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Gusev E, Sarapultsev A. Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement. Int J Mol Sci 2024; 25:6389. [PMID: 38928096 PMCID: PMC11204317 DOI: 10.3390/ijms25126389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/05/2024] [Accepted: 06/07/2024] [Indexed: 06/28/2024] Open
Abstract
Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features.
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Affiliation(s)
| | - Alexey Sarapultsev
- Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia;
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Yaow CYL, Hong ASY, Chong NZY, Chong RIH, Mai AS, Tan EK. Risk of Parkinson's disease in hepatitis B and C populations: a systematic review and meta-analysis. J Neural Transm (Vienna) 2024; 131:609-616. [PMID: 37899363 DOI: 10.1007/s00702-023-02705-7] [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: 05/04/2023] [Accepted: 09/27/2023] [Indexed: 10/31/2023]
Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder, and its association with viral hepatitis has been debated. We performed a meta-analysis to examine the association between PD risk and viral hepatitis. Medline, EMBASE, and the Cochrane library were searched from inception till July 2022. Meta-analysis was conducted using a fixed-effect model with the inverse variance method. Three groups were compared to controls: infection with either hepatitis B or C virus (HBV and HCV, respectively), or coinfection with both viruses. We found 551 records, and six studies comprising of 2,566,947 patients were included in the analysis. PD risk was increased in HCV-infected population (OR 1.10, 95% CI 1.03-1.17, p = 0.005) and (HR 1.37, 95% CI 1.26-1.49, p < 0.001). This increase was not observed for the HBV-infected and HBV-HCV-coinfected coinfection populations. For pooled OR, the risk was significantly lower in HBV-infected (OR 0.79, 95% CI 0.76-0.83, p < 0.001) but not significantly different in HBV-HCV-coinfected populations (OR 0.96, 95% CI 0.82-1.12, p = 0.57). For pooled HR, the risk was significantly higher in both HBV-infected (HR 1.22, 95% CI 1.14-1.31, p < 0.001) and HBV-HCV-coinfected populations (HR 1.29, 95% CI 1.05-1.58, p = 0.013). We found that the risk of PD was increased in the HCV-infected population, but results were inconsistent in those with HBV and HBV-HCV infections. Our findings provide impetus for further clinical and functional studies to unravel the role of the adaptive immune system in PD.
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Affiliation(s)
- Clyve Yu Leon Yaow
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | | | | | - Ryan Ian Houe Chong
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Aaron Shengting Mai
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Eng-King Tan
- Department of Neurology, Singapore General Hospital Campus, National Neuroscience Institute, Duke NUS Medical School, Outram Road, Singapore, 169608, Singapore.
- Neuroscience and Behavioural Disorders, Duke-NUS Medical School, Singapore, Singapore.
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Androutsakos T, Tsantzali I, Karagiannakis DS, Flevari P, Iakovou D, Pouliakis A, Kykalos S, Doris S, Xyla V. Peripheral Neuropathy in Patients with Hepatitis C Infection-Reversibility after HCV Eradication: A Single Center Study. Viruses 2024; 16:522. [PMID: 38675865 PMCID: PMC11054011 DOI: 10.3390/v16040522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 03/22/2024] [Accepted: 03/24/2024] [Indexed: 04/28/2024] Open
Abstract
Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively (p value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR (p value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement.
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Affiliation(s)
- Theodoros Androutsakos
- Department of Pathophysiology, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Ioanna Tsantzali
- Second Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, “Attikon” General University Hospital, 124 62 Athens, Greece;
| | - Dimitrios S. Karagiannakis
- Academic Department of Gastroenterology, Laiko General Hospital, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Pagona Flevari
- Centre of Excellence in Rare Haematological (Haemoglobinopathies) & Rare Metabolic (Gaucher Disease) Diseases, Laiko General Hospital, 115 27 Athens, Greece;
| | - Despoina Iakovou
- West Suffolk Hospital NHS Foundation Trust, Bury St Edmunds IP33 2QZ, UK;
| | - Abraham Pouliakis
- Second Department of Pathology, National and Kapodistrian University of Athens, 124 62 Athens, Greece;
| | - Stylianos Kykalos
- Second Department of Propaedeutic Surgery, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
| | - Stylianos Doris
- Neurology Department, Metropolitan General Hospital, 155 62 Athens, Greece;
| | - Vasileia Xyla
- Department of Pathophysiology, National and Kapodistrian University of Athens, 115 27 Athens, Greece;
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Ferreira J, Bicho M, Serejo F. Effects of HCV Clearance with Direct-Acting Antivirals (DAAs) on Liver Stiffness, Liver Fibrosis Stage and Metabolic/Cellular Parameters. Viruses 2024; 16:371. [PMID: 38543737 PMCID: PMC10974411 DOI: 10.3390/v16030371] [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: 12/06/2023] [Revised: 02/20/2024] [Accepted: 02/22/2024] [Indexed: 05/23/2024] Open
Abstract
INTRODUCTION Chronic hepatitis C (CHC) is a clinical and pathological syndrome with various causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. It is a significant cause of liver transplantation and liver-related death worldwide. The hepatic manifestations of CHC are typically characterized by slowly progressing liver fibrosis, which is a non-specific and often disproportionate response to tissue damage. A large majority of HCV patients have extrahepatic manifestations with varying degrees of severity. HCV infection is a risk factor for cardiovascular disease and diabetes mellitus, which increases insulin resistance, oxidative stress, and iron overload and causes chronic systemic inflammation. HCV infection is treated using direct-acting antivirals (DAAs) with cure rates of over 95 percent, minimal side effects, and shorter therapeutic courses. Despite the effective elimination of the virus, it seemed pertinent to understand to what extent HCV clearance eliminates or attenuates all the systemic alterations already induced by the virus during infection and chronicity. OBJECTIVES Our study aimed to determine whether eliminating HCV with DAAs alters the severity of liver disease (liver stiffness and liver fibrosis stage by TE) and the metabolic/cellular profile of patients with CHC. MATERIALS AND METHODS A group of 329 CHC patients from a Gastroenterology and Hepatology outpatient department were prospectively studied. Of these, 134 were also studied with DAAs. The liver fibrosis stage was evaluated by transient elastography (TE) using a FibroScan® device, and two groups were established for the analysis of liver stiffness (LS): mild and moderate stiffness (fibrosis F1 and F2; F1/2) and severe stiffness (fibrosis and cirrhosis F3 and F4; F3/4). Metabolic/cellular parameters were evaluated before and after antiviral treatment using standard methods: alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl-transpeptidase (γ-GT), haptoglobin (Hp), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), free iron (Fe), transferrin saturation (TS), total iron binding capacity (TIBC), ferritin (Ft), glycemia, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and platelets count. The results were statistically analyzed using SPSS 24.0 for Windows. RESULTS Comparing the fibrosis stage before and after DAAs treatment, we verify a reduction in LS in 85.7% of patients and an improvement in liver fibrosis stage in 22.2% of them after DAAs treatment. Before DAAs treatment, patients showed a 2.410 risk for higher fibrosis stages (F3/4). Comparing metabolic/cellular parameters before and after DAAs treatment, patients showed lower ALP, AST, ALT, γGT, TG, Fe, TIBC, and Ft values and higher TC, LDL, and Hp values after treatment. As such, HCV elimination reduces iron overload and insulin resistance. On the other hand, it caused dyslipidemia, raising total cholesterol and LDL to levels outside the reference values. The improvement in the liver fibrosis stage by TE was mainly associated with higher baseline platelet count and HDL values and lower insulin resistance. CONCLUSIONS With this study, we were able to contribute to the knowledge of the effects of HCV elimination with DAAs on liver disease and metabolic profile to improve the quality of treatment and follow-up of these patients after HCV elimination.
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Affiliation(s)
- Joana Ferreira
- Institute for Scientific Research Bento Rocha Cabral, 1250-047 Lisbon, Portugal;
- TERRA, ISAMB, Genetics Laboratory, Lisbon Medical School, University of Lisbon, 1649-028 Lisbon, Portugal;
| | - Manuel Bicho
- Institute for Scientific Research Bento Rocha Cabral, 1250-047 Lisbon, Portugal;
- TERRA, ISAMB, Genetics Laboratory, Lisbon Medical School, University of Lisbon, 1649-028 Lisbon, Portugal;
| | - Fátima Serejo
- TERRA, ISAMB, Genetics Laboratory, Lisbon Medical School, University of Lisbon, 1649-028 Lisbon, Portugal;
- Gastroenterology and Hepatology Department, Hospital de Santa Maria, 1649-028 Lisbon, Portugal
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Singha PS, Ghosh S, Ghosh D. Levothyroxine and Non-alcoholic Fatty Liver Disease: A Mini Review. Mini Rev Med Chem 2024; 24:128-138. [PMID: 36918791 DOI: 10.2174/1389557523666230314113543] [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: 08/26/2022] [Revised: 11/24/2022] [Accepted: 11/29/2022] [Indexed: 03/16/2023]
Abstract
Levothyroxine or l-thyroxine is artificially manufactured thyroxine, which is used as a drug to treat underactive thyroid conditions in humans. The drug, levothyroxine, is consumed daily in a prescribed dose to replace the missing thyroid hormone thyroxine in an individual with an underactive thyroid, and it helps to maintain normal physiological conditions. Though it is a life-maintaining drug, it replaces the missing thyroid hormone and performs the necessary daily metabolic functions in our body. Like all other allopathic drugs, it comes with certain side effects, which include joint pain, cramps in muscle, weight gain/loss, hair loss, etc. The thyroid hormone, thyroxine, is known to mobilize fat in our body, including the ones from the hepatic system. An underactive thyroid may cause an accumulation of fat in the liver, leading to a fatty liver, which is clinically termed Non-Alcoholic Fatty Liver Disease (NAFLD). The correlation between hypothyroidism and NAFLD is now well-studied and recognized. As levothyroxine performs the functions of the missing thyroxine, it is anticipated, based on certain preliminary studies, that the drug helps to mobilize hepatic fat and thus may have a crucial role in mitigating the condition of NAFDL.
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Affiliation(s)
| | - Suvendu Ghosh
- Department of Physiology, Hooghly Mohsin College, Chinsura, Hooghly, 712 101, West Bengal, India
| | - Debosree Ghosh
- Department of Physiology, Government General Degree College, West Bengal, India
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Othman AM, Al-Hnhna AA, Al-Huraibi BS, Assayaghi RM, Al-Qahtani TY, Jahzar KH, Al-Huthaifi MM. Prevalence of hepatitis C virus among patients with arthralgia: is it logic for screening? Virol J 2023; 20:162. [PMID: 37480120 PMCID: PMC10360329 DOI: 10.1186/s12985-023-02124-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/10/2023] [Indexed: 07/23/2023] Open
Abstract
BACKGROUND Hepatitis C virus (HCV) is well-known to be associated with multiple extrahepatic manifestations such as arthralgia, myalgia, arthritis, and vasculitis. Many studies reported frequent rheumatologic manifestations among patients infected by HCV. The purpose of this study was to determine the prevalence of HCV among chronic unexplained arthralgia patients in order to aid in the early detection and treatment of silent HCV infection. METHODS This study was a cross-sectional observational study conducted from July 2020 to May 2022. It included 145 individuals suffering from chronic unexplained arthralgia, with vast majority having oligoarticular joint pain (110, 75.9%). They were 103 (71%) females and 42 (29%) males. Serum samples from all patients were examined for the presence of anti-HCV antibodies using a rapid immunochromatographic assay. Seropositive samples were further examined using polymerase chain reaction (PCR) for detection of HCV RNA to confirm HCV infection. RESULTS Out of 145 patients who complained of arthralgia, seven patients tested positive for anti-HCV with a seroprevalence of 4.8% while five patients tested positive for HCV-RNA with a molecular prevalence of 3.4%. All positive patients were males (11.9%) with high statistical significance (χ2 = 12.7 and p = 0.002). No association was found between HCV infection and age, blood transfusion, surgery, using personal shaving tools, or being a health-care worker. CONCLUSIONS The prevalence of HCV was high among males who complained of arthralgia. Patients with arthralgia, especially male patients, are recommended to perform HCV screening test.
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Affiliation(s)
- Arwa Mohammed Othman
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen.
| | - Asma'a Ahmed Al-Hnhna
- Gastroenterology and Hepatology, Medicine department, 21 September University, Sana'a, Yemen
| | - Belques Sharaf Al-Huraibi
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a-Yemen, Yemen
| | - Rowa Mohammed Assayaghi
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a-Yemen, Yemen
| | - Talal Yahya Al-Qahtani
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a-Yemen, Yemen
| | - Kamal Hamoud Jahzar
- Biomedical sciences department, Lebanese International University, Sana'a Compass, Yemen
| | - Marwan Mohammed Al-Huthaifi
- Microbiology and Immunology Department, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a-Yemen, Yemen
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Ismail R, Elansary A, Ezzatt O, Hamed M, Gamil Y. Hepatitis C associated oral lesions: A hospital-based retrospective case control study in Egypt. J Int Oral Health 2023; 15:52. [DOI: 10.4103/jioh.jioh_160_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
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Kryukov EV, Cherkashin DV, Saluhov VV, Matjushenko KV, Sobolev AD, Shcherbina NN. Extrahepatic manifestations of chronic viral hepatitis C. BULLETIN OF THE RUSSIAN MILITARY MEDICAL ACADEMY 2022; 24:341-352. [DOI: 10.17816/brmma103982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Chronic viral diseases of the liver are frequently characterized by clinical signs of intrahepatic complications. Infection caused by the hepatitis C virus should be considered as a systemic disorder associated with the frequent development of various extrahepatic complications, such as cryoglobulinemia, glomerulopathy, lymphoproliferative diseases, seronegative arthritis, type 2 diabetes mellitus, lichen planus, and late cutaneous porphyria. Often, extrahepatic complications become the main features of the clinical disease picture, forcing patients to seek medical help from various specialists and delaying diagnosis. In some cases, the treatment of extrahepatic manifestations becomes an independent, complex task, surpassing the actual treatment of chronic hepatitis C. The relationship between hepatic and extrahepatic complications of viral hepatitis C is not linear; rather, extrahepatic manifestations often outstrip the development of liver damage. The effects of hepatitis C virus on the organs and systems of the body are caused by the direct action of the virus, pathogenetically induced by the development of steatosis/steatohepatitis, and by the disruption of system regulation of hepatokines and cytokines. Treatment of chronic hepatitis C virus infection should be comprehensive and should include antiviral therapy, treatment of metabolic-associated fatty liver disease and treatment of hepatic-related disorders. Antiviral therapy with preparations of direct antiviral action allows the prevention of not only liver complications but also of many extrahepatic complications of hepatitis C virus. Comorbid states significantly increase the natural progression of chronic hepatitis C infection and vice versa: the hepatitis C virus increases the clinical manifestations of co-pathology. In the age of direct antiviral drugs, it is possible to eliminate the hepatitis C virus, but in some cases, elimination alone does not arrest the progression of liver disease.
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Derbak MA, Vorobets VV, Koval GM, Nikolska OІ, Ustych OV, Hechko MM, Ilko AV. ASSESSMENT OF COLON MICROBIOCENOSIS DISORDERS IN PATIENTS WITH CHRONIC HEPATITIS C. WIADOMOSCI LEKARSKIE (WARSAW, POLAND : 1960) 2022; 75:2334-2338. [PMID: 36472257 DOI: 10.36740/wlek202210104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
OBJECTIVE The aim: To investigate the peculiarities of colon microbiocenosis disorders in patients with chronic hepatitis C. PATIENTS AND METHODS Materials and methods: 142 patients with CHC were under observation, determination of the degree of liver fibrosis (FibroMax), bacteriological examination of stools and pancreatic elastase was performed. RESULTS Results: It was found that 59.2% of patients with CHC had gut dysbiosis (DB), of which 61.9% had increased body weight. Intestinal microbiocenosis disorders were manifested by constipation in 57.1% of patients, diarrhea in 31% of patients, and alternating constipation and diarrhea in 11.9% of patients. Bacteriologically, gut dysbiosis was character¬ized by suppression of the growth of normal microflora: Escherichia coli in 47.6%, bifidobacteria in 61.9%, lactobacilli in 53.6%, complete absence of bifidobacteria in 20.2% of cases. In patients with CHC combined with DB deep stages of liver fibrosis (F2-3 and F3-4) are registered 3.6 times more often compared to patients without intestinal dysbiosis (53.6% versus 24.1% and 11.9% versus 3.4%). The degree of gut DB increased in proportion to the stage of liver fibrosis (p<0.05). 32.1% of patients with CHC with dysbiosis were diagnosed with exocrine insufficiency of the pancreas. CONCLUSION Conclusions: Gut dysbiosis occurs more often in CHC patients with increased body weight and is characterized by constipation in 59.2% of patients. Intestinal microbiocenosis is characterized by suppression of the growth of normal microflora. In 32.1% of CHC patients with intestinal dysbiosis, according to the results of the pancreatic elastase-1 test, pancreatic exocrine insufficiency of various degrees was found.
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Garrido-Estepa M, Herruzo R, Flores-Herrera J. Co-infections, comorbidities, and alcohol or other substances abuses in chronic hepatitis C-related hospitalisations in Spain. GASTROENTEROLOGIA Y HEPATOLOGIA 2022; 45:677-689. [DOI: 10.1016/j.gastrohep.2022.01.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Revised: 12/08/2021] [Accepted: 01/14/2022] [Indexed: 11/26/2022]
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Nada A, Sabry A, Elabd NS, Abdu Allah AM, Elnaidany N, Abbasy M. B-type natriuretic peptide (BNP) in HCV-positive Egyptian patients: the impact of HCV eradication on plasma BNP levels. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00133-4] [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
Background
Chronic hepatitis C virus (HCV) infection represents a major health-related burden in Egypt. HCV is considered as a major cardiovascular risk factor. BNP (B-type natriuretic peptide) has been determined as a credible diagnostic and prognostic cardiac biomarker. We aimed to assess plasma BNP in HCV-positive Egyptian patients prior and after HCV eradication by direct-acting antiviral agents (DAAs) therapy. Eighty-nine chronic HCV-positive patients were enrolled in our prospective research. They were provided with DAAs therapy in the form of sofosbuvir and daclatasvir without or with ribavirin for 12 weeks. History, clinical evaluation, and laboratory assessment: CBC, liver and kidney function tests, viral markers (HCVAb, HBVsAg, and HIVAb) by ELISA, HCV RNA by real-time PCR, and BNP by ELISA were assessed. FIB-4 and aspartate aminotransferase-to-platelet ratio index (APRI) scores were ranked.
Results
Plasma BNP displayed a non-significant (p = 0.124) increase of its serum mean values in post eradication of HCV than its baseline values. Baseline BNP exhibited a significant positive correlation with FIB4 (r = 0.411, P < 0.001) and APRI score (r = 0.418, p < 0.001) with a considerably negative correlation with platelets (r = − 0.274, p = 0.009), in addition to higher pretreatment BNP values in cirrhotic than in non-cirrhotic patients (p < 0.001), while non-significant relations were found regarding sex, BMI, and drug regimen (with or without ribavirin) (p = 0.950, 0.845, and 0.738, respectively). Additionally, plasma BNP values considerably decreased post-treatment in patients presented with higher baseline BNP values and more advanced liver disease (higher FIB4, APRI, and the presence of liver cirrhosis).
Conclusion
Our findings propose on the one side, the necessity of cardiac monitoring during chronic HCV infection and, on the other, the valuable impacts of HCV eradication on HCV-associated cardiac morbidities.
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A Devastating Case of Hepatitis C-Induced Mixed Cryoglobulinemia. Case Reports Hepatol 2021; 2021:8244432. [PMID: 34659845 PMCID: PMC8519709 DOI: 10.1155/2021/8244432] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 09/24/2021] [Indexed: 11/25/2022] Open
Abstract
Hepatitis C-induced mixed cryoglobulinemia leading to rapidly progressive gangrene, necessitating amputations, is a rare presentation. We describe a case of a 55-year-old man with untreated chronic hepatitis C virus (HCV) presenting with arthralgia and palpable purpura, which rapidly progressed to life-threatening gangrene of all extremities requiring amputations in the setting of mixed cryoglobulinemia. Treatment for HCV was initiated which led to the arrest of gangrene progression and the patient's survival. Patients with HCV-induced cryoglobulinemia should be closely monitored and started on early therapy with direct-acting antiviral therapy to prevent progression of vasculitis to gangrene. Universal screening for HCV can aid in early diagnosis and treatment to prevent devastating consequences.
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Altomare A, Corrado A, Maruotti N, Cici D, Cantatore FP. Hcv and Autoimmunity in Rheumatic Diseases. Curr Rheumatol Rev 2021; 18:101-107. [PMID: 34387165 DOI: 10.2174/1573397117666210812141524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 06/04/2021] [Accepted: 06/14/2021] [Indexed: 11/22/2022]
Abstract
HCV is a global health problem affecting mainly the liver and often characterized by extrahepatic manifestions mediated by autoimmune reactions. Among these, arthritis and arthralgia are most frequent, as well as the presence of cryoglobulinemia that may induce vasculitis, and sicca syndrome. Thus, HCV appears to be a trigger for autoimmune response as demonstrated by the finding of autoantibody in a high percentage of serum of these patients. Therefore, it is important that clinicians recognize these autoimmune manifestations as symptoms due to an autoimmune activity triggered by HCV, in order to give the correct diagnosis and start an effective therapy strategy. Therefore, clinical examination, searching of markers of infection as well as autoantibody patterns should be performed to make a correct differential diagnosis. The treatment should be based on antiviral drugs associated to immunosuppressive drugs according to autoimmune manifestations.
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Affiliation(s)
- Alberto Altomare
- Rheumatology Clinic "Mario Carrozzo", Department of Medical and Surgical Sciences, University of Foggia, "Policlinico Riuniti" Universitary Hospital, Viale Pinto, 1 - 71121 Foggia. Italy
| | - Addolorata Corrado
- Rheumatology Clinic "Mario Carrozzo", Department of Medical and Surgical Sciences, University of Foggia, "Policlinico Riuniti" Universitary Hospital, Viale Pinto, 1 - 71121 Foggia. Italy
| | - Nicola Maruotti
- Rheumatology Clinic "Mario Carrozzo", Department of Medical and Surgical Sciences, University of Foggia, "Policlinico Riuniti" Universitary Hospital, Viale Pinto, 1 - 71121 Foggia. Italy
| | - Daniela Cici
- Rheumatology Clinic "Mario Carrozzo", Department of Medical and Surgical Sciences, University of Foggia, "Policlinico Riuniti" Universitary Hospital, Viale Pinto, 1 - 71121 Foggia. Italy
| | - Francesco Paolo Cantatore
- Rheumatology Clinic "Mario Carrozzo", Department of Medical and Surgical Sciences, University of Foggia, "Policlinico Riuniti" Universitary Hospital, Viale Pinto, 1 - 71121 Foggia. Italy
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Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story. Viruses 2021; 13:v13020277. [PMID: 33670195 PMCID: PMC7916951 DOI: 10.3390/v13020277] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Revised: 02/06/2021] [Accepted: 02/07/2021] [Indexed: 02/07/2023] Open
Abstract
A causal link between viral infections and autoimmunity has been studied for a long time and the role of some viruses in the induction or exacerbation of systemic lupus erythematosus (SLE) in genetically predisposed patients has been proved. The strength of the association between different viral agents and SLE is variable. Epstein-Barr virus (EBV), parvovirus B19 (B19V), and human endogenous retroviruses (HERVs) are involved in SLE pathogenesis, whereas other viruses such as Cytomegalovirus (CMV) probably play a less prominent role. However, the mechanisms of viral-host interactions and the impact of viruses on disease course have yet to be elucidated. In addition to classical mechanisms of viral-triggered autoimmunity, such as molecular mimicry and epitope spreading, there has been a growing appreciation of the role of direct activation of innate response by viral nucleic acids and epigenetic modulation of interferon-related immune response. The latter is especially important for HERVs, which may represent the molecular link between environmental triggers and critical immune genes. Virus-specific proteins modulating interaction with the host immune system have been characterized especially for Epstein-Barr virus and explain immune evasion, persistent infection and self-reactive B-cell "immortalization". Knowledge has also been expanding on key viral proteins of B19-V and CMV and their possible association with specific phenotypes such as antiphospholipid syndrome. This progress may pave the way to new therapeutic perspectives, including the use of known or new antiviral drugs, postviral immune response modulation and innate immunity inhibition. We herein describe the state-of-the-art knowledge on the role of viral infections in SLE, with a focus on their mechanisms of action and potential therapeutic targets.
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15
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Dalbeni A, Romano S, Bevilacqua M, Piccoli A, Imbalzano E, Mantovani A, Benati M, Montagnana M, Donato A, Torin G, Monaco C, Cattazzo F, Tagetti A, Paon V, Ieluzzi D, Iogna Prat L, Roccarina D, Ribichini F, Capra F, Minuz P, Fava C. Beneficial effects of DAAs on cardiac function and structure in hepatitis C patients with low-moderate liver fibrosis. J Viral Hepat 2020; 27:1214-1221. [PMID: 32593212 DOI: 10.1111/jvh.13355] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Revised: 06/06/2020] [Accepted: 06/08/2020] [Indexed: 12/31/2022]
Abstract
Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.
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Affiliation(s)
- Andrea Dalbeni
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.,Division of Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Simone Romano
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Michele Bevilacqua
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Anna Piccoli
- Division of Cardiology, Department of Cardiology, University and Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Egidio Imbalzano
- Division of Internal Medicine, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Anna Mantovani
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.,UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Marco Benati
- Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Biochemistry, University of Verona, Verona, Italy
| | - Martina Montagnana
- Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Biochemistry, University of Verona, Verona, Italy
| | - Angela Donato
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Gioia Torin
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Cinzia Monaco
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Filippo Cattazzo
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Angela Tagetti
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Veronica Paon
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.,Division of Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Donatella Ieluzzi
- Division of Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Laura Iogna Prat
- Division of Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.,UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Davide Roccarina
- UCL Institute for Liver and Digestive Health, Royal Free Hospital and UCL, London, UK
| | - Flavio Ribichini
- Division of Cardiology, Department of Cardiology, University and Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - Franco Capra
- Division of Liver Unit, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Pietro Minuz
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Cristiano Fava
- Division of General Medicine and Hypertension, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
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16
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Efficacy and safety of sofosbuvir-based, interferon-free therapy : The Management of rheumatologic extrahepatic manifestations associated with chronic hepatitis C virus infection. Z Rheumatol 2019; 77:621-628. [PMID: 28795238 DOI: 10.1007/s00393-017-0356-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The use of pegylated interferon alpha (IFN) has been of concern in chronic hepatitis C virus (HCV) patients with rheumatologic extrahepatic manifestations (EHM) due to the immunostimulatory effects of IFN. AIM To study the efficacy and safety of sofosbuvir-based, IFN-free antiviral therapy in chronic HCV patients with rheumatologic EHM. MATERIAL AND METHODS Group A included 24 patients with arthropathy (arthralgia or arthritis, n = 15) or vasculitis (n = 9) who received sofosbuvir and ribavirin (n = 17) or sofosbuvir and simeprevir (n = 7). Group B comprised 15 historical controls suffering from arthropathy who had received IFN and ribavirin. All patients were clinically evaluated and by detection of HCV viremia at baseline (V0), at the end of treatment (V1), 12 weeks after end of treatment (V2) and 24 weeks after end of treatment (V3). RESULTS Sustained viral response was obtained in all patients of group A (100%) versus 12 out of 15 of group B (80%). In group A, the tender joint count (TJC) and visual analogue scale for pain (VAS) improved (p = 0.001 for both) while the swollen joint count (SJC) decreased at V1 (p = 0.001) but returned to baseline values at V3. All vasculitis patients improved. Purpura, arthralgia and leg ulcers disappeared, but peripheral neuropathy persisted. In group B, TJC, SJC and VAS increased from baseline values (p = 0.034, 0.03 and 0.001, respectively). Side effects in group A were generally mild, but one patient developed deterioration of arthralgia. CONCLUSION The use of IFN-free regimens is safe and effective in the treatment of most HCV-related rheumatologic EHM.
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Kuna L, Jakab J, Smolic R, Wu GY, Smolic M. HCV Extrahepatic Manifestations. J Clin Transl Hepatol 2019; 7:172-182. [PMID: 31293918 PMCID: PMC6609844 DOI: 10.14218/jcth.2018.00049] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2018] [Revised: 02/21/2019] [Accepted: 03/17/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) has been shown to affect many tissues other than liver. However, of the many extrahepatic manifestations (EMs) that have been associated with HCV, including cryoglobulinemia, lymphoma, insulin resistance, type 2 diabetes and neurological disorders, only a few have been shown to be directly related to HCV infection of extrahepatic tissues. HCV-triggered immune-mediated mechanisms account for most of the EMs. It is estimated that up to 74% of patients with chronic hepatitis C can develop at least one EM. All HCV patients with EMs should be considered for antiviral therapy, although not all will resolve with sustained virological response.
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Affiliation(s)
- Lucija Kuna
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Jelena Jakab
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Internal Medicine, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - Robert Smolic
- Department of Pathophysiology and Physiology with Immunology, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Pharmacology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
| | - George Y Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Martina Smolic
- Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, J. J. Strossmayer University of Osijek, Osijek, Croatia
- Department of Pharmacology, Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia
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18
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Simoes CC, Saldarriaga OA, Utay NS, Stueck AE, Merwat SK, Merwat SN, Schiano TD, Fiel MI, Stevenson HL. Direct-Acting Antiviral Treatment of Patients with Hepatitis C Resolves Serologic and Histopathologic Features of Autoimmune Hepatitis. Hepatol Commun 2019; 3:1113-1123. [PMID: 31388631 PMCID: PMC6671831 DOI: 10.1002/hep4.1388] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 05/17/2019] [Indexed: 12/15/2022] Open
Abstract
Patients with hepatitis C virus (HCV) often have elevated serum markers and histologic features of autoimmune hepatitis (AIH). We evaluated an HCV-positive (HCV+) study group that had elevated serum markers of AIH before starting direct-acting antiviral (DAA) therapy (n = 21) and compared them to an HCV+ control group that did not have laboratory studies suggesting AIH (n = 21). Several patients in the study (17/21) and control (11/21) groups had liver biopsies before DAA treatment, and many were biopsied due to elevated serum markers of AIH. Evaluation of pre-DAA treatment liver biopsies showed histologic features suggestive of AIH in 64.7% (11/17) of the study group and 45.5% (5/11) of the control group. Patients who were HCV+ with elevated serum markers of AIH had significantly increased hepatitis activity (P < 0.001) and slightly increased fibrosis stages (P = 0.039) in their pretreatment liver biopsies compared to controls. We hypothesized that the elevated serum markers and histologic features of AIH would resolve following DAA treatment. Serum markers of AIH in the study group began decreasing by 6 months posttreatment, and 52.4% (11/21) had complete resolution. Alanine aminotransferase levels significantly decreased into the normal range for all patients (21/21). Even patients that had persistence of serum markers of AIH after DAA treatment had normal transaminases. Six patients from the study patient group and 4 patients from the control group had follow-up liver biopsies after DAA treatment, and all biopsies showed resolution of the histologic features of AIH. Conclusion: The majority of HCV+ patients that have serum markers and/or histopathologic features of AIH should initially be treated with DAA.
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Affiliation(s)
- Camila C Simoes
- Department of Pathology University of Texas Medical Branch Galveston TX
| | | | - Netanya S Utay
- Infectious Disease Division, Department of Internal Medicine University of Texas Health Science Center at Houston Houston TX
| | | | - Sheharyar K Merwat
- Department of Gastroenterology and Hepatology University of Texas Medical Branch Galveston TX
| | - Shehzad N Merwat
- Department of Gastroenterology and Hepatology University of Texas Medical Branch Galveston TX
| | - Thomas D Schiano
- Department of Hepatology Icahn School of Medicine at Mount Sinai New York NY
| | - Maria Isabel Fiel
- Department of Pathology Icahn School of Medicine at Mount Sinai New York NY
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19
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Georgescu SR, Tampa M, Mitran MI, Mitran CI, Sarbu MI, Nicolae I, Matei C, Caruntu C, Neagu M, Popa MI. Potential pathogenic mechanisms involved in the association between lichen planus and hepatitis C virus infection. Exp Ther Med 2018; 17:1045-1051. [PMID: 30679972 DOI: 10.3892/etm.2018.6987] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 08/14/2018] [Indexed: 12/11/2022] Open
Abstract
Lichen planus (LP) is an immune-mediated inflammatory disease that particularly affects the skin and mucous membranes. Its etiology remains elusive, however some trigger factors, including viral or bacterial antigens, drugs and metals, have been postulated. There is a higher prevalence of hepatitis C virus (HCV) infection among patients with LP, with some geographical variations. HCV is an enveloped RNA virus that belongs to the Flaviviridae family and in most instances causes chronic liver infections. It has been hypothesized that HCV may contribute to LP development, but the link between the two disorders is not fully understood. It is still debatable whether HCV leads to the occurrence of LP lesions directly by replication inside the infected cells or indirectly by activating immunological pathways. Molecular studies have revealed HCV RNA in specimens collected from patients with LP. The autoimmune theory was also suggested given that several studies have revealed viral replication and immune response activation associated with autoantibody synthesis. The aim of this review is to summarize the main potential mechanisms involved in the association between LP and HCV infection. Understanding the link between the two disorders may shed some light on the pathogenesis of LP, which is a challenging issue.
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Affiliation(s)
- Simona Roxana Georgescu
- Department of Dermatology, 'Victor Babes' Clinical Hospital for Infectious Diseases, 030303 Bucharest, Romania.,Department of Dermatology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Mircea Tampa
- Department of Dermatology, 'Victor Babes' Clinical Hospital for Infectious Diseases, 030303 Bucharest, Romania.,Department of Dermatology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Madalina Irina Mitran
- Department of Dermatology, 'Victor Babes' Clinical Hospital for Infectious Diseases, 030303 Bucharest, Romania.,Department of Microbiology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Cristina Iulia Mitran
- Department of Dermatology, 'Victor Babes' Clinical Hospital for Infectious Diseases, 030303 Bucharest, Romania.,Department of Microbiology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Maria Isabela Sarbu
- Department of Dermatology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ilinca Nicolae
- Department of Dermatology, 'Victor Babes' Clinical Hospital for Infectious Diseases, 030303 Bucharest, Romania
| | - Clara Matei
- Department of Dermatology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Constantin Caruntu
- Department of Dermatology, 'Prof. N. Paulescu' National Institute of Diabetes, Nutrition and Metabolic Diseases, 011233 Bucharest, Romania.,Department of Physiology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Monica Neagu
- Department of Immunology, 'Victor Babes' National Institute of Pathology, 050096 Bucharest, Romania.,Faculty of Biology University of Bucharest, 050095 Bucharest, Romania
| | - Mircea Ioan Popa
- Department of Microbiology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,'Cantacuzino' National Medico-Military Institute for Research and Development, 050096 Bucharest, Romania
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20
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Kuwano T, Akuta N, Suzuki F, Fujiyama S, Kawamura Y, Sezaki H, Hosaka T, Saitoh S, Kobayashi M, Suzuki Y, Kobayashi M, Arase Y, Ikeda K, Kumada H. A Patient with HCV Infection and a Sustained Virological Response to Direct-acting Antiviral Treatment Who Developed Inclusion Body Myositis. Intern Med 2018; 57:2511-2515. [PMID: 29607961 PMCID: PMC6172544 DOI: 10.2169/internalmedicine.0585-17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
We report the case of a 75-year-old woman who was found to have hepatitis C virus (HCV) infection in 1987. Before treatment in 2016, she was found to have mixed cryoglobulinemia (MC). Direct-acting antiviral (DAA) treatment produced a sustained virological response 12 (SVR12). She noticed gradual muscle weakness in 2015 and the gradual development of dysarthria and dysphagia in 2017. We performed a muscle biopsy that showed inclusion body myositis (IBM). To the best of our knowledge, this is first case of a patient with HCV infection, MC, and IBM, in which MC and IBM did not improve after an SVR12 was obtained by DAA treatment.
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Affiliation(s)
- Toru Kuwano
- Department of Hepatology, Toranomon Hospital, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Japan
| | | | | | | | | | | | | | | | | | | | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Japan
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21
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Chong LW, Hsu CC, Lee CY, Chou RH, Lin CL, Chang KH, Hsu YC. Association of viral hepatitis and bipolar disorder: a nationwide population-based study. J Transl Med 2018; 16:173. [PMID: 29929549 PMCID: PMC6013873 DOI: 10.1186/s12967-018-1542-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 06/07/2018] [Indexed: 12/14/2022] Open
Abstract
Background Bipolar disorder (BD), a type of psychiatric mood disorder, is manifested by chronic and recurrent mood fluctuations. This study aims to determine whether hepatitis B virus (HBV) or hepatitis C virus (HCV) infection is a risk factor for BD. Methods A total of 48,215 patients with newly diagnosed viral hepatitis from 2000 to 2010 were identified and frequency-matched with 192,860 people without hepatitis. Both groups were followed until diagnosis with BD, withdrawal from the national health insurance program, or the end of 2011. Patients with viral hepatitis were grouped into 3 cohorts: HBV infection, HCV infection, and HBV/HCV coinfection. The association between viral hepatitis and BD were examined using Cox proportional hazards regression models. Results The incidence of BD was higher in HBV/HCV coinfection than in the control group, with an adjusted hazard ratio of 2.16 (95% confidence interval 1.06–4.41) when adjusted for sex, age, and comorbidity. After further adjustment, we noted that an age more than 65 years and female may be associated with an increased risk of BD in patients with chronic hepatitis B and C. Conclusion Viral hepatitis may be associated with increased risk of subsequent BD. Electronic supplementary material The online version of this article (10.1186/s12967-018-1542-3) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.,School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chih-Chao Hsu
- Division of Psychiatry, Taitung Branch, Taipei Veterans General Hospital, Taitung, Taiwan
| | - Chang-Yin Lee
- College of Medicine, The School of Chinese Medicine for Post Baccalaureate, I-Shou University (Yancho Campus), Kaohsiung, Taiwan.,Department of Chinese Medicine, E-DA Hospital, Kaohsiung, Taiwan.,Department of Chinese Medicine, E-DA Cancer Hospital, Kaohsiung, Taiwan
| | - Ruey-Hwang Chou
- Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung, Taiwan.,Department of Biotechnology, Asia University, Taichung, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Kuang-Hsi Chang
- Department of Medical Research, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan. .,Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
| | - Yi-Chao Hsu
- Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan.
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22
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Mahroum N, Hejly A, Tiosano S, Gendelman O, Comaneshter D, Cohen AD, Amital H. Chronic hepatitis C viral infection among SLE patients: the significance of coexistence. Immunol Res 2018; 65:477-481. [PMID: 28111706 DOI: 10.1007/s12026-016-8886-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The association between viral infection and autoimmune diseases is an established phenomenon in medicine. Hepatitis C viral infection is known to have such an association; however, its association with systemic lupus erythematosus has not been studied in a real life study driven from a large national database. The objective of this study was to investigate the association between SLE and chronic hepatitis C viral infection. Patients with SLE were compared with age- and sex-matched controls regarding the proportion chronic HCV infection. Chi-square and t tests were used for univariate analysis, and a logistic regression model was used for multivariate analysis. The study was performed utilizing the medical database of Clalit Health Services in Israel. There was a significant higher proportion of hepatitis C viral infection in SLE patients as compared to controls (1.06 and 0.39%, respectively; p < 0.001). A significant association was also observed among patients of higher socioeconomic status. In a multivariate logistic regression analysis, SLE was significantly associated with hepatitis C viral infection (OR = 2.07, 95% CI = 1.46-2.90). To conclude, Patients with SLE have a greater proportion of chronic HCV infection than matched controls.
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Affiliation(s)
- Naim Mahroum
- Department of Medicine 'B', Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Ashraf Hejly
- Department of Medicine 'B', Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Shmuel Tiosano
- Department of Medicine 'B', Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | - Omer Gendelman
- Department of Medicine 'B', Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100, Israel
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel
| | | | - Arnon D Cohen
- Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel
- Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel
| | - Howard Amital
- Department of Medicine 'B', Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, 5262100, Israel.
- Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel.
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23
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Túlio M, Carvalho L, Bana E Costa T, Chagas C. Mixed cryoglobulinemia: a diagnostic and therapeutic challenge. BMJ Case Rep 2017; 2017:bcr-2017-219768. [PMID: 28490478 DOI: 10.1136/bcr-2017-219768] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Mixed cryoglobulinemia is frequently secondary to hepatitis C virus infection. Diagnosis and therapeutic management are challenging, depending on the spectrum and severity of manifestations, as well as on the presence of comorbidities. We describe a case of a 79-year-old woman with a non-cirrhotic hepatitis C virus infection presenting with weakness, arthralgias, purpuric rash with left leg ulcerative lesions, bilateral peripheral sensorimotor polyneuropathy, renal impairment and cardiac failure. The investigation was compatible with a severe type II mixed cryoglobulinemia with multisystemic involvement, including a low-grade B cell lymphoma and concomitant intestinal tuberculosis. Initial management with immunosuppressive therapy with glucocorticoids to control symptoms and simultaneous tuberculosis treatment was required. Unavailability of adequate antiviral treatment led to the need to control the severity of systemic manifestations with rituximab, before the effective aetiological treatment with sofosbuvir and ledipasvir was possible, allowing the definitive resolution of the disease.
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Affiliation(s)
- Maria Túlio
- Department of Gastroenterology, Hospital de Egas Moniz, Lisboa, Portugal
| | - Liliana Carvalho
- Department of Gastroenterology, Hospital de Egas Moniz, Lisboa, Portugal
| | - Tiago Bana E Costa
- Department of Gastroenterology, Hospital de Egas Moniz, Lisboa, Portugal
| | - Cristina Chagas
- Department of Gastroenterology, Hospital de Egas Moniz, Lisboa, Portugal
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24
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Wiznia LE, Laird ME, Franks AG. Hepatitis C virus and its cutaneous manifestations: treatment in the direct-acting antiviral era. J Eur Acad Dermatol Venereol 2017; 31:1260-1270. [PMID: 28252812 DOI: 10.1111/jdv.14186] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Accepted: 02/16/2017] [Indexed: 12/21/2022]
Abstract
New all-oral direct-acting antivirals (DAA) have changed the hepatitis C virus (HCV) treatment landscape. Given that dermatologists frequently encounter HCV-infected patients, knowledge of the current treatment options and their utility in treating HCV-associated dermatologic disorders is important. In addition to highlighting the new treatment options, we review four classically HCV-associated dermatologic disorders - mixed cryoglobulinaemia (MC), lichen planus (LP), porphyria cutanea tarda (PCT) and necrolytic acral erythema (NAE) - and examine the role for all-oral direct-acting antiviral (DAA) regimens in their treatment. A literature search of English-language publications was conducted of the PubMed and EMBASE databases using search terms including 'hepatitis C', 'direct acting antivirals', 'cutaneous', 'mixed cryoglobulinemia', 'necrolytic acral erythema', 'lichen planus', 'porphyria cutanea tarda', 'rash', as well as specific drug names, related terms and abbreviations. Currently, limited data exist on the use of DAAs in HCV-infected patients with cutaneous side-effects, although treatment of the underlying HCV is now recommended for nearly all patients, with the new drugs offering much-improved dosage schedules and side-effect profiles. The most data exist for MC, in which several studies suggest that DAAs and achievement of sustained virologic response (SVR) improve cutaneous symptoms. Studies of both older and newer regimens are limited by their small size, retrospective nature, lack of appropriate controls and wide variability in study protocols. Given the strong association, screening for HCV should be considered in patients with MC, LP, PCT and NAE.
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Affiliation(s)
- L E Wiznia
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA
| | - M E Laird
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA
| | - A G Franks
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA
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Wang RY, Bare P, De Giorgi V, Matsuura K, Salam KA, Grandinetti T, Schechterly C, Alter HJ. Preferential association of hepatitis C virus with CD19 + B cells is mediated by complement system. Hepatology 2016; 64:1900-1910. [PMID: 27641977 PMCID: PMC5115962 DOI: 10.1002/hep.28842] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 08/08/2016] [Accepted: 08/21/2016] [Indexed: 02/06/2023]
Abstract
Extrahepatic disease manifestations are common in chronic hepatitis C virus (HCV) infection. The mechanism of HCV-related lymphoproliferative disorders is not fully understood. Recent studies have found that HCV in peripheral blood mononuclear cells from chronically infected patients is mainly associated with cluster of differentiation 19-positive (CD19+ ) B cells. To further elucidate this preferential association of HCV with B cells, we used in vitro cultured virus and uninfected peripheral blood mononuclear cells from healthy blood donors to investigate the necessary serum components that activate the binding of HCV to B cells. First, we found that the active serum components were present not only in HCV carriers but also in HCV recovered patients and HCV-negative, healthy blood donors and that the serum components were heat-labile. Second, the preferential binding activity of HCV to B cells could be blocked by anti-complement C3 antibodies. In experiments with complement-depleted serum and purified complement proteins, we demonstrated that complement proteins C1, C2, and C3 were required to activate such binding activity. Complement protein C4 was partially involved in this process. Third, using antibodies against cell surface markers, we showed that the binding complex mainly involved CD21 (complement receptor 2), CD19, CD20, and CD81; CD35 (complement receptor 1) was involved but had lower binding activity. Fourth, both anti-CD21 and anti-CD35 antibodies could block the binding of patient-derived HCV to B cells. Fifth, complement also mediated HCV binding to Raji cells, a cultured B-cell line derived from Burkitt's lymphoma. CONCLUSION In chronic HCV infection, the preferential association of HCV with B cells is mediated by the complement system, mainly through complement receptor 2 (CD21), in conjunction with the CD19 and CD81 complex. (Hepatology 2016;64:1900-1910).
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Affiliation(s)
- Richard Y. Wang
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Patricia Bare
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
- Instituto de Investigaciones Hematológicas, Instituto de Medicina Experimental, CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina
| | - Valeria De Giorgi
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Kentaro Matsuura
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Kazi Abdus Salam
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh
| | - Teresa Grandinetti
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Cathy Schechterly
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
| | - Harvey J. Alter
- Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD
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Suzuki S, Mori KI, Higashino A, Iwasaki Y, Yasutomi Y, Maki N, Akari H. Persistent replication of a hepatitis C virus genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B in a New World monkey. Microbiol Immunol 2016; 60:26-34. [PMID: 26634303 DOI: 10.1111/1348-0421.12349] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 11/26/2015] [Accepted: 11/30/2015] [Indexed: 12/22/2022]
Abstract
The development of effective hepatitis C virus (HCV) vaccines is essential for the prevention of further HCV dissemination, especially in developing countries. Therefore the aim of this study is to establish a feasible and immunocompetent surrogate animal model of HCV infection that will help in evaluation of the protective efficacy of newly developing HCV vaccine candidates. To circumvent the narrow host range of HCV, an HCV genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B (GBV-B), which is closely related to HCV, was generated. The chimera between HCV and GBV-B, named HCV/G, replicated more efficiently as compared with the HCV clone in primary marmoset hepatocytes. Furthermore, it was found that the chimera persistently replicated in a tamarin for more than 2 years after intrahepatic inoculation of the chimeric RNA. Although relatively low (<200 copies/mL), the viral RNA loads in plasma were detectable intermittently during the observation period. Of note, the chimeric RNA was found in the pellet fraction obtained by ultracentrifugation of the plasma at 73 weeks, indicating production of the chimeric virus. Our results will help establish a novel non-human primate model for HCV infection on the basis of the HCV/G chimera in the major framework of the HCV genome.
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Affiliation(s)
- Saori Suzuki
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506
| | - Ken-Ichi Mori
- Advanced Life Science Institute, 2-10-23 Maruyamadai, Wako, Saitama 351-0112
| | - Atsunori Higashino
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506
| | - Yuki Iwasaki
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506
| | - Yasuhiro Yasutomi
- Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843
| | - Noboru Maki
- Advanced Life Science Institute, 2-10-23 Maruyamadai, Wako, Saitama 351-0112
| | - Hirofumi Akari
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506.,Laboratory of Evolutional Virology, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
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Younossi ZM, Park H, Dieterich D, Saab S, Ahmed A, Gordon SC. Assessment of cost of innovation versus the value of health gains associated with treatment of chronic hepatitis C in the United States: The quality-adjusted cost of care. Medicine (Baltimore) 2016; 95:e5048. [PMID: 27741116 PMCID: PMC5072943 DOI: 10.1097/md.0000000000005048] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND New direct-acting antiviral (DAA) therapy has dramatically increased cure rates for patients infected with hepatitis C virus (HCV), but has also substantially raised treatment costs. AIM The aim of this analysis was to evaluate the therapeutic benefit and net costs (i.e. efficiency frontier) and the quality-adjusted cost of care associated with the evolution of treatment regimens for patients with HCV genotype 1 in the United States. DESIGN A decision-analytic Markov model. DATA SOURCE Published literature and clinical trial data. TIME HORIZON Life Time. PERSPECTIVE Third-party payer. INTERVENTION This study compared four approved regimens in treatment-naïve genotype 1 chronic hepatitis C patients, including pegylated interferon and ribavirin (PR), first generation triple therapy (boceprevir + PR and telaprevir + PR), second generation triple therapy (sofosbuvir + PR and simeprevir + PR) and all-oral DAA regimens (ledipasvir/sofosbuvir and ombitasvir + paritaprevir/ritonavir + dasabuvir ± ribavirin). OUTCOME MEASURE Quality-adjusted cost of care (QACC). QACC was defined as the increase in treatment cost minus the increase in the patient's quality-adjusted life years (QALYs) when valued at $50,000 per QALY. RESULTS All-oral therapy improved the average sustained virologic response (SVR) rate to 96%, thereby offsetting the high drug acquisition cost of $85,714, which resulted in the highest benefit based on the efficiency frontier. Furthermore, while oral therapies increased HCV drug costs by $48,350, associated QALY gains decreased quality-adjusted cost of care by $14,120 compared to dual therapy. When the value of a QALY was varied from $100,000 to $300,000, the quality adjusted cost of care compared to dual therapy ranged from - $21,234 to - $107,861, - $89,007 to - $293,130, - $176,280 to - $500,599 for first generation triple, second generation triple, and all-oral therapies, respectively. Primary efficacy and safety measurements for drug regimens were sourced from clinical trials data rather than a real-world setting. Factors such as individual demographic characteristics, comorbidities and alcohol consumption of the individual patients treated may alter disease progression but were not captured in this analysis. CONCLUSION New DAA treatments provide short-term and long-term clinical and economic value to society. PRIMARY FUNDING SOURCE Gilead Sciences, Inc.
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Affiliation(s)
- Zobair M. Younossi
- Center For Liver Disease, Department of Medicine, Inova Fairfax Hospital
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA
- Correspondence: Zobair M. Younossi, Betty and Guy Beatty Center for Integrated Research, Claude Moore Health Education and Research Building, 3300 Gallows Road, Falls Church, VA 22042 (e-mail: )
| | | | | | - Sammy Saab
- University of California, Los Angeles, Los Angeles
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Domont F, Cacoub P. Chronic hepatitis C virus infection, a new cardiovascular risk factor? Liver Int 2016; 36:621-7. [PMID: 26763484 DOI: 10.1111/liv.13064] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 12/31/2015] [Indexed: 12/13/2022]
Abstract
Among the large scope of extrahepatic manifestations related to hepatitis C virus (HCV) infection, many studies recently evaluated the frequency and characteristics of cardiovascular involvement. To assess the current published data on HCV infection and cardiovascular diseases. Published studies on cardiovascular disease, i.e. cerebrovascular accident and ischaemic heart disease in subjects with HCV infection were analysed from literature databases. Subjects with HCV chronic infection have an increased prevalence of carotid atherosclerosis and increased intima-media thickness compared to healthy controls or those with hepatitis B or non-alcoholic steatohepatitis. Active chronic HCV infection appears as an independent risk factor for ischaemic cerebrovascular accidents. Active chronic HCV infection is associated with increased risk of ischaemic heart disease. In some studies, successful interferon-based therapy showed a beneficial impact on the cardiovascular risk. The risk of major cardiovascular events is higher in patients with HCV infection compared to controls, independent of the severity of the liver disease or the common cardiovascular risk factors. The beneficial impact of interferon-based therapy needs to be confirmed with new direct antiviral interferon-free agents in prospective studies with extended follow-up.
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Affiliation(s)
- Fanny Domont
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, Paris, France.,Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Patrice Cacoub
- Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, Paris, France.,Department of Internal Medicine and Clinical Immunology, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.,INSERM, UMR-S 959, Paris, France.,CNRS, FRE3632, Paris, France
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29
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Mathew S, Faheem M, Ibrahim SM, Iqbal W, Rauff B, Fatima K, Qadri I. Hepatitis C virus and neurological damage. World J Hepatol 2016; 8:545-556. [PMID: 27134702 PMCID: PMC4840160 DOI: 10.4254/wjh.v8.i12.545] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2015] [Revised: 03/19/2016] [Accepted: 04/07/2016] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis C virus (HCV) infection exhibits a wide range of extrahepatic complications, affecting various organs in the human body. Numerous HCV patients suffer neurological manifestations, ranging from cognitive impairment to peripheral neuropathy. Overexpression of the host immune response leads to the production of immune complexes, cryoglobulins, as well as autoantibodies, which is a major pathogenic mechanism responsible for nervous system dysfunction. Alternatively circulating inflammatory cytokines and chemokines and HCV replication in neurons is another factor that severely affects the nervous system. Furthermore, HCV infection causes both sensory and motor peripheral neuropathy in the mixed cryoglobulinemia as well as known as an important risk aspect for stroke. These extrahepatic manifestations are the reason behind underlying hepatic encephalopathy and chronic liver disease. The brain is an apt location for HCV replication, where the HCV virus may directly wield neurotoxicity. Other mechanisms that takes place by chronic HCV infection due the pathogenesis of neuropsychiatric disorders includes derangement of metabolic pathways of infected cells, autoimmune disorders, systemic or cerebral inflammation and alterations in neurotransmitter circuits. HCV and its pathogenic role is suggested by enhancement of psychiatric and neurological symptoms in patients attaining a sustained virologic response followed by treatment with interferon; however, further studies are required to fully assess the impact of HCV infection and its specific antiviral targets associated with neuropsychiatric disorders.
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Affiliation(s)
- Shilu Mathew
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Muhammed Faheem
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Sara M Ibrahim
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Waqas Iqbal
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Bisma Rauff
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Kaneez Fatima
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Ishtiaq Qadri
- Shilu Mathew, Muhammed Faheem, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah 21589, Saudi Arabia
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30
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Younossi ZM, LaLuna LL, Santoro JJ, Mendes F, Araya V, Ravendhran N, Pedicone L, Lio I, Nader F, Hunt S, Racila A, Stepanova M. Implementation of baby boomer hepatitis C screening and linking to care in gastroenterology practices: a multi-center pilot study. BMC Gastroenterol 2016; 16:45. [PMID: 27044402 PMCID: PMC4820944 DOI: 10.1186/s12876-016-0438-z] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Accepted: 02/17/2016] [Indexed: 02/08/2023] Open
Abstract
Background Estimates suggest that only 20 % of HCV-infected patients have been identified and <10 % treated. However, baby boomers (1945-1965) are identified as having a higher prevalence of HCV which has led the Centers for Disease Control and Prevention to make screening recommendations. The aim of this study was to implement the CDC’s screening recommendations in the unique setting of gastroenterology practices in patients previously unscreened for HCV. Methods After obtaining patient informed consent, demographics, clinical and health-related quality of life (HRQOL) data were collected. A blood sample was screened for HCV antibody (HCV AB) using the OraQuick HCV Rapid Antibody Test. HCV AB-positive patients were tested for presence of HCV RNA and, if HCV RNA positive, patients underwent treatment discussions. Results We screened 2,000 individuals in 5 gastroenterology centers located close to large metropolitan areas on the East Coast (3 Northeast, 1 Mid-Atlantic and 1 Southeast). Of the screened population, 10 individuals (0.5 %) were HCV AB-positive. HCV RNA testing was performed in 90 % (9/10) of HCV AB-positive individuals. Of those, 44.4 % (4/9) were HCV RNA-positive, and all 4 (100 %) were linked to caregiver. Compared to HCV AB negative subjects, HCV AB-positive individuals tended to be black (20.0 vs. 5.2 %, p = 0.09) and reported significantly higher rates of depression: 60.0 vs. 21.5 %, p = 0.009. These individuals also reported a significantly lower HRQOL citing having more fatigue, poorer concentration, and a decreased level of energy (p < 0.05). Discussion Although the prevalence of HCV AB-positive was low in previously unscreened subjects screened in the gastroenterology centers, the linkage to care was very high. The sample of patients used in this study may be biased, so further studies are needed to assess the effectiveness of the CDC screening recommendations. Conclusion Implementation of the Baby Boomer Screening for HCV requires identifying screening environement with high prevalence of HCV+ individuals as well as an efficient process of linking them to care.
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Affiliation(s)
- Zobair M Younossi
- Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA, USA. .,Center for Outcomes Research in Liver Diseases, Washington, DC, USA. .,Betty and Guy Beatty Center for Integrated Research, Claude Moore Health Education and Research Building, 3300 Gallows Road, Falls Church, VA, 22042, USA.
| | | | - John J Santoro
- AGA Clinical Research Associates, LLC, Egg Harbor Township, NJ, USA
| | | | - Victor Araya
- Central Bucks Specialists, Gastroenterology, Doylestown, PA, USA
| | | | - Lisa Pedicone
- Cantara Clinical Solutions, LLC, Morristown, NJ, USA
| | - Idania Lio
- Cantara Clinical Solutions, LLC, Morristown, NJ, USA
| | - Fatema Nader
- Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - Sharon Hunt
- Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - Andrei Racila
- Center for Outcomes Research in Liver Diseases, Washington, DC, USA
| | - Maria Stepanova
- Center for Outcomes Research in Liver Diseases, Washington, DC, USA
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31
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Cryoglobulinaemia in Egyptian Patients with Extrahepatic Cutaneous Manifestations of Chronic Hepatitis C Virus Infection. Dermatol Res Pract 2015; 2015:182609. [PMID: 26839534 PMCID: PMC4709666 DOI: 10.1155/2015/182609] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Accepted: 12/14/2015] [Indexed: 02/06/2023] Open
Abstract
Background. Hepatitis C is a global major health problem with extremely variable extrahepatic manifestations. Mixed cryoglobulinaemia (MC) shows a striking association with hepatitis C virus (HCV) infection, and it is sometimes asymptomatic. The skin is a frequently involved target organ in MC. Objective. To investigate the prevalence of cryoglobulinaemia in a sample of Egyptian patients with cutaneous manifestations of chronic HCV infection and to correlate its presence with clinical criteria and liver function tests. Methods. One hundred and eighteen patients with skin manifestations of chronic compensated hepatitis C were included. Venous blood was tested for liver function tests and serum cryoglobulins. Results. Twelve patients (10.169%) were positive for serum cryoglobulins (2 with pruritus, 4 with vasculitic lesions, 3 with livedo reticularis, one with oral lichen, one with chronic urticaria, and another with Schamberg's disease). Vasculitic lesions and livedo reticularis of the legs showed higher prevalence in cryoglobulin-positive than in cryoglobulin-negative patients. Presence of serum cryoglobulins did not relate to patients' demographic or laboratory findings. Conclusions. Fortunately, MC is not markedly prevalent among Egyptians with cutaneous lesions of chronic hepatitis C, and cryopositivity was commonly, but not exclusively, detected with cutaneous vasculitis and livedo reticularis. Laboratory testing for cryoglobulins in every HCV patient is advisable for earlier MC detection and management.
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Oliveira IS, Carvalho LP, Schinoni MI, Paraná R, Atta AM, Atta MLBS. Peripheral lymphocyte subsets in chronic hepatitis C: Effects of 12 weeks of antiviral treatment with interferon-alpha plus ribavirin. Microb Pathog 2015; 91:155-60. [PMID: 26718098 DOI: 10.1016/j.micpath.2015.12.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Revised: 11/04/2015] [Accepted: 12/17/2015] [Indexed: 12/24/2022]
Abstract
Chronic infection with hepatitis C virus (HCV) causes a quantitative and functional alteration in innate and adaptative immunity. In the present work, we determined by flow-cytometry the profile of blood lymphocyte of untreated HCV patients and in subjects of this group that achieved or not an early virologic response at 12-weeks of treatment with interferon-α plus ribavirin. Twenty-six untreated HCV patients and 20 control healthy individuals were enrolled in the study. Untreated HCV patients had a higher proportion of B cell and a lower proportion of CD8(+) T cell and NK cells than healthy individuals did, but the proportions of CD4(+) T cells and Treg cells (CD4(+)CD25(+)Foxp3(+)) were similar in these patients and controls. Untreated HCV patients presenting cryoglobulinemia had a lower proportion of Treg cells and a lower Treg/NK cell ratio when compared with those without cryoglobulins. Nineteen out of 26 untreated HCV patients remained in the study and were treated with Interferon-α plus ribavirin. At 12-weeks of treatment, 10 of them achieved early virologic response (EVR), whereas 9 were non-responders (NR). EVR patients differed from NR patients in the increase of their proportion of NK cells at 12 weeks of treatment. In conclusion, untreated HCV patients exhibit an altered profile of blood lymphocyte subsets, including a reduction in the proportion of CD4(+)CD25(+)FoxP3(+)T regulatory cells in patients that present cryoglobulinemia. An early virological response at 12-weeks of treatment with IFN-α plus ribavirin seems to be associated a significant improvement in the proportion of NK cells of HCV treated patients.
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Affiliation(s)
- Isabela S Oliveira
- Programa de Pós-Graduação em Imunologia, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Lucas P Carvalho
- Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Maria Isabel Schinoni
- Serviço de Gastro-Hepatologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Raymundo Paraná
- Serviço de Gastro-Hepatologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, BA, Brazil
| | - Ajax M Atta
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal da Bahia, 40170115, Rua Barão de Jeremoabo s/n, Salvador, BA, Brazil
| | - Maria Luiza B Sousa Atta
- Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal da Bahia, 40170115, Rua Barão de Jeremoabo s/n, Salvador, BA, Brazil
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Extrahepatic comorbidities associated with hepatitis C virus in HIV-infected patients. Curr Opin HIV AIDS 2015; 10:309-15. [DOI: 10.1097/coh.0000000000000175] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Soriano V, Labarga P, Fernandez-Montero JV, de Mendoza C, Esposito I, Benítez-Gutiérrez L, Barreiro P. Hepatitis C cure with antiviral therapy – benefits beyond the liver. Antivir Ther 2015; 21:1-8. [DOI: 10.3851/imp2975] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2015] [Indexed: 02/07/2023]
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