Hepatitis D virus RNA in acute delta infection: Serological profile and correlation with other markers of hepatitis D virus infection

Abstract

To evaluate the profile of hepatitis D virus replication and the corresponding immunoresponse after acute hepatitis D virus infection, sera from 50 patients with acute hepatitis D (36 with acute hepatitis B virus-hepatitis D virus coinfection and 14 HBsAg carriers with hepatitis D virus superinfection) were investigated for the presence of hepatitis D virus RNA and other serological hepatitis D virus markers. During the first week after onset of symptoms, hepatitis D virus RNA was detected by spot hybridization with a similar frequency among patients with coinfection (64%) and those with superinfection (71%). The presence of hepatitis D virus RNA in the first serum sample correlated with that of circulating hepatitis D antigen in both groups of patients. The presence of hepatitis D virus RNA was transient and its clearance paralleled that of serum hepatitis D antigen among patients with coinfection, so that 1 month after the onset of symptoms serum hepatitis D virus RNA was no longer detectable in any of these patients. Conversely, serum hepatitis D virus RNA was still present in 78% of those with superinfection, all of whom developed chronic liver disease, thus suggesting that the persistence of hepatitis D virus RNA in the serum for more than 4 weeks might indicate progression to chronicity. In nine of the 14 patients (64%) with hepatitis D virus superinfection progressing to chronicity, hepatitis D virus RNA was persistently detected throughout the follow-up, whereas in five patients it was detected occasionally. In four superinfected patients hepatitis D virus RNA and hepatitis B virus DNA were detected simultaneously in serial samples, thus suggesting that, at least during early stages of chronic hepatitis D virus infection, both viruses may replicate at the same time.

Correlation between hepatitis B viremia and the clinical and histological activity of chronic delta hepatitis

“…Recent studies in patients with orthotopic liver transplantation support this view; HDV can establish latent, nonpathogenic infections on the graft and that reactivation of these infections to disease depends on HBV replication [8,24]. Intrahepatic HDAg, serum IgM anti-HDV and serum HDV-RNA detectable by dot-blot hybridization are excellent markers for active HDV replication [2,15,27]. Classical studies have suggested that the mechanism of liver damage in HDV infection is directly cytopathic.…”

Delta hepatitis: molecular biology and clinical and epidemiological features

“…The sensitivity of the assay was later improved significantly by using longer radiolabeled RNA probes (185) produced by in vitro transcription. Several investigators showed that persistence of HDV RNA in serum may indicate a progression to chronicity (25,217). A method for detecting intrahepatic HDV RNA in frozen and formalin-fixed sections by in situ hybridization has also been developed (85); however, this assay does not appear to be more sensitive than the direct IF assay for HDAg.…”

Hepatitis Delta Virus: The Molecular Basis of Laboratory Diagnosis

“…153,154 In self-limited HDV/HBV coinfection, serum markers of HDV infection can be transient and therefore diffucult to detect (Figure 3). 153,155,156 Markers of HDV infection that appear early in acute coinfection, within 1 to 10 days of the onset of symptoms, include serum HDAg 149, 153,155,156 and HDV RNA 146,149,153,[155][156][157] (Table 3). Anti-HD IgM appears 2 to 3 weeks after the onset of symptoms.…”

“…Serum HDV RNA is a very sensitive early marker of HDV infection, and can be detected by slot-blot hybridization. [144][145][146][147][148][149][150][151][152][153][154][155][156][157] As few as 10 4 to 10 6 genomes can be detected using this simple assay. 159 When tests to detect serum HDAg and HDV RNA are not available for clinical purposes, HDV infection is confirmed somewhat after the fact by detection of total anti-HD Ab by competitive microplate assay.…”