Chronic Hepatitis C Virus is Associated with More Severe Asthma

Chronic Hepatitis C Virus Infection is Associated with More Severe Asthma

Nakashima T, Yokoyama A, Ohnishi H, Yamasaki M, Shiode M, Haruta Y, Hattori N, Hozawa S, Yamakido H, Kohno N
Allergology International 60 (3), 299-304 (Sep 2011)

Background: Chronic hepatitis C virus (HCV) infection causes intra- and extra-hepatic complications. The elimination of HCV has been reported to be beneficial for asthmatic patients with HCV infection. Therefore, we hypothesized that chronic HCV infection might be associated with the severity of asthma.

Methods: Asthmatic patients were prospectively enrolled from 13 outpatient settings. Hepatitis B surface (HBs) antigen and HCV-RNA were measured at the time of enrollment and evaluated along with the clinical characteristics of the patients including the age, sex, duration of asthma, atopic status, smoking history, and treatment step according to the Global Initiative for Asthma guideline.

Results: Of 1327 asthmatic patients, 1258 patients (94.8%) were treated with inhaled corticosteroids, 18 patients were positive for HBs antigen (1.4%), and 32 patients (2.4%) were positive for HCV-RNA. When compared with HCV-RNA-negative patients, HCV-RNA-positive patients required significantly more drugs for the treatment of asthma. No such relationship was observed in patients with positive HBs antigen. A multivariate logistic regression analysis showed that the male sex, a long duration of asthma, status as a current smoker, and HCV-RNA positivity were independently associated with more severe asthma.

Conclusions: These results suggest that chronic HCV infection is an independent factor that predisposes asthmatic patients to more severe asthma. The evaluation of chronic HCV infection may be helpful for the management of severe asthmatic patients without obvious factors associated with severe asthma.

DISCUSSION ONLY

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This study suggested that the existence in the blood stream of HCV-RNA, but not of anti-HCV antibody orHBs antigen, is associated with the severity of asthma. Univariate and multivariate analyses also demonstrated that chronic HCV infection is a significant and independent factor predisposing asthmatic patients to more severe asthma. Therefore, chronic HCV, but not HBV infection, was considered an important factor for predisposing asthmatic patients tomore severe asthma.

In addition, we also found that both HBs antigen and HCV antibody positivity rates in asthmatic patients were not significantly different from those of the general population when adjusted for age. These results suggest that chronic HCV infection is related to the more severe phenotype in asthma but is not a determinant of predisposition to asthma.

We speculate that the underlying mechanism predisposing asthmatic patients with chronic HCV infection to more severe asthma may be an alteration of airway inflammation caused by HCV. Kanazawa et al. reported that airway CD8+ T cells are increased in asthmatic patients complicated with chronic HCV infection when compared with asthmatic patients without HCV infection.18

They also found that successful treatment of HCV infection with interferon therapy in asthmatic patients resulted in a reduction of CD8+ Tcells in the airway. On the other hand, Moorman etal discovered that HCV core protein directly induces interleukin-8 expression and production from human lung fibroblasts.19

Because interleukin-8 is a key inflammatory mediator that contributes to neutrophilic inflammation and broncho constriction, they concluded that a direct pro-inflammatory role of HCV core protein may injure the airway in HCV-infected patients.

Our findings are consistent with these suggested notions, and HCV may worsen the severity of asthma via the alteration of airway inflammation. The altered airway inflammation in HCV-RNA positive asthmatics may result in remodeling of the airway and airflow obstruction as shown in Table 3.

In addition,it should be noted that the HCV-RNA positivity rate in HCV antibody positive patients (47.8%) was not high in the current study, suggesting half of patients had experienced a transient HCV infection.

Our results also demonstrated that a long duration of asthma, male sex, and current smoker status were independent factors involved in the severity of asthma. A recent review suggested that a longer duration of asthma is associated with more severe disease and irreversible airflow limitation, which was thought to be caused by airway remodeling.10

The association between a long duration of asthma and more severe asthma observed in the current study is consistent with this notion. Similarly, tobacco smoking in asthmatic patients is regarded as an important factor of severe asthma.7

In the current study, an association between current smoker status and more severe asthma was also observed. In addition, we found that male sex is associated with more severe asthma, a finding that may not be consistent with previous notions. Though there are several controversial reports, severe asthma seems to be more common in women than in men.4,5 There are several limitations in the current study

First, detailed information regarding asthma control and lung function was not available. However, we believe that the GINA treatment step evaluation reflected the severity of disease in this large scale population.

Second, the diagnosis of asthma was physician-based. All of the physicians who participated in the current study were pulmonologists, helping to explain the extremely high adoption rate of inhaled corticosteroids (94.8%). Therefore, we believe that the diagnosis is likely accurate.

Finally, the adherenceof patients to the therapy was also physician evaluated.Though we excluded patients who were judged as having poor adherence, the process may not be sufficiently rigorous. Recently, Gamble et al.tried to distinguish non-adherence to both inhaled and oral corticosteroid therapy in asthmatic patients by assessing prescription records and blood exams.12 Because non-adherence to medication is one of the important factors that predisposes asthmatic patients to false severe asthma, in future studies it will be necessary to precisely evaluate the adherence to medication regimens in asthmatic patients complicated with chronic HCV infection.12

In conclusion, this study demonstrated that chronic HCV infection is one of the independent factors predisposing asthmatic patients to more severe asthma. Although asthmatic patients complicated with chronic HCV infection account for just a fraction of asthmatic patients, we also conclude that the evaluation of chronic HCV infection should be considered to manage severe asthmatic patients without obvious factors associated with severe asthma.