Intrahepatic Hepatitis C Viral Rna Status of Serum Polymerase Chain Reaction-Negative Individuals With Histological Changes on Liver Biopsy

Abstract

Hepatitis C virus (HCV) infection is a major public health problem worldwide. 1 Diagnosis of HCV is based on serological detection of anti-HCV antibodies by enzyme-linked immunosorbent assay (ELISA) supplemented with recombinant immunoblot assay (RIBA) and detection of HCV RNA in serum by polymerase chain reaction (PCR), because anti-HCV antibodies alone cannot discriminate active from past infection. 2 Histological assessment is also important in assessing disease status. 3 For individuals testing anti-HCV positive but negative for HCV RNA in serum, the precise diagnosis remains unclear. Whether they have spontaneously resolved past infection or currently have active infection undetectable in serum but which could be detectable in liver, since viral levels have been demonstrated to be 10 4 -fold higher in liver than in serum, is unclear. [4][5][6][7][8] If the latter is true and low level active infection is present, then these individuals represent a group well suited for therapeutic intervention because a low viral load is accepted as a favorable prognostic factor for therapy. 9 Because few studies to date have investigated HCV RNA status in the liver of anti-HCV-positive serum HCV RNA individuals, it is important to assess intrahepatic HCV RNA status in these individuals to determine whether they have truly spontaneously resolved past infection or have current infection with similar clincial, histological, and virological profiles as serum PCR-positive patients. [4][5][6][7] The discovery in 1994 that HCV-contaminated anti-D immunoglobulin had been administered to Rhesus-negative women in 1977 and 1991 to 1993 led to a national screening program conducted by the Irish Blood Transfusion Service Board (BTSB). 10 As a result of this program, a large group of PCR-positive (n ϭ 490) and antibody positive PCR-negative individuals (n ϭ 526) were identified and referred to 6 designated Liver Centers for further evaluation. 10,11 The aim of this study was to assess the significance of histological changes in the liver of serum PCR-negative women who had undergone liver biopsy at this center by detailed investigation of clinical, histological, and intrahepatic HCV RNA status. For the purpose of comparison, some clinical and histological data from a large group of serum PCR-positive women who received HCV-contaminated anti-D over the same time period as the serum PCR-negative women is also presented. PATIENTS AND METHODSPatients. As a result of the national screening program, 100 PCRpositive and 96 PCR-negative women who had received HCV-contaminated anti-D were randomly referred to this center and constitute a representative cross-section of the total infected cohort.Of the 96 PCR-negative women, 42 (43.8%) were still RIBApositive and 6 (6.2%) had elevated ALT levels at the time of presentation. Symptoms, consisting mainly of fatigue and arthralgia dating from the time of inoculation were reported by 69 (71.9%) women. It

Rethinking the immune properties of bilirubin in viral hepatitis: from bench to bedside

“…This, in turn, would result in a release of adequate levels of IFN by CD8 + T cells to drive subsequent antiviral activity in those individuals who spontaneously clear the HCV during the acute phase of infection (Figure 2b). This model is consistent with retrospective studies of HCV‐infected patients who revealed an association between the presence of symptoms and jaundice during the acute stage and spontaneous viral clearance 51 , 55 . Based on these data, it is possible that those mild acute HCV infections that are not associated with a discernable increase of serum CBR cause the host to progress to chronic disease.…”

Occult hepatitis C: How convincing are the current data? #

“…25,[43][44][45][46][47][48][49] Data regarding detection of HCV RNA in compartments (PBMCs, liver) other than serum in populations of patients with spontaneously resolved hepatitis C (anti-HCV positive, serum HCV RNA negative, no former antiviral treatment) are conflicting. 7,47,[50][51][52][53][54] The rates of detectability of HCV RNA in PBMCs range from 0%-50%. 7,50,54 Within the largest study (n ϭ 69, including six patients with SVR after IFN-based antiviral therapy), HCV RNA could neither be detected by cell-associated transcription-mediated assay (TMA; sensitivity, 2-50 HCV RNA copies in 5 ϫ 10 6 PBMCs) nor by nested RT-PCR (sensitivity, 15-150 HCV RNA molecules in 5 ϫ 10 6 PBMCs), respectively.…”

“…Four studies reported a high percentage (27 7,[51][52][53] In contrast, within a cohort of 33 women, who had received HCV contaminated anti-D immunoglobulin, none was found to be intrahepatic HCV RNA positive. 47 (2) "Occult" HCV Infection Type B in Patients with (PEG-)IFN-Induced Sustained Virologic Response. In patients with chronic hepatitis C and (PEG-)IFN-induced SVR, late relapse is rare (Tables 2 and 3).…”

Evaluation of the Core Antigen Assay as a Second-Line Supplemental Test for Diagnosis of Active Hepatitis C Virus Infection

“…In contrast, pharmacotherapy with the current combination of pegylated interferon and ribavirin can result in a sustained virologic response in about 55% of treated patients (8,21,23). A sustained viral response has been associated with a sustained reduction in hepatic inflammation and fibrosis and improved long-term outcomes (4,24). These findings underscore the need for the timely and accurate identification of active HCV infection.…”