Onset of Tuberculosis from a Pulmonary Latent Tuberculosis Infection during Antiviral Triple Therapy for Chronic Hepatitis C

Abstract

A 62-year-old man was diagnosed with the onset of tuberculosis (Tb) from a pulmonary latent tuberculosis infection (LTBI) during triple therapy with pegylated interferon α2a, ribavirin, and telaprevir for a chronic hepatitis C infection in 2013 before interferon (IFN)-free anti-viral therapy was introduced in Japan. A liver biopsy before IFN treatment revealed the presence of epithelioid cell granulomas (ECGs). IFN may also be employed for chronic hepatitis B infection and malignant tumors, thus, special attention must be paid to the development of Tb from a LTBI when ECGs are observed before treatment. It is also necessary to review the significance of the liver biopsy.

Type I interferon-driven susceptibility to Mycobacterium tuberculosis is mediated by IL-1Ra

“…In addition, a partial loss-of-function polymorphism in the type I IFN receptor (IFNAR1) is associated with resistance to TB in humans 21 . A small number of cases also link IFN treatment during chronic viral infections with increased susceptibility to TB 6,7,[22][23][24] . In addition, numerous animal studies have demonstrated causal roles for type I IFNs in susceptibility to Mtb 6,7,9,15,16,[25][26][27] and other bacterial infections 18,28 .…”

Type I interferons in tuberculosis: Foe and occasionally friend

“…Several clinical studies have reported reactivation of tuberculosis in patients undergoing IFN-α based therapy for chronic viral hepatitis ( Sabbatani et al, 2006 ; Farah and Awad, 2007 ; Telesca et al, 2007 ; Belkahla et al, 2010 ; Guardigni et al, 2012 ; Abutidze et al, 2016 ; de Oliveira Uehara et al, 2016 ; Matsuoka et al, 2016 ). In addition, a very recent study showed that impaired type I IFN signaling due to a rare East Asian functional mutation in the IFNAR1 gene was associated with increased resistance to tuberculosis ( Zhang et al, 2018 ).…”

Interactions between Type 1 Interferons and the Th17 Response in Tuberculosis: Lessons Learned from Autoimmune Diseases

“…All studies found a positive influence of adjuvant T1-IFN therapy on clinical outcomes in active TB (45–49). Conversely, IFN-α treatment without concomitant antibiotic treatment, e.g., for hepatitis C, has been described to cause reactivation of latent TB (50–57). While reactivation of latent TB and treatment of active TB are two distinct clinical situations, the latter finding suggests an unfavorable role for T1-IFNs in TB pathogenesis.…”

“…However, case reports of TB reactivation under IFN-α treatment without concomitant antibiotics have put T1-IFNs in a negative spotlight (50–57). Furthermore, a T1-IFN transcriptional signature in circulating leukocytes is associated with active TB.…”

“…Reactivation of TB has been reported specifically after treatment of patients with IFN-α, but not IFN-β (50–57). Also, mice infected with virulent Mtb strains specifically show higher IFN-α levels in the lungs compared to less virulent strains (64, 65).…”