Persistence of Hepatitis C Virus Traces after Spontaneous Resolution of Hepatitis C

Abstract

Hepatitis C virus (HCV) frequently causes chronic hepatitis, while spontaneous recovery from infection is infrequent. Persistence of HCV after self-limited (spontaneous) resolution of hepatitis C was rarely investigated. The current study aimed to assess incidence and robustness of HCV persistence after self-resolved hepatitis C in individuals with normal liver enzymes and undetectable virus by conventional tests. Applying high sensitivity HCV RNA detection approaches, we analyzed plasma and peripheral blood mononuclear cells (PBMC) from individuals with previous hepatitis C infection. Parallel plasma and PBMC from 24 such non-viraemic individuals followed for 0.3–14.4 (mean 6.4) years were examined. Additional samples from 9 of them were obtained 4.5–7.2 (mean 5.9) years later. RNA was extracted from 250 μl plasma and, if HCV negative, from ~5 ml after ultracentrifugation, and from ex vivo stimulated PBMC. PBMC with evidence of HCV replication from 4 individuals were treated with HCV protease inhibitor, telaprevir. HCV RNA was detected in 14/24 (58.3%) plasma and 11/23 (47.8%) PBMC obtained during the first collection. HCV RNA replicative strand was evident in 7/11 (63.6%) PBMC. Overall, 17/24 (70.8%) individuals carried HCV RNA at mean follow-up of 5.9 years. Samples collected 4.5–7.2 years later revealed HCV in 4/9 (44.4%) plasma and 5/9 (55.5%) PBMC, while 4 (80%) of these 5 PBMC demonstrated virus replicative strand. Overall, 6/9 (66.7%) individuals remained viraemic for up to 20.7 (mean 12.7) years. Telaprevir entirely eliminated HCV replication in the PBMC examined. In conclusion, our results indicate that HCV can persist long after spontaneous resolution of hepatitis C at levels undetectable by current testing. An apparently effective host immune response curtailing hepatitis appears insufficient to completely eliminate the virus. The long-term morbidity of asymptomatic HCV carriage should be examined even in individuals who achieve undetectable HCV by standard testing and their need for treatment should be assessed.

Detection of hepatitis C virus (HCV) core–specific antibody suggests occult HCV infection among blood donors

“…In conclusion, these findings reinforce the notion of OCI as part of the natural history of the HCV infection, [26][27][28][29][30] although a couple of points remain obscure. First, the discrepancy between the results obtained by PCR on samples of serum and plasma taken at once from the same donor, which perhaps reflects unknown technical issues that could be critical when the viral load is extremely low.…”

Prevalence of Occult Hepatitis C Virus Infection among Blood Donors in Jiangsu, China

“…It is uncertain whether OCI is a different clinical entity or just a form of chronic HCV infection. Chen et al [29] detected HCV RNA in 24 patients with spontaneous resolution of hepatitis C who were followed up for 0.3-14.4 years. The RNA was extracted from plasma and, if HCV negative, from ultracentrifugation and ex vivo stimulated PBMCs.…”

Authentic Patient-Derived Hepatitis C Virus Infects and Productively Replicates in Primary CD4 + and CD8 + T Lymphocytes In Vitro

“…In addition to symptomatic chronic infection, which is normally accompanied by circulating HCV RNA and anti-HCV antibodies, HCV also persists as an essentially clinically silent (occult) infection accompanied by very low levels of HCV RNA in serum (usually below 100 to 200 virus genome copies or virus genome equivalents [vge]/ml), liver, and peripheral blood mononuclear cells (PBMC) (3). This occult HCV infection (OCI) may continue for decades after spontaneous (self-limited) or antiviral therapy-induced resolution of hepatitis C (4)(5)(6)(7)(8)(9)(10)(11). In this context, the accumulated experimental data indicate that HCV propagates not only in the liver but also in the immune system, where it can modify the proliferation and function of affected cells (12)(13)(14)(15)(16)(17)(18).…”