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Pulmonary arterial hypertension (PAH, or PH Group 1), a disease of aberrant pulmonary vascular remodeling, causing progressive right heart failure (RHF) due to elevation of pulmonary vascular resistance (PVR). Patient mortality risk stratification guides choice and intensity of pharmacological intervention and is assessed by haemodynamics (especially PVR) as well as noninvasive tools including WHO functional class (FC), 6-min walk distance (6MWD), and NT-proBNP levels. Quality of life (QOL) assessment is acknowledged as a central aspect of patient-centered care, but our study sought to extend QOL's role as an additional noninvasive risk marker that could further refine risk stratification and hence therapeutic choices within a "treatment to target" paradigm (aiming to achieve low-risk status). This study found that QOL assessment using the PAH-SYMPACT© physical activity tool provided enhanced, independent mortality risk information, with one unit rise in this score associated with a 41% increase in likelihood risk (odds ratio 1.41, 95% confidence interval: 1.01-1.98 (p < 0.05)) of falling within intermediate versus low-group category. We therefore found further support for additional prognostic value being conferred by measurement of QOL as part of routine PAH evaluation, reinforcing its critical role.
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Siloed or singular system approach to disease management is common practice, developing out of traditional medical school education. Textbooks of medicine describe a huge number of discrete diseases, usually in a systematic fashion following headings like etiology, pathology, investigations, differential diagnoses, and management. This approach suggests that the body has a multitude of ways to respond to harmful incidences. However, physiology and systems biology provide evidence that there is a simple mechanism behind this phenotypical variability. Regardless if an injury or change was caused by trauma, infection, non-communicable disease, autoimmune disorders, or stress, the typical physiological response is: an increase in blood supply to the area, an increase in white cells into the affected tissue, an increase in phagocytic activity to remove the offending agent, followed by a down-regulation of these mechanisms resulting in healing. The cascade of inflammation is the body's unique mechanism to maintain its integrity in response to macroscopic as well as microscopic injuries. We hypothesize that chronic disease development and progression are linked to uncontrolled or dysfunctional inflammation to injuries regardless of their nature, physical, environmental, or psychological. Thus, we aim to reframe the prevailing approach of management of individual diseases into a more integrated systemic approach of treating the "person as a whole," enhancing the patient experience, ability to a make necessary changes, and maximize overall health and well-being. The first part of the paper reviews the local immune cascades of pro- and anti-inflammatory regulation and the interconnected feedback loops with neural and psychological pathways. The second part emphasizes one of nature's principles at work-system design and efficiency. Continually overwhelming this finely tuned system will result in systemic inflammation allowing chronic diseases to emerge; the pathways of several common conditions are described in detail. The final part of the paper considers the implications of these understandings for clinical care and explore how this lens could shape the physician-patient encounter and health system redesign. We conclude that healthcare professionals must advocate for an anti-inflammatory lifestyle at the patient level as well as at the local and national levels to enhance population health and well-being.
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OBJECTIVE: To assess the prevalence of thyroid disease in triple combination therapy with interferon (IFN)-α, ribavirin (RBV), and protease inhibitors (boceprevir and telaprevir) for the treatment of chronic hepatitis C virus (HCV) infection in an Australian hepatitis C cohort. Also, to compare with those who received dual RBV and IFN in the past. METHODS: A preliminary, retrospective, and nested case control study of thyroid disease in patients who underwent triple combination therapy for chronic HCV infection compared with dual therapy at a major tertiary referral hospital center. Fifty-nine patients were treated with such therapy at the Hunter New England Area Hepatitis C Treatment Center. Of these, 38 were treated with boceprevir and 21 with telaprevir. All had genotype 1 HCV infection. The main outcome measures included (1) the prevalence of thyroid disease (TD), including hyperthyroidism and hypothyroidism, and (2) thyroid outcome comparison with patients who had received dual therapy. RESULTS: There was no case of TD detected for the entire duration of therapy with triple anti-HCV therapy. There was a significant absence of TD in the protease inhibitor-treated group. CONCLUSION: No case of TD was detected during the treatment of HCV patients with protease inhibitor-based triple therapy. The reasons for this are unclear. Larger studies are necessary to confirm this finding.
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Hepatitis C/tratamiento farmacológico , Interferón-alfa/efectos adversos , Inhibidores de Proteasas/uso terapéutico , Ribavirina/uso terapéutico , Enfermedades de la Tiroides/inducido químicamente , Enfermedades de la Tiroides/epidemiología , Adulto , Australia/epidemiología , Estudios de Casos y Controles , Quimioterapia Combinada , Femenino , Humanos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Oligopéptidos/uso terapéutico , Prolina/análogos & derivados , Prolina/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: The development of effective orally administered medical therapy for pulmonary arterial hypertension (PAH) has made a significant impact on outcome in patients with PAH. Identification of patient groups likely to derive optimal benefit is important, given cost and potential side effects; the clinical effectiveness of these therapies in older patients with PAH is unclear as the presence of co-morbidity may limit benefits of therapy. AIMS: We evaluated the epidemiology of PAH in a contemporary cohort to assess the influence of age on long-term outcome using PAH-specific therapies. RESULTS: A total of 119 patients (88% female; mean age 65±12 years) were reviewed, comprising 52% with underlying connective tissue disease. Bosentan was the PAH specific agent most frequently used. The baseline 6MWT distance in the entire cohort was 304m with age associated with a significant decline in 6MWT. CONCLUSIONS: In a large cohort of patients treated with PAH-specific therapies, patients less than 55 years of age showed improvement in 6MWT with older patients demonstrating stabilisation or decline.
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Hipertensión Pulmonar/epidemiología , Factores de Edad , Anciano , Femenino , Humanos , Hipertensión Pulmonar/terapia , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: The number of chemicals in household products has driven concern about potential adverse health through their use. Most research concentrates on product chemicals with reproductive and carcinogenic consequences, however some evidence exists that immune effects can lead to exacerbation of autoimmune illnesses such as lupus (SLE). OBJECTIVES: This paper examines household and personal product exposure patterns in a pilot case/control study of female Australians. We also examined associations between common product exposure and SLE symptom exacerbation over a year period. METHODS: We enrolled 41 control and 80 SLE participants aged 18-80 years. Qualitative techniques of structured interview and thematic analysis retrospectively explored patterns of product use, and flare history data of SLE participants. Negative binomial regression models explored associations between self-reported flare (SRF) days and exposure to 34 common home product groups. RESULTS: Mean product counts did not differ between participant groups (mean 33.1: SD 11.8), or flare groups (flare mean 32.6:SD 12, no-flare 31.8:SD 6.6). Products used for personal hygiene and general house cleaning were most frequently used.Significant association with increased SRF day relative risk (IRR) was seen for bath oil use (IRR 1.008, CI 1.00-1.02). Paradoxical "protective" effects, (reduced SRF days) were found for cleansing beauty (IRR 0.999, CI 0.998-0.999), make-up (IRR 0.998, CI 0.997-0.999); adhesives (IRR 0.994, CI 0.991-0.997) and paint (IRR 0.99, CI 0.986-0.995). CONCLUSIONS: Everyday product exposures can impact on symptom exacerbation in SLE. Some offering protection and others increased health risk. Identifying environmental associations offer the possibility of life-style interventions to reduce illness impact.
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This study explores links between vitamin D deficiency (25(OH)D = 50 nmol/L) and serological autoimmunity (ANA > 1 : 80) and frequency of self-reported flares (SRF) in participants with clinical autoimmunity (SLE). 25(OH)D levels of 121 females were quantified and compared. The cohort consisted of 80 ACR defined SLE patients and 41 age and sex matched controls. Association analysis of log2 (25(OH)D) levels and ANA 80 positivity was undertaken via two-sample t-tests and regression models. Significant differences were found for 25(OH)D levels (mean: control 74 nmol/L (29.5 ng/ml); SLE 58 nmol/L (23.1 ng/ml), P = 0.04), 25(OH)D deficiency (P = 0.02). Regression models indicate that, for a twofold rise in 25(OH)D level, the odds ratio (OR) for ANA-positivity drops to 36% of the baseline OR. No link was found between SRF-days and 25(OH)D levels. Our results support links between vitamin D deficiency and expression of serological autoimmunity and clinical autoimmunity (SLE). However, no demonstrable association between 25(OH)D and SRF was confirmed, suggesting independent influences of other flare-inducing factors. Results indicate that SLE patients have high risk of 25(OH)D deficiency and therefore supplementation with regular monitoring should be considered as part of patient management.
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INTRODUCTION: Environmental effectors, such as ultraviolet radiation exposure, infection and stress, have been established as having a role in exacerbating lupus symptoms. However, unpredictable patterns of flare events still remain a mystery. Occupational effectors have also been suggested as having a contributing role; however, they are not widely researched. In this paper we report a pilot study designed to generate focus areas for future research regarding occupational exposures and systemic lupus erythematosus (SLE). METHODS: The study explored potential links between exposures and the occurrence of patient-reported flare events in 80 Australian women with SLE (American College of Rheumatology (ACR) criteria classified). Specifically, the study assessed the hypothesis that occupational exposure is associated with significant changes in the likelihood of lupus flares. Lifetime employment history was analysed with the Finnish Job Exposure Matrix (FINJEM), 40 different semiquantified exposure class estimates for a wide number of occupations based on probability of exposure (p≥5%=exposed) were analysed with the construction of negative binomial regression models to test relationships between occupational agents and flare days. A backward stepwise elimination was used to generate a parsimonious model. RESULTS: Significant associations were noted for exposure classes of manual handling burden, (p=0.02, incidence rate ratio (IRR) 1.01), Iron (p=0.00, IRR 1.37), wood dust (p=0.00, IRR 3.34) and asbestos (p=0.03, IRR 2.48). CONCLUSION: Exposure assessment results indicated that occupations, such as nursing, with a high manual handling burden, posed increased risk to patients with SLE, however, the greatest risk was associated with wood dust and iron exposure with teachers and specialist labourers.
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Individuals living with lupus commonly experience daily backgrounds of symptoms managed to acceptable tolerance levels to prevent organ damage. Despite management, exacerbation periods (flares) still occur. Varied clinical presentations and unpredictable symptom exacerbation patterns provide management and assessment challenges. Patient perceptions of symptoms vary with perceived impact, lifestyles, available support, and self-management capacity. Therefore, to increase our understanding of lupus' health impacts and management, it was important to explore lupus flare characteristics from the patient viewpoint. Lupus flares in 101 Australian female patients were retrospectively explored with the use of a novel flare definition. Qualitative methods were used to explore patient-perceived flare symptoms, triggers, and management strategies adopted to alleviate symptom exacerbations. A mean of 29.9 flare days, with 6.8 discrete flares, was experienced. The study confirmed that patients perceive stress, infection, and UV light as flare triggers and identified new potential triggers of temperature and weather changes, work, and chemical exposure from home cleaning. The majority of flares were self-managed with patients making considered management choices without medical input. Barriers to seeking medical support included appointment timings and past negative experiences reflecting incongruence between clinician and patient views of symptom impact, assessment, and ultimately flare occurrence.
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BACKGROUND: The detection of microvascular damage in type 1 diabetes is difficult and traditional investigations do not detect changes until they are well established. The purpose of this study was to investigate the combined ability of nailfold capillaroscopy, laser Doppler flowmetry, retinal vessel analysis and 24-hr ambulatory blood pressure monitoring to detect early microvascular changes in a paediatric and adolescent population with type 1 diabetes. METHODS: Patients aged between 8 - 18 years with type I diabetes and no other autoimmune conditions were studied. The participants underwent the above cardiac and vascular investigations in a single three-hour session. Standard parameters including HbA1c were also investigated. Associations between all parameters were described by correlation analysis. Fisher's exact and t-tests determined the association with clinical findings. RESULTS: 26 participants were recruited. The mean HbA1c was 8.1% (SD ± 1.1) with a mean duration of type 1 diabetes of 7.9 years (SD ± 3.4). Three participants had microalbuminuria and one had early signs of retinopathy. Participants with microvascular complications had more avascular areas on nailfold capillaroscopy (p = 0.03). Recent HbA1c was positively associated with the number of nailfold microhaemorrhages (p = 0.03) Decreased baseline perfusion by laser Doppler flowmetry was associated with increased capillary density (p = 0.001) and an increased number of microaneurysms (p = 0.04) on nailfold capillaroscopy. CONCLUSIONS: This pilot study has shown that in children and adolescents with established type 1 diabetes, abnormal microvasculature can be detected by these investigations. These markers were also positively associated with evidence of suboptimal diabetes control as assessed by HbA1c. Further research will be necessary to determine the practical role of these investigations in the management and progress of the complications of type 1 diabetes. TRIAL REGISTRATION: Clinical Trial number NCT01279928, ClinicalTrials.gov.
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OBJECTIVE: Hepatitis C virus (HCV) infection is one of the major epidemics afflicting young people in both developed and developing countries. The most common endocrine disorder associated with this infection, especially in conjunction with interferon-α (IFN-α)-based therapy, is thyroid disease (TD). This review examines the development of TD before, during, and after the completion of treatment with combination IFN-α and ribavirin (RBV) for chronic HCV infection. We also summarize the current understanding of the natural history of the condition and propose management and follow-up guidelines. METHODS: PubMed was searched up to June 30, 2011 for English-language publications that contained the search terms "hepatitis C virus," "chronic hepatitis C," "HCV," "thyroid disease," "thyroiditis," "autoimmunity," "interferon-alpha," and "ribavirin." Additional publications were identified from the reference lists of identified papers. The included studies were original research publications and included combination IFN-α and RBV use in patients that developed TD. RESULTS: The prevalence of TD before combination IFN-α and RBV therapy ranges from 4.6 to 21.3%; during therapy, 1.1 to 21.3%; and after therapy, 6.7 to 21.3%. The most common TD is thyroiditis. Thyroid function testing (TFT) frequency and diagnostic criteria for various thyroid conditions are not standardized, and many of the existing studies are retrospective. CONCLUSION: Patients undergoing this therapy should be assessed with a standardized protocol to appropriately detect and manage developed TD. Based on the currently available literature, we recommend that patients receiving combination interferon-α and RBV therapy undergo monthly thyrotropin (TSH) level testing.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Enfermedades de la Tiroides/etiología , Antivirales/efectos adversos , Susceptibilidad a Enfermedades , Monitoreo de Drogas , Quimioterapia Combinada/efectos adversos , Medicina Basada en la Evidencia , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/fisiopatología , Humanos , Interferón-alfa/efectos adversos , Guías de Práctica Clínica como Asunto , Ribavirina/efectos adversos , Enfermedades de la Tiroides/inducido químicamente , Enfermedades de la Tiroides/inmunología , Enfermedades de la Tiroides/terapia , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/inmunología , Tiroiditis/inducido químicamente , Tiroiditis/etiología , Tiroiditis/inmunología , Tiroiditis/terapiaRESUMEN
BACKGROUND: Single nucleotide polymorphism in the interleukin28B (IL28B) gene was recently shown to be associated with a significant increase in response to interferon-α and ribavirin treatment in patients with chronic hepatitis C. Similarly, thyroid disease (TD) occurring during treatment confer an improved sustained virologic response (SVR). OBJECTIVES: To determine the role of IL28B genotypes in a cohort of hepatitis C patients who develop TD during treatment and its relationship to SVR. PATIENTS AND METHODS: IL28B gene profiles including rs12979860, rs12980275 and rs 8099917 and their genotypes were determined in a cohort of 23 hepatitis C patients who developed TD during treatment and their relationship to SVR. RESULTS: Out of 23 studies cases, 19 has one or more favorable genotypes, of which 15 (78.9%) achieved SVR. Eleven has all three unfavorable genotypes and yet achieved 72.7 % SVR. The presence of more than one favorable genotype only correctly predicts SVR vs. non- SVR in ~50 % of cases, i.e. by chance. CONCLUSIONS: Despite the small number of subjects, the presence of one or more unfavorable IL28B genotype does not portend a poor SVR prognostic outcome. This suggests that TD in this clinical context may be a critical factor in the achievement of SVR, probably above that of the genetic predisposition.
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BACKGROUND: Interferon-α in combination with ribavirin is the current gold standard for treatment of chronic hepatitis C. It is unknown if the development of autoimmune thyroid disease (TD) during treatment confers an improved chance of achieving sustained virologic response. The aim of this study is to assess the chance of achieving sustained virologic response (SVR) in patients who developed TD during treatment when compared with those who did not. METHODS: We performed a tertiary hospital-based retrospective nested case-control analysis of 19 patients treated for hepatitis C who developed thyroid disease, and 76 controls (matched for age, weight, gender, cirrhosis and aminotransferase levels) who did not develop TD during treatment. Multivariate logistic-regression models were used to compare cases and controls. RESULTS: The development of TD was associated with a high likelihood of achieving SVR (odds ratio, 6.0; 95% confidence interval, 1.5 to 24.6) for the pooled group containing all genotypes. The likelihood of achieving SVR was increased in individuals with genotype 1 HCV infection who developed TD (odds ratio, 5.2; 95% confidence interval, 1.2 to 22.3), and all genotype 3 patients who developed TD achieved SVR. CONCLUSIONS: Development of TD during treatment for hepatitis C infection is associated with a significantly increased chance of achieving SVR. The pathophysiogical mechanisms for this observation remain to be determined. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRB12610000830099.
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BACKGROUND: Autoimmune thyroid disease is a common complication of patients with chronic hepatitis C undergoing combination pegylated interferon-α and ribavirin treatment. A small proportion develops interferon-induced thyroiditis of which the long term natural history is unknown and how it compares with de novo thyroiditis. The aim of the study is to determine the natural history of thyroid disease including antibody profile in this particular setting 36 months from the completion of therapy. METHODS: A cohort of 18 hepatitis C patients (mean age 45 ± 8 years (standard deviation)) who developed exclusively thyroiditis in this setting was followed every 12 months after the completion of therapy for 36 months. Investigations included thyrotropin, free tetra-iodothyronine, free tri-iodothyronine levels and thyroid autoantibodies. RESULTS: None of the patients developed any long term thyroid disease. Two patients had a prolonged hypothyroid phase of the thyroiditis early after the completion of treatment but recovered fully. The remaining 16 patients remained euthyroid. Similarly, thyroid autoantibodies all declined and returned to reference range. CONCLUSIONS: The long term natural history in this small series of interferon induced thyroiditis was benign. If a larger series confirms a similar outcome then there is no long term residual effect on thyroid function and follow-up testing would not be warranted.
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OBJECTIVE: To assess the frequency of new thyroid disease, in patients who did not develop thyroid disease during treatment with interferon-α in combination with ribavirin for hepatitis C, during the 6-month period after the end of therapy. METHODS: A prospective study was performed in 190 patients who underwent a combination of interferon-α and ribavirin therapy for hepatitis C infection during the 36-month period between 2006 and 2008. Thyroid function tests were performed at the completion of treatment and at 4, 12, and 24 weeks of follow-up. RESULTS: During the 6 months after the completion of interferon-α and ribavirin therapy in the 190 study patients with hepatitis C infection, there were 2 cases of thyroid disease. One patient had the typical biphasic thyroiditis, and the other had primary hypothyroidism. Thus, the prevalence of thyroid disease in this setting was 2 of 190 patients (1.0%). CONCLUSION: The majority (99%) of patients had normal thyroid outcomes at 6-month follow-up. Only 1 patient had symptoms. This finding is reassuring and eliminates the need for ongoing thyroid surveillance during this time and probably longer. In the absence of symptoms, only a single thyroid-stimulating hormone measurement at 6-month review is recommended.
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Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Femenino , Hepatitis C Crónica/sangre , Hepatitis C Crónica/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pruebas de Función de la Tiroides , Glándula Tiroides/efectos de los fármacos , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreAsunto(s)
Autoanticuerpos/sangre , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/genética , Pruebas Genéticas , Procedimientos Innecesarios , Adulto , Enfermedad Celíaca/sangre , Reacciones Falso Positivas , Femenino , Predisposición Genética a la Enfermedad , Antígenos HLA-DQ/genética , Humanos , Deficiencia de IgA/sangreRESUMEN
OBJECTIVE: To assess the histologic prevalence of immune-mediated thyroid, pituitary, and adrenal diseases in postmortem cases with hepatitis C. METHODS: We reviewed 108 consecutive cases of chronic hepatitis C in patients in whom a complete postmortem examination was performed. All microscopic and histologic slides of the thyroid, pituitary, and adrenal reports were reviewed and assessed for evidence of autoimmune diseases. These were compared with a control group of 100 postmortem cases without hepatitis C. RESULTS: In chronic hepatitis C infection, there is a heightened immune response resulting in many autoimmune diseases. The commonest endocrinopathy in association with this chronic infection is thyroid disease, a finding confirmed in our current study. Among the 108 postmortem cases of hepatitis C, there were 14 cases (13%) with evidence of thyroiditis. No cases of pituitary or adrenal disease were found. The mean age of the patients was 52 years (range, 29 to 68). This frequency compared with 7 cases of thyroid disease (7%) in the control group (no significant difference between the 2 groups). CONCLUSION: On the basis of our postmortem data, thyroid disease was the only major endocrinopathy associated with hepatitis C infection, with a prevalence of 13%. This was comparable with other serologic and nonhistologic antemortem findings. There was no evidence of pituitary or adrenal involvement.
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Enfermedades de las Glándulas Suprarrenales/inmunología , Autoinmunidad , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/patología , Enfermedades de la Hipófisis/inmunología , Tiroiditis Autoinmune/patología , Enfermedades de las Glándulas Suprarrenales/epidemiología , Adulto , Anciano , Femenino , Hepatitis C Crónica/sangre , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Hipófisis/epidemiología , Enfermedades de la Hipófisis/patología , Prevalencia , Estudios Retrospectivos , Tiroiditis Autoinmune/epidemiologíaRESUMEN
Autoimmune thyroid diseases are common manifestations of hepatitis C infection, exacerbated by interferon-based treatment. However, the occurrence and pattern of thyroid disease in the short/medium term following the completion of IFN-based therapy is relatively unknown and there are very few previous reports regarding the specific spectrum of autoimmune thyroid disease that may follow such therapy. We hereby report 3 cases which demonstrate the range of thyroid diseases that may occur following interferon therapy. The hypothesis advanced is that in the pathogenesis of these conditions there must be both triggering and sustaining mechanisms as thyroid diseases occur well outside the immediate effect window of pegylated interferon. This paper suggests the need to continue thyroid surveillance in IFN-treated HCV patients following the completion of therapy, perhaps for the first 6 months.
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BACKGROUND: Hepatitis C virus is a highly immunogenic pathogen often inducing autoimmune activation changes and this can often be further exacerbated by Interferon therapy. As HCV is lymphocytotropic, it can modulate T cell and B cell antibody responses, affecting many endocrine organs, most commonly the thyroid. CASE PRESENTATION: We hereby describe a case of fluctuating and wavering thyrotropin autoantibodies of both stimulating and blocking nature in the setting of Graves's ophthalmopathy, hepatitis C infection and interferon-alpha, causing hypo- and subsequently hyper-thyroidism. The autoantibody profile was clearly modified during interferon therapy and settled into a new equilibrium at the completion of treatment. CONCLUSION: The case highlights the possible existence of a dual thyroid autoantibody population associated with hepatitis C, and its modulation by interferon therapy, which further compounds the difficulties in the assessment thyroid disease in this setting.
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BACKGROUND AND AIM: Thyroid dysfunction is the most common endocrinopathy associated with hepatitis C and its interferon-based treatment. When undergoing treatment, interferon and ribavirin synergize to potently stimulate the immune system in order to eradicate the virus. One of the innocent bystanders in this accentuated response is the thyroid. The present study investigated whether thyroid dysfunction while undergoing combination treatment for hepatitis C is a favorable prognostic maker for a sustained virological response. METHODS: We carried out a prospective clinical audit in 201 patients treated with combination ribavirin and alpha-interferon and determined the prevalence of sustained virological response in patients in association with thyroid disease. A meta-analysis was also carried out pooling 741 patients from four previous studies on this topic. RESULTS: There was positive and significant association between thyroid disease and viral clearance. This was not supported by the meta-analysis, however, and some plausible explanations are proffered for this inconsistency. CONCLUSION: Despite lacking supportive evidence from the meta-analysis, it is important that this information is confirmed (or refuted) in future studies.