Hepatitis C Virus Persistence After Sustained Virological Response to Antiviral Therapy in Patients With or Without Past Exposure to Hepatitis B Virus

T. N. Q. Pham; C. S. Coffin; N. D. Churchill; S. J. Urbanski; S. S. Lee; T. I. Michalak

Disclosures

J Viral Hepat. 2012;19(2):103-111. 

In This Article

Discussion

In this study, we examined the prevalence of OCI in patients with clinically resolved hepatitis C who had or did not have past exposure to HBV. Our findings overall suggest that low-level HBV DNA carriage in plasma, PBMC or liver does not have a noticeable effect on the prevalence, virological characteristics and, most likely, features of liver histology encountered in the course of OCI. The data also indicate that regardless of the existence of past HBV exposure, the levels of HCV RNA, especially in plasma, could vary significantly over time in OCI. Given that both HCV and HBV genomes were detectable in the same compartments in many of the cases examined, it can be proposed that the reciprocal inhibition of HBV and HCV replication observed in highly viraemic hepatitis patients[22,24,26,41] is not evident in low-level coinfection with these viruses.

Since its discovery in recent years,[14] OCI continuing after clinical resolution of hepatitis C has been a subject of investigations by many groups. Although we and others have collectively documented the presence of low-level HCV persistence in plasma, PBMC and/or liver in individuals with spontaneous or treatment-induced recovery from CHC,[13–15] studies from other groups came to rather opposite conclusions.[42–44] As evidenced in this study, HCV RNA, in both plasma and PBMC, could fluctuate considerably over time in low-level HCV infection. This, in consequence, highlights the importance of testing multiple samples and, if required, using a larger amount of starting material for nucleic acid extraction. In addition, as ex vivo stimulation of lymphoid cells with mitogens could greatly enhance virus detection,[14,39] we routinely adopt this approach to our investigation of OCI in PBMC. Nevertheless, this methodology was not used by most, if not all, studies that had refuted the existence of occult HCV persistence.[42–44] Perhaps, a combination of the differences mentioned elsewhere, together with other factors discussed elsewhere,[17,18] could help reconcile the discrepancies between the data that argued for[13–15] and those that were against[42–44] the notion of OCI persisting after clinically diagnosed recovery. Further, it is important to note that in this study, as well in those published elsewhere [8,13–15,36], low-level occult HCV persistence was not just about mere detection of HCV RNA. Indeed, not only the persistent expression of HCV replicative strand in PBMC and liver tissue was documented, but also HCV sequence polymorphisms in PBMC compared with plasma or liver, circulating virion-like particles and their replication competence were demonstrated.[36]

In most cases evaluated, liver histology showed improvement after otherwise successful treatment. Nevertheless, there was also an indication of persistent low-grade liver inflammation and fibrosis (see Table 3), which was seemingly irrespective of whether the individuals were concurrently positive or not for HBV DNA. The question of whether OBI could contribute to such alterations after achieving SVR could not be conclusively addressed in this study and will require a similar investigation with a larger number of cases. At this point, our finding of hepatic changes after SVR is consistent with that reported by others.[13,15,45]

Taken together, the current study provides new insights into characteristics of occult HCV persistence in general and in individuals with past exposure to HBV in particular. It also offers a standardized approach with greater uniformity and sensitivity in the identification of OCI. Our data indicate that a past encounter with HBV may not negatively influence the prevalence and characteristics of low-level HCV persistence continuing after resolution of CHC achieved following antiviral therapy.

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