High Rate of Spontaneous Negativity for Hepatitis C Virus RNA after Establishment of Chronic Infection in Alaska Natives

Abstract

Background. Hepatitis C virus (HCV) leads to chronic infection in 70%-85% of exposed patients. Spontaneous clearance of the virus after chronic infection is believed to occur rarely.Methods. Alaska Natives who tested positive for HCV antibodies were enrolled in a prospective study that began in 1994 and were followed up on a regular basis. Individuals who tested positive for HCV RNA on 3 separate dates, each of which were at least 1 year apart, were included. Being negative for the virus was defined as having at least 1 negative HCV RNA test result after chronic viremia had been established.Results. Of the 815 patients enrolled in the cohort, 139 met entry criteria and were observed for a mean period of 7.0 years. Eleven (8%) of the persons had at least 1 test in which HCV RNA was undetectable; 7 were classified as having either possible or probable clearance of the virus, corresponding to an annualized clearance rate of 0.74% per person-year (95% CI, 0.30%-1.53%). Of 9 patients who underwent subsequent HCV RNA testing, 5 (56%) had negative test results. A low HCV RNA level was significantly associated with spontaneous nondetectability of HCV RNA.Conclusion. Spontaneous HCV RNA negativity during chronic HCV infection is a surprisingly frequent event and is associated with low HCV RNA titers. Knowledge of immunologic determinants of clearance may open up avenues of novel therapy.

Impact of aboriginal ethnicity on HCV core-induced IL-10 synthesis: Interaction with IL-10 gene polymorphisms

“…[15][16][17] Alaskan Natives have been reported to have rates of spontaneous clearance as a high as 56% compared with 35% in CAs. 18 Similarly, data from a large, community-based cohort of illicit drug users in Vancouver demonstrated that HCV clearance occurred more frequently in individuals of Aboriginal ethnicity compared with CAs (adjusted OR 2.4; P Ͻ 0.01). 19 Taken together, these results suggest that for reasons currently unknown, the immune systems of North American indigenous peoples are more efficient at resolving spontaneous HCV infection.…”

Hepatitis C virus (HCV) infection: A systemic disease

“…The detection of HCV RNA is required to establish a diagnosis of active HCV infection. Results from longitudinal viremia studies have indicated that spontaneous resolution of chronic HCV infections occurs at a rate of 0.50-0.74% per person-year annually (Scott et al, 2006;Watanabe et al, 2003). On the other side, at least 20% of individuals with chronic hepatitis C eventually develop liver cirrhosis, which may be complicated by hepatocellular carcinoma, hepatic decompensation, or death (Lauer and Walker, 2001).…”

“…A negative NAT result following a positive serological test result is usually indicative of a resolved infection. However, intermittent or low-level viremia may occur during chronic infection (Scott et al, 2006), and for this reason a second NAT should be performed 6-12 months later. In addition, those patients with ongoing exposure to HCV can be reinfected.…”

How sustained is sustained viral response in patients with hepatitis C virus infection?

“…SVR rates with Peg-IFN-ribavirin treatment are 42-52% of those with genotype 1 HCV infection, and 80% in those with genotype 2 or 3 HCV infection [1]. Successful eradication of HCV is associated with regression of fibrosis and clinical improvement [2,3].…”