Occult Hepatitis B (OBH) in Clinical Settings of anti-HBc) (14, 15) to 8% (isolated anti-HBc) (16) (Table 1). As in other viral infections, HBV infectivity depends on two main factors: the infectious dose and the immune competence of the host. Considering the volume of in- fectious material involved in the transfusion of whole blood or a blood component, it is generally accepted that should any HBV DNA be present, infection may oc- cur (even with a viral load of < 20 IU/mL) (17). However, some scientists have argued that blood containing anti- HBc with anti-HBs does not appear to transmit HBV com- ponents (even through viral loads ranging between 20 and 500 IU/mL) (8, 17) if the neutralizing antibody level is sufficiently high. 3.2. Chronic Carriers OHB in apparently healthy HBV chronic carriers is es- sentially found in four types of clinical conditions: 1) recovery from infection defined by the presence of anti- HBs (spontaneous HBsAg seroclearance in a carrier) (18); 2) chronic hepatitis, where the infection is related to es- cape mutants that are not (or are only poorly) recognized by either natural polyclonal or monoclonal antibodies in the assays (19); 3) low-replicative phase of chronicity at the healthy carriage stage marked by the presence of anti-HBc, with or without detectable antibody to hepa- titis B e antigen (anti-HBe) (20); and 4) chronic hepatitis or healthy carriage without any marker of HBV infection other than HBV DNA (21, 22), this illustrates the fact that some patients may have had serological markers of HBV infection, but subsequently lost them while still continu- ing to have a low- grade HBV infection (22). OHB has been described in chronic HBV infection with different out- comes from asymptomatic carriers to HCC patients with genotypes A through F and H (23-27). Several authors have investigated HBV influence ,and different HBV genotypes on OHB prevalence in specific regions. For instance, Wein- berger et al. (28) suggested an association between occult HBV infection and genotype D in individuals from West- ern Europe, where genotype A is more prevalent. How- ever, the findings from a French study did not support this association (29). Cohort studies that include differ- ent HBV genotype patients are needed to compare OHB implications in these genetic groups of patients HBV. 3.3. HCV Among 350 million HBV carriers worldwide, the num- ber of individuals with HCV–HBV dual infection is around 5 – 7 million. However, it is very likely that the dual HBV– HCV infection prevalence rate is underestimated because occult HBV infection is often not taken into account (30). Since HBV and HCV share many risk factors and the same transmission routes, the high prevalence of occult HBV infection reported in patients with chronic hepatitis C, ranging from 6.7% to 91.1%, is not surprising (31, 32). It is well established in the medical literature that HCV-pos- itive HCV positive patients exhibit the anti-HBc-alone Alavian S M et al. pattern more often than do HCV-negative HCV negative patients, and anti-HBc reported prevalence in patients with chronic HCV infection ranges from 28 % to 71 % (33- 35) (Table 1). These differences in prevalence rates might be respon- sible for inconsistencies in results on specimen types, recruitment of chronic HCV-infected patients, HBV infec- tion endemicity in the study areas, and study methods in general. One clear example comes from Sagnelly et al. (31) who found prevalence rates of OHB in HCV -infected pa- tients as high as 91.1 % in liver samples compared to just 62.2 % and 32.4 % in PBMC and plasma samples, respective- ly. Regarding the clinical consequences of occult HBV in- fection in patients with chronic hepatitis C, studies have indicated the negative influence of cryptogenic HBV in- fection on histologic activity and severity of liver disease and HCC, possibly by integration with the host genome or synthesis of pro-oncogenic proteins by free intrahe- patic HBV genomes (34, 36-38). Also, in HCV- infected pa- tients, occult HBV infection may contribute to increased plasma HCV-RNA loads and liver transaminase levels (39, 40). On the other hand, some studies have reported that OHB occult HBV infection does not affect the pathological findings in the liver, changes in aminotransferase levels, or occurrence of HCC in patients with chronic HCV (32, 41, 42). It should be noted, however, that all of these stud- ies are cross-sectional, and therefore prospective studies are needed to confirm that occult HBV accelerates liver lesions progression in patients with chronic hepatitis C. Occult HBV infection also might affect the response to antiviral therapy in patients with chronic hepatitis C (43, 44), but the available data do not allow any firm conclu- sions in this regard, partly because of the heterogeneity of the patients enrolled, and the lack of data on care cur- rent standards for treatment (45). One study (43) found that HCV patients with occult HBV had lower intrahepat- ic mRNA levels of IFNAR2 (one of the two subunits of the IFN receptor), which the authors argued was one of the factors that could have led to a poor IFN response. How- ever, the mechanism by which occult HBV may inhibit the patient’s response to IFN therapy in chronic hepa- titis C remains unknown and therefore merits further research. Regarding the interaction between different HCV genotypes and OHB, Fukuda et al. (43) observed that patients with occult HBV infection were more frequently infected by HCV genotype 1a, but this association was not observed in other studies (32, 44). Altogether, these data highlight the clinical implications of occult HBV infec- tion in the clinical setting of HCV infection and suggest that screening for OHB should be an essential practice. 3.4. HIV Due to transmission shared modes and risk factors, co- infection with HBV and HIV and even triple infection with HCIV is common. A high HBV DNA prevalence in HBsAg- negative samples from HIV-positive patients indicates Hepat Mon. 2012;12(8):e6126 Published by Kowsar, © BRCGL 2012 3