
- Liver Disease Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Rai A, Bhagchandani T, Tandon R. Transcriptional landscape of long non-coding RNAs (lncRNAs) and its implication in viral diseases. BIOCHIMICA ET BIOPHYSICA ACTA. GENE REGULATORY MECHANISMS 2024; 1867:195023. [PMID: 38513793 DOI: 10.1016/j.bbagrm.2024.195023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 02/26/2024] [Accepted: 03/13/2024] [Indexed: 03/23/2024]
Abstract
Long non-coding RNAs (lncRNAs) are RNA transcripts of size >200 bp that do not translate into proteins. Emerging data revealed that viral infection results in systemic changes in the host at transcriptional level. These include alterations in the lncRNA expression levels and triggering of antiviral immune response involving several effector molecules and diverse signalling pathways. Thus, lncRNAs have emerged as an essential mediatory element at distinct phases of the virus infection cycle. The complete eradication of the viral disease requires more precise and novel approach, thus manipulation of the lncRNAs could be one of them. This review shed light upon the existing knowledge of lncRNAs wherein the implication of differentially expressed lncRNAs in blood-borne, air-borne, and vector-borne viral diseases and its promising therapeutic applications under clinical settings has been discussed. It further enhances our understanding of the complex interplay at host-pathogen interface with respect to lncRNA expression and function.
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Affiliation(s)
- Ankita Rai
- Laboratory of AIDS Research and Immunology, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Tannu Bhagchandani
- Laboratory of AIDS Research and Immunology, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India
| | - Ravi Tandon
- Laboratory of AIDS Research and Immunology, School of Biotechnology, Jawaharlal Nehru University, New Delhi, India.
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Abu Baker F, Kopelman Y, Taher R, Abu Much S, Green I, Mari A, Davidov Y, Ben-Ari Z, Israel A. Hepatitis B virus infection and risk of colorectal cancer: a large, population-based cohort study from Israel. Minerva Med 2024; 115:185-190. [PMID: 38197570 DOI: 10.23736/s0026-4806.23.08964-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Abstract
BACKGROUND Recent population-based studies have suggested a possible link between hepatitis B (HBV) infection and extra-hepatic malignancies. We aimed to evaluate the association between HBV and colorectal cancer (CRC) using a large, population-based cohort study utilizing data from a large health maintenance organization (HMO). METHODS The study included patients with non-cirrhotic HBV based on relevant ICD-9-CM codes and supportive serology identified from the HMO's database. Age-, sex-, ethnicity-, and BMI-matched non-HBV patients in a 1:10 ratio were included in the control group. We assessed the overall diagnosis rate of CRC and hepatocellular carcinoma (HCC) during the study period and calculated the diagnosis rate of CRC in each age category (≤50, 51-70, and ≥70) in both groups. RESULTS A total of 3430 HBV patients and 34,300 controls were included in the study. The mean age, sex, BMI, and ethnic composition were similar, and the rates of family history of CRC did not differ between both groups. The overall follow-up period was 134±16 months. The diagnosis rate of HCC (1.6% vs. 0.1%; P<0.0001) was significantly higher in the HBV patients. However, the proportion of CRC was comparable for both groups (0.6% vs. 0.8%, P=0.404), which was evident in all age subgroups. CONCLUSIONS Our findings suggest that HBV infection is associated with an increased risk of HCC diagnosis but is not linked to an elevated risk of CRC. These findings may inform future clinical practice and research regarding the relationship between HBV and extrahepatic malignancies.
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Affiliation(s)
- Fadi Abu Baker
- Department of Gastroenterology and Hepatology, Hillel Yaffe Medical Center, Hadera, Israel
| | - Yael Kopelman
- Department of Gastroenterology and Hepatology, Hillel Yaffe Medical Center, Hadera, Israel
| | - Randa Taher
- Department of Gastroenterology and Hepatology, Hillel Yaffe Medical Center, Hadera, Israel -
- Department of Internal Medicine, Hillel Yaffe Medical Center, Hadera, Israel
| | - Saif Abu Much
- Department of Internal Medicine, Hillel Yaffe Medical Center, Hadera, Israel
| | - Ilan Green
- Leumit Healthcare Service, Tel Aviv, Israel
| | - Amir Mari
- Department of Gastroenterology and Hepatology, EMMS Hospital, Nazareth, Israel
| | - Yana Davidov
- Center for Liver Diseases, Tel HaShomer Hospital, Ramat Gan, Israel
| | - Ziv Ben-Ari
- Center for Liver Diseases, Tel HaShomer Hospital, Ramat Gan, Israel
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10
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Cooke GS. Viral Hepatitis. MANSON'S TROPICAL DISEASES 2024:152-166. [DOI: 10.1016/b978-0-7020-7959-7.00018-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Kim HR, Kim HS, Kwon YK. Intrahepatic Cholangiocarcinoma Identified in a Zoo-Housed Sandhill Crane ( Grus canadensis): An Anatomopathological and Metagenomic Study. Animals (Basel) 2023; 13:3469. [PMID: 38003087 PMCID: PMC10668867 DOI: 10.3390/ani13223469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/06/2023] [Accepted: 11/09/2023] [Indexed: 11/26/2023] Open
Abstract
Tumors in birds can be caused by a variety of factors such as species, age, sex, virus, chemicals, and environment. In particular, tumors are a major cause of death in long-lived birds such as parrots and zoo birds. A male sandhill crane that was bred for 8 years in a zoo was diagnosed with intrahepatic cholangiocarcinoma (ICC). At necropsy, the liver revealed a multinodular mass of variable colors, and severe cirrhosis and hemorrhages were present. Histologically, ICC was characterized by the presence of both types of ICC: small-duct type and large-duct type. Large-duct-type ICC was distinguished by the presence of multifocal biliary neoplasia, characterized by the diffuse papillary proliferation of columnar cells resembling large cholangiocytes. Small-duct-type ICC was characterized by the presence of non-mucin-producing cuboidal cells such as bile duct cells. In this case, no viral cause was identified from the metagenomic analysis and PCR of ICC; however, a contributing role of Cutibacterium sp. and E. coli identified from the metagenomics could not be excluded. This study is the first to describe the anatomopathological characteristics of ICC in the studied sandhill crane and attempts to determine its potential infectious etiology using metagenomics.
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Affiliation(s)
- Hye-Ryoung Kim
- Avian Disease Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon-si 39660, Gyeongsangbuk-do, Republic of Korea; (H.-S.K.); (Y.-K.K.)
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12
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Al-Toukhy GM, Suef RA, Hassan S, Farag MMS, El-Tayeb TA, Mansour MTM. Photobiological modulation of hepatoma cell lines and hepatitis B subviral particles secretion in response to 650 nm low level laser treatment. J Egypt Natl Canc Inst 2023; 35:33. [PMID: 37870653 DOI: 10.1186/s43046-023-00190-3] [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: 04/25/2022] [Accepted: 09/06/2023] [Indexed: 10/24/2023] Open
Abstract
BACKGROUND Chronic hepatitis B virus (HBV) infection is a serious global health concern, with an increased incidence and risk of developing cirrhosis and hepatocellular carcinoma (HCC). Patients chronically infected with HBV are likely to experience chronic oxidative stress, leading to mitochondrial dysfunction. Photobiomodulation is induced by the absorption of low-level laser therapy (LLLT) with a red or infrared laser by cytochrome C oxidase enzyme, resulting in mitochondrial photoactivation. Although it is widely used in clinical practice, the use of LLL as adjuvant therapy for persistent HBV infection is uncommon. This study aimed to investigate the effect of LLLT dosage from 2 J/cm2 to 10 J/cm2 of red diode laser (650 nm) on both hepatoma cell lines (HepG2.2.15 [integrated HBV genome stable cell model] and non-integrated HepG2), with a subsequent impact on HBVsvp production. METHODS The present study evaluated the effects of different fluences of low-level laser therapy (LLLT) irradiation on various aspects of hepatoma cell behavior, including morphology, viability, ultrastructure, and its impact on HBVsvp synthesis. RESULTS In response to LLLT irradiation, we observed a considerable reduction in viability, proliferation, and HBVsvp production in both hepatoma cell lines HepG2.2.15 and HepG2. Ultrastructural modification of mitochondria and nuclear membranes: This effect was dose, cell type, and time-dependent. CONCLUSIONS The use of LLLT may be a promising therapy for HCC and HBV patients by reducing cell proliferation, HBVsvp production, and altering mitochondrial and nuclear structure involved in cellular death inducers. Further research is required to explore its clinical application.
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Affiliation(s)
- Ghada M Al-Toukhy
- Department of Virology and Immunology, Children's Cancer Hospital, Cairo, 57357, Egypt.
| | - Reda A Suef
- Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt
| | - Sarah Hassan
- Pathology and Electron Microscopy, Theodor Bilharz Research Institute, Giza, Egypt
| | - Mohamed M S Farag
- Department of Botany and Microbiology, Faculty of Science, Al-Azhar University, Cairo, 11884, Egypt
- Biomedical Research Department, Armed Forces College of Medicine, Cairo, Egypt
| | - Tarek A El-Tayeb
- National Institute of Laser Enhanced Science (NILES), Cairo University, Cairo, Egypt
| | - Mohamed T M Mansour
- Department of Virology and Immunology, National Cancer Institute, Cairo University, Cairo, Egypt
- Children Cancer Hospital, Cairo, 57357, Egypt
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13
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Tenofovir for children and adults with chronic hepatitis B. Cochrane Database Syst Rev 2023; 2023:CD015586. [PMCID: PMC10485896 DOI: 10.1002/14651858.cd015586] [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] [Indexed: 09/13/2024]
Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of tenofovir versus no intervention or placebo for children and adults with chronic hepatitis B.
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14
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Ahmed K, Jha S. Oncoviruses: How do they hijack their host and current treatment regimes. Biochim Biophys Acta Rev Cancer 2023; 1878:188960. [PMID: 37507056 DOI: 10.1016/j.bbcan.2023.188960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 07/05/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023]
Abstract
Viruses have the ability to modulate the cellular machinery of their host to ensure their survival. While humans encounter numerous viruses daily, only a select few can lead to disease progression. Some of these viruses can amplify cancer-related traits, particularly when coupled with factors like immunosuppression and co-carcinogens. The global burden of cancer development resulting from viral infections is approximately 12%, and it arises as an unfortunate consequence of persistent infections that cause chronic inflammation, genomic instability from viral genome integration, and dysregulation of tumor suppressor genes and host oncogenes involved in normal cell growth. This review provides an in-depth discussion of oncoviruses and their strategies for hijacking the host's cellular machinery to induce cancer. It delves into how viral oncogenes drive tumorigenesis by targeting key cell signaling pathways. Additionally, the review discusses current therapeutic approaches that have been approved or are undergoing clinical trials to combat malignancies induced by oncoviruses. Understanding the intricate interactions between viruses and host cells can lead to the development of more effective treatments for virus-induced cancers.
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Affiliation(s)
- Kainat Ahmed
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
| | - Sudhakar Jha
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA.
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15
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Ghufran SM, Sharma P, Roy B, Jaiswal S, Aftab M, Sengupta S, Ghose S, Biswas S. Transcriptome wide functional analysis of HBx expressing human hepatocytes stimulated with endothelial cell cross-talk. Genomics 2023; 115:110642. [PMID: 37209778 PMCID: PMC7615065 DOI: 10.1016/j.ygeno.2023.110642] [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: 01/26/2023] [Revised: 05/11/2023] [Accepted: 05/17/2023] [Indexed: 05/22/2023]
Abstract
Identification of genes dysregulated during the hepatitis B virus (HBV)-host cell interaction adds to the understanding of underlying molecular mechanisms and aids in discovering effective therapies to improve prognosis in hepatitis B virus (HBV)-infected individuals. Through bioinformatics analyses of transcriptomics data, this study aimed to identify potential genes involved in the cross-talk of human hepatocytes expressing the HBV viral protein HBx with endothelial cells. Transient transfection of HBV viral gene X (HBx) was performed in THLE2 cells using pcDNA3 constructs. Through mRNA Sequencing (RNA Seq) analysis, differentially expressed genes (DEGs) were identified. THLE2 cells transfected with HBx (THLE2x) were further treated with conditioned medium from cultured human umbilical vein derived endothelial cells (HUVEC-CM). Gene Ontology (GO) enrichment analysis revealed that interferon and cytokine signaling pathways were primarily enriched for the downregulated DEGs in THLE2x cells treated with HUVEC-CM. One significant module was selected following protein-protein interaction (PPI) network generation, and thirteen hub genes were identified from the module. The prognostic values of the hub genes were evaluated using Kaplan-Meier (KM) plotter, and three genes (IRF7, IFIT1, and IFITM1) correlated with poor disease specific survival (DSS) in HCC patients with chronic hepatitis. A comparison of the DEGs identified in HUVEC-stimulated THLE2x cells with four publicly available HBV-related HCC microarray datasets revealed that PLAC8 was consistently downregulated in all four HCC datasets as well as in HUVEC-CM treated THLE2x cells. KM plots revealed that PLAC8 correlated with worse relapse free survival and progression free survival in HCC patients with hepatitis B virus infection. This study provided molecular insights which may help develop a deeper understanding of HBV-host stromal cell interaction and open avenues for future research.
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Affiliation(s)
| | - Prachi Sharma
- Amity Institute of Molecular Medicine & Stem Cell Research, AUUP, Noida, India
| | - Bornika Roy
- Amity Institute of Molecular Medicine & Stem Cell Research, AUUP, Noida, India
| | - Shivani Jaiswal
- Amity Institute of Molecular Medicine & Stem Cell Research, AUUP, Noida, India
| | - Mehreen Aftab
- Division of Cellular and Molecular Oncology, National Institute of Cancer Prevention and Research, Noida, India
| | - Shinjinee Sengupta
- Amity Institute of Molecular Medicine & Stem Cell Research, AUUP, Noida, India
| | - Sampa Ghose
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.
| | - Subhrajit Biswas
- Amity Institute of Molecular Medicine & Stem Cell Research, AUUP, Noida, India.
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16
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Jagirdhar GSK, Pulakurthi YS, Chigurupati HD, Surani S. Gastrointestinal tract and viral pathogens. World J Virol 2023; 12:136-150. [PMID: 37396706 PMCID: PMC10311582 DOI: 10.5501/wjv.v12.i3.136] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 03/17/2023] [Accepted: 04/27/2023] [Indexed: 06/21/2023] Open
Abstract
Viral gastroenteritis is the most common viral illness that affects the gastrointestinal (GI) tract, causing inflammation and irritation of the lining of the stomach and intestines. Common signs and symptoms associated with this condition include abdominal pain, diarrhea, and dehydration. The infections commonly involved in viral gastroenteritis are rotavirus, norovirus, and adenovirus, which spread through the fecal-oral and contact routes and cause non-bloody diarrhea. These infections can affect both immunocompetent and immunocompromised individuals. Since the pandemic in 2019, coronavirus gastroenteritis has increased in incidence and prevalence. Morbidity and mortality rates from viral gastroenteritis have declined significantly over the years due to early recognition, treatment with oral rehydration salts, and prompt vaccination. Improved sanitation measures have also played a key role in reducing the transmission of infection. In addition to viral hepatitis causing liver disease, herpes virus, and cytomegalovirus are responsible for ulcerative GI disease. They are associated with bloody diarrhea and commonly occur in im-munocompromised individuals. Hepatitis viruses, Epstein-Barr virus, herpesvirus 8, and human papillomavirus have been involved in benign and malignant diseases. This mini review aims to list different viruses affecting the GI tract. It will cover common symptoms aiding in diagnosis and various important aspects of each viral infection that can aid diagnosis and management. This will help primary care physicians and hospitalists diagnose and treat patients more easily.
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Affiliation(s)
| | | | | | - Salim Surani
- Department of Pulmonary, Critical Care and Sleep Medicine, Texas A&M University, College Station, TX 77843, United States
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17
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Xu JQ, Su SB, Chen CY, Gao J, Cao ZM, Guan JL, Xiao LX, Zhao MM, Yu H, Hu YJ. Mechanisms of Ganweikang Tablets against Chronic Hepatitis B: A Comprehensive Study of Network Analysis, Molecular Docking, and Chemical Profiling. BIOMED RESEARCH INTERNATIONAL 2023; 2023:8782892. [PMID: 37197593 PMCID: PMC10185428 DOI: 10.1155/2023/8782892] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 03/03/2023] [Accepted: 03/15/2023] [Indexed: 05/19/2023]
Abstract
The hepatitis B virus (HBV) is one of the major viral infection problems worldwide in public health. The exclusive proprietary Chinese medicine Ganweikang (GWK) tablet has been marketed for years in the treatment of chronic hepatitis B (CHB). However, the pharmacodynamic material basis and underlying mechanism of GWK are not completely clear. This study is aimed at investigating the pharmacological mechanism of the GWK tablet in the treatment of CHB. The chemical ingredient information was obtained from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), and Shanghai Institute of Organic Chemistry of CAS. Ingredients and disease-related targets were defined by a combination of differentially expressed genes from CHB transcriptome data and open-source databases. Target-pathway-target (TPT) network analysis, molecular docking, and chemical composition analysis were adopted to further verify the key targets and corresponding active ingredients of GWK. Eight herbs of GWK were correlated to 330 compounds with positive oral bioavailability, and 199 correlated targets were identified. The TPT network was constructed based on the 146 enriched targets by KEGG pathway analysis, significantly associated with 95 pathways. Twenty-five nonvolatile components and 25 volatile components in GWK were identified in UPLC-QTOF/MS and GC-MS chromatograms. The key active ingredients of GWK include ferulic acid, oleanolic acid, ursolic acid, tormentic acid, 11-deoxyglycyrrhetic acid, dibenzoyl methane, anisaldehyde, wogonin, protocatechuic acid, psoralen, caffeate, dimethylcaffeic acid, vanillin, β-amyrenyl acetate, formonentin, aristololactam IIIa, and 7-methoxy-2-methyl isoflavone, associated with targets CA2, NFKB1, RELA, AKT1, JUN, CA1, CA6, IKBKG, FOS, EP300, CREB1, STAT1, MMP9, CDK2, ABCB1, and ABCG2.
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Affiliation(s)
- Jia-Qi Xu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
- Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao 999078, China
| | - Shi-Bing Su
- Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - C. Y. Chen
- Jiaheng (Hengqin, Zhuhai) Pharmaceutical Technology Co., Ltd., Zhuhai, China
- National Engineering Research Center for Modernization of Traditional Chinese Medicine, Zhuhai, China
| | - J. Gao
- National Engineering Research Center for Modernization of Traditional Chinese Medicine, Zhuhai, China
| | - Z. M. Cao
- Jiaheng (Hengqin, Zhuhai) Pharmaceutical Technology Co., Ltd., Zhuhai, China
| | - J. L. Guan
- Henan Fusen Pharmaceutical Co., Ltd., Henan, China
| | - Lin-Xuan Xiao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
| | - Ming-Ming Zhao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
| | - Hua Yu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
| | - Yuan-Jia Hu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China
- Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, Macao 999078, China
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18
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Xue J, Zhao H, Fu Y, Liu X, Wu X. Integrated analysis of multiple transcriptomic data identifies ST8SIA6‑AS1 and LINC01093 as potential biomarkers in HBV‑associated liver cancer. Oncol Lett 2023; 25:185. [PMID: 37065781 PMCID: PMC10091192 DOI: 10.3892/ol.2023.13771] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 12/02/2022] [Indexed: 04/18/2023] Open
Abstract
The mechanisms of long-non-coding RNAs (lncRNAs) in hepatitis B virus (HBV) infection-associated liver cancer remain largely unclear. Therefore, the aim of the present study was to investigate the regulatory mechanisms of lncRNAs in this disease. HBV-liver cancer related transcriptome expression profile data (GSE121248 and GSE55092) from the Gene Expression Omnibus database and survival prognosis information from The Cancer Genome Atlas (TCGA) database were obtained for analysis. The limma package was used to identify the overlapped differentially expressed RNAs (DERs), including DElncRNAs and DEmRNAs, in the GSE121248 and GSE55092 datasets. The screened optimized lncRNA signatures were used to develop a nomogram model based on the GSE121248 dataset, which was validated using the GSE55092 and TCGA datasets. A competitive endogenous RNA (ceRNA) network was constructed based on the screened prognosis-associated lncRNA signatures from TCGA dataset. In addition, the levels of specific lncRNAs were evaluated in HBV-infected human liver cancer tissues and cells, and Cell Counting Kit-8, ELISA and Transwell assays were performed to evaluate the effects of the lncRNAs in HBV-expressing liver cancer cells. A total of 535 overlapped DERs, including 30 DElncRNAs and 505 DEmRNAs, were identified in the GSE121248 and GSE55092 datasets. An optimized DElncRNA signature comprising 10 lncRNAs was used to establish a nomogram. ST8SIA6-AS1 and LINC01093 were identified as lncRNAs associated with HBV-liver cancer prognosis in TCGA dataset, and were applied to construct a ceRNA network. Reverse transcription-quantitative PCR analysis showed that ST8SIA6-AS1 was upregulated and LINC01093 was downregulated in HBV-infected human liver cancer tissues and HBV-expressing liver cancer cells compared with non-HBV-infected controls. ST8SIA6-AS1 knockdown and LINC01093 overexpression independently reduced the number of copies of HBV DNA, the levels of hepatitis B surface antigen and hepatitis B e antigen, as well as cell proliferation, migration and invasion. In summary, the present study identified ST8SIA6-AS1 and LINC01093 as two potential biomarkers that may be effective therapeutic targets for HBV-associated liver cancer.
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Affiliation(s)
- Jianhua Xue
- Department of Infectious Diseases, Hospital for Infectious Diseases of Pudong District, Shanghai 201318, P.R. China
| | - Hui Zhao
- Department of Infectious Diseases, Hospital for Infectious Diseases of Pudong District, Shanghai 201318, P.R. China
| | - Yifei Fu
- Department of Infectious Diseases, Hospital for Infectious Diseases of Pudong District, Shanghai 201318, P.R. China
| | - Xu Liu
- Department of Infectious Diseases, Hospital for Infectious Diseases of Pudong District, Shanghai 201318, P.R. China
| | - Xiangxiang Wu
- Department of Traditional Chinese Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, P.R. China
- Correspondence to: Dr Xiangxiang Wu, Department of Traditional Chinese Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou, Shanghai 200437, P.R. China, E-mail:
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19
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Padarath K, Deroubaix A, Kramvis A. The Complex Role of HBeAg and Its Precursors in the Pathway to Hepatocellular Carcinoma. Viruses 2023; 15:v15040857. [PMID: 37112837 PMCID: PMC10144019 DOI: 10.3390/v15040857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/23/2023] [Accepted: 03/24/2023] [Indexed: 03/30/2023] Open
Abstract
Hepatitis B virus (HBV) is one of the seven known human oncogenic viruses and has adapted to coexist with a single host for prolonged periods, requiring continuous manipulation of immunity and cell fate decisions. The persistence of HBV infection is associated with the pathogenesis of hepatocellular carcinoma, and various HBV proteins have been implicated in promoting this persistence. The precursor of hepatitis e antigen (HBeAg), is translated from the precore/core region and is post-translationally modified to yield HBeAg, which is secreted in the serum. HBeAg is a non-particulate protein of HBV and can act as both a tolerogen and an immunogen. HBeAg can protect hepatocytes from apoptosis by interfering with host signalling pathways and acting as a decoy to the immune response. By evading the immune response and interfering with apoptosis, HBeAg has the potential to contribute to the hepatocarcinogenic potential of HBV. In particular, this review summarises the various signalling pathways through which HBeAg and its precursors can promote hepatocarcinogenesis via the various hallmarks of cancer.
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20
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Ma GX, Zhu L, Tan Y, Zhai S, Ma X, Ogunwobi OO, Yang WJ, Ting T, Kim S, Wang MQ. A Comparative Trial of Improving Care for Underserved Asian Americans Infected with Hepatitis B Virus. Dig Dis Sci 2023; 68:2333-2343. [PMID: 36749506 DOI: 10.1007/s10620-023-07840-5] [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: 07/19/2022] [Accepted: 01/15/2023] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC). Asian Americans have the highest incidence and mortality rates of HCC among all US racial/ethnic groups. Inadequate monitoring and treatment of chronic hepatitis B contribute to poor health outcomes and increased healthcare costs among Asian Americans. AIMS The goal of this study is to assess the effect of a patient-led strategy on chronic hepatitis B monitoring and treatment adherence specifically among Asian Americans with culturally tailored Patient Navigator-led Intervention. METHODS From 2015 to 2018, 532 eligible participants living with chronic hepatitis B in the greater Philadelphia and New York city metropolitan areas were randomly assigned to either the intervention group or the control group. Generalized linear mixed-effects models were used to estimate the odds ratio (OR) for rates of doctor visits for chronic hepatitis B and rates of alanine aminotransferase testing for evidence of liver damage. RESULTS Intervention group had higher rates of doctor visits than the control group at both 6-month (77.22% vs. 45.75%) and 12-month assessments (90.73% vs. 60.61%). Significantly more intervention group participants received ALT testing than control group participants at 6-month (52.90% vs. 25.10%) and 12-month (75.40% vs. 46.75%) follow-up. CONCLUSIONS Culturally and linguistically appropriate intervention has strong effects on adherence to follow-up care among Asian American hepatitis B patients experiencing challenges to medication adherence and follow up care. These findings further identify opportunities for practical implementation of evidence-based intervention that could lead to reductions in disparities in chronic liver disease and liver cancer among high-risk, underserved populations.
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Affiliation(s)
- Grace X Ma
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Kresge Hall, Suite 320, 3440 N Broad St., Philadelphia, PA, 19140, USA. .,Department of Urban Health and Population Science, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
| | - Lin Zhu
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Kresge Hall, Suite 320, 3440 N Broad St., Philadelphia, PA, 19140, USA.,Department of Urban Health and Population Science, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
| | - Yin Tan
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Kresge Hall, Suite 320, 3440 N Broad St., Philadelphia, PA, 19140, USA
| | - Shumenghui Zhai
- School of Nursing, University of Washington, Seattle, WA, USA
| | - Xiaoli Ma
- Hepatology Clinic, Philadelphia, PA, USA
| | - Olorunseun O Ogunwobi
- Department of Biological Sciences, Hunter College, City University of New York, New York, NY, USA
| | - Wei Jenny Yang
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Kresge Hall, Suite 320, 3440 N Broad St., Philadelphia, PA, 19140, USA
| | - Tsunyou Ting
- Faith Hope Love Chinese Church, Philadelphia, PA, USA
| | - Sara Kim
- Korean Community Services of Metropolitan New York, New York, NY, USA
| | - Min Qi Wang
- Department of Behavioral and Community Health, School of Public Health, University of Maryland, College Park, MD, USA
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21
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Virolainen SJ, VonHandorf A, Viel KCMF, Weirauch MT, Kottyan LC. Gene-environment interactions and their impact on human health. Genes Immun 2023; 24:1-11. [PMID: 36585519 PMCID: PMC9801363 DOI: 10.1038/s41435-022-00192-6] [Citation(s) in RCA: 80] [Impact Index Per Article: 40.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/09/2022] [Accepted: 12/13/2022] [Indexed: 12/31/2022]
Abstract
The molecular processes underlying human health and disease are highly complex. Often, genetic and environmental factors contribute to a given disease or phenotype in a non-additive manner, yielding a gene-environment (G × E) interaction. In this work, we broadly review current knowledge on the impact of gene-environment interactions on human health. We first explain the independent impact of genetic variation and the environment. We next detail well-established G × E interactions that impact human health involving environmental toxicants, pollution, viruses, and sex chromosome composition. We conclude with possibilities and challenges for studying G × E interactions.
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Affiliation(s)
- Samuel J Virolainen
- Division of Human Genetics, Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA
- Immunology Graduate Program, University of Cincinnati College of Medicine, 3230 Eden Ave, Cincinnati, OH, 45229, USA
| | - Andrew VonHandorf
- Division of Human Genetics, Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA
| | - Kenyatta C M F Viel
- Division of Human Genetics, Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA
| | - Matthew T Weirauch
- Division of Human Genetics, Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA.
- Immunology Graduate Program, University of Cincinnati College of Medicine, 3230 Eden Ave, Cincinnati, OH, 45229, USA.
- Divisions of Biomedical Informatics and Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA.
- Department of Pediatrics, University of Cincinnati College of Medicine, 3230 Eden Ave, Cincinnati, OH, 45229, USA.
| | - Leah C Kottyan
- Division of Human Genetics, Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, 45229, USA.
- Immunology Graduate Program, University of Cincinnati College of Medicine, 3230 Eden Ave, Cincinnati, OH, 45229, USA.
- Department of Pediatrics, University of Cincinnati College of Medicine, 3230 Eden Ave, Cincinnati, OH, 45229, USA.
- Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., MLC 15012, Cincinnati, OH, 45229, USA.
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22
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Many Ways to Communicate-Crosstalk between the HBV-Infected Cell and Its Environment. Pathogens 2022; 12:pathogens12010029. [PMID: 36678377 PMCID: PMC9866324 DOI: 10.3390/pathogens12010029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 12/19/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
Chronic infection with the hepatitis B virus (HBV) affects an estimated 257 million people worldwide and can lead to liver diseases such as cirrhosis and liver cancer. Viral replication is generally considered not to be cytopathic, and although some HBV proteins may have direct carcinogenic effects, the majority of HBV infection-related disease is related to chronic inflammation resulting from disrupted antiviral responses and aberrant innate immune reactions. Like all cells, healthy and HBV-infected cells communicate with each other, as well as with other cell types, such as innate and adaptive immune cells. They do so by both interacting directly and by secreting factors into their environment. Such factors may be small molecules, such as metabolites, single viral proteins or host proteins, but can also be more complex, such as virions, protein complexes, and extracellular vesicles. The latter are small, membrane-enclosed vesicles that are exchanged between cells, and have recently gained a lot of attention for their potential to mediate complex communication and their potential for therapeutic repurposing. Here, we review how HBV infection affects the communication between HBV-infected cells and cells in their environment. We discuss the impact of these interactions on viral persistence in chronic infection, as well as their relation to HBV infection-related pathology.
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23
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Sugimori H, Hirao M, Igarashi A, Yatsuhashi H, Ikeda S, Masaki N, Yotsuyanagi H, Yoda T, Odajima T, Takura T, Hirao T. Health state utilities of patients with hepatitis B and C and hepatitis-related conditions in Japan. Sci Rep 2022; 12:17139. [PMID: 36229479 PMCID: PMC9561176 DOI: 10.1038/s41598-022-21470-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 09/27/2022] [Indexed: 01/04/2023] Open
Abstract
Health state utilities are global measurements of quality of life and have been used to evaluate health outcomes for the cost-utility analysis. This study aimed to estimate the health state utilities of patients with hepatitis B (HB), hepatitis C (HC), and hepatitis-related diseases in Japan. We distributed a self-administered questionnaire, including the EuroQol 5-Dimension 5-Level (EQ-5D-5L), to 9,952 outpatients with several clinical conditions caused by HB or HC virus infection (such as asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, and decompensated cirrhosis) and estimated the condition-specific utilities of patients with HB or HC. In patients with more severe conditions (patients with acute hepatitis, fulminant hepatitis, and hepatocellular carcinoma and patients undergoing post-liver transplantation), the utilities of these severe conditions were estimated by three hepatitis experts using the EQ-5D-5L. The means of the utilities for acute hepatitis, fulminant hepatitis, asymptomatic chronic hepatitis, chronic hepatitis, compensated cirrhosis, compensated cirrhosis, hepatocellular carcinoma stage I/II, hepatocellular carcinoma stage III/IV, and post-liver transplantation were 0.529, - 0.111, 0.904, 0.868, 0.845, 0.722, 0,675, 0,428, and 0.651 and 0.876, 0.821, 0.737, 0.671, 0.675, 0.428, and 0.651 in HB and HC, respectively. To the best of our knowledge, this is the first study that comprehensively assessed the health state utilities of patients with HB, HC and hepatitis-related conditions from a nationwide survey in Japan using the EQ-5D-5L.
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Affiliation(s)
- Hiroki Sugimori
- Department of Nursing, Faculty of Sports and Health Science, Daito Bunka University, 560 Iwadono, Higashimatsuyama City, Saitama, 3558501, Japan.
| | - Maki Hirao
- Division of Hematology, Department of Medicine, Saiseikai Central Hospital, Tokyo, Japan
| | - Ataru Igarashi
- Unit of Public Health and Preventive Medicine, School of Medicine Medical Course, Yokohama City University, Kanagawa, Japan
| | - Hiroshi Yatsuhashi
- National Hospital Organization (NHO) Nagasaki Medical Center, Nagasaki, Japan
| | - Shunya Ikeda
- School of Medicine, International University of Health and Welfare, Chiba, Japan
| | | | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Takeshi Yoda
- Department of Public Health, Kawasaki Medical School, Okayama, Japan
| | - Takeshi Odajima
- Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Tokyo, Japan
| | - Tomoyuki Takura
- Department of Healthcare Economics and Health Policy, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomohiro Hirao
- Department of Public Health, Faculty of Medicine, Kagawa University, Kagawa, Japan
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24
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Dysregulation of miRISC Regulatory Network Promotes Hepatocellular Carcinoma by Targeting PI3K/Akt Signaling Pathway. Int J Mol Sci 2022; 23:ijms231911300. [PMID: 36232606 PMCID: PMC9569668 DOI: 10.3390/ijms231911300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 09/18/2022] [Accepted: 09/19/2022] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) remains the third leading malignancy worldwide, causing high mortality in adults and children. The neuropathology-associated gene AEG-1 functions as a scaffold protein to correctly assemble the RNA-induced silencing complex (RISC) and optimize or increase its activity. The overexpression of oncogenic miRNAs periodically degrades the target tumor suppressor genes. Oncogenic miR-221 plays a seminal role in the carcinogenesis of HCC. Hence, the exact molecular and biological functions of the oncogene clusters miR-221/AEG-1 axis have not yet been examined widely in HCC. Here, we explored the expression of both miR-221 and AEG-1 and their target/associate genes by qRT-PCR and western blot. In addition, the role of the miR-221/AEG-1 axis was studied in the HCC by flow cytometry analysis. The expression level of the AEG-1 did not change in the miR-221 mimic, and miR-221-transfected HCC cells, on the other hand, decreased the miR-221 expression in AEG-1 siRNA-transfected HCC cells. The miR-221/AEG-1 axis silencing induces apoptosis and G2/M phase arrest and inhibits cellular proliferation and angiogenesis by upregulating p57, p53, RB, and PTEN and downregulating LSF, LC3A, Bcl-2, OPN, MMP9, PI3K, and Akt in HCC cells.
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Ma GX, Zhu L, Lu W, Tan Y, Truehart J, Johnson C, Handorf E, Nguyen MT, Yeh MC, Wang MQ. Examining the Influencing Factors of Chronic Hepatitis B Monitoring Behaviors among Asian Americans: Application of the Information-Motivation-Behavioral Model. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:4642. [PMID: 35457509 PMCID: PMC9027209 DOI: 10.3390/ijerph19084642] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 04/05/2022] [Accepted: 04/08/2022] [Indexed: 02/07/2023]
Abstract
Background: Compared to non-Hispanic whites, Asian Americans are 60% more likely to die from the disease. Doctor visitation for chronic hepatitis B (CHB) infection every six months is an effective approach to preventing liver cancer. Methods: This study utilized baseline data from an ongoing randomized controlled clinical trial aimed at improving long-term adherence to CHB monitoring/treatment. Guided by the information-motivation-behavioral skills (IMB) model, we examined factors associated with CHB monitoring adherence among Asian Americans with CHB. Multivariable logistic regression was conducted to test the associations. Results: The analysis sample consisted of 382 participants. Multivariable logistic regression showed that HBV knowledge (OR = 1.24, p < 0.01) and CHB-management motivation (OR = 1.06, p < 0.05) are significant predictors of having a doctor’s visit in the past six months. Both factors were positively associated with the likelihood of having had blood tests for HBV in the past six months. Conclusion: We found that greater HBV-related knowledge and CHB-management motivation are significantly associated with performing CHB-monitoring behaviors in the past six months. The findings have critical implications for the development and implementation of evidence-based interventions for CHB monitoring and liver cancer prevention in the Asian American community.
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Affiliation(s)
- Grace X. Ma
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; (L.Z.); (W.L.); (Y.T.); (J.T.)
- Department of Urban Health and Population Science, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
| | - Lin Zhu
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; (L.Z.); (W.L.); (Y.T.); (J.T.)
- Department of Urban Health and Population Science, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA
| | - Wenyue Lu
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; (L.Z.); (W.L.); (Y.T.); (J.T.)
- Department of Sociology, College of Liberal Arts, Temple University, Philadelphia, PA 19120, USA
| | - Yin Tan
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; (L.Z.); (W.L.); (Y.T.); (J.T.)
| | - Jade Truehart
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA; (L.Z.); (W.L.); (Y.T.); (J.T.)
| | - Cicely Johnson
- Center for Cancer Health Disparities Research (CCHDR), Hunter College, City University of New York, New York, NY 10065, USA;
| | - Elizabeth Handorf
- Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA 19111, USA; (E.H.); (M.T.N.)
| | - Minhhuyen T. Nguyen
- Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA 19111, USA; (E.H.); (M.T.N.)
| | - Ming-Chin Yeh
- Nutrition Program, Hunter College, City University of New York, New York, NY 10065, USA;
| | - Min Qi Wang
- School of Public Health, University of Maryland, College Park, MD 20742, USA;
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Xiao J, Yong JN, Ng CH, Syn N, Lim WH, Tan DJH, Tan EY, Huang D, Wong RC, Chew NWS, Tan EXX, Noureddin M, Siddiqui MS, Muthiah MD. A Meta-Analysis and Systematic Review on the Global Prevalence, Risk Factors, and Outcomes of Coronary Artery Disease in Liver Transplantation Recipients. Liver Transpl 2022; 28:689-699. [PMID: 34626045 DOI: 10.1002/lt.26331] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 10/02/2021] [Accepted: 10/06/2021] [Indexed: 12/12/2022]
Abstract
The shift in the changing etiology of cirrhosis requiring liver transplantation (LT) has resulted in an increasing prevalence of coronary artery disease (CAD) that can potentially impact post-LT outcomes. This systematic review and meta-analysis evaluates the prevalence of CAD, risk factors, and outcomes of patients diagnosed with CAD before LT. MEDLINE and EMBASE were searched for articles describing CAD in pre-LT patients. Meta-analysis of proportions using the generalized linear mix model was conducted to analyze the pooled prevalence of CAD in pre-LT patients. Associated risk factors for CAD in pre-LT patients and outcomes were evaluated in conventional pairwise meta-analysis. A total of 39 studies were included. The pooled prevalence of patients diagnosed with CAD before LT was 15.9% (95% CI, 9.8%-24.7%). Age, male sex, diabetes mellitus, hypertension, hyperlipidemia, smoking, nonalcoholic steatohepatitis, hepatitis B virus, and hepatocellular carcinoma were significantly associated with CAD. Patients from high-income countries especially North America, Europe, and South America, with the associated risk factors were at increased risk for CAD before LT. CAD before LT was associated with an increased odds of overall mortality (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.4-1.4; P = 0.01) and cardiac-related mortality (OR, 1.2; 95% CI, 1.1-1.3; P = 0.03). A total of 48.7% of included articles considered the presence of cardiovascular risk factors for CAD screening. However, 10.3% of the studies screened for CAD in pre-LT patients via invasive coronary angiography only, without stress testing or risk stratification. This study demonstrates the high prevalence of CAD in pre-LT patients, associated risk factors, and outcomes. There is heterogeneity among guidelines and practice in screening for pre-LT CAD, and more studies are needed to establish consensus.
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Affiliation(s)
- Jieling Xiao
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Jie Ning Yong
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Cheng Han Ng
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Nicholas Syn
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore
| | - Wen Hui Lim
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - Darren Jun Hao Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore
| | - En Ying Tan
- Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Daniel Huang
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Raymond C Wong
- Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore
| | - Nicholas W S Chew
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Department of Cardiology, National University Heart Centre, National University Hospital, Singapore, Singapore
| | - Eunice Xiang Xuan Tan
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
| | - Mazen Noureddin
- Cedars-Sinai Fatty Liver Program, Division of Digestive and Liver Diseases, Department of Medicine, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Mohammad Shadab Siddiqui
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University Singapore, Singapore, Singapore.,Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.,National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore
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Proulx J, Ghaly M, Park IW, Borgmann K. HIV-1-Mediated Acceleration of Oncovirus-Related Non-AIDS-Defining Cancers. Biomedicines 2022; 10:biomedicines10040768. [PMID: 35453518 PMCID: PMC9024568 DOI: 10.3390/biomedicines10040768] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 03/22/2022] [Accepted: 03/22/2022] [Indexed: 11/25/2022] Open
Abstract
With the advent of combination antiretroviral therapy (cART), overall survival has been improved, and the incidence of acquired immunodeficiency syndrome (AIDS)-defining cancers has also been remarkably reduced. However, non-AIDS-defining cancers among human immunodeficiency virus-1 (HIV-1)-associated malignancies have increased significantly so that cancer is the leading cause of death in people living with HIV in certain highly developed countries, such as France. However, it is currently unknown how HIV-1 infection raises oncogenic virus-mediated cancer risks in the HIV-1 and oncogenic virus co-infected patients, and thus elucidation of the molecular mechanisms for how HIV-1 expedites the oncogenic viruses-triggered tumorigenesis in the co-infected hosts is imperative for developing therapeutics to cure or impede the carcinogenesis. Hence, this review is focused on HIV-1 and oncogenic virus co-infection-mediated molecular processes in the acceleration of non-AIDS-defining cancers.
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Danso KA, Akuaku RS, Taylor RR, Amoako E, Ulzen‐Appiah K, Jimah BB, Tagoe LG. A case report of a teenager with hepatitis B surface antigen-positive multifocal hepatocellular carcinoma in a noncirrhotic liver. Clin Case Rep 2022; 10:e05622. [PMID: 35340653 PMCID: PMC8935124 DOI: 10.1002/ccr3.5622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 02/23/2022] [Accepted: 03/07/2022] [Indexed: 11/20/2022] Open
Abstract
Hepatitis B virus is a known carcinogen for hepatocellular carcinoma, which is rare in the pediatric population. We report a 13-year-old patient with hepatitis B surface antigen-positive multifocal hepatocellular carcinoma in a noncirrhotic liver. Her APRI score was 0.24. Her BCLC stage was C, and her caregiver opted for palliative care.
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Affiliation(s)
- Kwadwo Apeadu Danso
- Department of Paediatrics and Child HealthCape Coast Teaching HospitalCape CoastGhana
| | | | - Rebekah Ruth Taylor
- Department of Paediatrics and Child HealthCape Coast Teaching HospitalCape CoastGhana
| | - Emmanuella Amoako
- Department of Paediatrics and Child HealthCape Coast Teaching HospitalCape CoastGhana
- School of Medical SciencesUniversity of Cape CoastCape CoastGhana
| | - Kofi Ulzen‐Appiah
- School of Medical SciencesUniversity of Cape CoastCape CoastGhana
- Department of PathologyCape Coast Teaching HospitalCape CoastGhana
| | - Bashiru Babatunde Jimah
- Department of Medical ImagingSchool of Medical SciencesUniversity of Cape CoastCape CoastGhana
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Huang C, Fang M, Xiao X, Wang H, Gao Z, Ji J, Liu L, Gu E, Li Y, Wang M, Gao C. Validation of the GALAD model for early diagnosis and monitoring of hepatocellular carcinoma in Chinese multicenter study. Liver Int 2022; 42:210-223. [PMID: 34679250 DOI: 10.1111/liv.15082] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 10/18/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND GALAD is an algorithm model estimating the presence of hepatocellular carcinoma (HCC). However, the participants enrolled in the GALAD differ from those of Chinese subjects whose HCCs are mainly hepatitis B virus infection related. Therefore, the cross-sectional as well as longitudinal multicenter study was designed to assess the clinical performances of GALAD in the Chinese population. METHODS A case-control study of 602 patients with HCC (34.10% within Barcelona Clinic Liver Cancer 0-A stage) and 923 subjects without HCC from five Chinese medical centres was conducted. Longitudinally the performances of GALAD identifying HCC were assessed using receiver operating characteristic curves analyses. Furthermore, the surveillance performance of GALAD for 204 HCC patients after radical surgery and for the early detection of HCC prospectively in an independent cohort of chronic hepatitis B were analysed, respectively. RESULTS We found the GALAD identified early stage HCC at an area under the receiver operating characteristic curve (AUC) above 0.85 and outperformed significantly than AFP, PIVKAII, AFP-L3 and BALAD-2 respectively. Meanwhile the GALAD could stratify HCC into two distinct subgroups with high or low risks of overall survival and recurrence. The GALAD could detection HCC 24 (AUC: 0.848) or even 48 (AUC: 0.833) weeks before clinical diagnosis. CONCLUSIONS Our study indicates that the GALAD exhibits outstanding performance in the early diagnosis, prognosis prediction as well as risk monitoring of HCC in our cross-sectional and longitudinal multicenter study of 1561 patients. GALAD should be implanted into clinical practice early so as to improve the clinical efficacy of individual biomarkers in HCC early monitoring and prognosis prediction.
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Affiliation(s)
- Chenjun Huang
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.,Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Meng Fang
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Xiao Xiao
- Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Hong Wang
- Department of Hepatology and Gastroenterology, Jing'an District Centre Hospital, Fudan University, P.R. China
| | - Zhiyuan Gao
- Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jun Ji
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
| | - Lijuan Liu
- Department of Laboratory Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
| | - Erli Gu
- Department of Hepatology and Gastroenterology, Jing'an District Centre Hospital, Fudan University, P.R. China
| | - Ya Li
- Department of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China
| | - Mengmeng Wang
- Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R. China
| | - Chunfang Gao
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.,Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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Abstract
Hepatitis B virus (HBV) is a non-cytopathic, hepatotropic virus with the potential to cause a persistent infection, ultimately leading to cirrhosis and hepatocellular carcinoma. Over the past four decades, the basic principles of HBV gene expression and replication as well as the viral and host determinants governing infection outcome have been largely uncovered. Whereas HBV appears to induce little or no innate immune activation, the adaptive immune response mediates both viral clearance as well as liver disease. Here, we review our current knowledge on the immunobiology and pathogenesis of HBV infection, focusing in particular on the role of CD8+ T cells and on several recent breakthroughs that challenge current dogmas. For example, we now trust that HBV integration into the host genome often serves as a relevant source of hepatitis B surface antigen (HBsAg) expression during chronic infection, possibly triggering dysfunctional T cell responses and favouring detrimental immunopathology. Further, the unique haemodynamics and anatomy of the liver - and the changes they frequently endure during disease progression to liver fibrosis and cirrhosis - profoundly influence T cell priming, differentiation and function. We also discuss why therapeutic approaches that limit the intrahepatic inflammatory processes triggered by HBV-specific T cells might be surprisingly beneficial for patients with chronic infection.
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Zhang X, Wang Y, Yang G. Research progress in hepatitis B virus covalently closed circular DNA. Cancer Biol Med 2021; 19:j.issn.2095-3941.2021.0454. [PMID: 34931766 PMCID: PMC9088183 DOI: 10.20892/j.issn.2095-3941.2021.0454] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 11/16/2021] [Indexed: 11/28/2022] Open
Abstract
Hepatitis B virus (HBV) infections are a global public health issue. HBV covalently closed circular DNA (cccDNA), the template for the transcription of viral RNAs, is a key factor in the HBV replication cycle. Notably, many host factors involved in HBV cccDNA epigenetic modulation promote the development of hepatocellular carcinoma (HCC). The HBV cccDNA minichromosome is a clinical obstacle that cannot be efficiently eliminated. In this review, we provide an update on the advances in research on HBV cccDNA and further discuss factors affecting the modulation of HBV cccDNA. Hepatitis B virus X protein (HBx) contributes to HBV cccDNA transcription and the development of hepatocarcinogenesis through modulating host epigenetic regulatory factors, thus linking the cccDNA to hepatocarcinogenesis. The measurable serological biomarkers of continued transcription of cccDNA, the effects of anti-HBV drugs on cccDNA, and potential therapeutic strategies targeting cccDNA are discussed in detail. Thus, this review describes new insights into HBV cccDNA mechanisms and therapeutic strategies for cleaning cccDNA, which will benefit patients with liver diseases.
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Affiliation(s)
- Xiaodong Zhang
- Department of Gastrointestinal Cancer Biology, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Yufei Wang
- Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China
| | - Guang Yang
- Department of Gastrointestinal Cancer Biology, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
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Health care resources utilization and costs associated with different clinical stages of chronic hepatitis B in Egypt. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00162-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Introduction
Chronic hepatitis B (CHB) is associated with many serious clinical and social consequences. Despite Egypt being classified as a country of low endemicity, the infection is associated with a 15–25% risk of premature death from liver cancer or end-stage liver disease. The national committee of treatment and control of viral hepatitis has already offered a high-quality service for the diagnosis and treatment of CHB on a free basis. The current study aims to estimate the health care resources utilization and the annual direct medical cost associated with different clinical stages of CHB-related disease in Egypt.
Methodology
The data was retrieved through record review for three months in the General Administration of Hepatitis Viruses Control, Egypt. Then, the data was extrapolated to the population level by multiplying the prevalence in Egypt with a focus on the productive age groups (25–59 years).
Results
The cost and utilization of different health care resources increase with disease progression. The total annual direct medical costs due to CHB in Egypt is 21.3 L.E. Billion (4.7 Int$ billion/year) for the management of estimated 1,420,700 CHB patients. The direct medical costs among the productive age group (25–59 years) constitute more than half of the total cost (57%). The highest disease burden is encountered among (25–29 years) age group; 2.695 L.E. billion (0.59 Int$ billion/year). Despite liver transplantation phase being associated with the highest annual cost/patient, the number of patients in this stage is the lowest. Then, it only constitutes 0.04% of the disease direct medical cost in the country. The chronic hepatitis clinical stage constitutes 57.26% of the disease direct medical cost in Egypt’s working age group.
Conclusion
Strengthening the preventive and control measures is mandatory to alleviate the disease’s direct medical costs. Close monitoring of the chronic hepatitis stage is mandatory to prevent disease progression. Enhancement of vaccination efforts will lower the disease prevalence and its cost. The universal health insurance system which is gradually implemented in Egypt nowadays will be a cornerstone in relieving the economic stresses by allowing more access to high-quality health care services.
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Yang Y, Li G, Lu Z, Liu Y, Kong J, Liu J. Progression of Prothrombin Induced by Vitamin K Absence-II in Hepatocellular Carcinoma. Front Oncol 2021; 11:726213. [PMID: 34900676 PMCID: PMC8660097 DOI: 10.3389/fonc.2021.726213] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 10/11/2021] [Indexed: 12/14/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related death worldwide. Due to the lack of efficient tools for early detection, asymptomatic HCC patients are diagnosed at an advanced stage, leading to a poor prognosis. To improve survival, serum biomarker prothrombin induced by vitamin K absence-II (PIVKA-II) was under investigation. PIVKA-II is an abnormal protein produced in HCC. The coagulation function was insufficient due to the lack of Gla residues. Elevated PIVKA-II was associated with bad tumor behavior in terms of proliferation, metastasis, and invasion. Three major signaling pathways were proposed to clarify the mechanism. With the advantages including affordability, minimal invasiveness, convenience, and efficiency, PIVKA-II could improve HCC management consisting of four aspects. First, PIVKA-II was an effective and dynamic tool for improving HCC surveillance in high-risk population. Changes in the serum levels of PIVKA-II provided valuable molecular alteration information before imaging discovery. Second, PIVKA-II offered a complementary approach for HCC early detection. Compared to traditional diagnostic approaches, the combination of PIVKA-II and other biomarkers had better performance. Third, PIVKA-II was an indicator for the assessment of response to treatment in HCC. Preoperative assessment was for selecting personalized therapy, and postoperative measurement was for assessing treatment efficacy. Fourth, PIVKA-II was considered as a prognostic predictor for HCC. Patients with elevated PIVKA-II were more likely to develop microvascular invasion, metastasis, and recurrence.
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Affiliation(s)
- Yang Yang
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Guangbing Li
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Ziwen Lu
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yong Liu
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Junjie Kong
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Jun Liu
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Liver Transplantation and Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
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Datfar T, Doulberis M, Papaefthymiou A, Hines IN, Manzini G. Viral Hepatitis and Hepatocellular Carcinoma: State of the Art. Pathogens 2021; 10:pathogens10111366. [PMID: 34832522 PMCID: PMC8619105 DOI: 10.3390/pathogens10111366] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Revised: 09/26/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.
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Affiliation(s)
- Toofan Datfar
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
- Correspondence: ; Tel.: +41-76-4930834
| | - Michael Doulberis
- Department of Gastroenterology and Hepatology, Hospital of Aarau, 5001 Aarau, Switzerland;
| | | | - Ian N. Hines
- Department of Nutrition Science, East Carolina University, Greenville, NC 27858, USA;
| | - Giulia Manzini
- Department of General and Visceral Surgery, Hospital of Aarau, 5001 Aarau, Switzerland;
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GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients. Sci Rep 2021; 11:20014. [PMID: 34625583 PMCID: PMC8501054 DOI: 10.1038/s41598-021-99345-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 08/23/2021] [Indexed: 11/08/2022] Open
Abstract
Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p < 0.001), while the dominant CC was a protective factor (p = 0.004). Regarding miR-137 rs1625579, the mutant genotype TT was reported as a risk factor for CHBV (p < 0.001) and the normal GG genotype was a protective factor, p < 0.001. The serum GAS5 was significantly higher in the mutant TT genotype of GAS5 SNP as compared to the other genotypes (p = 0.007). Concerning miR-137 rs1625579, the mutant TT genotype was significantly associated with a lower serum expression level of miR-137 (p = 0.018). We revealed the dysregulated expression levels of GAS5 and miR-137 linked to their functioning SNPs were associated with CHBV risk and might act as potential therapeutic targets.
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Åström H, Ndegwa N, Hagström H. External validation of the Toronto hepatocellular carcinoma risk index in a Swedish population. JHEP Rep 2021; 3:100343. [PMID: 34611618 PMCID: PMC8476346 DOI: 10.1016/j.jhepr.2021.100343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/11/2021] [Accepted: 07/29/2021] [Indexed: 11/28/2022] Open
Abstract
Background & Aims The Toronto hepatocellular carcinoma (HCC) risk index (THRI) is a predictive model to determine the risk of HCC in patients with cirrhosis. This study aimed to externally validate the THRI in a Swedish setting to investigate whether it could identify patients not requiring HCC surveillance. Methods From 2004-2017, 2,491 patients with cirrhosis at the Karolinska University Hospital were evaluated. Patients were classified into low-, intermediate- and high-risk groups for future HCC according to the THRI. Harrell’s C-index, calibration-in-the-large, calibration slope and goodness-of-fit estimates were calculated to assess model discrimination and calibration. Cox proportional hazards regression was used to determine the risk of HCC. Results Most patients were male (n = 1,638, 66%). The most common etiologies of cirrhosis were steatohepatitis (n = 1,182, 48%) followed by viral hepatitis (n = 987, 40%). In all, 131 patients (5.3%) were designated as low risk for HCC. Harrell’s C-index was 0.69. Calibration-in-the-large (0.11), calibration slope (1.24, not different from 1, p = 0.66) and goodness-of-fit showed good model calibration. Patients in the high-risk group had a 7.1-fold (95% CI 2.9–17.2) higher risk of HCC and patients in the intermediate-risk group had a 2.5-fold (95% CI 1.0–6.3) higher risk compared to the low-risk group. Conclusions In a Swedish setting, the THRI could differentiate between low- and high-risk of HCC development. However, because the low-risk group was relatively small (5.3%), the clinical applicability of the THRI could be limited. Lay summary The Toronto hepatocellular carcinoma (HCC) risk index (THRI) is a novel prediction model used to stratify patients with cirrhosis based on future risk of HCC. In this study, the THRI was validated in an external cohort using the TRIPOD guidance. Few patients were identified as low-risk, and the THRI had a modest discriminative ability, limiting its clinical applicability.
The THRI is a simple and non-invasive method to estimate 5- and 10-year HCC risk. This was the largest validation of the THRI to date. The THRI had a modest discriminative ability and was well-calibrated. However, the THRI could only identify few patients at low risk of HCC, limiting its clinical use.
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Affiliation(s)
- Hanne Åström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Nelson Ndegwa
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Division of Surgery, Department of Clinical Science Intervention and Technology, Karolinska Institutet, and Oesophageal and Gastric Cancer Unit, Karolinska University Hospital, Stockholm, Sweden
| | - Hannes Hagström
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.,Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden.,Clinical Epidemiology Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
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Kwon J, Liu YV, Gao C, Bassal MA, Jones AI, Yang J, Chen Z, Li Y, Yang H, Chen L, Di Ruscio A, Tay Y, Chai L, Tenen DG. Pseudogene-mediated DNA demethylation leads to oncogene activation. SCIENCE ADVANCES 2021; 7:eabg1695. [PMID: 34597139 PMCID: PMC10938534 DOI: 10.1126/sciadv.abg1695] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 08/10/2021] [Indexed: 06/13/2023]
Abstract
Pseudogenes, noncoding homologs of protein-coding genes, once considered nonfunctional evolutionary relics, have recently been linked to patient prognoses and cancer subtypes. Despite this potential clinical importance, only a handful of >12,000 pseudogenes in humans have been characterized in cancers to date. Here, we describe a previously unrecognized role for pseudogenes as potent epigenetic regulators that can demethylate and activate oncogenes. We focused on SALL4, a known oncogene in hepatocellular carcinoma (HCC) with eight pseudogenes. Using a locus-specific demethylating technology, we identified the critical CpG region for SALL4 expression. We demonstrated that SALL4 pseudogene 5 hypomethylates this region through interaction with DNMT1, resulting in SALL4 up-regulation. Intriguingly, pseudogene 5 is significantly up-regulated in a hepatitis B virus model before SALL4 induction, and both are increased in patients with HBV-HCC. Our results suggest that pseudogene-mediated demethylation represents a novel mechanism of oncogene activation in cancer.
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Affiliation(s)
- Junsu Kwon
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
| | - Yanjing V. Liu
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
| | - Chong Gao
- Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
| | - Mahmoud A. Bassal
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
- Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115 USA
| | - Adrianna I. Jones
- Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115 USA
| | - Junyu Yang
- Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
| | - Zhiyuan Chen
- Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
| | - Ying Li
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
| | - Henry Yang
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
| | - Leilei Chen
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
| | - Annalisa Di Ruscio
- Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02115, USA
- Department of Translational Medicine, University of Eastern Piedmont, Novara 28100, Italy
- Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02214, USA
| | - Yvonne Tay
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore
| | - Li Chai
- Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA
| | - Daniel G. Tenen
- Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
- Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115 USA
- Harvard Medical School Initiative for RNA Medicine, Harvard Medical School, Boston, MA 02115, USA
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Ecological Study of Variability in the Relationship between Liver Cancer Mortality and Racial Residential Segregation. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18189732. [PMID: 34574655 PMCID: PMC8465489 DOI: 10.3390/ijerph18189732] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Revised: 09/03/2021] [Accepted: 09/07/2021] [Indexed: 01/16/2023]
Abstract
Racial segregation has been identified as a predictor for the burden of cancer in several different metropolitan areas across the United States. This ecological study tested relationships between racial segregation and liver cancer mortality across several different metropolitan statistical areas in Wisconsin. Tract-level liver cancer mortality rates were calculated using cases from 2003-2012. Hotspot analysis was conducted and segregation scores in high, low, and baseline mortality tracts were compared using ANOVA. Spatial regression analysis was done, controlling for socioeconomic advantage and rurality. Black isolation scores were significantly higher in high-mortality tracts compared to baseline and low-mortality tracts, but stratification by metropolitan areas found this relationship was driven by two of the five metropolitan areas. Hispanic isolation was predictive for higher mortality in regression analysis, but this effect was not found across all metropolitan areas. This study showed associations between liver cancer mortality and racial segregation but also found that this relationship was not generalizable to all metropolitan areas in the study area.
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Xiong J, Luo J, Bian J, Wu J. Overall diagnostic accuracy of different MR imaging sequences for detection of dysplastic nodules: a systematic review and meta-analysis. Eur Radiol 2021; 32:1285-1296. [PMID: 34357448 DOI: 10.1007/s00330-021-08022-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Revised: 03/24/2021] [Accepted: 04/27/2021] [Indexed: 01/04/2023]
Abstract
OBJECTIVE To assess the overall diagnostic accuracy of different MR imaging sequences in the detection of the dysplastic nodule (DN). METHODS PubMed, Cochrane Library, and Web of Science were systematically searched. Study selection and data extraction were conducted by two authors independently. Quality assessment of diagnostic accuracy studies (QUADAS) 2 in RevMan software was used to score the included studies and assess their methodological quality. A random-effects model was used for statistical pooling by Meta-Disc. Subgroup analysis and sensitivity analysis were used to explore potential sources of heterogeneity. RESULTS Fourteen studies (335 DN lesions in total) were included in our meta-analysis. The area under the curve (AUC) of summary receiver operating characteristic (SROC) of T2WI was 0.87. Pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of DWI were 0.81 (95%CI, 0.73-0.87), 0.90 (95%CI, 0.86-0.93), 7.04 (95%CI, 4.49-11.04), and 0.24 (95%CI, 0.17-0.33) respectively. In the arterial phase, pooled sensitivity, specificity, PLR, and NLR were 0.89 (0.84-0.93), 0.75 (0.72-0.79), 3.72 (2.51-5.51), and 0.17 (0.12-0.25), respectively. Pooled sensitivity, specificity, PLR, and NLR of the delayed phase were 0.78 (0.72-0.83), 0.60 (0.55-0.65), 2.19 (1.55-3.10), and 0.36 (0.23-0.55) separately. Pooled sensitivity, specificity, PLR, and NLR of the hepatobiliary phase were 0.77 (0.71-0.82), 0.92 (0.89-0.94), 8.74 (5.91-12.92), and 0.24 (0.14-0.41) respectively. Pooled sensitivity, specificity, and PLR were higher on DWI and hepatobiliary phase in diagnosing LGDN than HGDN. CONCLUSION MR sequences, particularly DWI, arterial phase, and hepatobiliary phase imaging demonstrate high diagnostic accuracy for DN. KEY POINTS • MRI has dramatically improved the detection and accurate diagnosis of DNs and their differentiation from hepatocellular carcinoma. • Overall diagnostic accuracy of different MRI sequences in the detection of DN has not been studied before. • Our meta-analysis demonstrates that MRI achieves a high diagnostic value for DN, especially when using DWI, arterial phase imaging, and hepatobiliary phase imaging.
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Affiliation(s)
- Jingtong Xiong
- Department of Radiology, The Second Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning Province, China
| | - Jiawen Luo
- Department of Radiology, The Second Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning Province, China.
| | - Jie Bian
- Department of Radiology, The Second Hospital of Dalian Medical University, No. 467, Zhongshan Road, Shahekou District, Dalian, 116023, Liaoning Province, China
| | - Jianlin Wu
- Department of Radiology, Affiliated Zhongshan Hospital of Dalian University, No. 6, Jiefang Road, Zhongshan District, Dalian, 116001, Liaoning Province, China
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Role of Ultrasound for Chronic Liver Disease and Hepatocellular Carcinoma Surveillance. Magn Reson Imaging Clin N Am 2021; 29:279-290. [PMID: 34243917 DOI: 10.1016/j.mric.2021.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Ultrasound plays a vital role in the evaluation of patients with chronic liver disease and in hepatocellular carcinoma (HCC) surveillance in populations at risk for developing HCC. Semiannual ultrasound for HCC surveillance is universally recommended by all liver societies around the world. Advanced ultrasound techniques, such as elastography and contrast-enhanced ultrasound, offer additional benefits in imaging evaluation of chronic liver disease. Major benefits of ultrasound include its high safety profile and relatively low cost.
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Huang DQ, Hoang JK, Leong J, Riveiro-Barciela M, Maeda M, Yang JD, Accarino EV, Thin K, Trinh L, Cheung RC, Roberts LR, Buti M, Schwartz M, Nguyen MH. Differential characteristics and outcomes of Asian and non-Asian patients with HBV-related hepatocellular carcinoma. Liver Int 2021; 41:1922-1932. [PMID: 33713386 DOI: 10.1111/liv.14877] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/16/2021] [Accepted: 03/07/2021] [Indexed: 12/25/2022]
Abstract
BACKGROUND & AIMS The epidemiology of hepatitis B virus (HBV) infection differs between Asians and non-Asians, but little is known regarding the effect of ethnicity on outcomes of HBV-related hepatocellular carcinoma (HCC). We aim to characterize the presentation and survival outcomes in Asian and non-Asian patients with HBV-related HCC. METHODS We analyzed the baseline characteristics and long-term survival of 613 Asian and 410 non-Asian patients with HBV-related HCC from three US and one Spanish centre. RESULTS Overall, non-Asian patients were more likely to have HIV or hepatitis C co-infection, cirrhosis, decompensated liver disease and advanced BCLC stage (all P ≤ .04). Compared with Asians, non-Asians were more likely to be listed for transplantation (P < .0001) and undergo HCC treatment with curative intent (P = .003). Propensity-score matching on HCC diagnosis year, gender and age was performed to balance the two groups for survival analysis and yielded 370 pairs of patients. There was no significant difference in survival overall (P = .43) and among patients with cirrhosis (P = .57). Among patients without cirrhosis, non-Asians had poorer 5-year survival compared with Asians (37.6% vs 53.7%, P = .01), and was associated with poorer survival after adjusting for age, gender, diabetes, alcohol, co-infections, diagnosis date, antiviral therapy, BCLC stage and HCC treatment (adjusted HR 2.01 [95% CI 1.07-3.74], P = .03). CONCLUSION Among HBV-related HCC patients, non-Asians presented with more advanced BCLC stage compared to Asians. Non-Asian ethnicity was independently associated with twice the risk of mortality among patients without cirrhosis, but not among those with cirrhosis. Additional studies are needed to clarify this disparity.
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Affiliation(s)
- Daniel Q Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.,Division of Gastroenterology and Hepatology, National University Health System, Singapore
| | - Joseph K Hoang
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Jennifer Leong
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.,CIBERehd, Instituto Carlos III, Madrid, Spain
| | - Mayumi Maeda
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Ju Dong Yang
- Division of Digestive and Liver Diseases, Department of Medicine, Cedars Sinai Medical Center, Los Angeles, USA
| | - Elena Vargas Accarino
- Liver Unit, Internal Medicine Department, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.,CIBERehd, Instituto Carlos III, Madrid, Spain
| | - Khin Thin
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Lindsey Trinh
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Ramsey C Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA
| | - Lewis R Roberts
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Maria Buti
- Liver Unit, Internal Medicine Department, Hospital Universitari Valle d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain.,CIBERehd, Instituto Carlos III, Madrid, Spain
| | - Myron Schwartz
- Recanati-Miller Transplantation Institute, Mount Sinai School of Medicine, New York, NY, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA.,Department of Epidemiology and Population Health, Stanford University, Palo Alto, CA, USA
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De Crignis E, Hossain T, Romal S, Carofiglio F, Moulos P, Khalid MM, Rao S, Bazrafshan A, Verstegen MM, Pourfarzad F, Koutsothanassis C, Gehart H, Kan TW, Palstra RJ, Boucher C, IJzermans JN, Huch M, Boj SF, Vries R, Clevers H, van der Laan LJ, Hatzis P, Mahmoudi T. Application of human liver organoids as a patient-derived primary model for HBV infection and related hepatocellular carcinoma. eLife 2021; 10:e60747. [PMID: 34328417 PMCID: PMC8384419 DOI: 10.7554/elife.60747] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 07/29/2021] [Indexed: 02/06/2023] Open
Abstract
The molecular events that drive hepatitis B virus (HBV)-mediated transformation and tumorigenesis have remained largely unclear, due to the absence of a relevant primary model system. Here we propose the use of human liver organoids as a platform for modeling HBV infection and related tumorigenesis. We first describe a primary ex vivo HBV-infection model derived from healthy donor liver organoids after challenge with recombinant virus or HBV-infected patient serum. HBV-infected organoids produced covalently closed circular DNA (cccDNA) and HBV early antigen (HBeAg), expressed intracellular HBV RNA and proteins, and produced infectious HBV. This ex vivo HBV-infected primary differentiated hepatocyte organoid platform was amenable to drug screening for both anti-HBV activity and drug-induced toxicity. We also studied HBV replication in transgenically modified organoids; liver organoids exogenously overexpressing the HBV receptor sodium taurocholate co-transporting polypeptide (NTCP) after lentiviral transduction were not more susceptible to HBV, suggesting the necessity for additional host factors for efficient infection. We also generated transgenic organoids harboring integrated HBV, representing a long-term culture system also suitable for viral production and the study of HBV transcription. Finally, we generated HBV-infected patient-derived liver organoids from non-tumor cirrhotic tissue of explants from liver transplant patients. Interestingly, transcriptomic analysis of patient-derived liver organoids indicated the presence of an aberrant early cancer gene signature, which clustered with the hepatocellular carcinoma (HCC) cohort on The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset and away from healthy liver tissue, and may provide invaluable novel biomarkers for the development of HCC and surveillance in HBV-infected patients.
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Affiliation(s)
- Elisa De Crignis
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Tanvir Hossain
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Shahla Romal
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Fabrizia Carofiglio
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Panagiotis Moulos
- Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece
| | - Mir Mubashir Khalid
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Shringar Rao
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Ameneh Bazrafshan
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Monique Ma Verstegen
- Department of Surgery, Erasmus University Medical Center, Rotterdam, Netherlands
| | | | | | - Helmuth Gehart
- Hubrecht Institute-KNAW, University Medical Centre Utrecht, Utrecht, Netherlands
| | - Tsung Wai Kan
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Robert-Jan Palstra
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Charles Boucher
- Department of Viroscience, Erasmus Medical Centre, Rotterdam, Netherlands
| | - Jan Nm IJzermans
- Department of Surgery, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Meritxell Huch
- Max Plank Institute of Molecular Cell Biology and Genetics, Dresden, Germany
| | - Sylvia F Boj
- Foundation Hubrecht Organoid Technology (HUB), Utrecht, Netherlands
| | - Robert Vries
- Foundation Hubrecht Organoid Technology (HUB), Utrecht, Netherlands
| | - Hans Clevers
- Hubrecht Institute-KNAW, University Medical Centre Utrecht, Utrecht, Netherlands
| | - Luc Jw van der Laan
- Department of Surgery, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Pantelis Hatzis
- Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece
| | - Tokameh Mahmoudi
- Department of Biochemistry, Erasmus University Medical Center, Rotterdam, Netherlands
- Department of Urology, Erasmus University Medical Center, Rotterdam, Netherlands
- Department of Pathology, Erasmus University Medical Center, Rotterdam, Netherlands
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Mallick S, Mallik M, Chatterjee RN, Chowdhury PS. Role of Cell Block Technology as an Adjunct to Fine Needle Aspiration in Evaluating as well as Differentiating Liver Lesions. IRANIAN JOURNAL OF PATHOLOGY 2021; 16:392-402. [PMID: 34567188 PMCID: PMC8463751 DOI: 10.30699/ijp.20201.522897.2569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Accepted: 06/05/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND & OBJECTIVE Liver lesions are difficult to diagnose and to differentiate primary from metastatic carcinoma, while Biopsy has its limitations. Cell block technology is easily accessible with high diagnostic accuracy. Our aim is 1) To find the role of cell block technology as an alternative to biopsy in identifying liver lesions; 2) To find the efficacy of cell block along with immunohistochemistry (IHC) and ancillary studies in differentiating primary from metastatic lesions; 3) To identify the site of origin of metastatic lesions. This is a descriptive study undertaken in two tertiary care hospitals over a period of three years. METHODS Retrospective review of adequate samples from fine needle aspirations from liver lesions under radiological coverage, converted into cell block was done. IHC was applied as needed. Usefulness of cell block preparation was evaluated, and the final diagnosis correlated with the biopsy results. RESULTS Analysis of 323 cases found sensitivity of 98.75% and positive predictive value of 99% for all lesions. Sensitivity for metastatic carcinomas was slightly more than hepatocellular carcinoma. However, accuracy of cell block results for individual metastatic lesions and site of origin was less. IHC and morphological pattern worked as an important adjunct in the final diagnosis. On the other hand, contribution of viral markers as a supplement in the final work up was ambiguous. CONCLUSION High precision of validity results of cell block technology in comparison with biopsy highlights its pivotal role in conjunction with supportive tests for diagnosing and differentiating liver lesions as well as identifying primary sites in liver metastasis.
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Affiliation(s)
- Sujata Mallick
- Department of Pathology, KPC Medical College, West Bengal University of health Sciences, Kolkata, India
| | - Mahasweta Mallik
- Department of Pathology, Nalanda Medical College, Assistant professor, Aryabhatta Knowledge University, Patna, India
| | | | - Puskar Shyam Chowdhury
- Department of Pathology, KPC Medical College, West Bengal University of health Sciences, Kolkata, India
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Jiang JJ, Shiels MS, O'Brien TR. Death certificates compared to SEER-Medicare data for surveillance of liver cancer mortality due to hepatitis B or hepatitis C infection. J Viral Hepat 2021; 28:934-941. [PMID: 33720473 DOI: 10.1111/jvh.13498] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 02/26/2021] [Indexed: 12/09/2022]
Abstract
Hepatocellular carcinoma (HCC) is often caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. To investigate the completeness of death certificates for recording viral hepatitis in HCC death, we compared the proportion of HCC deaths with hepatitis virus infection reported on death certificates to that reported as claims in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database among individuals ≥66 years of age. For 2001-2015, we tabulated proportions of HCC deaths with HBV or HCV infection in each database overall, and by demographic factors. To correct for under ascertainment of viral hepatitis-associated HCC on death certificates, we multiplied by the reciprocal ratio of death certificates to SEER-Medicare. Among HCC decedents, HBV infection was reported on 3.6% of death certificates and 17.2% of Medicare claims. For HCV, corresponding proportions were 14.9% and 26.9%. The ratio of HBV-attributable HCC deaths in death certificates to SEER-Medicare remained ~0.21 over time. The ratio of HCV-attributable HCC deaths decreased 22.1% per year, from 0.70 in 2001 to 0.37 in 2003, and increased 4.1% per year, from 0.47 in 2004 to 0.66 in 2015. Following correction, the 2015 mortality rate from death certificate data increased from 0.2 to 0.9 per 100,000 for HBV-attributable HCC and from 2.3 to 3.5 per 100,000 for HCV-attributable HCC. In conclusion, among older Americans dying from HCC, death certificates captured 21% of HBV and 55% of HCV infections compared to Medicare claims. Our results suggest that death certificates provide incomplete data for viral hepatitis-associated HCC surveillance.
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Affiliation(s)
- Joy J Jiang
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Meredith S Shiels
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
| | - Thomas R O'Brien
- Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland, USA
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The Combination of Shear Wave Elastography and Platelet Counts Can Effectively Predict High-Risk Varices in Patients with Hepatitis B-Related Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6635963. [PMID: 33928154 PMCID: PMC8051526 DOI: 10.1155/2021/6635963] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 03/15/2021] [Accepted: 03/19/2021] [Indexed: 12/13/2022]
Abstract
Background Baveno VI criteria, based on liver stiffness (LS) measured by transient elastography and platelet counts (PLT), have been proposed to avoid unnecessary endoscopy screening for high-risk varices (HRVs). However, the cut-off value of LS measured by 2D-SWE and PLT to predict HRVs in compensated hepatitis B-related cirrhotic patients remains unknown. Aims To prospectively analyze the cut-off of the combination of LS measured by 2D-SWE and PLT in predicting HRVs and the influence of antiviral therapies in its efficacy. Methods Serum parameters, LS, and endoscopy results were obtained from 160 compensated hepatitis B-related cirrhotic patients. The accuracy of the combined algorithm was assessed in the whole cohort and subgroups with or without consecutive antiviral therapies in the past 6 months. Results In the whole cohort, the optimal cut-off value of LS for HRVs was 14.5 kPa. Patients with a LS value < 14.5 kPa with a PLT value > 110 × 109/L can be excluded from HRVs (NPV = 0.99, endoscopy saved rates = 0.68). Conversely, a LS value of ≥14.5 kPa and a PLT value of ≤110 × 109/L indicated HRVs, with accurate rates of 82.35%, and 10.63% of patients can avoid additional endoscopy screening. Moreover, antiviral therapy had no significant effect on the accuracy and rates saved from further endoscopy screening, when comparing patients with or without antiviral therapies (all p values > 0.05). Conclusions The combination of LS (14.5 kPa) measured by 2D-SWE and PLT (110 × 109/L) can predict HRVs accurately in compensated hepatitis B-related cirrhotic patients without significant interference of antiviral therapy histories.
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Bubie A, Zoulim F, Testoni B, Miles B, Posner M, Villanueva A, Losic B. Landscape of oncoviral genotype and co-infection via human papilloma and hepatitis B viral tumor in situ profiling. iScience 2021; 24:102368. [PMID: 33889830 PMCID: PMC8050859 DOI: 10.1016/j.isci.2021.102368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/07/2021] [Accepted: 03/24/2021] [Indexed: 02/06/2023] Open
Abstract
The role of oncoviral genotype and co-infection driving oncogenesis remains unclear. We have developed a scalable, high throughput tool for sensitive and precise oncoviral genotype deconvolution. Using tumor RNA sequencing data, we applied it to 537 virally infected liver, cervical, and head and neck tumors, providing the first comprehensive integrative landscape of tumor-viral gene expression, viral antigen immunogenicity, patient survival, and mutational profiling organized by tumor oncoviral genotype. We find that HBV and HPV genotype and co-infection serve as significant predictors of patient survival and immune activation. Finally, we demonstrate that HPV genotype is more associated with viral oncogene expression than cancer type, implying that expression may be similar across episomal and stochastic integration-based infections. While oncoviral infections are known risk factors for oncogenesis, viral genotype and co-infection are shown to strongly associate with disease progression, patient survival, mutational signatures, and putative tumor neoantigen immunogenicity, facilitating novel clinical associations with infections.
ViralMine parses oncoviral genotypes and co-infection from in situ tumor data Oncoviral genotyping of TCGA CESC, HNSC, and LIHC cohorts Tumor fitness, immunogenicity, and mutational signatures associate with oncoviral genotype
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Affiliation(s)
- Adrian Bubie
- Departments of Genetics and Genomic Sciences, New York, NY 10029, USA
| | - Fabien Zoulim
- INSERM, U1052, Cancer Research Center of Lyon (CRCL), Lyon, 69008, France
| | - Barbara Testoni
- INSERM, U1052, Cancer Research Center of Lyon (CRCL), Lyon, 69008, France
| | - Brett Miles
- Department of Otolaryngology Head and Neck Surgery, New York, NY 10029, USA
| | - Marshall Posner
- Division of Hematology Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Augusto Villanueva
- Departments of Genetics and Genomic Sciences, New York, NY 10029, USA.,Division of Liver Diseases, Division of Hematology/Oncology, Department of Medicine, Graduate School of Biomedical Sciences, Tisch Cancer Institute, Diabetes, Obesity, and Metabolism Institute, New York, NY 10029, USA
| | - Bojan Losic
- Departments of Genetics and Genomic Sciences, New York, NY 10029, USA.,Division of Liver Diseases, Division of Hematology/Oncology, Department of Medicine, Graduate School of Biomedical Sciences, Tisch Cancer Institute, Diabetes, Obesity, and Metabolism Institute, New York, NY 10029, USA
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Genome Sequences of 26 White Sucker Hepatitis B Virus Isolates from White Sucker, Catostomus commersonii, Inhabiting Transboundary Waters from Alberta, Canada, to the Great Lakes, USA. Microbiol Resour Announc 2021; 10:10/11/e01425-20. [PMID: 33737368 PMCID: PMC7975886 DOI: 10.1128/mra.01425-20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
We report 26 genome sequences of the white sucker hepatitis B virus (WSHBV) from the white sucker, Catostomus commersonii The genome length ranged from 3,541 to 3,543 bp, and nucleotide identity was 96.7% or greater across genomes. This work suggests a geographical range of this virus that minimally extends from the Athabasca River, Alberta, Canada, to the Great Lakes, USA.
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Talla C, Uchenna Itanyi I, Tsuyuki K, Stadnick N, Grace Ogidi A, Oluwaseun Olakunde B, Patel D, Okpanachi Oko J, Aarons G, Ariel Onoka C, Edozie Ezeanolue E. Hepatitis B infection and risk factors among pregnant women and their male partners in the Baby Shower Programme in Nigeria: a cross-sectional study. Trop Med Int Health 2021; 26:316-326. [PMID: 33247862 PMCID: PMC7925376 DOI: 10.1111/tmi.13531] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To determine the population prevalence and determinants of hepatitis B (Hep B) status, and status discordance, among pregnant women and their male partners in Nigeria. METHODS Cross-sectional study assessing the seroprevalence of Hep B virus in a cohort of 16 920 pregnant women and their male partners in northcentral Nigeria. Rapid HBsAg antibody test was used for Hep B diagnosis. Demographic, socio-economic and behavioural information was collected through interviewer-administered questionnaires and evaluated as determinants of Hep B status and couple status discordance using logistic regression. RESULTS Of 16 920 participants who had a Hep B test result, 6750 couples and 1316 discordant couples were identified. The prevalence of Hep B among all participants was 10.9%, with lower prevalence among pregnant women (10.2%) than their male partners (11.9%), P < 0.001. The prevalence of Hep B sero-discordance among couples was 19.5% (1316/6750). Younger age, prior Hep B testing and a prior positive Hep B test increased the odds of Hep B infection while being a woman decreased the odds of Hep B among all participants, and among couples. Furthermore, polygamy (adjusted odds ratio [AOR]: 1.49, 95% confidence interval [CI]: 1.19-1.87), prior Hep B testing (AOR: 2.38, 95% CI: 1.14-4.97) and a prior positive Hep B test result were significant determinants of status discordance among the participating couples. CONCLUSION The prevalence of Hep B among pregnant women and their male partners in northcentral Nigeria is high. A large-scale intervention is required to reduce Hep B prevalence in this setting.
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Affiliation(s)
- Carol Talla
- Caritas Nigeria, Abuja, Federal Capital Territory, Nigeria
| | - Ijeoma Uchenna Itanyi
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Department of Community Medicine, University of Nigeria Nsukka, Enugu, Nigeria
| | - Kiyomi Tsuyuki
- Division of Infectious Diseases & Global Public Health, Department of Medicine, University of California, San Diego, USA
| | - Nicole Stadnick
- Department of Psychiatry, University of California, San Diego, USA
- UC San Diego Dissemination and Implementation Science Center, USA
| | - Amaka Grace Ogidi
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
| | - Babayemi Oluwaseun Olakunde
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- National Agency for the Control of AIDS, Abuja, Nigeria
| | | | | | - Gregory Aarons
- Department of Psychiatry, University of California, San Diego, USA
- UC San Diego Dissemination and Implementation Science Center, USA
| | - Chima Ariel Onoka
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Department of Community Medicine, University of Nigeria Nsukka, Enugu, Nigeria
| | - Echezona Edozie Ezeanolue
- Center for Translation and Implementation Research, University of Nigeria Nsukka, Enugu, Nigeria
- Healthy Sunrise Foundation, USA
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Wang XH, Liu QB, Xiang CL, Mao XH, Yang B, Li Q, Zhou QF, Li SQ, Zhou ZG, Chen MS. Multi-institutional validation of novel models for predicting the prognosis of patients with huge hepatocellular carcinoma. Int J Cancer 2021; 149:127-138. [PMID: 33586134 DOI: 10.1002/ijc.33516] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 01/25/2021] [Accepted: 01/29/2021] [Indexed: 01/06/2023]
Abstract
The population of patients with huge hepatocellular carcinoma (H-HCC diameter > 10.0 cm) is an odd group that is not well adjudicated in the current staging systems, whose prognosis after curative resection varies. We aimed to develop novel models to predict the long-term outcomes of patients with H-HCC without portal vein tumor thrombus after hepatectomy. There were 1076 H-HCC patients enrolled who underwent curative liver resection in five institutions in China. In total, 670 patients were recruited from our center and randomly divided into the training cohort (n = 502) and internal validation (n = 168) cohorts. Additionally, 406 patients selected from other four centers as the external validation cohort. Novel models were constructed based on independent preoperative and postoperative predictors of postsurgical recurrence (PSR) and postsurgical mortality (PSM) determined in multivariable cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell's concordance index (C index) and calibration curve and compared with five conventional HCC staging systems. PSR model and PSM model were constructed based on tumor number, microscopic vascular invasion, tumor differentiation, preoperative alpha-fetoprotein level, albumin-bilirubin grade, liver segment invasion, neutrophil-to-lymphocyte ratio or platelet-to-neutrophil ratio, and surgical margin or intraoperative blood transfusion. The C-indexes were 0.84 (95% CI, 0.78-0.90) and 0.85 (95% CI, 0.78-0.91) for the PSR and PSM models, respectively, which were substantially higher than those of the five conventional HCC staging systems (0.63-0.75 for PSR; 0.66-0.77 for PSM). The two novel models achieved more accurate prognostic predictions of PSR and PSM for H-HCC patients after curative liver resection.
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Affiliation(s)
- Xiao-Hui Wang
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Qing-Bo Liu
- Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan, Guangdong Province, China
| | - Cai-Ling Xiang
- Department of General Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, China
| | - Xian-Hai Mao
- Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, China
| | - Bing Yang
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Qiang Li
- Department of General Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, China
| | - Qun-Fang Zhou
- Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, China
| | - Shao-Qiang Li
- Department of Liver Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
| | - Zhong-Guo Zhou
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Min-Shan Chen
- Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.,Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
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Genera M, Quioc-Salomon B, Nourisson A, Colcombet-Cazenave B, Haouz A, Mechaly A, Matondo M, Duchateau M, König A, Windisch MP, Neuveut C, Wolff N, Caillet-Saguy C. Molecular basis of the interaction of the human tyrosine phosphatase PTPN3 with the hepatitis B virus core protein. Sci Rep 2021; 11:944. [PMID: 33441627 PMCID: PMC7806630 DOI: 10.1038/s41598-020-79580-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 12/10/2020] [Indexed: 12/13/2022] Open
Abstract
Interactions between the hepatitis B virus core protein (HBc) and host cell proteins are poorly understood, although they may be essential for the propagation of the virus and its pathogenicity. HBc has a C-terminal PDZ (PSD-95, Dlg1, ZO-1)-binding motif (PBM) that is responsible for interactions with host PDZ domain-containing proteins. In this work, we focused on the human protein tyrosine phosphatase non-receptor type 3 (PTPN3) and its interaction with HBc. We solved the crystal structure of the PDZ domain of PTPN3 in complex with the PBM of HBc, revealing a network of interactions specific to class I PDZ domains despite the presence of a C-terminal cysteine in this atypical PBM. We further showed that PTPN3 binds the HBc protein within capsids or as a homodimer. We demonstrate that overexpression of PTPN3 significantly affects HBV infection in HepG2 NTCP cells. Finally, we performed proteomics studies on both sides by pull-down assays and screening of a human PDZ domain library. We identified a pool of human PBM-containing proteins that might interact with PTPN3 in cells and that could be in competition with the HBc PBM during infection, and we also identified potential cellular partners of HBc through PDZ-PBM interactions. This study opens up many avenues of future investigations into the pathophysiology of HBV.
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Affiliation(s)
- Mariano Genera
- Channel-Receptors Unit, UMR 3571, CNRS, Institut Pasteur, 75015, Paris, France.,Complexité du Vivant, Sorbonne Université, 75005, Paris, France
| | - Barbara Quioc-Salomon
- UMR 3569, CNRS, 75015, Paris, France.,Department of Virology, Institut Pasteur, Paris, France.,Université Paris Diderot, Sorbonne Paris Cité, Paris, France
| | - Antonin Nourisson
- Channel-Receptors Unit, UMR 3571, CNRS, Institut Pasteur, 75015, Paris, France
| | - Baptiste Colcombet-Cazenave
- Channel-Receptors Unit, UMR 3571, CNRS, Institut Pasteur, 75015, Paris, France.,Complexité du Vivant, Sorbonne Université, 75005, Paris, France
| | - Ahmed Haouz
- Crystallography Platform-C2RT, Department of Structural Biology and Chemistry, CNRS, UMR-3528, Institut Pasteur, 75015, Paris, France
| | - Ariel Mechaly
- Crystallography Platform-C2RT, Department of Structural Biology and Chemistry, CNRS, UMR-3528, Institut Pasteur, 75015, Paris, France
| | - Mariette Matondo
- Proteomics Platform, Mass Spectrometry for Biology Utechs (MSBio), USR 2000, CNRS, Institut Pasteur, 75724, Paris, France
| | - Magalie Duchateau
- Proteomics Platform, Mass Spectrometry for Biology Utechs (MSBio), USR 2000, CNRS, Institut Pasteur, 75724, Paris, France
| | - Alexander König
- Applied Molecular Virology Laboratory, Institut Pasteur Korea, 696 Sampyung-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea
| | - Marc P Windisch
- Applied Molecular Virology Laboratory, Institut Pasteur Korea, 696 Sampyung-dong, Bundang-gu, Seongnam-si, Gyeonggi-do, South Korea
| | - Christine Neuveut
- UMR 3569, CNRS, 75015, Paris, France.,Department of Virology, Institut Pasteur, Paris, France.,Institute of Human Genetics, 141 rue de la Cardonille, 34090, Montpellier, France
| | - Nicolas Wolff
- Channel-Receptors Unit, UMR 3571, CNRS, Institut Pasteur, 75015, Paris, France
| | - Célia Caillet-Saguy
- Channel-Receptors Unit, UMR 3571, CNRS, Institut Pasteur, 75015, Paris, France.
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