[Show abstract][Hide abstract] ABSTRACT: Amplification of Hepatitis C virus (HCV) RNA from blood detected occult HCV in 30.9% of 210 HCV-seronegative dialysis patients with abnormal liver enzymes that had evaded standard HCV testing practices. Isolated HCV Core-specific antibody detection identified three additional anti-HCV screening-negative patients lacking HCV RNA amplification in blood who were considered as potentially infectious. Together, these findings may impact the management of the dialysis setting.
Journal of Clinical Microbiology 05/2014; · 4.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The association of hepatitis C virus (HCV) infection and glomerulonephritis is well known. However, the relationship between immune-mediated glomerulonephritis and occult HCV, characterized by the presence of HCV-RNA in liver or in peripheral blood mononuclear cells in the absence of serological markers, is unknown. We tested this in 113 anti-HCV-negative patients; 87 with immune-mediated glomerulonephritis and 26 controls with hereditary glomerular nephropathies. All patients were serum HCV-RNA negative by conventional real-time PCR. Significantly, occult HCV-RNA (detectable viral RNA in peripheral blood mononuclear cells or in serum after ultracentrifugation) was found in 34 of 87 patients with immune-mediated glomerulonephritis versus 1 of 26 control patients. The serum creatinine levels were significantly higher in patients with immune-mediated glomerulonephritis with than in those without occult HCV (1.5 versus 1.1 mg/dl, respectively). A multivariate analysis adjusted for gender showed a significantly increased risk of occult HCV in patients with immune-mediated glomerulonephritis versus the controls (odds ratio of 13.29). Progression to end-stage renal disease tended to be faster in patients with immune-mediated glomerulonephritis and occult HCV than in the negative cases. Thus, occult HCV is strongly associated with immune-mediated glomerulonephritis and may have a role in the progression of the disease.Kidney International advance online publication, 19 March 2014; doi:10.1038/ki.2014.68.
Kidney International 03/2014; · 8.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV-RNA was tested in the liver samples of 52 patients with chronic HBV infection and 21 (40%) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.
Journal of Medical Microbiology 05/2013; · 2.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Occult hepatitis C virus (HCV) infection, defined as the presence of HCV RNA in liver and in peripheral blood mononuclear cells (PBMCs) in the absence of detectable viral RNA in serum by standard assays, can be found in anti-HCV positive patients with normal serum levels of liver enzymes and in anti-HCV negative patients with persistently elevated liver enzymes of unknown etiology. Occult HCV infection is distributed worldwide and all HCV genotypes seem to be involved in this infection. Occult hepatitis C has been found not only in anti-HCV positive subjects with normal values of liver enzymes or in chronic hepatitis of unknown origin but also in several groups at risk for HCV infection such as hemodialysis patients or family members of patients with occult HCV. This occult infection has been reported also in healthy populations without evidence of liver disease. Occult HCV infection seems to be less aggressive than chronic hepatitis C although patients affected by occult HCV may develop liver cirrhosis and even hepatocellular carcinoma. Thus, anti-HCV negative patients with occult HCV may benefit from antiviral therapy with pegylated-interferon plus ribavirin. The persistence of very low levels of HCV RNA in serum and in PBMCs, along with the maintenance of specific T-cell responses against HCV-antigens observed during a long-term follow-up of patients with occult hepatitis C, indicate that occult HCV is a persistent infection that is not spontaneously eradicated. This is an updated report on diagnosis, epidemiology and clinical implications of occult HCV with special emphasis on anti-HCV negative cases.
World Journal of Gastroenterology 06/2012; 18(23):2887-94. · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with occult hepatitis C virus (HCV) infection (HCV-RNA in liver without detectable anti-HCV and serum HCV-RNA) may have viral RNA in peripheral blood mononuclear cells (PBMCs) and in serum after ultracentrifugation, and may present HCV-specific T-cell responses, but it is unknown whether these markers persist to be detectable over time.
To perform a prospective virological long-term follow up of patients with occult HCV.
Viral markers were tested every 3-4 months during 55.7 ± 20.3 months in 37 patients with occult HCV who were under ursodeoxycholic acid treatment.
Viral RNA was detectable in PBMCs of 31 patients during the follow up. In 23 of them, viral RNA in PBMCs was detected intermittently and in the other eight patients HCV-RNA was positive in a single sample. After ultracentrifugation, serum HCV-RNA was detected in 33 patients, being the viraemia intermittently detectable in 28, whereas in the remaining five patients, serum HCV-RNA was positive only once. Only one patient tested always HCV-RNA negative in PBMCs and in ultracentrifuged serum during follow up. Specific Core, NS3, and/or NS4 T-cell responses were found in 31 of the patients. The patient who was always HCV-RNA negative in PBMCs and in ultracentrifuged serum had specific HCV-T-cell responses.
Occult HCV infection persists over time with fluctuating viraemia levels that induce and maintain specific T-cell responses against viral proteins.
Liver international: official journal of the International Association for the Study of the Liver 11/2011; 31(10):1519-24. · 4.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Medical Virology 09/2010; 82(9):1554-9. · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemodialysis induces production of the hepatocyte growth factor (HGF) and decrease of serum hepatitis C virus (HCV) RNA in patients with HCV infection, but it is not known if the hemodialysis schedule or type of membrane affect both the HGF production and HCV viremia. The effects on both parameters of alternate-day intermittent hemodialysis and short-daily hemodialysis and high and low flux membranes were investigated in 41 patients treated by hemodialysis. Sixteen (39%) patients were anti-HCV positive and 11 (69%) had HCV RNA. Twenty-six patients were on alternate-day intermittent and 15 on short-daily hemodialysis. High flux membranes were used for 29 patients and low flux membranes for 12 patients. A decrease in HCV RNA was observed at the end of hemodialysis (8.6 x 10(5) +/- 1.1 x 10(6) IU/ml vs. 4.4 x 10(5) +/- 7.3 x 10(5) IU/ml, P = 0.003). The proportion of HCV RNA decrease was similar in patients dialyzed with both schedules and with both types of membranes. The HGF levels increased from 2,605.9 +/- 1,428.7 to >8,000 pg/ml at 15 min. At the end of the session, the HGF levels decreased to 5,106.7 +/- 2,533.9 pg/ml. The HGF levels at the start of the next session were similar to those at baseline (2,680.0 +/- 1,209.3 pg/ml). The increase and dynamics of the HGF levels were similar in patient's hemodialyzed with both schedules and with both types of membranes. These results suggest that changes in HCV RNA and HGF levels during hemodialysis are not influenced by the schedule or type of membrane used.
Journal of Medical Virology 03/2010; 82(5):763-7. · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Journal of Medical Virology 08/2009; 81(7):1198-203. · 2.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Concentration of viral particles by ultracentrifugation of serum prior to PCR allows detection of hepatitis C virus (HCV) RNA in patients with undetectable viral RNA by conventional PCR assays.
To analyse if HCV-RNA is detected after serum ultracentrifugation in chronic hepatitis C patients with a sustained virological response to antiviral therapy (defined as serum HCV-RNA negativity by conventional assays 6 months after the end of therapy).
HCV-RNA was tested using real-time PCR in ultracentrifuged sera collected during the post-treatment follow-up (mean: 42 +/- 27 months) in 57 sustained virological responders (SVR).
After serum ultracentrifugation, HCV-RNA was detected on at least one occasion during the follow-up in 29/57 (51%) SVR. Thirteen (23%) of these 57 SVR suffered a reactivation 18 +/- 8 months after the end of therapy (reappearance of serum HCV-RNA detectable by conventional assays). Among reactivated patients, 11/13 (85%) had HCV-RNA in ultracentrifuged serum samples (detectable 10 +/- 5 months before reactivation), while HCV-RNA was positive after ultracentrifugation in 18/44 (41%) long-term SVR (P = 0.01). Persistence of detectable HCV-RNA after serum ultracentrifugation was associated with reactivation (P = 0.001).
Serum ultracentrifugation prior to PCR allows detection of HCV-RNA in SVR and its persistence may predict late reactivation.
[Show abstract][Hide abstract] ABSTRACT: Occult HCV infection has been described among anti-HCV-HCV RNA-negative individuals with abnormal transaminase values in whom HCV RNA is detected in liver.
IgG antibody to an HCVcore-derived peptide (anti-HCVcore) was investigated in 145 patients with serologically silent occult HCV infection.
At the time of the diagnostic biopsy 45/145 (31%) occult HCV-infected patients tested IgG anti-HCVcore-positive but none of the 140 patients with HCV-unrelated liver disease (P<0.001). Among 23 IgG anti-HCVcore-positive patients at baseline, 22 remained antibody-reactive (one became antibody-negative). Similarly, 17/31 baseline anti-HCVcore-negative patients remained non-reactive whereas 14 seroconverted to IgG anti-HCVcore (although transiently in 10 patients). Thus, a total of 59/145 (40.7%) patients with occult HCV infection showed IgG anti-HCVcore reactivity at any time point analyzed, including 14 initially non-reactive patients. By supplemental immunoblot assay 16 sera reacted weakly with an HCVcore-peptide band (indeterminate result) of which 10 (62.5%) reacted in the IgG anti-HCVcore assay. Occult HCV-infected patients who tested anti-HCVcore-positive showed more frequently signs of necro-inflammation (P=0.035) and greater percentages of HCV RNA-positive hepatocytes (P=0.004) compared with those anti-HCVcore-negative.
This work documents that IgG anti-HCVcore testing identifies occult HCV infection among seronegative, non-viremic patients using screening tests and may be useful in tracking anti-HCV-negative infections.
Journal of Hepatology 11/2008; 50(2):256-63. · 10.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Occult hepatitis C virus (HCV) infection (i.e., detectable HCV-RNA in the liver or peripheral blood mononuclear cells) in the absence of both serum HCV-RNA and anti-HCV antibodies has not been investigated in hemodialysis patients. In this study, real-time PCR and in situ hybridization was used to test for the presence of genomic and antigenomic HCV-RNA in peripheral blood mononuclear cells of 109 hemodialysis patients with abnormal levels of liver enzymes. Occult HCV infection, determined by the presence of genomic HCV-RNA, was found in 45% of the patients; 53% of these patients had ongoing HCV replication, indicated by the presence of antigenomic HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on hemodialysis and had significantly higher mean alanine aminotransferase levels during the 6 mo before study entry. Logistic regression analysis revealed that mortality was associated with age >60 yr (odds ratio 3.30; 95% confidence interval 1.05 to 10.33) and the presence of occult HCV infection (odds ratio 3.84; 95% confidence interval 1.29 to 11.43). In conclusion, the prevalence of occult HCV infection is high among hemodialysis patients with persistently abnormal values of liver enzymes of unknown cause. The clinical significance of occult HCV infection in these patients requires further study.
Journal of the American Society of Nephrology 08/2008; 19(12):2288-92. · 9.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic infection with hepatitis C virus (HCV) is associated with several extrahepatic manifestations, including neuromuscular and joint disorders, and HCV RNA has been detected in muscle fibers of patients with myosistis and chronic hepatitis C. However, whether HCV infects muscle cells in patients without myosistis is unknown. The presence of HCV in other sites of the musculoskeletal system has not been investigated. In the present study the presence of HCV RNA was sought in muscle (2 cases), intervertebral disk (1 case) and meniscus (1 case) samples from patients with chronic hepatitis C. HCV RNA was not detected by reverse transcription and real-time polymerase chain reaction in any of the samples tested. In conclusion, the results do not support a direct role of HCV in musculoskeletal disorders associated with chronic hepatitis C.
Journal of Medical Virology 01/2008; 79(12):1818-20. · 2.22 Impact Factor