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

Abstract

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. Case presentationA 55 year old post menopausal Caucasian female presented with vitiligo on her face, arms and legs. Her past medical history included only mild asthma requiring only intermittent bronchodilators without glucocorticoids. There was no other significant personal or family medical history. Clinical examination showed a well woman, weight of 69.1 kg, height 1.67 metre (body mass index 25). Her blood pressure was 120/75 lying and 120/70 sitting with a regular pulse of 78 beats per minute. RR, 80-1040), plasma renin activity > 35.7 ng/mL/hr (RR, 1.2-2.8). In essence, they showed mild hyperkalaemic metabolic acidosis and hepatocellular dysfunction. Because the latter persisted, chronic hepatitis C was confirmed with positive serology of genotype 1. The liver biopsy showed changes consistent with chronic persistent hepatitis, the inflammatory and fibrotic changes were both graded 1 according to the scoring method [1].

Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to InterferonsIn Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines

“…This study was performed to investigate whether an abnormal IFN signature is present in the peripheral blood of patients with AAD, and if this can explain the elevated serum levels of CXCL10 in AAD patients. The involvement of IFNs, either type I or II or both, in the immunopathogenesis of AAD is strongly suggested by several observations in both clinical and experimental settings: Individuals treated with IFN-α for viral infections or cancer have developed autoantibodies against 21OH, with or without concomitant clinical adrenocortical insufficiency (Wesche and others 2001 ; Tran and others 2008 ; Krysiak and others 2011 ). Individuals with subclinical and established AAD treated with IFN-α have shown an exacerbation of the condition and an increased need for glucocorticoid replacement (Knost and others 1981 ; Oshimoto and others 1994 ).…”

The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease

“…This effect was less than their individual effects combined, possibly reflecting the activation of overlapping signalling pathways. In relation to IFN‐α therapy, a direct cytotoxic effect of IFN‐α on the adrenal cortex, resulting in loss of hormone‐producing cells, may contribute to the increased need for glucocorticoid replacement observed in some patients with subclinical or established AAD . In individuals with a normal adrenocortical function this would probably only have a minor influence on the hormone‐producing capacity of the organ, as clinical adrenocortical insufficiency does not occur before 90% of the hormone‐producing cells are destroyed , and progenitor cells from the adrenal capsule or subcapsular region might replace the lost cells .…”

“…One report described transient occurrence of 21OH autoantibodies and clinical adrenocortical insufficiency in a woman carrying the HLA class II high‐risk genotype for AAD over a 2‐year period of IFN‐α treatment . Furthermore, exacerbation of subclinical and established Addison's disease with an increased need for glucocorticoid replacement has been noted in individuals on IFN‐α therapy . The adrenal cortex is also permissive to certain herpesviruses , which could trigger a local IFN response in the case of an infection.…”

Assessment of adrenal function in liver diseases

“…However, altered adrenal functions seen with ALD with less than four weeks of disease duration suggest primary adrenal involvement as adrenal function get altered after four weeks in secondary adrenal insufficiency. Adrenal involvement has been reported in HCV[35] and HBV[36] infection. Thirdly, as this was a cross sectional study we could not assess factors which could have predicted mortality or morbidity.…”