The myth of occult hepatitis C infection

Abstract

We read with interest the review by Welker and Zeuzem on occult hepatitis C virus (HCV) infection and also the reply by Carreno et al. 1,2 The latter reported in their answer to Welker and Zeuzem that HCV can replicate in patients with occult HCV infection. Because this conclusion would have substantial consequences for patients considered cured of their HCV infection, as well as for the health care system, the data must be interpreted most carefully. They reported two studies that "unconvincingly failed to detect occult HCV infection in cryptogenic hepatitis because of several concerns with the methodology employed." 3,4 We would like to correct Carreno et al. on these two important points. In the first study published by Tanari et al., it was shown that the ability for HCV RNA detection is more sensitive in whole blood instead of peripheral blood mononuclear cells (PBMCs), due to circulation of the infectious virus in patient sera in the form of triglyceriderich particles which is present in the whole blood and not in PBMCs. 5 In the second study, we looked for the so-called "occult hepatitis C", in a different population of patients and controls, including patients with long-term normal alanine aminotransferase level, by using an original ultrasensitive validated real-time polymerase chain reaction (PCR) method. We failed to find any occult hepatitis C. 4 Moreover, we would like to underscore that for a long time, Carreno et al. reported the same results on the same cohort of patients. 6 The method proposed used PBMCs from a patient chronically infected with HCV for RNA isolation and HCV RNA detection. Serial dilutions of the isolated RNA cannot be a gold standard due to the limit of detection of HCV RNA by an in-house reverse transcription PCR method. PBMCs from our patients were subjected to HCV RNA transcription-mediated amplification assays without any HCV RNA detectable using this high sensitivity assay. 6 The second issue addressed is related to the concept of the presence of HCV RNA in the liver in the absence of HCV RNA detected in PBMCs. Carreno et al. suggested that negativity for HCV-RNA in PBMC does not exclude the existence of occult HCV infection because the gold standard method to identify this occult infection is by detection of viral RNA in liver cells. To address this question, Maylin et al. recently assessed the presence of residual HCV RNA in serum, liver, and PBMCs using TMA (sensitivity Ͻ9.6 IU/mL) in a long-term follow-up study of patients infected with chronic hepatitis C who achieved a sustained virological response after interferon-based treatment. 6 A total of 114 patients had a posttreatment liver tissue and 156 had PBMCs. Serum HCV RNA remained undetectable (1300 samples), indicating that none of the patients had a relapse. HCV RNA was detectable in 2 of 114 (1.7%) liver specimens, and in none of 156 PBMC specimens. These authors strongly suggest that SVR may be considered to show eradication of HCV infection. 7 This latest observation was confirmed by another recent study with a ...

Is psychosocial and cognitive dysfunction misattributed to the virus in hepatitis C infection? Select psychosocial contributors identified

“…The possibility of occult infection causing symptoms in our clearedv HCV sample also appears highly improbable given their consistent PCR ‘negative’ status over 20 years of annual surveillance. This is further supported by recent publications purporting to debunk the ‘myth’ of occult HCV infection . This investigation, which to the author's knowledge is the first to examine both chronically infected and cleared HCV individuals with an iatrogenic exposure history as a single sample, found relatively equal representation of CHC and cleared HCV individuals in both impaired and nonimpaired HRQoL subgroups.…”

Prevalence and Follow-Up of Occult HCV Infection in an Italian Population Free of Clinically Detectable Infectious Liver Disease

“…Barril and colleagues found an OCI prevalence of 45% in 109 haemodialysis patients [13], and the same group of investigators claimed there was a potential transmission risk of OCI [14], as they found a high OCI prevalence among relatives of OCI patients, comparable to that found among family members of patients with chronic HCV infection. Conversely, other authors did not find OCI in immune-suppressed subjects [15]–[16], in 28 onco-haematological [17] patients, or in 26 kidney-transplant patients [18].…”

A New Twist to a Chronic HCV Infection: Occult Hepatitis C

“…Specifically, they found that the presence of OCI among the relatives of individuals they studied was comparable to that found among family members of patients with overt HCV infection. The Barril et al report [ 60 ] and others [ 64 , 65 ] however stand in contrast to that of other authors [ 39 , 66 ] who were not able to identify cases of OCI in different cohorts of immune-suppressed subjects consisting of 28 oncohematological patients [ 67 ] and 26 kidney-transplant recipients [ 68 ].…”