Bronchoalveolar lavage fluid analysis in individuals with chronic hepatitis C

Abstract

A number of disorders for which an association with hepatitis C virus infection exist. These disorders include essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, and idiopathic pulmonary fibrosis. This study was initiated to investigate the cellular content and lymphocyte subpopulations of bronchoalveolar lavage fluid obtained from individuals with chronic hepatitis C and to compare the results to those of controls. Eighteen patients with chronic hepatitis C (male/female, 6/12) and 14 healthy volunteers (male/female, 6/8), were studied. Bronchoalveolar lavage fluid was obtained from each; and the lymphocyte subtypes and the presence of HCV-RNA in the bronchoalveolar lavage fluid were determined. All anti-HCV positive subjects were HCV-RNA positive in serum. One (5.6%) had a HCV-RNA positive bronchoalveolar lavage. The total cell and neutrophil counts of the bronchoalveolar lavage fluid were significantly greater in patients with chronic hepatitis C as compared to controls (5,799.6 +/- 957.4 x 10(3)/ml vs. 1,835.7 +/- 447.8 x 10(3)/ml, P = 0.001; 1,175.8 +/- 634.7 x 10(3)/ml vs. 53.1 +/- 28.1 x 10(3)/ml, P = 0.029). In contrast, the lymphocyte, macrophage and eosinophil counts did not differ. No difference in the percentage, median or range of individual T cell subsets or B cell numbers in the bronchoalveolar lavage fluid existed between the groups. It is concluded that hepatitis C virus infection may be associated with an occult pulmonary inflammatory reaction manifested by an increased number of polymorphonuclear neutrophils in bronchoalveolar lavage fluid. This finding may contribute to the process that leads to idiopathic pulmonary fibrosis seen in a minority of cases of chronic hepatitis C.

Induction of p38- and gC1qR-dependent IL-8 expression in pulmonary fibroblasts by soluble hepatitis C core protein

“…In such a model, circulating core antigen would bind to gC1qR displayed on the surface of pulmonary fibroblasts and trigger the phosphorylation/activation of p38, NFκB, and possibly other MAPK mediators. This would lead to enhanced IL-8 gene transcription and protein expression, increased neutrophil recruitment at the local level, and ultimately the deterioration in pulmonary function observed in HCV-infected patients with lung disease [4,5,7]. It is noteworthy that patients with HCV infection even in the absence of pulmonary symptoms have been found to have increased numbers of neutrophils in bronchoalveolar fluid samples [7].…”

“…[5] Some data suggests that HCV infection may alter acetylcholine-mediated airway tone [5]. Other smaller studies also suggest a role for HCV infection in various pulmonary diseases, including idiopathic pulmonary fibrosis [6,7]. …”

Immune modulation of ovalbumin-induced lung injury in mice using β-glucosylceramide and a potential role of the liver

“…The authors suggested that chronic HCV infection might induce CD8+ T lymphocytes that cause asthma with a COPD-like inflammation. The few studies analyzing BAL fluid from groups with HCV infection have found varying results, with significant increases in neutrophils alone (Idilman et al 2002), lymphocytes and neutrophils (Yamaguchi et al 1997), or lymphocytes and eosinophils (Kubo et al 1996). Increases in the numbers of CD2+, CD3+, CD4+, and human leukocyte antigen-DR+ T lymphocytes were also noted; these were, however, small studies that were done in asymptomatic patients with no clinical or radiologic evidence of respiratory disease.…”

Viral infection and aging as cofactors for the development of pulmonary fibrosis

“…While HCV is not generally believed to replicate in the lung, at least one study has documented HCV RNA in the pulmonary parenchyma [31]. Furthermore, Idilman et al have reported on increases in neutrophil counts in the lung lavage of patients with HCV [32]. Thus, it is possible that HCV infection may result in changes to the inflammatory cell composition within the lung alveoli, and that this may enhance the development of fibrosis within the lung.…”