Prevalence and follow-up of occult HCV infection in an Italian population free of clinically detectable infectious liver disease

Abstract

Background: Occult hepatitis C virus infection (OCI) is a recently described phenomenon characterized by undetectable levels of HCV-RNA in serum/plasma by current laboratory assays, with identifiable levels in peripheral blood mononuclear cells (PBMCs) and/or liver tissue by molecular tests with enhanced sensitivity. Previous results from our group showed an OCI prevalence of 3.3% in a population unselected for hepatic disease. The present study aimed to evaluate OCI prevalence in a larger cohort of infectious liver disease-free (ILDF) subjects. Clinical follow-up of OCI subjects was performed to investigate the natural history of the infection.

Methods and findings: 439 subjects referred to a Turin Blood Bank for phlebotomy therapy were recruited. They included 314 ILDF subjects, 40 HCV-positive subjects and 85 HBV-positive subjects, of whom 7 were active HBV carriers. Six subjects (4/314 ILDF subjects [1.27%] and 2/7 active HBV carriers [28%]) were positive for HCV-RNA in PBMCs, but negative for serological and virological markers of HCV, indicating OCI. HCV genotypes were determined in the PBMCs of 3/6 OCI subjects two had type 1b; the other had type 2a/2c. OCI subjects were followed up for at least 2 years. After 12 months only one OCI persisted, showing a low HCV viral load (3.73×10(1) UI/ml). By the end of follow-up all OCI subjects were negative for HCV. No seroconversion, alteration of liver enzyme levels, or reduction of liver synthesis occurred during follow-up.

Conclusions: This study demonstrated the existence of OCI in ILDF subjects, and suggested a high OCI prevalence among active HBV carriers. Follow-up suggested that OCI could be transient, with a trend toward the decrease of HCV viral load to levels undetectable by conventional methods after 12-18 months. Confirmation studies with a longer follow-up period are needed for identification of the OCI clearance or recurrence rates, and to characterize the viruses involved.

Figure 1. Flow chart of distribution of subjects enrolled in the study based on presence of serological markers of human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV).

Subjects positive for HBsAg and/or HBV-DNA were considered carriers of HBV. Subjects positive for anti-HCV and HCV-RNA or anti-HCV positive confirmed by the RIBA assay even though negative for HCV-RNA were considered HCV infection. Subjects HBsAg negative, anti-HBc positive with or without anti-HBs and HBV-DNA negative with normal alanine aminotransferase levels were considered previously HBV infected and naturally immunized. Abbreviations: anti-HIV, HIV antibodies; anti-HCV, antibodies against HCV; HBsAg, hepatitis B surface antigen; anti-HBc, hepatitis B core antibodies; pos, positive; neg, negative.