‘Seronegative’ subjects are negative for both anti-HBc and anti-HBs. The HBV-DNA detection rate is highest in subjects who are anti-HBc positive/anti-HBs negative, intermediate in subjects who are positive for both anti-HBc and anti-HBs, and lowest in seronegative ones.4 A recent study from Italy showed that the different serological profiles were related to the HBV-specific T-cell response.9 In rare conditions, patients might be infected by HBV mutants that cannot be detected

by serological assays. Because HBV-DNA detection is the key to diagnosis of occult HBV infection, it is currently recommended that a PCR-based technique is better to detect the presence of viral DNA in serum, PBMC or liver. The sensitivity of PCR assays for HBV DNA in studies on occult HBV infection varies from 101 to 103 copies/mL (2–500 IU/mL). Therefore, the prevalence of occult HBV in the current MLN0128 supplier study may have been higher if a PCR-based technique

was applied. More importantly, specificity and reproducibility of assay results must be ensured, PCI-32765 especially for in-house design. This requires meticulous steps to prevent contamination of samples, inclusion of negative controls, and performance of assays in duplicate using two independent sets of HBV primers specific for different HBV genomic regions. Other factors that may affect the detection rates of HBV DNA include the volume of sample used and the material tested. The sensitivity of detection can be

increased if a larger volume of serum was used. Most studies on occult HBV infection have reported higher rates of HBV-DNA detection in liver or PBMC as compared with serum or plasma. Loperamide Although the presence of occult hepatitis B in chronic HCV infection is well established, the clinical relevance is still being assessed. Regarding the clinical consequences of occult HBV infection in patients with CHC, some studies have shown that the severity of liver damage and fibrosis is higher in patients with occult HBV infection than in those without it.10–12 However, this finding was not confirmed by other studies.8,13–16 More importantly, it should be stated that all of these studies are cross-sectional in design; prospective studies are needed to confirm whether occult HBV accelerates the progression of hepatic necroinflammation and fibrosis in patients with CHC. Epidemiological studies have linked the development of HCC in individuals with chronic HCV infection to co-infection with HBV, including many patients who had apparently cleared their HBV infection.17,18 A high proportion of individuals with HCV infection who develop HCC have demonstrable HBV viral DNA and proteins in the neoplastic and adjacent non-neoplastic liver.19 Furthermore, HBV DNA is present in the serum of up to 52% of HCV-infected individuals who are HBsAg negative and develop HCC.