THE ABSENCE OF THYROID DISEASE IN AN AUSTRALIAN HEPATITIS C COHORT TREATED WITH TRIPLE COMBINATION THERAPY: A PARADIGM SHIFT.

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.

Thyroid disease in chronic hepatitis C infection treated with combination interferon-α and ribavirin: management strategies and future perspective.

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.

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.

Thyroid disease is a favorable prognostic factor in achieving sustained virologic response in chronic hepatitis C undergoing combination therapy: A nested case control study.

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.

Predictors of deferral of treatment for hepatitis C infection in Australian clinics.

OBJECTIVE: To determine uptake of treatment for hepatitis C virus (HCV) infection and predictors of deferral of treatment for HCV by using prospectively collected data from the Australian Chronic Hepatitis C Observational Study (ACHOS). DESIGN, PATIENTS AND SETTING: Cohort study involving interview and medical record review at enrolment and routine follow-up clinic visits of patients with chronic HCV and compensated liver disease attending a national network of 24 HCV clinics between April 2008 and December 2009. Eligible patients were those who had not been previously treated, were enrolled within 6 months of their first clinic visit, were eligible for treatment and had been enrolled for at least 6 months. MAIN OUTCOME MEASURE: Predictors of patients undergoing HCV treatment within the first 6 months of assessment. RESULTS: 1239 patients were enrolled in ACHOS, of whom 406 met the criteria for inclusion in the subcohort for this study. Among this subcohort, 171 (42%) received treatment within 6 months of their first clinic visit. Current injecting drug use (odds ratio [OR], 0.26; 95% CI, 0.08-0.77), past and current treatment for drug dependency (OR, 0.34; 95% CI, 0.18-0.67, and OR, 0.42; 95% CI, 0.22-0.81, respectively) and alcohol use above 20 g/day (OR, 0.20; 95% CI, 0.08-0.46) were independent predictors of deferral of treatment. At least one of these factors applied to 41% of the subcohort. Clinical factors, including HCV genotype, HCV RNA level, and stage of liver disease were not associated with deferral of treatment for HCV. CONCLUSION: Factors related to drug and alcohol use, rather than clinical factors, influenced uptake of treatment for HCV. Further support for patients with drug and alcohol dependency is required to optimise treatment uptake.

The natural history of interferon-α induced thyroiditis in chronic hepatitis c patients: a long term study.

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.

Pegylated interferon-alpha2beta in combination with ribavirin does not aggravate thyroid dysfunction in comparison to regular interferon-alpha2beta in a hepatitis C population: meta-analysis.

BACKGROUND: Interferon (IFN) has been well documented to cause thyroid dysfunction, especially in high risk patients and when combined with ribavirin (RBV). There is very sparse data to assess if pegylated IFN will further aggravate the thyroid disease risk in comparison to regular IFN. The purpose of this study was to assess the risk of developing thyroid disease with pegylated IFN (pIFN) versus regular IFN (rIFN) therapy (in combination with RBV). We also pooled our results with previous studies in a meta-analysis. METHODS: An observational study was made retrospectively of 24 patients who underwent a combination of rIFN and RBV therapy for hepatitis C virus (HCV) infection. As these patients failed to obtain an initial satisfactory response, they were retreated using pIFN and RBV. Monthly thyrotropin (TSH) levels were assessed while undergoing both treatment regimens. A meta-analysis was performed using available published data in PubMed. RESULTS: No difference in TSH levels was observed when comparing rIFN/RBV with pIFN/RBV. None of the patients developed hypo- or hyperthyroidism. TSH levels fluctuated during the treatment but did not extend outside the reference range. No further investigation was carried out in the absence of clinical and biochemical thyroid disease. The result of the meta-analysis failed to find any excess risk of thyroid dysfunction using pIFN above that of rIFN. CONCLUSIONS: The pegylation of IFN, in combination with RBV, did not aggravate thyroid diseases in the hepatitis C population. This finding is reassuring and dictates that no deviation from current practice regarding thyroid surveillance is required whilst undergoing HCV treatment.

The spectrum of thyroid dysfunction in an Australian hepatitis C population treated with combination Interferon-alpha2beta and Ribavirin.

BACKGROUND: The study aims to assess the pattern of thyroid response to combination Interferon-alpha2beta (IFN-alpha) and Ribavirin (RBV) anti-viral therapy in an Australian hepatitis C cohort. These include the prevalence of thyroid dysfunction (TD) including hyperthyroidism and hypothyroidism and their possible predictors, the common overall pattern of thyroid function tests whilst receiving therapy and TD outcomes, and the correlation with HCV status outcome. METHODS: A retrospective analysis of all medical records was performed to assess thyroid function in Hepatitis C Virus (HCV) patients who were treated at the Hunter Area hepatitis C treatment center between 1995 and March 2004. The centre is part of the John Hunter hospital, a major tertiary referral centre in New South Wales, Australia. RESULTS: There were 272 cases available for review. The prevalence of TD is 6.7 percent and is made up predominantly of females (80 percent). There were 3 (1.1 percent) cases of hyperthyroidism with 2 (67 percent) females. Thirteen out of fifteen (80 percent) cases of hypothyroidism were females with the overall prevalence of 5.5 percent. The majority of hypothyroid patients still required Thyroxine supplement at the end of follow up. CONCLUSION: Ninety three percent of HCV treated patients have intact thyroid function at the end of treatment. The predominant TD is hypothyroidism. The predominant pattern of thyrotoxicosis (TTX) is that of thyroiditis although the number is small. Graves' like disease was not observed. People with pre-existing thyroid auto-antibodies should be closely monitored for thyroid dysfunction, particularly hypothyroidism.