Esophageal Tuberculosis: A Manifestation of TB Reactivation during Treatment of Hepatitis C

Abstract

Purpose: Hepatitis C and tuberculosis often co-exist, especially among patients from regions in which TB is endemic. In spite of this association, TB reactivation is not commonly seen in patients being treated for HCV. We describe a patient who developed esophageal tuberculosis as the manifestation of TB reactivation during combination therapy for hepatitis C. A 42 year old HIV-negative Ethiopian female with genotype 4 hepatitis C at 15 weeks of treatment with Peg-IFN and ribavirin presents with worsening dysphagia and odynophagia for three weeks. She also noted a mild cough with swallowing, but no hemoptysis. Other than general malaise, subjective fevers and chills since starting HCV treatment, she had no other complaints. Physical exam and routine laboratory studies were unremarkable. Upper endoscopy showed two deep ulcers in the proximal and mid-esophagus. Biopsies revealed multiple non-necrotizing granulomas. Chest CT showed right apical and subcarinal heterogeneous masses. Lymph node cultures from EUS/FNA and respiratory samples both grew organisms resembling Mycobacterium tuberculosis, thus, the diagnosis of esophageal tuberculosis was made. Given the temporal relationship of HCV treatment and development of esophageal TB, the salient question is if there is a relationship between hepatitis C and tuberculosis. Multiple characteristics increased this patients' risk for developing active TB. Among African immigrants, over 50% are PPD positive and over 10% have signs of pulmonary TB. Additionally, HCV and TB often co-exist; patients with HCV are about 3 times as likely to also have latent TB. Furthermore, reactivation of TB during HCV treatment, while rare, has been described in at least 4 case reports and a series describing tuberculous lymphadenopathy. While the mechanism is unclear, clinical studies have found an increased risk of infection with HCV treatment, independent from drug-induced neutropenia, and particularly associated with Peg-IFN. This may represent the impairment of macrophage phagocytosis from the accumulation of polyethylene glycol in patients treated with Peg-IFN. Additionally, in vitro models have shown that treatment of human monocytes and macrophages with IFN results in unrestrained mycobacterial growth. To our knowledge, this is the first case of esophageal tuberculosis occurring as a result of hepatitis C treatment. As we treat more immigrants from areas where TB is endemic, TB reactivation may become more common. This potential complication highlights the need for heightened awareness, and consideration of screening, in high risk patients undergoing HCV treatment.