Prevalence and impact of occult hepatitis B infection in chronic hepatitis C patients treated with pegylated interferon and ribavirin

The prevalence of occult hepatitis B, defined by absence of HBsAg and HBV DNA, ranges widely in patients with hepatitis C. This may influence the treatment of hepatitis C and the severity of liver disease. Sensitive and specific real‐time PCR techniques are available commercially and can detect more reliably low HBV DNA levels. The aim of this study was to determine the prevalence of occult hepatitis B virus infection using the COBAS Taqman assay (Roche Diagnostics, Meylan, France) in the serum and liver of HBsAg negative patients with chronic hepatitis C and to evaluate its clinical consequences on liver pathology and its impact on the response to treatment with peg‐IFNα and Ribavirin. HBV DNA detection was assessed retrospectively on 140 sera and 113 liver biopsies of HCV positive/HBsAg negative patients before treatment. A 4.4% (5/113) prevalence of occult hepatitis B was recorded in liver samples and in none of the sera. Anti‐HBc was not detected in one, three of whom were sustained virological responders to treatment, one was relapsed responder and one was non‐responder. Furthermore, in this cohort composed of 12% anti‐HBs negative/anti‐HBc positive and 20% anti‐HBs positive/anti‐HBc positive patients, anti‐HBc was not associated with pre‐therapeutic viral load, ALT serum levels, and histological activity or fibrosis. Using a commercial real‐time PCR assay, we observed a low prevalence of occult B hepatitis. This, just as anti‐HBC status, had no clinical impact in a large cohort of hepatitis C patients. It therefore does not appear useful to screen for occult hepatitis B in these patients with this test before beginning HCV treatment. J. Med. Virol. 82: 000–000, 2010. © 2010 Wiley‐Liss, Inc. J. Med. Virol. 82: 747–754, 2010. © 2010 Wiley‐Liss, Inc.     

Frequent detection of hepatitis B virus DNA in hepatocellular carcinoma of patients with sustained virologic response for hepatitis C virus

Hepatocellular carcinoma (HCC) develops several years after the eradication of hepatitis C virus (HCV) by interferon therapy. Risk factors for the development of HCC are only partly understood. To elucidate the role of occult hepatitis B virus (HBV) infection in hepatocarcinogenesis in patients with sustained virologic response, the prevalences of HBV‐related makers were examined. Study group comprised 16 patients with sustained virologic response (group A) and 50 with HCV (group B). Anti‐HBc and anti‐HBs in serum were examined by enzyme‐linked immunoassay. HBV DNA in liver was examined by nested polymerase chain reaction, using primers specific for genes encoding for HBx, HBsAg, HBcAg, and HBV cccDNA. Sequence of the amplified HBV DNA for ‘a’ determinant of HBsAg was determined in HCC. Anti‐HBc was positive in 10 of 16 in group A and 25 of 50 in group B. HBV DNA in liver was detected in 12 of 16 in group A and 21 of 50 in group B (P = 0.044). In group A, HBV DNA in liver was detected frequently in patients without cirrhosis and in those with a longer period from the time of HCV eradication to the development of HCC. Mutation in ‘a’ determinant of HBsAg was found in three HCC of group A. Occult HBV infection may be one of the most important risk factors in hepatocarcinogenesis of Japanese patients with sustained virologic response. J. Med. Virol. 81:1009–1014, 2009. © 2009 Wiley‐Liss, Inc.     

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 infection does not affect liver histology or response to therapy with interferon alpha and ribavirin in intravenous drug users with chronic hepatitis C.

BACKGROUND: the frequency and the impact of occult HBV infection in patients with chronic hepatitis C infection is still a matter of some controversy. OBJECTIVES: our aim was to evaluate the prevalence of occult HBV infection and assess its impact on liver biochemistry, HCV viral titre, liver histology and on outcome of therapy in patients with chronic hepatitis C. STUDY DESIGN: paired liver biopsies and serum samples were collected from 51 patients (84% IVDUS) with HBsAg negative chronic hepatitis C, and tested for HBV-DNA with nested PCR. Liver biopsies were further studied histologically, with morphometric analyses and immunostaining techniques. Twenty-five were treated with alpha Interferon and ribavirin and followed for at least 18 months. RESULTS: HBV DNA was detected in 29.4% of liver tissue specimens and in only one (1.9%) serum sample. Three liver specimens were positive for surface gene, nine for core gene, three for both and none for the X gene. No significant difference in mean transaminase values, HCV viral titre, HCV genotype, or grading and staging and morphometric analysis was observed in patients with or without HBV DNA. Moreover, all 51 liver specimens were negative for both HBsAg and HBcAg. Sustained response to combination therapy was achieved in 40% of patients with and in 53% of patients without HBV DNA in the liver specimens (P=NS). CONCLUSIONS: HBV DNA is frequently found in the liver of patients with chronic hepatitis C. However, the lack of any significant impact on HCV viral titre, liver enzymes, histological parameters and response to therapy, suggests that in most cases HBV DNA detected in the liver by PCR may be either an integrated or low level replicative form.     

Presence of occult HBV, but near absence of active HBV and HCV infections in people infected with HIV in rural South Africa

Human immunodeficiency (HIV), hepatitis B (HBV), and hepatitis C (HCV) viruses are endemic in Sub‐Saharan Africa, but data regarding the prevalence of hepatitis co‐infections in HIV‐positive individuals residing there are limited. The aim of the study was to determine the prevalence of HBV, HCV, and occult HBV (presence of HBV‐DNA in the absence of HBsAg) in a rural, South African cohort. The results were compared to various ethnic groups in a Dutch cohort of people infected with HIV. Antiretroviral‐naïve individuals with HIV from both a rural South African clinic (n = 258), and a Dutch University hospital (n = 782), were included. Both serological (HBV and HCV) and molecular (occult HBV) assays were performed. Logistic regression analysis was used to define independent predictors of a hepatitis co‐infection. HBV and HCV prevalence rates in the South African cohort were exceptionally low (0.4%, 1/242 and 0.8%, 2/242, respectively), compared to those observed in Caucasians (HBV 4.4% and HCV 10.9%) and African immigrants (HBV 8.9% and HCV 4.8%). Conversely, occult HBV was observed in a considerable proportion (10%, 6/60) of South African patients who were anti‐HBc‐positive but HBsAg‐negative. Occult infections were less frequent in Caucasians and Africans in the Dutch cohort (3.2% and 1.4%, respectively). Independent predictors for occult HBV were not identified, but a trend towards more occult HBV at lower CD4 counts was observed. Local HBV/HCV prevalence data are needed to optimize vaccination and antiretroviral treatment strategies. Occult HBV in patients with HIV may be missed regularly when molecular analyses are not available. J. Med. Virol. 83:929–934, 2011. © 2011 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.     

Prevalence and clinical implications of occult hepatitis B viral infection in hemophilia patients in Japan

The prevalence and clinical implications of occult hepatitis B virus (HBV) infection were investigated in the Japanese patients with hemophilia in whom a high prevalence of infection with transfusion-transmissible viruses has been reported. HBV DNA was detected in the sera of 22 of 43 (51.2%) patients with hemophilia who were negative for HBV surface antigen (HBs), indicating that these patients had occult HBV infection. No factor, including age, type or severity of hemophilia, presence of HBs or HBV core (HBc) antibody, or coinfection with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) was associated with occult HBV infection, except for high anti-HBc titer and/or coinfection with HCV genotype 1 (1a or 1b). In general, occult HBV infection did not appear to have significant clinical implications. However, in patients in whom HBV was detected by PCR specific for the surface (S)-region, higher alanine aminotransferase levels were observed. The genotype of the occult HBV in the present study was exclusively the domestic type indigenous to Japan (genotype C), suggesting a different route of transmission for HBV in comparison to HCV and HIV in this population.     

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.     

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.     

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.     

Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients

Background/Aims

We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease.

Methods

Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR.

Results

Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity.

Conclusions

Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.     

Histological improvement of chronic liver disease after spontaneous serum hepatitis C virus clearance

The long-term histological and virological outcomes of spontaneous circulating hepatitis C virus (HCV) clearance were studied in chronic liver disease. Between 1979 and 1984, three patients underwent laparoscopy for chronic non-A, non-B liver disease, and two were found to have cirrhosis and one with chronic active hepatitis. After HCV assays became available in 1990, they were positive persistently for HCV antibody without serum HCV RNA. Reductions of antibody levels to HCV core and/or nonstructural proteins were observed, and liver biopsies were undertaken between 1995 and 2000. Liver biopsies at 11-19 years after laparoscopy disclosed marked alleviation of liver inflammation and fibrosis in each case although a low grade of inflammation remained. The two patients with cirrhosis no longer showed histological features of cirrhosis, and the poor liver function in one patient had been ameliorated. Liver specimens from two patients were subjected to polymerase chain reaction to detect positive and negative HCV RNA strands and hepatitis B virus DNA. Only the positive HCV RNA strand was detected for one patient who had previously cirrhosis. Liver specimens were examined from another six nonviremic HCV-seropositive individuals without chronic liver disease. Five patients displayed low-grade liver inflammation without evident fibrosis, but none had any viral genome in the liver. These findings suggest that spontaneous circulating HCV clearance in chronic liver disease confers favorable liver histological outcome, although occult HCV infection persists. J. Med. Virol. 69:41-49, 2003.     

Diagnosis of occult hepatitis C without the need for a liver biopsy

The diagnosis of occult hepatitis C virus (HCV) infection is based on the presence of HCV‐RNA in the liver. This study aimed to evaluate the use of combining non‐invasive assays to diagnose occult HCV. A total of 122 patients with occult HCV (HCV‐RNA in the liver without detectable anti‐HCV and serum HCV‐RNA) and 45 patients with cryptogenic chronic hepatitis (without HCV‐RNA in the liver and negative for anti‐HCV and serum HCV‐RNA) were included. HCV‐RNA was tested in peripheral blood mononuclear cells (PBMCs) and in 2 ml of ultracentrifuged serum. Anti‐core HCV was examined by a non‐commercial enzyme‐linked immunosorbent assay. All controls were negative for the three HCV markers studied. Among patients with occult HCV, 36% were anti‐core HCV positive, 57% had serum HCV‐RNA after ultracentrifugation, and 61% had HCV‐RNA in PBMCs. Combining the results of the assays, 91% of the patients were positive for at least one marker. Intrahepatic HCV‐RNA load was significantly higher in patients who were positive simultaneously for the three HCV markers than in patients who were negative for all markers (P = 0.006) and than in those with one or two HCV markers (P = 0.039). Replication of HCV in liver was detected more frequently in patients with three (93%, P = 0.002), two (82%, P = 0.001), and one HCV marker (73%, P = 0.011) than in those without markers (27%). In conclusion, testing for all these markers allows diagnosis of occult HCV without the need for a liver biopsy and these assays may help to elucidate the clinical significance of occult HCV infection. J. Med. Virol. 82:1554–1559, 2010. © 2010 Wiley‐Liss, Inc.     

Isolated core antibody hepatitis B in sub-Saharan African immigrants

Chronic hepatitis B virus (HBV) infection is a major health problem in sub-Saharan Africa, where prevalence is > or =8%, and is increasingly seen in African immigrants to developed countries. A retrospective audit of the medical records of 383 immigrants from sub-Saharan Africa attending the infectious diseases clinics at the Royal Melbourne Hospital was performed from 2003 to 2006. The HBV, human immunodeficiency virus (HIV) and hepatitis C virus (HCV) serological results are reported, with a focus on the isolated core antibody HBV pattern (detection of anti-HBc without detection of HBsAg or anti-HBs). Two-thirds (118/174, 68%) of those tested had evidence of HBV infection with detectable anti-HBc. Chronic HBV infection (serum HBsAg detected) was identified in 38/174 (22%) and resolved HBV infection (both serum anti-HBs and anti-HBc detected) in 45/174 (26%). The isolated core antibody pattern was identified in 35/174 (20%), of whom only 1/35 (3%) had detectable serum HBV DNA on PCR testing, indicating occult chronic HBV (OCHB). Only 8/56 (14%) patients with negative anti-HBc had serological evidence of vaccination (serum anti-HBs detected). HIV infection was detected in 26/223 (12%). HCV antibodies were detected in 10/241 (4%), of whom 8 (80%) had detectable HCV RNA. Viral co-infection was detected in only 2/131 (1.5%) patients tested for all three viruses. The isolated core antibody HBV pattern was common among sub-Saharan African patients in our study. These patients require assessment for OCHB infection and monitoring for complications of HBV.     

中国北方地区隐源性肝炎及乙型肝炎表面抗原阴性肝癌患者中隐匿性HBV感染流行状况分析

目的调查中国北方地区隐源性肝炎及乙肝表面抗原（HBsAg）阴性肝癌患者中隐匿性乙型肝炎病毒（HBV）感染的流行状况。方法收集393个受试者的血清,其中包括隐源性慢性肝炎患者215名、HBsAg阴性肝癌患者178名。使用巢式PCR的方法检测血清中的HBV-DNA,同时使用实时定量PCR的方法检测HBV—DNA的载量。结果在隐源性慢性肝炎患者、HBsAg阴性肝癌患者中隐匿性HBV感染流行率分别为23．7％（51／215）和68．5％（122／178）。在IgGanti—HBc阳性者中,隐匿性HBV感染率较高。所有隐匿性感染者的病毒载量均较低（〈10^5拷贝／ml）。结论在中国北方隐源性肝炎及肝癌患者中,隐匿性HBV感染率较高。因此,对隐匿性HBV感染应给及足够的重视,避免因输血及器官移植造成HBV的传播。     

Detection of Occult Hepatitis C and Hepatitis B Virus Infections from Peripheral Blood Mononuclear Cells

Purpose: To investigate the problem of occult HCV & HBV infections in patients with persistently longstanding abnormal liver function test results of unknown etiology and to investigate occult HCV in patients with sustained virological response (SVR). Methods: The study included two groups; first group included 40 patients with persistently longstanding abnormal liver function test, in addition to 62 patients with history of hepatitis C who developed SVR. HCV RNA status was tested in serum by conventional RT-PCR and by real-time PCR in Peripheral Blood Mononuclear Cells (PBMCs). HBV DNA in PBMCs was done in first group only. Results: In first group, PCR in PBMCs was positive for HCV RNA in 4 patients with elevated liver enzymes and HBV DNA was positive in PBMCs in 3 patients. In patients with SVR, 7 patients were positive for HCV RNA in PBMCs. Conclusions: Patients with long-standing abnormal results of liver-function tests with unknown etiology may have HCV RNA or HBV DNA in their PBMCs in the absence of anti-HCV antibodies, HBV markers, serum HBV DNA and serum HCV RNA.In Patients with SVR, HCV RNA in PBMCs is recommended to detect residual infection especially in those with high serum HCV RNA levels before treatment.