RESUMEN
Viral hepatitis represents a major danger to public health, and is a globally leading cause of death. The five liver-specific viruses: Hepatitis A virus, hepatitis B virus, hepatitis C virus, hepatitis D virus, and hepatitis E virus, each have their own unique epidemiology, structural biology, transmission, endemic patterns, risk of liver complications, and response to antiviral therapies. There remain few options for treatment, in spite of the increasing prevalence of viral-hepatitis-caused liver disease. Furthermore, chronic viral hepatitis is a leading worldwide cause of both liver-related morbidity and mortality, even though effective treatments are available that could reduce or prevent most patients' complications. In 2016, the World Health Organization released its plan to eliminate viral hepatitis as a public health threat by the year 2030, along with a discussion of current gaps and prospects for both regional and global eradication of viral hepatitis. Today, treatment is sufficiently able to prevent the disease from reaching advanced phases. However, future therapies must be extremely safe, and should ideally limit the period of treatment necessary. A better understanding of pathogenesis will prove beneficial in the development of potential treatment strategies targeting infections by viral hepatitis. This review aims to summarize the current state of knowledge on each type of viral hepatitis, together with major innovations.
Asunto(s)
Antivirales , Hepatitis Viral Humana , Humanos , Antivirales/uso terapéutico , Hepatitis Viral Humana/epidemiología , Hepatitis Viral Humana/virología , Hepatitis Viral Humana/terapia , Hepatitis Viral Humana/diagnóstico , Virus de Hepatitis/patogenicidad , Virus de Hepatitis/efectos de los fármacos , Virus de Hepatitis/genética , Prevalencia , Hígado/virología , Hígado/patologíaRESUMEN
Although human hepatocyte-transplanted immunodeficient mice support infection with hepatitis viruses, these mice fail to develop viral hepatitis due to the lack of an adaptive immune system. In this study, we generated new immunodeficiency cDNA-urokinase-type plasminogen activator (uPA)/SCID/Rag2-/- /Jak3-/- mice and established a mouse model with both a humanized liver and immune system. Transplantation of human hepatocytes with human leukocyte antigen (HLA)-A24 resulted in establishment of a highly replaced liver in cDNA-uPA/SCID/Rag2-/- /Jak3-/- mice. These mice were successfully infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) for a prolonged period and facilitate analysis of the effect of anti-HCV drugs. Administration of peripheral blood mononuclear cells (PBMCs) obtained from an HLA-A24 donor resulted in establishment of 22.6%-81.3% human CD45-positive mononuclear cell chimerism in liver-infiltrating cells without causing graft-versus-host disease in cDNA-uPA/SCID/Rag2-/- /Jak3-/- mice without human hepatocyte transplantation. When mice were transplanted with human hepatocytes and then administered HLA-A24-positive human PBMCs, an alloimmune response between transplanted human hepatocytes and PBMCs occurred, with production of transplanted hepatocyte-specific anti-HLA antibody. In conclusion, we succeeded in establishing a humanized liver/immune system characterized by an allo-reaction between transplanted human immune cells and human liver using a novel cDNA-uPA/SCID/Rag2-/- /Jak3-/- mouse. This mouse model can be used to generate a chronic hepatitis mouse model with a human immune system with application not only to hepatitis virus virology but also to investigation of the pathology of post-transplantation liver rejection.
Asunto(s)
Hepatitis C , Virus de Hepatitis , Animales , Humanos , Ratones , Modelos Animales de Enfermedad , ADN Complementario , Hepacivirus , Hepatitis C/inmunología , Hepatitis C/patología , Virus de Hepatitis/patogenicidad , Hepatocitos , Antígeno HLA-A24 , Janus Quinasa 3/inmunología , Janus Quinasa 3/metabolismo , Leucocitos Mononucleares , Hígado/patología , Ratones SCID , Ratones Transgénicos , Activador de Plasminógeno de Tipo Uroquinasa/genéticaRESUMEN
Commonly misused substances such as alcohol, cocaine, heroin, methamphetamine, and opioids suppress immune responses and may impact viral pathogenesis. In recent years, illicit use of opioids has fueled outbreaks of several viral pathogens, including the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). This review focuses on the myriad of mechanisms by which drugs of abuse impact viral replication and disease progression. Virus-drug interactions can accelerate viral disease progression and lead to increased risk of virus transmission.
Asunto(s)
Infecciones por VIH/virología , VIH/efectos de los fármacos , Virus de Hepatitis/efectos de los fármacos , Hepatitis/virología , Drogas Ilícitas/efectos adversos , Trastornos Relacionados con Sustancias/virología , Animales , VIH/genética , VIH/patogenicidad , VIH/fisiología , Infecciones por VIH/inmunología , Hepatitis/inmunología , Virus de Hepatitis/genética , Virus de Hepatitis/patogenicidad , Virus de Hepatitis/fisiología , Humanos , Trastornos Relacionados con Sustancias/inmunologíaRESUMEN
Aflatoxin exposure is a crucial factor in promoting the development of primary hepatocellular carcinoma (HCC) in individuals infected with the hepatitis virus. However, the molecular pathways leading to its bioactivation and subsequent toxicity in hepatocytes have not been well-defined. Here, we carried out a genome-wide CRISPR-Cas9 genetic screen to identify aflatoxin B1 (AFB1) targets. Among the most significant hits was the aryl hydrocarbon receptor (AHR), a ligand-binding transcription factor regulating cell metabolism, differentiation, and immunity. AHR-deficient cells tolerated high concentrations of AFB1, in which AFB1 adduct formation was significantly decreased. AFB1 triggered AHR nuclear translocation by directly binding to its N-terminus. Furthermore, AHR mediated the expression of P450 induced by AFB1. AHR expression was also elevated in primary tumor sections obtained from AFB1-HCC patients, which paralleled the upregulation of PD-L1, a clinically relevant immune regulator. Finally, anti-PD-L1 therapy exhibited greater efficacy in HCC xenografts derived from cells with ectopic expression of AHR. These results demonstrated that AHR was required for the AFB1 toxicity associated with HCC, and implicate the immunosuppressive regimen of anti-PD-L1 as a therapeutic option for the treatment of AFB1-associated HCCs.
Asunto(s)
Antígeno B7-H1/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Receptores de Hidrocarburo de Aril/genética , Transporte Activo de Núcleo Celular/efectos de los fármacos , Aflatoxina B1/farmacología , Animales , Antígeno B7-H1/antagonistas & inhibidores , Sistemas CRISPR-Cas/efectos de los fármacos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Genoma Humano/efectos de los fármacos , Virus de Hepatitis/patogenicidad , Hepatocitos/efectos de los fármacos , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/virología , Ratones , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The liver is well recognized as a non-immunological visceral organ that is involved in various metabolic activities, nutrient storage, and detoxification. Recently, many studies have demonstrated that resident immune cells in the liver drive various immunological reactions by means of several molecular modulators. Understanding the mechanistic details of interactions between hepatic host immune cells, including Kupffer cells and lymphocytes, and various hepatic pathogens, especially viruses, bacteria, and parasites, is necessary. MicroRNAs (miRNAs), over 2600 of which have been discovered, are small, endogenous, interfering, noncoding RNAs that are predicted to regulate more than 15,000 genes by degrading specific messenger RNAs. Several recent studies have demonstrated that some miRNAs are associated with the immune response to pathogens in the liver. However, the details of the underlying mechanisms of miRNA interference in hepatic host-pathogen interactions still remain elusive. In this review, we summarize the relationship between the immunological interactions of various pathogens and hepatic resident immune cells, as well as the role of miRNAs in the maintenance of liver immunity against pathogens.
Asunto(s)
Interacciones Huésped-Patógeno/genética , Hígado/microbiología , Hígado/parasitología , Hígado/virología , MicroARNs/genética , Animales , Regulación de la Expresión Génica , Hepatitis/genética , Virus de Hepatitis/patogenicidad , Humanos , Hígado/inmunología , Absceso Hepático/genética , Absceso Hepático/microbiología , Enfermedad Inflamatoria Pélvica/genética , Peritonitis/genética , Peritonitis/microbiologíaAsunto(s)
Enfermedades del Sistema Digestivo/mortalidad , Gastroenterólogos/educación , Salud Global/economía , África del Sur del Sahara/epidemiología , Actitud del Personal de Salud , Enfermedades del Sistema Digestivo/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Gastroenterólogos/normas , Carga Global de Enfermedades , Salud Global/estadística & datos numéricos , Helicobacter pylori/patogenicidad , Virus de Hepatitis/patogenicidad , Humanos , Control de Infecciones/métodos , MasculinoRESUMEN
In this chapter, we discuss the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in the establishment of hepatocellular carcinoma (HCC), highlighting the key role of the multiple, non-mutually exclusive, pathways involved in the modulation of immune responses and in the orchestration of a chronic low-level inflammation state favouring HCC development. In particular, we discuss (i) HCC as a classical paradigm of inflammation-linked cancer; (ii) the role of the most relevant inflammatory cytokines involved (i.e. IL-6, TNF-α, IL-18, IL-1ß, TGF-ß IL-10); (iii) the role of T cell exhaustion by immune checkpoints; (iv) the role of the Wnt3a/ß-catenin signalling pathway and (v) the role of different subsets of suppressor cells.
Asunto(s)
Carcinoma Hepatocelular/virología , Virus de Hepatitis/patogenicidad , Inflamación/virología , Neoplasias Hepáticas/virología , Microambiente Tumoral , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Humanos , Inflamación/inmunología , Inflamación/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/patologíaRESUMEN
Viral hepatitis is a major global public health problem affecting hundreds of millions of people and is associated with significant morbidity and mortality. Five major biologically unrelated hepatotropic viruses cause most of the global burden of viral hepatitis. Hepatitis B and hepatitis C are associated with a significant number of chronic infections. Most deaths from viral hepatitis are due to hepatitis B and hepatitis C. An estimated 257 million people were living with HBV and 71 million people were living with HCV. Most people are asymptomatic. New diagnostics and highly effective, pangenotypic direct-acting antivirals provide opportunities to cure and eradicate chronic hepatitis C virus infection.
Asunto(s)
Virus de Hepatitis/clasificación , Hepatitis Viral Humana/epidemiología , Hepatitis Viral Humana/virología , Salud Global , Virus de Hepatitis/patogenicidad , Hepatitis Viral Humana/prevención & control , Hepatitis Viral Humana/terapia , HumanosRESUMEN
Theiler disease (serum hepatitis or idiopathic acute hepatic necrosis) has long been suspected to have a viral etiology. Four viruses have been described in association with hepatitis in horses. Further investigation suggests equine pegivirus and Theiler disease-associated virus (a second pegivirus) are neither hepatotropic nor pathogenic. Nonprimate hepacivirus (NPHV) causes subclinical disease in experimental models and has been associated with hepatitis in some clinical cases. Equine parvovirus-hepatitis (EqPV-H) experimentally causes subclinical-to-clinical liver disease and is found in the vast majority of Theiler disease cases. EqPV-H is likely of clinical significance, whereas the significance of NPHV is unknown.
Asunto(s)
Virus de Hepatitis/fisiología , Hepatitis Viral Animal/virología , Enfermedades de los Caballos/virología , Animales , Virus de Hepatitis/aislamiento & purificación , Virus de Hepatitis/patogenicidad , Enfermedades de los Caballos/patología , CaballosAsunto(s)
Antivirales/uso terapéutico , Toma de Decisiones Clínicas , Ensayos Clínicos como Asunto/métodos , Hepatitis C Crónica/tratamiento farmacológico , Virus de Hepatitis/efectos de los fármacos , Neoplasias/terapia , Selección de Paciente , Algoritmos , Antivirales/efectos adversos , Técnicas de Apoyo para la Decisión , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/virología , Virus de Hepatitis/patogenicidad , Humanos , Neoplasias/diagnóstico , Neoplasias/epidemiología , Factores de Riesgo , Resultado del TratamientoRESUMEN
In 1964, the first human oncovirus, Epstein-Barr virus, was identified in Burkitt lymphoma cells. Since then, 6 other human oncoviruses have been identified: human papillomavirus, Merkel cell polyomavirus, hepatitis B and C viruses, human T-cell lymphotropic virus-1, and human herpesvirus-8. These viruses are causally linked to 12% of all cancers, many of which have mucocutaneous manifestations. In addition, oncoviruses are associated with multiple benign mucocutaneous diseases. Research regarding the pathogenic mechanisms of oncoviruses and virus-specific treatment and prevention is rapidly evolving. Preventative vaccines for human papillomavirus and hepatitis B virus are already available. This review discusses the mucocutaneous manifestations, pathogenesis, diagnosis, treatment, and prevention of oncovirus-related diseases. The first article in this continuing medical education series focuses on diseases associated with human papillomavirus and Merkel cell polyomavirus, while the second article in the series focuses on diseases associated with hepatitis B and C viruses, human T-cell lymphotropic virus-1, human herpesvirus-8, and Epstein-Barr virus.
Asunto(s)
Deltaretrovirus/patogenicidad , Herpesviridae/patogenicidad , Retroviridae/patogenicidad , Neoplasias Cutáneas/virología , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/virología , Terapia Combinada , Deltaretrovirus/aislamiento & purificación , Educación Médica Continua , Femenino , Virus de Hepatitis/aislamiento & purificación , Virus de Hepatitis/patogenicidad , Herpesviridae/aislamiento & purificación , Herpesvirus Humano 4/aislamiento & purificación , Herpesvirus Humano 4/patogenicidad , Humanos , Masculino , Prevención Primaria , Pronóstico , Retroviridae/aislamiento & purificación , Medición de Riesgo , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/fisiopatología , Neoplasias Cutáneas/terapia , Análisis de Supervivencia , Infecciones Tumorales por Virus/fisiopatología , Infecciones Tumorales por Virus/terapiaRESUMEN
Hepatitis viruses are major threats to human health. During the last decade, highly diverse viruses related to human hepatitis viruses were found in animals other than primates. Herein, we describe both surprising conservation and striking differences of the unique biological properties and infection patterns of human hepatitis viruses and their animal homologues, including transmission routes, liver tropism, oncogenesis, chronicity, pathogenesis and envelopment. We discuss the potential for translation of newly discovered hepatitis viruses into preclinical animal models for drug testing, studies on pathogenesis and vaccine development. Finally, we re-evaluate the evolutionary origins of human hepatitis viruses and discuss the past and present zoonotic potential of their animal homologues.
Asunto(s)
Antivirales/farmacología , Desarrollo de Medicamentos/métodos , Virus de Hepatitis , Hepatitis Viral Humana , Vacunas contra Hepatitis Viral/farmacología , Animales , Evolución Biológica , Virus de Hepatitis/clasificación , Virus de Hepatitis/patogenicidad , Virus de Hepatitis/fisiología , Hepatitis Animal/virología , Hepatitis Viral Humana/tratamiento farmacológico , Hepatitis Viral Humana/fisiopatología , Hepatitis Viral Humana/virología , Humanos , Modelos AnimalesRESUMEN
While the life cycles of hepatitis viruses (A, B, C, D, and E) have been modestly characterized, recent intensive studies have provided new insights. Because these viruses "hijack" the membrane trafficking of the host cell machinery during replicative propagation, it is essential to determine and understand these specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus are well known as leading causes of liver cirrhosis and hepatocellular carcinoma. While substantial inroads toward treating hepatitis C virus patients have recently been made, patients with HBV continue to require lifelong treatment, which makes a thorough understanding of the HBV life cycle essential. Importantly, these viruses have been observed to "hijack" the secretory and endocytic membrane trafficking machineries of the hepatocyte. These can include the canonical clathrin-mediated endocytic process that internalizes virus through cell surface receptors. While these receptors are encoded by the host genome for normal hepatocellular functions, they also exhibit virus-specific recognition. Further, functions provided by the multivesicular body, which include endosomal sorting complexes required for transport, are now known to envelope a variety of different hepatitis viruses. In this review, we summarize the recent findings regarding the cellular membrane trafficking machineries used by HBV in the context of other hepatitis viruses. (Hepatology 2018; 00:000-000).
Asunto(s)
Membrana Celular/fisiología , Virus de Hepatitis/patogenicidad , Hepatocitos/virología , Transporte de Proteínas/fisiología , Hepatocitos/fisiología , HumanosRESUMEN
BACKGROUND: Molecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this study, we focused on G protein-coupled receptor 155 (GPR155), a cell surface signaling protein, as a candidate biomarker. METHODS: We analyzed GPR155 expression, DNA methylation, and copy number in HCC cell lines. The clinical significance of GPR155 expression was evaluated using 144 pairs of surgically resected liver and normal tissues with subgroup analysis based on hepatitis virus infection. RESULTS: GPR155 mRNA expression levels were differential and were decreased in 89% of HCC cell lines. No DNA methylation was detected, whereas copy number alterations were present in five (56%) HCC cell lines. GPR155 mRNA expression level was independent of background liver status and significantly lower in HCC tissues than corresponding normal liver tissues. The expression patterns of GPR155 protein by immunohistochemical staining were significantly associated with those of GPR155 mRNA. Downregulation of GPR155 was significantly associated with more aggressive HCC phenotypes including high preoperative α-fetoprotein, poor differentiation, serosal infiltration, vascular invasion, and advanced disease stage. Patients with downregulation of GPR155 were more likely to have worse prognosis after curative resection irrespective of hepatitis virus infection. Patients who experienced extrahepatic (distant) recurrences had significantly lower GPR155 expression than those with intrahepatic (liver confined) recurrences. CONCLUSIONS: Downregulation of GPR155 may serve as a prognosticator that also predicts initial recurrence sites independent of hepatitis virus infection.
Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Pronóstico , Receptores Acoplados a Proteínas G/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Metilación de ADN/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Hepatectomía/efectos adversos , Virus de Hepatitis/patogenicidad , Humanos , Hígado/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , ARN Mensajero/genéticaRESUMEN
A chefe do Ambulatório de Hepatites Virais do IOC, Lia Lewis, esclarece sobre as características da doença e faz um alerta para a importância do diagnóstico precoce. “O objetivo é iniciar logo o tratamento, quando indicado, para evitar a progressão da doença para formas mais graves”, destaca.
Asunto(s)
Hepatitis Viral Humana/etiología , Virus de Hepatitis/patogenicidad , Prevención de Enfermedades , Hepatitis Viral Humana/prevención & controlRESUMEN
The aim of this study was to clarify the significance of DNA methylation alterations during non-alcoholic steatohepatitis (NASH)-related hepatocarcinogenesis. Single-CpG-resolution genome-wide DNA methylation analysis was performed on 264 liver tissue samples using the Illumina Infinium HumanMethylation450 BeadChip. After Bonferroni correction, 3331 probes showed significant DNA methylation alterations in 113 samples of non-cancerous liver tissue showing NASH (NASH-N) as compared with 55 samples of normal liver tissue (NLT). Principal component analysis using the 3331 probes revealed distinct DNA methylation profiles of NASH-N samples that were different from those of NLT samples and 37 samples of non-cancerous liver tissue showing chronic hepatitis or cirrhosis associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (viral-N). Receiver operating characteristic curve analysis identified 194 probes that were able to discriminate NASH-N samples from viral-N samples with area under the curve values of more than 0.95. Jonckheere-Terptsra trend test revealed that DNA methylation alterations in NASH-N samples from patients without hepatocellular carcinoma (HCC) were inherited by or strengthened in NASH-N samples from patients with HCC, and then inherited by or further strengthened in 22 samples of NASH-related HCC (NASH-T) themselves. NASH- and NASH-related HCC-specific DNA methylation alterations, which were not evident in viral-N samples and 37 samples of HCC associated with HBV or HCV infection, were observed in tumor-related genes, such as WHSC1, and were frequently associated with mRNA expression abnormalities. These data suggested that NASH-specific DNA methylation alterations may participate in NASH-related multistage hepatocarcinogenesis.
Asunto(s)
Carcinoma Hepatocelular/genética , Metilación de ADN/genética , Neoplasias Hepáticas/genética , Enfermedad del Hígado Graso no Alcohólico/genética , Adulto , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Islas de CpG/genética , Femenino , Virus de Hepatitis/patogenicidad , Humanos , Hígado/metabolismo , Hígado/patología , Hígado/virología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/patologíaAsunto(s)
Carcinoma Hepatocelular/genética , Hígado Graso , Hepatitis Viral Humana , Neoplasias Hepáticas/genética , Trasplante de Hígado/métodos , Hígado , Animales , ARN Helicasas DEAD-box/genética , Hígado Graso/genética , Hígado Graso/terapia , Virus de Hepatitis/clasificación , Virus de Hepatitis/genética , Virus de Hepatitis/patogenicidad , Hepatitis Viral Humana/inmunología , Hepatitis Viral Humana/terapia , Hepatitis Viral Humana/virología , Humanos , Hígado/inmunología , Hígado/metabolismo , Hígado/patología , Ratones , MicroARNs/farmacología , Terapia Molecular Dirigida/métodos , Ribonucleasa III/genéticaRESUMEN
BACKGROUND: The existing seroepidemiological data on viral hepatitis in Ethiopia showed a wide variation in prevalence pattern and the clinical and public health burden have been underestimated. The aim of this systematic review and meta-analysis was to provide a clear and comprehensive estimation of viral hepatitis epidemiology and the potential clinical burdens in Ethiopia. METHODS: A comprehensive literature search was carried out from five decades (1968-2015) published studies from biomedical databases; PubMed, Google scholar, Medline and Web of Science. RESULTS: The overall pooled prevalence of hepatitis B virus (HBV) was 7.4% (95%CI: 6.5-8.4). The pooled prevalence among subgroups showed 5.2% (95%CI: 3.7-7.4) in human immunodeficiency virus (HIV) infected individuals, 8.0% (95%CI: 5.9-10.7) in community based studies, 8.4% (95%CI: 5.4-12.7) in blood donors, 11.0% (95%CI: 7.5-15.9) in immigrants and 6.9% (95%CI: 5.6-8.5) in other groups. Among study parameters considered during meta-regression analysis, only study years were associated with a decreasing HBV prevalence rate over time. The overall pooled prevalence of anti-hepatitis C virus antibody (anti-HCV) was 3.1% (95%CI: 2.2-4.4). Unlike HBV, the anti-HCV prevalence in HIV infected individuals was higher (5.5%, 95%CI: 3.8-7.8%, p = 0.01) than the prevalence observed in the other subgroup of study population. Although relatively few data were available, hepatitis virus A (HAV), D (HDV) and E (HEV) were also circulated in Ethiopia. CONCLUSIONS: This review indicates that all types of viral hepatitis origins are endemic in Ethiopia. Adapting a recommended diagnostic and treatment algorithm of viral hepatitis in the routine healthcare systems and implementing prevention and control policies in the general population needs an urgent attention.
Asunto(s)
Hepatitis Viral Humana/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Adolescente , Adulto , Donantes de Sangre/estadística & datos numéricos , Coinfección/epidemiología , Etiopía/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Hepatitis B/epidemiología , Hepatitis B/virología , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/patogenicidad , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Virus de Hepatitis/patogenicidad , Hepatitis Viral Humana/virología , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: The influence of sex on hepatitis C virus (HCV)-related outcomes is often neglected. The effects of sex on liver fibrosis progression and the effect of socioeconomic status on management are unclear. PATIENTS AND METHODS: Data were evaluated from patients followed at The Ottawa Hospital and Regional Viral Hepatitis Program. RESULTS: Of 1978 chronic HCV-infected patients, 630 (32%) were women. Women had lower liver enzyme levels, HCV RNA levels, and weight compared with men. Women were more likely to be non-genotype-1 infected, Black or Asian, and immigrants from Africa and Asia (all P<0.01). Under 50 years of age, women on average had lower fibrosis scores than men. Beyond the age of 50 years, the mean fibrosis scores were similar, suggesting a 'catch-up' phase. Women were less likely to have initiated interferon-based HCV antiviral therapy (35.3 vs. 43.3%, P=0.01). Crude sustained virological responses were higher in women (65.3 vs. 56.3%, P=0.03), but were similar to men as determined by multivariable analysis (odds ratio: 0.92, 95% confidence interval: 0.58-1.46). Women of low socioeconomic status were more likely to be HIV coinfected and had higher rates of fibrosis progression. Women living in low-income neighborhoods were less likely to achieve sustained virological response (odds ratio: 0.50, 95% confidence interval: 0.34-0.75, P=0.01) compared with women in higher income regions. CONCLUSION: Sex differences have been identified as a potential barrier to overcome when managing viral infections. Our analysis suggests that sex influences fibrosis progression, likelihood of initiating HCV antiviral therapy, and treatment outcomes.