The treatment of hepatitis C has dramatically improved over the past decade. Unlike any other chronic viral infection, a significant proportion of patients with chronic hepatitis C can be cured. However, the current standard therapy—pegylated interferon alpha and ribavirin—has its limitations. Limited efficacy in patients with hepatitis C virus (HCV) genotype 1 and the side effect profile will necessitate the development of new therapeutic approaches. This review describes the efficacy and optimisation of the current standard therapy of hepatitis C and its problems in special patient populations. New treatment directions beyond interferon alpha based therapies are on the horizon.

Early identification of patients with acute HCV infection is important for their optimal management. The rate of chronic evolution is 50–90%, and the natural course of chronic hepatitis C can be associated with severe complications. Patients with chronic hepatitis C have the potential risk of developing liver cirrhosis and hepatocellular carcinoma.1 The social burden of HCV infection is high, including for health care workers. Extrahepatic manifestations of HCV are often troublesome and may not be reversible with viral eradication.2 These are good reasons for the design of a prophylactic vaccine but as this has yet to be accomplished, early treatment of acute HCV infection with interferon alpha (IFN) is the only option to prevent chronicity.

Immediate treatment of patients with symptomatic acute hepatitis C with recombinant IFN or pegylated IFN (PEG-IFN) monotherapy for 24 weeks can prevent the development of chronic hepatitis C in approximately 90% of cases.3–5 Combination with ribavirin is not necessary.6 However, symptomatic patients also have a good chance to clear HCV spontaneously.7,8 This usually occurs in the first 12 weeks after the onset of symptoms. A wait and see strategy (that is, treatment of only those patients who remain HCV-RNA …

/pdf/treating-viral-hepatitis-c-efficacy-side-effects-and-d1lczqz62m.pdf

Treating viral hepatitis C: efficacy, side effects, and complications

Side effects of alpha interferon in chronic hepatitis C.

The autoimmune thyroid diseases (AITD) are complex diseases that are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility, in combination with external factors (e.g., dietary iodine), is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been used to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT), and some are common to both diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g., human leukocyte antigen, cytotoxic T lymphocyte antigen-4) and thyroid-specific genes (e.g., TSH receptor, thyroglobulin). Most likely these loci interact, and their interactions may influence disease phenotype and severity. It is hoped that in the near future additional AITD susceptibility genes will be identified and the mechanisms by which they induce AITD will be unraveled.

/pdf/searching-for-the-autoimmune-thyroid-disease-susceptibility-2piwgq967h.pdf

Searching for the autoimmune thyroid disease susceptibility genes: from gene mapping to gene function.

Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment.

/pdf/viruses-and-thyroiditis-an-update-p806ah6r8c.pdf

Viruses and thyroiditis: an update

The etiology of autoimmune thyroid disease: a story of genes and environment.

BACKGROUND AND AIMS Hepatitis C virus is involved in the induction of autoimmunity and interferon can also induce hepatic and non-hepatic autoimmune reactions. This study assessed the prevalence of thyroid autoantibodies and autoimmune thyroid disorders in patients with chronic hepatitis C before and during interferon therapy.

PATIENTS AND METHODS We studied prospectively 207 patients positive for anti-HCV and viral RNA. One hundred and forty-four of them received a therapeutic trial of one year with interferon-α. Free thyroxine, TSH and autoantibodies to thyroglobulin and thyroid microsomes were systematically tested at entry and at weeks 12 and 24 in both untreated and treated patients.

RESULTS Sixteen of the 207 patients (7.7%) had thyroid dysfunction, including positive antithyroid antibodies in 14 (6.7%) and hypothyroidism in 10 (4.8%) prior to interferon therapy. In addition, during pretreatment evaluation one patient developed clinical hyperthyroidism after transient subclinical hypothyroidism and another had subclinical hyperthyroidism. Prevalences of positive antithyroid antibodies and hypothyroidism were significantly higher in women (14.7 and 10.5%, respectively, vs 0% in men, P < 0.01) and were directly associated with increasing age (P < 0.01). The incidence of thyroid dysfunction was also significantly higher in patients with other autoantibodies such as anti-nuclear (ANA) (P < 0.01). A trial with interferon was initiated in 144 patients and 8 of 142 (5.6%) without previous thyroid abnormalities developed thyroid dysfunction, including positive antithyroid antibodies in 7 (4.9%) and hypothyroidism in 4 (2.8%) with a prevalence again significantly higher in women (12.7 and 8.3%, respectively, vs 1% in men, P < 0.01) and also directly related to increasing age (P < 0.01). An association was found between the development of thyroid dysfunction during interferon therapy and the presence of other autoantibodies, including ANA, anti-DNA and anti-Sjogren’s antibodies (P < 0.01), as well as with the induction of autoimmune hepatitis and Sjogren's syndrome (P < 0.01 and < 0.05 respectively). Thyroid abnormalities were reversed in all patients when interferon therapy was discontinued.

CONCLUSIONS No significant association was found between chronic hepatitis C and the presence of thyroid autoimmunity in female patients. On the contrary, interferon therapy induced antithyroid autoantibodies and thyroid dysfunction de novo in patients with chronic hepatitis C without pre-existing thyroid abnormalities. Thyroid dysfunction secondary to interferon was reversible after discontinuation of therapy.

B. González‐Fernández

Papers

Thyroid autoimmune disorders in patients with chronic hepatitis C before and during interferon‐α therapy

Subacute thyroiditis associated with interferon-alpha 2a therapy.