Glenn Reeves

Diagnostic accuracy of coeliac serological tests: a prospective study.

Objective The best way to test serologically for coeliac disease (CD) remains controversial, with endomysial (EMA), transglutaminase (TTG), and gliadin antibodies (AGA) being assessed in various combinations with no apparent standardization. The objective of this study was to evaluate whether TTG-IgA+/−TTG-IgG could be used as a replacement for endomysial antibodies as a reliable screen for CD in patients presenting to a major Australian tertiary referral hospital for assessment of symptoms consistent with CD. Methods Individuals referred for gastroscopic assessment of possible CD were prospectively evaluated by duodenal biopsy assessment. The following diagnostic methods were compared: dual-isotype transglutaminase (TTG-dual), combined-isotype transglutaminase (TTG-IgA+G), TTG-IgA, combined-isotype gliadin antibodies (AGA-IgA+G), AGA-IgA, and endomysial antibody assays. Clinical performance characteristics (sensitivity, specificity, area under the curve for receiver-operating characteristic analysis; AUROC) were assessed for all kits. Results The correlation between transglutaminase kits was generally good, with the best transglutaminase kit demonstrating high correlation (r=0.86) with endomysial antibodies. A comparison of different types of endomysial antibody assays displayed variable diagnostic performance (sensitivity 61.90–68.42%; specificity 80.00–98.57%; AUROC 0.71–0.83). Sensitivity (90.48–92.31%), specificity (80.77–82.89%) and AUROC values (0.92–0.94) for dual-isotype transglutaminase kits displayed narrow ranges. AGA assays were less sensitive (AGA-IgA: 42.31–46.15%; AGA-IgG: 61.54%) and less specific (AGA-IgA: 85.09–87.73%; AGA-IgG: 82.46–84.09%). Dual-isotype transglutaminase testing was diagnostically equivalent to transglutaminase-IgA (AUROC 0.92 versus 0.91, P=0.33). Conclusions Our study suggests that transglutaminase screening (using the IgA±IgG isotype) is a sensitive and specific alternative to endomysial antibody testing in the serological assessment of CD. On the basis of our findings, AGA antibody testing no longer appears to be an essential part of the diagnostic strategy for adult CD.

The natural history of interferon-α2b-induced thyroiditis and its exclusivity in a cohort of patients with chronic hepatitis C infection

BACKGROUND Interferon-alpha2b (IFN-alpha2b) is well known to cause both hyper- and hypo-thyroidism. In the former, the commonest aetiology is thyroiditis. As there is no previous data to fully characterize the entity of IFN-related thyroiditis, the aim of this study is to document in detail its evolution in a cohort of hepatitis C patients treated with pegylated IFN-alpha2b and Ribavirin (RBV). METHODS A prospective observational study was conducted in patients who developed thyroid diseases whilst receiving combination of pegylated IFN-alpha2b and RBV for hepatitis C. The patients were followed with monthly thyrotropin (TSH). Where TSH was undetectable, free tetra- (fT4) and tri-iodothyronine (fT3) were added. Anti-thyroperoxidase (TPO), anti-thyroglobulin (Tg) and thyroid stimulating immunoglobulin (TSI) levels were also performed at diagnosis, during and at the end of IFN therapy. All patients were assessed and followed up closely with monthly TSH, fT4 and fT3 levels until the completion, after 6 and 12 months of treatment. RESULTS There were seven females and four males over a 30-month period. All patients were found to have thyroiditis. On average, the time to the development of thyroid disease was 10 weeks and duration of disease 9 weeks. All patients eventually recovered normal biochemical thyroid function although two required short-term supplementation. CONCLUSION Thyroiditis was found exclusively in our patients. Both the hyper- and hypo-thyroid phase can be short lived, extreme and transient in nature which warrants strict monthly TSH monitoring. Careful follow-up of all patients is mandatory as complete recovery is expected.

The Spectrum of Autoimmune Thyroid Disease in the Short to Medium Term Following Interferon-alpha Therapy for Chronic Hepatitis C.

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.

Vitamin D Levels Are Associated with Expression of SLE, but Not Flare Frequency

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.

Exacerbation of hepatitis C induced subclinical hypoadrenalism by Interferon-alpha2beta: A case report

Adrenal disease is an uncommon manifestation of hepatitis C infection and its related treatment regimen. This is a case of subclinical hypoadrenalism, probably induced by hepatitis C infection and further exacerbated by interferon-α2β and Ribavirin therapy. The adrenal deterioration during the treatment course was observed closely with 24-hour salivary profiles and 250 μg adrenocorticotropin stimulation tests using parallel serum and salivary cortisol concentrations. A number of possible pathogenic mechanisms are discussed, and the controversy over its management is emphasized.

Exploring lifetime occupational exposure and SLE flare: a patient-focussed pilot study.

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.

Thyroid function outcomes after pegylated interferon-α and ribavirin therapy for chronic hepatitis C.

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.

The Reduced Predictive Value of Interleukin 28b Gene Polymorphisms in a Cohort of Patients With Thyroiditis Developed During Antiviral Therapy For Chronic Hepatitis C: A Preliminary Study

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.

Influence of Age on Outcome in Patients with Pulmonary Arterial Hypertension

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.

HIsTOPATHOlOgIC FINDINgs OF AuTOImmuNITy IN THyROID, PITuITARy, AND ADRENAl DIsEAsEs IN CHRONIC HEPATITIs C POsTmORTEm CAsEs

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.