Hepatitis C virus RNA in peripheral blood mononuclear cells: Relation with response to interferon treatment

Abstract

The polymerase chain reaction (PCR) was used to investigate the presence of positive and negative hepatitis C virus (HCV) RNA strands in serum and peripheral blood mononuclear cells (PBMC) of 20 patients with histologically proven HCV-related chronic liver disease. All patients completed a course of interferon (IFN) treatment (6 MU of IFN-alpha 2b three times a week for 24 weeks) and were followed-up for 12 months after treatment was discontinued. Pre-treatment, end-treatment and 6-month follow-up serum and PBMC samples were examined. At enrollment, the positive strand of HCV-RNA was detected in serum of 18 patients (90%), the negative strand in none. Positive-stranded HCV-RNA was detected in PBMC of 15 patients (75%), 13 of whom also had detectable levels of negative-stranded HCV-RNA in PBMC. By the end of the treatment, 12 patients (60%) were responders. The pre-treatment HCV infection of PBMC, indicated by the presence of both RNA strands, was found in 8 (66.7%) responders compared to 5 (62.5%) non-responders (P = n.s.). End-treatment loss of PBMC HCV-RNA correlated significantly with the response since it occurred in all responders compared to 2 non-responders (P = 0.02). However, end-treatment-negative serum and PBMC HCV-RNA did not predict the occurrence of a sustained response, which was observed at month 12 in 5 of 12 responders (P = n.s.). On the other hand, the persistent absence of HCV RNA in serum and PBMC at the end of the 6-month follow-up was significantly associated with the occurrence of a sustained response (P < 0.0001).

Assessment of Hepatitis C Virus RNA in Peripheral Blood Mononuclear Cells as a Predictor of Response to Pegylated-Interferon and Ribavirin: A Cohort Study

“…In contrast to the current study, Chen et al (19) and Taliani et al (20) found that detection of HCV RNA in PBMCs specimens could not predict relapse after treatment. One of the weak points of Chen's study was the small number of patients with detectable HCV RNA in their PBMCs (19).…”

Extrahepatic replication of HCV: Insights into clinical manifestations and biological consequences

“…For example, several studies have found that HCV RNA may be present in PBMCs but not the corresponding serum or liver. [98][99][100][101] Thus, current detection systems may underestimate the true extent of replication. Moreover, HCV RNA, including replicative intermediate forms, can persist at very low levels in peripheral lymphoid cells for many years after apparently complete spontaneous or treatment-induced resolution of chronic HCV, 102 strongly suggesting that sub-populations within PBMCs may represent true reservoirs of HCV replication.…”

“…103 Thus, it is provocative to speculate that low-level replication of HCV in PBMCs may lead to reactivation of HCV after termination of therapy and/or predict response to therapy. 80,99,100,[102][103][104][105] As reviewed elsewhere, HCV is likely involved in several neurologic syndromes. 16 While central nervous system (CNS) involvement is less frequent, the detection of negative-strand HCV RNA in the CNS 29 suggests a potential link between HCV and these extrahepatic pathol- ogies.…”

Hepatitis C virus persistence in human hematopoietic cells injected into SCID mice

“…Among the 10 tested samples, we obtained clear evidence for the detection of such negative strands in 2 mice (injected with NHL cells). The specificity of the results of our assay was assessed by the following points: 1) we used capsid-specific sequences that were shown to dramatically reduce or eliminate false-positive results 19 ; 2) we performed serial dilutions of liver HCV RNA obtained from an anti-HCV-positive subject. We thus verified that, when the HCV-RNA level compared with those shown in our mouse samples, there is no evidence for self-or mispriming.…”

“…Positive-strand HCV RNA has indeed been detected by reverse-transcription polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMC) in several studies investigating patients at various stages of the viral infection. [8][9][10][11][12][13][14][15][16][17][18][19][20][21] Furthermore, it was possible in some cases to detect the negative strand of HCV RNA, and thus to suggest that HCV RNA might replicate in these cells. [11][12][13][14][15][16][17][18][19][20][21] These findings were further substantiated by the detection of HCV genomes in PBMC and liver mononuclear cells by using in situ hybridization.…”