Comparative study on the clinical and virological characteristics among patients with single occult hepatitis B virus (HBV), single occult hepatitis C virus (HCV) and occult HBV and HCV dual infection

Occult hepatitis B virus (HBV) and occult hepatitis C virus (HCV) infection are two recently described different forms of HBV and HCV infections. This work compares the clinical, virologic, and histologic characteristics of patients with occult dual infection to those of patients with single occult HBV or HCV infection. Seventy-six patients with abnormal liver function tests of unknown etiology (serum HBsAg, anti-HCV, HBV-DNA, and HCV-RNA negative) were included in the study. Viral genomes were tested in liver by real-time PCR and confirmed by in situ hybridization. Of the 76 patients, 17 had occult HBV infection (intrahepatic HBV-DNA positive, HCV-RNA negative), 35 had occult HCV infection (intrahepatic HCV-RNA positive, HBV-DNA negative) and 24 occult dual infection (intrahepatic HCV-RNA and HBV-DNA). No differences among the three groups were found regarding clinical and epidemiologic data. The median load of intrahepatic genomic and antigenomic HCV-RNA strands was similar between single occult HCV infection and occult HBV and HCV dual infection. The percentage of HCV-infected hepatocytes did not differ between these groups. In occult single HBV infection, intrahepatic levels of HBV-DNA and percentage of HBV-infected hepatocytes were similar to the group of patients with occult dual infection. Finally, no differences were found in histological liver damage among the three groups. In conclusion, liver disease in patients with occult dual infection was not more severe than in patients with single occult HBV or occult HCV infection. Moreover, in occult dual infection there is no a reciprocal inhibition of the viral genomes.     

Occult hepatitis B virus infection in patients with chronic hepatitis C liver disease.

BACKGROUND: Hepatitis B virus (HBV) infections in patients who lack detectable hepatitis B surface antigen (HBsAg) are called occult infections. Although such infections have been identified in patients with chronic hepatitis C liver disease, their prevalence and clinical significance are not known. METHODS: With the polymerase chain reaction, we searched for HBV DNA in liver and serum samples from 200 HBsAg-negative patients with hepatitis C virus (HCV)-related liver disease (147 with chronic hepatitis, 48 with cirrhosis, and 5 with minimal histologic changes). One hundred of the patients had detectable antibodies to the HBV core antigen (anti-HBc); 100 were negative for all HBV markers. Eighty-three were treated with interferon alfa. We also studied 50 patients with liver disease who were negative both for HBsAg and for HCV markers. In six patients found to have occult HBV infection, we evaluated possible genomic rearrangements through cloning or direct sequencing procedures. RESULTS: Sixty-six of the 200 patients with chronic hepatitis C liver disease (33 percent) had HBV sequences, as did 7 of the 50 patients with liver disease unrelated to hepatitis C (14 percent, P=0.01). Among the 66 patients, 46 were anti-HBc-positive and 20 were negative for all HBV markers (P<0.001). Twenty-two of these 66 patients (33 percent) had cirrhosis, as compared with 26 of the 134 patients with hepatitis C infection but no HBV sequences (19 percent, P=0.04). HBV sequences were detected in 26 of the 55 patients in whom interferon therapy was ineffective and 7 of the 28 patients in whom interferon therapy was effective (P=0.06). None of the sequenced HBV genomes had changes known to interfere with viral activity and gene expression. CONCLUSIONS: Occult hepatitis B infection occurs frequently in patients with chronic hepatitis C liver disease and may have clinical significance.     

Analysis of HCV co-infection with occult hepatitis B virus in patients undergoing IFN therapy.

BACKGROUND/AIM: Occult hepatitis B virus (HBV) infection is characterized by the presence of HBV DNA in the absence of hepatitis B surface antigen (HBsAg) in the patient serum. Although such infections have been identified in patients with chronic hepatitis C, the clinical significance of those co-infections is still not understood. Our aim was, therefore, to assess the prevalence and clinical consequences of occult HBV infection in chronic hepatitis C patients undergoing antiviral therapy. METHODS: The study population consisted of 53 HBsAg-negative patients with chronic hepatitis C treated with IFN/ribavirin or IFN/ribavirin/amantadine. Nine patients experienced a viral breakthrough (BT), 30 were non-responders (NR) and 14 were responders (R). HBV-DNA detection by PCR was performed using primers specific for the S region of the HBV genome and HCV-RNA detection by PCR with primers localised in both the 5'NC and core region of HCV genome, before, during and after treatment. Viral genome sequences were also studied. RESULTS: Occult HBV genomes were found in the serum of four of 53 (7.5%) patients, unrelated to anti-HBc status. No significant differences in biochemical, virological, or histological markers, age, duration of infection, were observed in patients with or without HBV DNA. There was an inverse correlation in the evolution of HBV DNA and HCV RNA levels. Direct sequencing showed that S gene of occult HBV presented mutations in the "a" determinant while no specific mutation in the core region of HCV was observed. None of the four patients co-infected with HBV and HCV were responders to anti-HCV therapy. CONCLUSION: In our clinical setting, the prevalence of occult HBV co-infection among patients with chronic hepatitis C was low and independent of the presence of markers of previous HBV infection. Further studies in larger cohort of patients are warranted to determine if occult HBV co-infection may be involved in HCV resistance to combination therapy.     

Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C

Although occult hepatitis B virus (HBV) infections in individuals without detectable hepatitis B surface antigen (HBsAg) may occur and have been reported to be common in patients with chronic hepatitis C, the clinical relevance remains controversial. We searched for serum HBV DNA in 210 HBsAg-negative patients with hepatitis C virus (HCV)-related liver disease (110 patients with chronic hepatitis, 50 patients with cirrhosis, and 50 patients with hepatocellular carcinoma) by PCR. Most of the patients had detectable antibodies to HBsAg or HBV core antigen. All of the 110 chronic hepatitis C patients were treated with a combination therapy consisting of interferon plus ribavirin. In addition, 100 HBsAg-negative healthy adults served as controls. Thirty-one of the 210 patients (14.8%) had HBV DNA in their sera, as did 15 of the 100 healthy controls (15%). HBV DNA was not detected in the sera of those negative for serological markers of HBV infection. In patients with chronic HCV infection, the prevalence of occult HBV infection did not parallel the severity of liver disease (14.5% in patients with chronic hepatitis, 8% in patients with liver cirrhosis, and 22% in patients with hepatocellular carcinoma). In addition, the sustained response to combination therapy against hepatitis C was comparable between patients with and without occult HBV infection (38 versus 39%). In conclusion, these data suggest that occult HBV infection does not have clinical significance in chronic hepatitis C patients residing in areas where HBV infection is endemic.     

Occult hepatitis B virus infection in Lebanese patients with chronic hepatitis C liver disease

Occult hepatitis B virus (HBV) infection, characterised by the presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg), was investigated in 98 Lebanese patients with chronic hepatitis C liver disease and 85 control subjects recruited from eight institutions in different parts of the country. The prevalence of occult HBV infection ranged from 11.9% to 44.4% in hepatitis C virus (HCV)-infected patients and it increased with increasing severity of the liver disease. The overall rate of HBV DNA in our 98 HCV-infected patients was 16.3%. On the other hand, the rate of HBV DNA was 41.0% in anti-HBc alone positive patients compared to only 7.1% in healthy controls who were also anti-HBc alone positive (p < 0.001). Moreover, the prevalence HBV DNA increased with increasing severity of the liver disease, but this increase was only marginally significant and, perhaps, could have been significant if more patients were involved in the study. Although Lebanon is an area of low endemicity for both HBV and HCV, occult HBV infection is common in HCV-infected patients. The presence of HBV DNA, therefore, presents a challenge for the effective laboratory diagnosis of hepatitis B, particularly if polymerase chain reaction (PCR)-based HBV detection methods are not used.     

Fibrosis progression in chronic hepatitis C patients with occult hepatitis B co-infection.

Occult hepatitis B virus (HBV) infection in individuals without hepatitis B surface antigen (HBsAg) can be identified in hepatitis C virus (HCV) infected patients. However, its role in fibrosis progression remains uncertain. This retrospective study compared the fibrosis progression (defined as fibrosis progression by at least one stage) and progression to severe fibrosis (fibrosis stage 3 or 4) in HCV patients with occult HBV infection. Occult HBV infection was diagnosed by the detection of HBV DNA in the serum of 74 consecutive anti-HCV positive patients by PCR. Thirty-one patients (41.9%) had occult HBV infection. All 74 patients had a median of 2 (range 2-3) liver biopsies. The median time between the first and last liver biopsy was 57.7 (range 15.0-132.8) months. Eleven of the 31 patients with occult HBV infection compared with 12 of the 43 patients without occult HBV infection had fibrosis progression (35.5% versus 27.9%, respectively, p=0.608). Six of the 31 patients with occult HBV infection compared with 8 of the 43 patients without occult HBV infection developed severe fibrosis (19.4% versus 18.6%, respectively, p=0.946). In conclusion, chronic HCV patients with occult HBV co-infection does not seem to progress more than patients without occult HBV infection. However, more large-scale studies are needed before a definite conclusion can be obtained.     

Hepatitis B infection of the liver in chronic hepatitis C without detectable hepatitis B virus DNA in serum

Hepatitis B virus (HBV) DNA may persist in the liver in the absence of serum HBV-DNA after a self-limited acute hepatitis B. This may also occur in patients with chronic hepatitis C virus (HCV) infection but its prevalence and its impact on liver histology is unknown. HBV-DNA was tested by polymerase chain reaction (PCR) and by in situ hybridisation in liver biopsies from 98 patients with chronic hepatitis C who were hepatitis B surface antigen negative and serum HBV-DNA negative by PCR. HBV-DNA resulted positive in the liver of 37/98 (37.7%) patients without serum HBV-DNA. To test whether these patients had serum HBV-DNA levels under the detection limit of the PCR assay used in this study (50 copies/ml), PCR products in which HBV-DNA was undetectable after visualization of agarose gels were analysed by dot-blot hybridisation. With this method, HBV-DNA was positive in serum of 12/37 patients with liver HBV-DNA. Thus, 25/98 (25.5%) patients have HBV-DNA detectable only in liver. This was confirmed by in situ hybridisation, the percentage of infected hepatocytes ranging from 0.1% to 12%. In patients in whom the HCV infection was shorter than 20 years, HBV infected patients had higher (P = 0.01) fibrosis score (1.64 +/- 1.21) than HBV negative cases (0.53 +/- 0.66). In conclusion, a significant proportion of patients with chronic HCV infection have HBV-DNA in the liver in the absence of viral DNA in serum. The impact of this finding on liver histology deserves further research.     

非甲-非戊型慢性病毒性肝炎患者隐匿性HBV感染的研究

目的 观察非甲-非戊型慢性病毒性肝炎患者隐匿性HBV感染的状况,探讨荧光定量聚合酶链反应(FQ-PCR)技术对隐匿性HBV感染的诊断价值.方法 应用FQ-PCR技术对57例非甲-非戊型慢性病毒性肝炎患者进行了血清、肝组织HBV-DNA定量检测,并将肝组织HBV DNA定量水平与肝脏炎症活动度的关系进行了分析.结果 血清、肝组织HBV DrqA定量阳性分别为13例(22.81%)、22例(38.60%).13例血清HBV DNA定量阳性患者其肝组织定量亦均阳性,但9例肝组织HBV DrqA定量阳性患者其血清定量为阴性,差异有统计学意义(P<0.01);同时13例血清与肝组织定量均阳性患者比较.显示肝组织HBV DNA定量水平显著高于血清定量水平[(6.62±1.21)拷贝,gvs.(4.03±1.06)拷贝/ml,(P<0.01)].肝组织HBV DNA水平与肝脏炎症活动度并无相关性,10例G2,7例G3,5例G4患者HB'q DNA定量分别为(6.13±1.65)拷贝/g、(5.92±1.81)拷贝,g、(5.83±1.89)拷贝/g,(P0.05),但HBV DNA定量阳性患者均为活动性肝脏病变.结论 HBV隐匿性感染是部分非甲-非戊型慢性病毒性肝炎患者的病因.单纯检测血清免疫学标志物对HBV感染诊断存在漏诊,对非甲-非戊型慢性病毒性肝炎患者应用FQ-PCR技术开展血清定量尤其是肝组织中HBV DNA定量检测可提高HBV感染的诊断.对隐匿性HBV感染的慢性病毒性肝炎亦应给予有效的抗病毒治疗.     

Sequence analysis of pre-S/surface and pre-core/core promoter genes of hepatitis B virus in chronic hepatitis C patients with occult HBV infection

Although occult hepatitis B virus (HBV) infection in individuals without detectable hepatitis B surface antigen (HBsAg) may occur and has been reported to be common in patients with chronic hepatitis C, the related molecular mechanisms remain unknown. With the polymerase chain reaction, serum HBV DNA was sought in 100 HBsAg-negative patients with chronic hepatitis C virus (HCV)-infection. In those with occult HBV infection, possible genomic variability of HBV was evaluated by amplification and direct sequencing of pre-S, surface, and pre-core/core promoter genes. In total, 10 of the 100 patients (10%) had detectable serum HBV DNA, documenting an occult HBV infection. A deletion mutant in the pre-S gene was found in one patient and mutations of the a determinant of HBsAg were observed in 2. In addition, a novel core promoter mutant (a dinucleotide substitution: T-to-C at nucleotide 1,802 and T-to-G at nucleotide 1,803, T1802C/T1803G) was found frequently in patients with occult HBV infection as compared to sex- and age-matched HBsAg-positive patients (80 vs. 10%, P < 0.001). In conclusion, the data suggest occult HBV infection is not uncommon in chronic hepatitis C patients in Taiwan, and a novel core promoter mutant may be associated with the absence of circulating HBsAg in these patients.     

Distribution of hepatitis B virus in the liver of chronic hepatitis C patients with occult hepatitis B virus infection

Although occult hepatitis B virus (HBV) infection (HBV-DNA in serum in the absence of hepatitis B surface antigen [HBsAg]) is common in chronic hepatitis C, its characteristics are not well known. In this work, the presence of HBV-DNA (by polymerase chain reaction; PCR) and its distribution (by in situ hybridization) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 32 patients with chronic hepatitis C and occult HBV infection and in 20 HBsAg chronic carriers were determined. The results showed that serum HBV-DNA levels were statistically lower (P = 0.001) in patients with occult HBV infection than in HBsAg chronic carriers. The HBV infection pattern in liver cells was identical between patients with occult HBV infection and those with chronic hepatitis B. However, the mean percentage of HBV-infected hepatocytes was significantly lower (P = 0.001) in patients with occult HBV infection (5 +/- 4.44%) than in HBsAg chronic carriers (17.99 +/- 11.58%). All patients with chronic hepatitis B have HBV-DNA in their PBMCs while this occurred in 50% of the cases with occult HBV infection. In conclusion, patients with occult HBV infection have a low number of HBV-infected hepatocytes and this fact could explain the lack of HBsAg detection and low viremia levels found in these cases.     

Hepatitis C virus superinfection in hepatitis B virus chronic carriers: a reciprocal viral interaction and a variable clinical course.

BACKGROUND: The virological and clinical impact of hepatitis C virus (HCV) superinfection in chronic hepatitis B virus (HBV) carriers has been poorly characterized. OBJECTIVE: To evaluate the viral interaction, clinical presentation and course of the disease in four HBsAg/HBV-DNA positive chronic hepatitis patients who developed acute HCV infection. STUDY DESIGN: To evaluate clinical, virological and laboratory data for at least 6 months from the onset of acute HCV infection in patients with chronic HBV infection. RESULTS: Three patients with acute HCV infection had a normal clinical course, but the remaining patient had severe disease with ascites and a marked decrease in prothrombin activity. In all cases, plasma HBV-DNA, which had been detectable prior to the HCV infection, was no longer detectable when the acute HCV infection occurred. The inhibition exerted by HCV on HBV-DNA persisted throughout the follow-up period in three patients, but was temporary in the one patient who experienced an acute exacerbation of chronic HBV infection. HCV-RNA became persistently undetectable in two patients and reduced to low levels in the other two. CONCLUSIONS: Acute HCV infection in the four HBV chronic carriers was characterized by a reciprocal inhibition of HBV-HCV genomes and, in one case, by a severe course of disease.     

Dominant replication of either virus in dual infection with hepatitis viruses B and C

To characterize the state of dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), HBV-DNA and HCV-RNA levels were determined by spot hybridization or polymerase chain reaction in the sera of patients who were positive for both hepatitis B surface antigen and HCV antibody. Among 27 patients who showed evidence of double infection, 21 (77.8%) had detectable levels of only either HBV or HCV genome in their sera, 2 (7.4%) showed none of the viral genomes, and 4 (14.8%) had both HBV-DNA and HCV-RNA. In the 4 patients with both HBV-DNA and HCV-RNA, the titers of HCV-RNA or HBV-DNA were lower than those in the patients with HCV-RNA or HBV-DNA alone. In some patients with chronic hepatitis, the viruses appeared to replicate in turn in the course of the disease. These results indicate that the viruses show alternating dominance in replication in most of the patients who have dual infection with HBV and HCV, probably due to interference of the viruses. © 1995 Wiley-Liss, Inc.     

Occult HBV infection may represent a major risk factor of non-response to antiviral therapy of chronic hepatitis C

Occult hepatitis B virus (HBV) infection is common in chronic hepatitis C patient. However, its significance and consequences are still unclear. The aim of this study was to evaluate the prevalence of occult HBV among HCV chronic carriers in France and to assess its impact on liver histology and response to antiviral therapy. To this end a cohort of 203 patients with chronic hepatitis C without hepatitis B surface antigen (HBsAg) has been examined. Serum HBV-DNA was detected using a highly sensitive PCR with primers located in the S and X genes. HBV viraemia levels were further determined by real-time PCR. Results showed that 47 of 203 (23%) patients had occult HBV infection with a low HBV load (10(2)-10(4) copies/ml) but significantly higher HCV-RNA titers (P < 0.05). No significant difference in age, gender, serum ALT level, HCV genotypes, and the presence of anti-HBc was observed between patients with or without HBV-DNA. When compared histologically, patients with occult HBV infection had higher activity (A2-A3 in 53% vs. 38%, P < 0.01) and more advanced fibrosis (60% vs. 33%, P < 0.001) than HBV-DNA negative cases. Sustained response to combination therapy against Chronic hepatitis C was achieved in 11 (28%) of 40 HBV-DNA positive cases, compared with 65 (45%) of the 144 HBV-DNA negative cases (P < 0.05). Among the 144 HBV-DNA negative HCV patients those with genotype 1 responded less frequently to therapy as compared to other genotypes infected patients (38% vs. 55%, P < 0.05). Surprisingly, when considering all patients studied, irrespective to the HBV-DNA status no significant difference was observed in response to combination therapy regarding HCV genotypes (39% vs. 44%, P > 0.05). In conclusion, HBV-DNA is found in 1/4 of French chronic hepatitis C patients regardless of the presence of anti-HBc. Such an occult HBV co-infection is associated with more severe liver disease, higher HCV viral load and decreased response to antiviral therapy irrespective of HCV genotypes.     

Hepatitis C virus infection in the family setting of patients with occult hepatitis C

Family members of patients with chronic hepatitis C virus (HCV) infection are at increased risk of HCV infection but the prevalence of HCV among family members of patients with occult HCV infection is not known. Anti‐HCV, serum HCV RNA and levels of liver enzymes were determined in 102 family members of 50 index patients with occult HCV infection and in 118 family members of 59 chronic hepatitis C index patients. HCV RNA and/or anti‐HCV were detected in 10/102 (9.8%) relatives of patients with occult HCV infection and in 4/118 (3.4%) of patients with chronic hepatitis C. Fourteen additional family members (seven were relatives of index patients with occult HCV infection) had abnormal values of liver enzymes without serological markers of HCV infection. Two of these patients (who were relatives of two index patients with occult HCV infection) underwent a liver biopsy and were diagnosed with an occult HCV infection because HCV RNA was detected in the liver cells in the absence of serological HCV markers. In conclusion, the prevalence of HCV infection among family members of patients with occult HCV infection was similar to that found among family members of patients with chronic hepatitis C. This stresses the need to adopt strategies to prevent the transmission of HCV in the family setting of patients with occult HCV infection. J. Med. Virol. 81:1198–1203, 2009. © 2009 Wiley‐Liss, Inc.     

Concurrent hepatitis C virus and hepatitis delta virus superinfection in patients with chronic hepatitis B virus infection.

Since hepatitis C virus (HCV) and hepatitis delta virus (HDV) are transmitted by the same routes as hepatitis B virus (HBV), simultaneous or concurrent HCV and HDV infection in patients with chronic HBV infection may occur. To test this hypothesis and to examine the clinicohistological and immunopathological presentations of such multiple hepatitis virus infections, acute and/or convalescent serum specimens from 86 patients with acute HDV superinfection were tested by enzyme immunoassay for antibodies to HCV. Of the 86 patients, 18 (20.9%) were associated with HCV infection. Although patients with early mortality cannot be evaluated by the HCV markers used in this study, the results showed that the clinical and histologic features were similar except that patients with HCV infection were older than those without HCV infection (P less than 0.01). Immunopathological studies carried out within 2 months after the onset of acute HDV superinfection demonstrated that hepatitis B core antigen (HBcAg) was not detected in any patient and HDV antigen was detected in 18.2% of the patients with HCV infection whereas HBcAg and HDAg were found in 7% and 65.1%, respectively, of those without HCV coinfection (P less than 0.02). It is concluded that concurrent HCV and HDV superinfections can and do occur in patients with chronic HBV infection. In these triple viral infections, HCV may even transiently suppress HDV and HBV.     

Occult hepatitis B virus infection in the setting of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) co‐infection: Clinically relevant or a diagnostic problem?

The clinical relevance of occult hepatitis B virus (HBV) infection, defined as detectable HBV DNA serum/liver, in the absence of hepatitis B surface antigen (HBsAg), is unclear. We determined the prevalence of serum occult HBV infection in HIV/HCV co-infected patients enrolled in APRICOT, a randomized multinational trial that investigated the efficacy and safety of peginterferon alfa-2a (40 kDa) plus ribavirin for treatment of HCV. We also examined the effect of prior HBV exposure to liver histology at baseline. Only HBsAg-negative patients were eligible. At screening, serum HBV DNA was assessed by commercial assay (detection limit = 200 copies/mL). Patients were divided into four serological groups: anti-HBs+/anti-HBc+; anti-HBs-/anti-HBc+; anti-HBs+/ anti-HBc-; anti-HBs-/anti-HBc-. Baseline liver biopsy grade and stage were compared among groups. Serum HBV DNA was undetectable in all patients, (n = 866). Results of anti-HBs and anti-HBc was available for 176 patients: 60 (34.1%) anti-HBs+/anti-HBc+; 60 (34.1%) anti-HBs-/anti-HBc+; 11 (6.3%) anti-HBs+/anti-HBc-; 45 (25.6%) anti-HBs-/anti-HBc-. There were no differences among the groups in the histological grade or stage at baseline liver biopsies. Occult HBV infection in serum was not detected in this large immunocompetent cohort. Moreover, prior exposure to HBV did not appear to have any affect on baseline liver histology.     

Occult hepatitis B virus (HBV) infection in healthy blood donors

Blood transfusion is an important route of transmission of hepatitis B virus (HBV). Occult HBV infection can exist in the absence of HBsAg and can be detected by determining HBV DNA. To determine the occult HBV infection in healthy blood donors. One hundred adult healthy blood donors, negative for HBsAg, anti HCV, HIV-1 and other risk factors were screened for HBV DNA by PCR. All the healthy blood donors were negative for HBV DNA by PCR. Occult HBV infection does not occur in the healthy blood donors in the population studied.     

Diagnosis and clinical impact of occult hepatitis B infection in patients with biopsy proven chronic hepatitis C: a multicenter study

Occult hepatitis B virus (HBV) infection in patients with chronic hepatitis C has been found associated with severe liver damage, low response to interferon treatment and increased risk of developing HCC. However, doubts remain on its clinical impact and the sensitivity and specificity of its detection. HBV-DNA was sought by PCR in plasma, peripheral blood mononuclear cells (PBMCs) and liver compartments of 89 patients with biopsy proven chronic hepatitis C, using sets of primers for core ("c"), surface ("s"), and x ("x") regions of HBV genome. Occult HBV infection was defined by the presence of HBV-DNA in at least two different PCRs in at least one compartment. Occult HBV infection was detected in 37 (41.6%) of the 89 patients investigated. It was more frequent (80.8%) in 26 anti- HBs negative/anti-HBc positive patients than in 18 anti-HBs/anti-HBc positive (61.1%, P < 0.01) and 45 anti-HBs/anti-HBc negative (11.1%, P < 0.0001), and more frequently in liver (91.9%) than in PBMCs (62.2%) and plasma (32.4%). No association was found between occult HBV infection and the degree of liver necroinflammation and fibrosis. However, considering the 52 patients without occult HBV infection, 51.4% of 35 patients with genotype 1 and 5.9% of 17 with genotype non-1 showed severe fibrosis (P = 0.003); patients with occult HBV infection did not show such difference. Instead of seeking occult HBV infection in patients with chronic hepatitis C, both anti-HBs negative/anti-HBc positive and anti-HBs positive/anti-HBc positive, in plasma alone, more reliable information can also be obtained from the liver tissue and PBMCs.