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Gvinjilia L, Baliashvili D, Shadaker S, Averhoff F, Kandelaki L, Kereselidze M, Tsertsvadze T, Chkhartishvili N, Butsashvili M, Metreveli D, Gamkrelidze A, Armstrong PA. Impact of Hepatitis C Virus Infection and Treatment on Mortality in the Country of Georgia, 2015-2020. Clin Infect Dis 2023; 77:405-413. [PMID: 37099136 PMCID: PMC10527899 DOI: 10.1093/cid/ciad182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/17/2023] [Accepted: 03/24/2023] [Indexed: 04/27/2023] Open
Abstract
BACKGROUND Mortality related to hepatitis C virus (HCV) infection is a key indicator for elimination. We assessed the impact of HCV infection and treatment on mortality in the country of Georgia during 2015-2020. METHODS We conducted a population-based cohort study using data from Georgia's national HCV Elimination Program and death registry. We calculated all-cause mortality rates in 6 cohorts: (1) Negative for anti-HCV; (2) anti-HCV positive, unknown viremia status; (3) current HCV infection and untreated; (4) discontinued treatment; (5) completed treatment, no sustained virologic response (SVR) assessment; (6) completed treatment and achieved SVR. Cox proportional hazards models were used to calculate adjusted hazards ratios and confidence intervals. We calculated the cause-specific mortality rates attributable to liver-related causes. RESULTS After a median follow-up of 743 days, 100 371 (5.7%) of 1 764 324 study participants died. The highest mortality rate was observed among HCV infected patients who discontinued treatment (10.62 deaths per 100 PY, 95% confidence interval [CI]: 9.65, 11.68), and untreated group (10.33 deaths per 100 PY, 95% CI: 9.96, 10.71). In adjusted Cox proportional hazards model, the untreated group had almost 6-times higher hazard of death compared to treated groups with or without documented SVR (adjusted hazard ratio [aHR] = 5.56, 95% CI: 4.89, 6.31). Those who achieved SVR had consistently lower liver-related mortality compared to cohorts with current or past exposure to HCV. CONCLUSIONS This large population-based cohort study demonstrated the marked beneficial association between hepatitis C treatment and mortality. The high mortality rates observed among HCV infected and untreated persons highlights the need to prioritize linkage to care and treatment to achieve elimination goals.
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Affiliation(s)
- Lia Gvinjilia
- Eastern Europe and Central Asia Regional Office, Centers for Disease Control and Prevention, Tbilisi, Georgia
| | | | - Shaun Shadaker
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Francisco Averhoff
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Levan Kandelaki
- Department of Medical Statistics, National Center for Disease Control and Public Health, Tbilisi, Georgia
| | - Maia Kereselidze
- Department of Medical Statistics, National Center for Disease Control and Public Health, Tbilisi, Georgia
| | - Tengiz Tsertsvadze
- Clinic "Hepa," Tbilisi, Georgia
- Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia
| | | | | | | | - Amiran Gamkrelidze
- Department of Medical Statistics, National Center for Disease Control and Public Health, Tbilisi, Georgia
| | - Paige A Armstrong
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
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2
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Baliashvili D, Blumberg HM, Gandhi NR, Averhoff F, Benkeser D, Shadaker S, Gvinjilia L, Turdziladze A, Tukvadze N, Chincharauli M, Butsashvili M, Sharvadze L, Tsertsvadze T, Zarkua J, Kempker RR. Hepatitis C care cascade among patients with and without tuberculosis: Nationwide observational cohort study in the country of Georgia, 2015-2020. PLoS Med 2023; 20:e1004121. [PMID: 37141386 PMCID: PMC10194957 DOI: 10.1371/journal.pmed.1004121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 05/18/2023] [Accepted: 04/13/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND The Eastern European country of Georgia initiated a nationwide hepatitis C virus (HCV) elimination program in 2015 to address a high burden of infection. Screening for HCV infection through antibody testing was integrated into multiple existing programs, including the National Tuberculosis Program (NTP). We sought to compare the hepatitis C care cascade among patients with and without tuberculosis (TB) diagnosis in Georgia between 2015 and 2019 and to identify factors associated with loss to follow-up (LTFU) in hepatitis C care among patients with TB. METHODS AND FINDINGS Using national ID numbers, we merged databases of the HCV elimination program, NTP, and national death registry from January 1, 2015 to September 30, 2020. The study population included 11,985 adults (aged ≥18 years) diagnosed with active TB from January 1, 2015 through December 31, 2019, and 1,849,820 adults tested for HCV antibodies between January 1, 2015 and September 30, 2020, who were not diagnosed with TB during that time. We estimated the proportion of patients with and without TB who were LTFU at each step of the HCV care cascade and explored temporal changes. Among 11,985 patients with active TB, 9,065 (76%) patients without prior hepatitis C treatment were tested for HCV antibodies, of which 1,665 (18%) had a positive result; LTFU from hepatitis C care was common, with 316 of 1,557 (20%) patients with a positive antibody test not undergoing viremia testing and 443 of 1,025 (43%) patients with viremia not starting treatment for hepatitis C. Overall, among persons with confirmed viremic HCV infection, due to LTFU at various stages of the care cascade only 28% of patients with TB had a documented cure from HCV infection, compared to 55% among patients without TB. LTFU after positive antibody testing substantially decreased in the last 3 years, from 32% among patients diagnosed with TB in 2017 to 12% among those diagnosed in 2019. After a positive HCV antibody test, patients without TB had viremia testing sooner than patients with TB (hazards ratio [HR] = 1.46, 95% confidence intervals [CI] [1.39, 1.54], p < 0.001). After a positive viremia test, patients without TB started hepatitis C treatment sooner than patients with TB (HR = 2.05, 95% CI [1.87, 2.25], p < 0.001). In the risk factor analysis adjusted for age, sex, and case definition (new versus previously treated), multidrug-resistant (MDR) TB was associated with an increased risk of LTFU after a positive HCV antibody test (adjusted risk ratio [aRR] = 1.41, 95% CI [1.12, 1.76], p = 0.003). The main limitation of this study was that due to the reliance on existing electronic databases, we were unable to account for the impact of all confounding factors in some of the analyses. CONCLUSIONS LTFU from hepatitis C care after a positive antibody or viremia test was high and more common among patients with TB than in those without TB. Better integration of TB and hepatitis C care systems can potentially reduce LTFU and improve patient outcomes both in Georgia and other countries that are initiating or scaling up their nationwide hepatitis C control efforts and striving to provide personalized TB treatment.
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Affiliation(s)
- Davit Baliashvili
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America
| | - Henry M. Blumberg
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America
- Department of Global Health, Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - Neel R. Gandhi
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America
- Department of Global Health, Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - Francisco Averhoff
- Department of Family and Preventive Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America
| | - David Benkeser
- Department of Biostatistics and Bioinformatics, Emory University Rollins School of Public Health, Atlanta, Georgia, United States of America
| | - Shaun Shadaker
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Lia Gvinjilia
- Eastern Europe and Central Asia Regional Office, Centers for Disease Control and Prevention, Tbilisi, Georgia
| | | | - Nestani Tukvadze
- National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia
| | | | | | - Lali Sharvadze
- Clinic “Hepa”, Tbilisi, Georgia
- The University of Georgia, Tbilisi, Georgia
| | - Tengiz Tsertsvadze
- Infectious Diseases, AIDS and Clinical Immunology Research Center, Tbilisi, Georgia
| | | | - Russell R. Kempker
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America
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Salah RA, Nasr MA, El-Derby AM, Abd Elkodous M, Mohamed RH, El-Ekiaby N, Osama A, Elshenawy SE, Hamad MHM, Magdeldin S, Gabr MM, Abdelaziz AI, El-Badri NS. Hepatocellular carcinoma cell line-microenvironment induced cancer-associated phenotype, genotype and functionality in mesenchymal stem cells. Life Sci 2022; 288:120168. [PMID: 34826437 DOI: 10.1016/j.lfs.2021.120168] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 11/08/2021] [Accepted: 11/18/2021] [Indexed: 12/21/2022]
Abstract
Mesenchymal stromal cells (MSCs) have shown promise in liver cancer treatment. However, when MSCs are recruited to hepatic site of injury, they acquire cancerous promoting phenotype. AIMS To assess the influence of Hepatocellular carcinoma (HCC) microenvironment on human adipose MSCs (hA-MSCs) and predict hA-MSCs intracellular miRNAs role. MATERIALS AND METHODS After indirect co-culturing with Huh-7 cells, hA-MSCs were characterized via cell cycle profile, proliferation and migration potentials by MTT and scratch assays respectively. Functional enrichment analysis of deregulated proteins and miRNA targets was also analyzed. KEY FINDINGS Co-cultured hA-MSCs could acquire a cancer-associated phenotype as shown by upregulation of CAF, cancer markers, and downregulation of differentiation markers. Migration of these cancer-associated cells was increased concomitantly with upregulation of adhesion molecules, but not epithelial to mesenchymal transition markers. Co-cultured cells showed increased proliferation confirmed by downregulation in cell percentage in G0/G1, G2/M and upregulation in S phases of cell cycle. Upregulation of miR-17-5p and 615-5p in co-cultured hA-MSCs was also observed. Functional enrichment analysis of dysregulated proteins in co-cultured hA-MSCs, including our selected miRNAs targets, showed their involvement in development of cancer-associated characteristics. SIGNIFICANCE This study suggests an interaction between tumor cells and surrounding stromal components to generate cancer associated phenotype of some CAF-like characteristics, known to favor cancer progression. This sheds the light on the use of hA-MSCs in HCC therapy. hA-MSCs modulation may be partially achieved via dysregulation of intracellular miR17-5P and 615-5p expression, suggesting an important role for miRNAs in HCC pathogenesis, and as a possible therapeutic candidate.
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Affiliation(s)
- Radwa Ayman Salah
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Egypt
| | - Mohamed A Nasr
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Egypt
| | - Azza M El-Derby
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Egypt
| | - M Abd Elkodous
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Egypt
| | - Rania Hassan Mohamed
- Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Nada El-Ekiaby
- School of Medicine NewGiza University (NGU), Cairo, Egypt
| | - Aya Osama
- Proteomics and metabolomics Research Program, Basic Research Department, Children Cancer Hospital Egypt, 57357 Cairo, Egypt
| | - Shimaa E Elshenawy
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Egypt
| | | | - Sameh Magdeldin
- Proteomics and metabolomics Research Program, Basic Research Department, Children Cancer Hospital Egypt, 57357 Cairo, Egypt; Department of Physiology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
| | - Mahmoud M Gabr
- Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
| | | | - Nagwa S El-Badri
- Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Egypt.
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4
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Guardigni V, Toschi A, Badia L, Rosselli Del Turco E, Salsi E, Cristini F, Sighinolfi L, Fabbri G, Massari M, Cuomo G, Viale P, Verucchi G. Patients with HIV and cirrhosis: the risk for hepatocellular carcinoma after direct-acting antivirals for hepatitis C virus. AIDS 2021; 35:1967-1972. [PMID: 34101631 DOI: 10.1097/qad.0000000000002973] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Hepatocellular carcinoma (HCC) has become a major issue in coinfected HIV/HCV patients with liver cirrhosis. We aimed to determine the rate of HCC occurrence after a direct-acting antiviral (DAA) treatment and to evaluate the factors associated with the risk of HCC in this population. DESIGN We conducted a retrospective multicenter observational study including cirrhotic HIV/HCV-coinfected patients treated with DAAs, between October 2014 and January 2017. METHODS We collected demographics characteristics, data regarding HIV and HCV infections and treatment with DAAs. We investigated the rate and the time of occurrence of HCC. Statistical analysis explored the factors associated to development of liver cancer. RESULTS During a median follow-up of 55 months, 24 out of 232 patients developed HCC, after a median of 22.5 months from starting DAAs. Factors associated with HCC were a higher Child--Pugh Turcotte (CPT) score (P = 0.002), HCV genotype 3 (P = 0.04), previous HCC (P < 0.001) and CD4+ cell count nadir greater than 350 cells/μl (P = 0.001), whereas antiretroviral therapy (ART) was associated to a lower rate of cancer (P = 0.02). At multivariable analysis CPT score and a history of HCC remained independently associated with HCC after DAAs (P = 0.003 and P < 0.001, respectively), and ART administration maintained its protective role (P = 0.047), regardless of HIV RNA at baseline. CONCLUSION Our study highlights the importance of a long-lasting follow-up for HCC after HCV eradication, mostly in those patients with advanced cirrhosis and history of HCC. Furthermore, our data showed a potential role of ART itself (and not of undetectable HIV RNA) in reducing the risk for HCC development.
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Affiliation(s)
- Viola Guardigni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna
| | - Alice Toschi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna
| | - Lorenzo Badia
- Department of Medical and Surgical Sciences, University of Bologna, Bologna
| | | | - Eleonora Salsi
- Department of Infectious Diseases and Hepatology, Azienda Ospedaliera di Parma, Parma
| | | | | | | | - Marco Massari
- Infectious Diseases Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio nell'Emilia
| | - Gianluca Cuomo
- Department of Infectious Diseases, Azienda Ospedaliero-Universitaria Policlinico of Modena, Modena, Italy
| | - Pierluigi Viale
- Department of Medical and Surgical Sciences, University of Bologna, Bologna
| | - Gabriella Verucchi
- Department of Medical and Surgical Sciences, University of Bologna, Bologna
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Lin D, Reddy V, Osman H, Lopez A, Koksal AR, Rhadhi SM, Dash S, Aydin Y. Additional Inhibition of Wnt/β-Catenin Signaling by Metformin in DAA Treatments as a Novel Therapeutic Strategy for HCV-Infected Patients. Cells 2021; 10:790. [PMID: 33918222 PMCID: PMC8065725 DOI: 10.3390/cells10040790] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 03/24/2021] [Accepted: 03/27/2021] [Indexed: 12/17/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). Although HCV clearance has been improved by the advent of direct-acting antiviral agents (DAA), retrospective studies have shown that the risk of subsequent HCC, while considerably decreased compared with active HCV infection, persists after DAA regimens. However, either the mechanisms of how chronic HCV infection causes HCC or the factors responsible for HCC development after viral eradication in patients with DAA treatments remain elusive. We reported an in vitro model of chronic HCV infection and determined Wnt/β-catenin signaling activation due to the inhibition of GSK-3β activity via serine 9 phosphorylation (p-ser9-GSK-3β) leading to stable non-phosphorylated β-catenin. Immunohistochemical staining demonstrated the upregulation of both β-catenin and p-Ser9-GSK-3β in HCV-induced HCC tissues. Chronic HCV infection increased proliferation and colony-forming ability, but knockdown of β-catenin decreased proliferation and increased apoptosis. Unexpectedly, Wnt/β-catenin signaling remained activated in chronic HCV-infected cells after HCV eradication by DAA, but metformin reversed it through PKA/GSK-3β-mediated β-catenin degradation, inhibited colony-forming ability and proliferation, and increased apoptosis, suggesting that DAA therapy in combination with metformin may be a novel therapy to treat HCV-associated HCC where metformin suppresses Wnt/β-catenin signaling for HCV-infected patients.
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Affiliation(s)
- Dong Lin
- Laboratory Medicine and Department of Pathology, Tulane University School of Medicine, New Orleans, LA 70112, USA; (V.R.); (H.O.); (A.L.); (A.R.K.); (S.M.R.); (S.D.)
| | | | | | | | | | | | | | - Yucel Aydin
- Laboratory Medicine and Department of Pathology, Tulane University School of Medicine, New Orleans, LA 70112, USA; (V.R.); (H.O.); (A.L.); (A.R.K.); (S.M.R.); (S.D.)
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6
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Pipe SW, Kruse‐Jarres R, Mahlangu JN, Pierce GF, Peyvandi F, Kuebler P, De Ford C, Sanabria F, Ko RH, Chang T, Hay CRM. Establishment of a framework for assessing mortality in persons with congenital hemophilia A and its application to an adverse event reporting database. J Thromb Haemost 2021; 19 Suppl 1:21-31. [PMID: 33331042 PMCID: PMC7756842 DOI: 10.1111/jth.15186] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 10/15/2020] [Accepted: 10/28/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Despite recent therapeutic advances, life expectancy in persons with congenital hemophilia A (PwcHA) remains below that of the non-HA population. As new therapies are introduced, a uniform approach to the assessment of mortality is required for comprehensive evaluation of risk-benefit profiles, timely identification of emerging safety signals, and comparisons between treatments. OBJECTIVES Develop and test a framework for consistent reporting and analysis of mortality across past, current, and future therapies. PATIENTS/METHODS We identified known causes of mortality in PwcHA through literature review, analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, and expert insights. Leading causes of death in general populations are those recognized by the Centers for Disease Control and Prevention and the World Health Organization. We developed an algorithm for assessing fatalities in PwcHA and used this to categorize FAERS data as a proof of concept. RESULTS PwcHA share mortality causes with the non-HA population including cardiovascular disease, malignancy, infections, pulmonary disease, dementias, and trauma/suicide. Causes associated with HA include hemorrhage, thrombosis, human immunodeficiency virus, hepatitis C virus, and liver dysfunction. We propose an algorithm employing these classes to categorize fatalities and use it to classify FAERS fatality data between 01/01/2000 and 03/31/2020; the most common causes were hemorrhage (22.2%) and thrombosis (10.4%). CONCLUSIONS A conceptual framework for examining mortality in PwcHA receiving any hemophilia therapy is proposed to analyze and interpret fatalities, enabling consistent and objective assessment. Application of the framework using FAERS data suggests a generally consistent pattern of reported mortality across HA treatments, supporting the utility of this unified approach.
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Affiliation(s)
- Steven W. Pipe
- Departments of Pediatrics and PathologyUniversity of Michigan Medical SchoolAnn ArborMIUSA
| | - Rebecca Kruse‐Jarres
- University of WashingtonSeattleWAUSA
- Washington Center for Bleeding DisordersSeattleWAUSA
| | | | | | - Flora Peyvandi
- IRCCS Fondazione Ca' Granda Ospedale Maggiore PoliclinicoAngelo Bianchi Bonomi Hemophilia and Thrombosis CenterMilanItaly
- Department of Pathophysiology and TransplantationUniversity of MilanMilanItaly
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7
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Direct-Acting Antiviral Therapy in Liver Transplant Patients With Hepatocellular Carcinoma and Hepatitis C. Transplant Direct 2020; 7:e635. [PMID: 33324740 PMCID: PMC7725260 DOI: 10.1097/txd.0000000000001049] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 06/09/2020] [Accepted: 06/11/2020] [Indexed: 01/11/2023] Open
Abstract
Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC).
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8
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Moullet B, Kolev M, Ebner L, Langer R, Gräni C, Obmann V, Maurer M, Semmo N, Christe A, Huber AT. Adult form of Langerhans cell histiocytosis with pulmonary and hepatic involvement mimicking malignancy in a patient with chronic hepatitis C infection. Radiol Case Rep 2020; 16:327-333. [PMID: 33318775 PMCID: PMC7724096 DOI: 10.1016/j.radcr.2020.11.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 11/09/2020] [Accepted: 11/11/2020] [Indexed: 11/28/2022] Open
Abstract
Langerhans cell histiocytosis (LCH) is a myeloid neoplasm with inflammatory properties. There are few published reports of adult LCH with liver involvement, which is still poorly understood, but shows high morbidity and mortality. We report a case of a 37-year-old woman suffering from hepatitis C showing a LCH affecting the lung as well as the liver. Consistent with histology, we found an early stage of a proliferative/granulomatous phase of hepatobiliary LCH, whereas pulmonary findings showed a nodular stage of adult pulmonary LCH. Although hepatocellular carcinoma is a common malignancy in patients suffering from hepatitis C, it is crucial to keep in mind differential diagnosis for newly appearing liver lesions.
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Affiliation(s)
- Barbara Moullet
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital University Hospital, University of Bern, Freiburgstrasse 10, Inselspital, 3010, Bern, Switzerland
| | - Mirjam Kolev
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital University Hospital, University of Bern, Bern, Switzerland
| | - Lukas Ebner
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital University Hospital, University of Bern, Freiburgstrasse 10, Inselspital, 3010, Bern, Switzerland
| | - Rupert Langer
- Department of Pathology, Inselspital University Hospital, University of Bern, Bern, Switzerland
| | - Christoph Gräni
- Department of Cardiology, Inselspital University Hospital, University of Bern, Bern, Switzerland
| | - Verena Obmann
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital University Hospital, University of Bern, Freiburgstrasse 10, Inselspital, 3010, Bern, Switzerland
| | - Martin Maurer
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital University Hospital, University of Bern, Freiburgstrasse 10, Inselspital, 3010, Bern, Switzerland
| | - Nasser Semmo
- Hepatology, Department of Visceral Surgery and Medicine, Inselspital University Hospital, University of Bern, Bern, Switzerland
| | - Andreas Christe
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital University Hospital, University of Bern, Freiburgstrasse 10, Inselspital, 3010, Bern, Switzerland
| | - Adrian Thomas Huber
- Department of Diagnostic, Interventional and Pediatric Radiology, Inselspital University Hospital, University of Bern, Freiburgstrasse 10, Inselspital, 3010, Bern, Switzerland
- Corresponding author.
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9
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Bâldea V, Sporea I, Lupușoru R, Bende F, Mare R, Popescu A, Șirli R. Comparative Study Between the Diagnostic Performance of Point and 2-D Shear-Wave Elastography for the Non-invasive Assessment of Liver Fibrosis in Patients With Chronic Hepatitis C Using Transient Elastography as Reference. ULTRASOUND IN MEDICINE & BIOLOGY 2020; 46:2979-2988. [PMID: 32807571 DOI: 10.1016/j.ultrasmedbio.2020.07.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 07/08/2020] [Accepted: 07/14/2020] [Indexed: 06/11/2023]
Abstract
The study compared the diagnostic performance of two shear-wave elastography techniques, elastography point quantification (ElastPQ) and 2-D shear-wave elastography by General Electric (2-D-SWE.GE), for the non-invasive assessment of liver fibrosis in a cohort of patients with chronic hepatitis C virus (HCV) infection, using transient elastography (TE) as the reference method. There was no significant difference between the feasibility rates of TE, ElastPQ and 2-D-SWE.GE (p = 0.507). A good correlation was found between the liver stiffness (LS) values obtained using the two elastographic methods (r = 0.78). The mean LS values obtained using the ElastPQ technique were significantly higher than those obtained using 2-D-SWE.GE (12.1 ± 7.3 kPa vs. 10.4 ± 4.0 kPa, p < 0.0001). Pairwise comparisons of receiver operator characteristics curves between 2-D-SWE.GE and ElastPQ have shown that there are no significant differences in their performance for staging F ≥ 2 fibrosis (p = 0.89), F ≥ 3 fibrosis (p = 0.76) and F = 4 fibrosis (p = 0.86) in patients with chronic HCV infection.
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Affiliation(s)
- Victor Bâldea
- Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, România
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, România.
| | - Raluca Lupușoru
- Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, România
| | - Felix Bende
- Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, România
| | - Ruxandra Mare
- Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, România
| | - Alina Popescu
- Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, România
| | - Roxana Șirli
- Department of Gastroenterology and Hepatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, România
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10
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Stem Cell Therapy for Hepatocellular Carcinoma: Future Perspectives. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1237:97-119. [PMID: 31728916 DOI: 10.1007/5584_2019_441] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common types of cancer and results in a high mortality rate worldwide. Unfortunately, most cases of HCC are diagnosed in an advanced stage, resulting in a poor prognosis and ineffective treatment. HCC is often resistant to both radiotherapy and chemotherapy, resulting in a high recurrence rate. Although the use of stem cells is evolving into a potentially effective approach for the treatment of cancer, few studies on stem cell therapy in HCC have been published. The administration of stem cells from bone marrow, adipose tissue, the amnion, and the umbilical cord to experimental animal models of HCC has not yielded consistent responses. However, it is possible to induce the apoptosis of cancer cells, repress angiogenesis, and cause tumor regression by administration of genetically modified stem cells. New alternative approaches to cancer therapy, such as the use of stem cell derivatives, exosomes or stem cell extracts, have been proposed. In this review, we highlight these experimental approaches for the use of stem cells as a vehicle for local drug delivery.
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Colussi G, Donnini D, Brizzi RF, Maier S, Valenti L, Catena C, Cavarape A, Sechi LA, Soardo G. Sustained virologic response to direct-acting antiviral agents predicts better outcomes in hepatitis C virus-infected patients: A retrospective study. World J Gastroenterol 2019; 25:6094-6106. [PMID: 31686765 PMCID: PMC6824275 DOI: 10.3748/wjg.v25.i40.6094] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/09/2019] [Accepted: 09/09/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Direct-acting antiviral agents (DAAs) are extremely effective in eradicating hepatitis C virus (HCV) in chronically infected patients. However, the protective role of the sustained virologic response (SVR) achieved by second- and third-generation DAAs against the onset of hepatocellular carcinoma (HCC) and mortality is less well established.
AIM To examine the occurrence of HCC or death from any cause in a retrospective-prospective study of patients treated with DAAs.
METHODS Patients were enrolled from a tertiary academic hospital center for liver disease management that collects subject data mainly from northeastern Italy. The study was conducted in 380 patients (age: 60 ± 13 years, 224 males, 32% with cirrhosis) treated with DAAs with or without SVR (95/5%), with a median follow up of 58 wk (interquartile range: 38-117). The baseline anthropometric features, HCV viral load, severity of liver disease, presence of extra-hepatic complications, coinfection with HIV and/or HBV, alcohol consumption, previous interferon use, alpha-fetoprotein levels, and renal function were considered to be confounders.
RESULTS The incidence rate of HCC in patients with and without SVR was 1.3 and 59 per 100 person-years, respectively (incidence rate ratio: 44, 95%CI: 15-136, P < 0.001). Considering the combined endpoint of HCC or death from any cause, the hazard ratio (HR) for the SVR patients was 0.070 (95%CI: 0.025-0.194, P < 0.001). Other independent predictors of HCC or death were low HCV viremia (HR: 0.808, P = 0.030), low platelet count (HR: 0.910, P = 0.041), and presence of mixed cryoglobulinemia (HR: 3.460, P = 0.044). Considering SVR in a multi-state model, the independent predictors of SVR achievement were absence of cirrhosis (HR: 0.521, P < 0.001) and high platelet count (HR: 1.019, P = 0.026). Mixed cryoglobulinemia predicted the combined endpoint in patients with and without SVR (HR: 5.982, P = 0.028 and HR: 5.633, P = 0.047, respectively).
CONCLUSION DAA treatment is effective in inducing SVR and protecting against HCC or death. A residual risk of HCC persists in patients with advanced liver disease or with complications, such as mixed cryoglobulinemia or renal failure.
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Affiliation(s)
| | - Debora Donnini
- Department of Medicine, University of Udine, Udine 33100, Italy
| | | | - Silvia Maier
- Department of Medicine, University of Udine, Udine 33100, Italy
| | - Luca Valenti
- Department of Medicine, University of Udine, Udine 33100, Italy
| | | | | | | | - Giorgio Soardo
- Department of Medicine, University of Udine, Udine 33100, Italy
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