Role of nitric oxide (NO) in interferon-alpha therapy for hepatitis C.
OBJECTIVE
The role of nitric oxide in infectious disease is gaining increased attention because antiviral effects of nitric oxide. In addition, there is evidence that nitric oxide synthase-2 expression was noted in chronic hepatitis C found within mononuclear cells.


METHODS
We studied serum levels of nitrite and nitrate before and during interferon alpha therapy in 66 patients with chronic hepatitis C.


RESULTS
There was no significant difference of their levels between the healthy control subjects and the patients before the treatment with interferon (55.9+/-21.8 microM vs. 60.9+/-30.0 microM). Their levels were determined at 2 weeks after the initiation of treatment with interferon and compared with those before the treatment in the patients with chronic hepatitis C. In the total patients treated, there was no significant difference between their levels before and at 2 weeks after the treatment (60.9+/-30.0 microM vs. 65.5+/-30.0 microM, P=0.14). However, when the levels were compared between sustained responders, in whom hepatitis C virus was eradicated, and non-responders, in whom the virus was not eradicated, the former had significantly higher levels of nitrite and nitrate than the latter at 2 weeks after the initiation of treatment (83.7+/-40.9 microM vs. 57.6+/-19.5 microM, P<0.01). The multivariate logistic regression analysis showed that the rise of nitrite and nitrate was an independent predictive factor for efficacy of interferon treatment.


CONCLUSIONS
Nitric oxide may be an important factor for antiviral therapy by interferon treatment for chronic hepatitis C, which suggests an additional therapeutic pathway for further study.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato, Tokyo 105-0003, Japan. hokari_a@jikei.ac.jp
Atsushi
A
Hokari
Mikio
M
Zeniya
Hiroyasu
H
Esumi
Tomohisa
T
Ishikawa
Yukiko
Y
Kurasima
Gotaro
G
Toda
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D009573:Nitrites / Q000097:blood; D012044:Regression Analysis
D000998:Antiviral Agents; D016898:Interferon-alpha; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide