A novel stop codon mutation within the hepatitis B surface gene is detected in the liver but not in the peripheral blood mononuclear cells of HIV‐infected individuals with occult HBV infection

Abstract

To characterize occult HBV infection (OHB) in different compartments of HIV+ individuals. This retrospective study involved 38 consecutive HIV+ patients; 24 HBsAg negative (HBV-) and 14 HBsAg positive (HBV+). OHB was assessed in serum samples, liver tissue (LT) and peripheral blood mononuclear cells (PBMC) by genomic amplification of the partial S, X and precore/core regions. HBV genomic analysis was inferred by direct sequencing of PCR products. The intracellular HBV-DNA was measured by a quantitative real-time PCR. HBV+ patients were used as a control for HBV replication and genomic profile. In HBV- patients, HBV-DNA was undetectable in all serum samples, while it was found positive in 7/24 (29%) LT in which genotype D prevailed (57%). HBV-DNA was found in 6/7 (86%) PBMC of occult-positive and none of occult-negative LT. Significantly lower HBV-DNA load was present in both compartments in OHB+ with respect to the HBV+ group (LT: P = 0.002; PBMC: P = 0.026). In the occult-positive cases, HBV replication was significantly higher in LT than in PBMC (P = 0.028). A hyper-mutated S gene in PBMC and a nucleotide mutation at position C695 in LT that produces a translational stop codon at amino acid 181 of the HBs gene characterized OHB. In this group of HIV+ persons, OHB is frequent and exhibits lower replication levels than chronic HBV in the different compartments examined. HBV-DNA detection in PBMC may offer a useful tool to identify OHB in serum-negative cases. The novel HBs gene stop codon found in LT could be responsible for reduced production leading to undetectability of HBsAg.

Low prevalence of occult hepatitis B virus infection in chronic haemodialysis and kidney transplant patients

“…Additional testing for HBV DNA in PBMCs has been suggested to uncover occult infections not detected by serologic methods or virus determination in serum, avoiding the potential risk of a liver biopsy . Though the existence of HBV in extrahepatic tissue had been debated controversially, there is evidence that HBV can infect and replicate in PBMCs .…”

“…Though the detection of HBV DNA in the liver is the most accurate way to identify OBI, it is limited by the risk of an invasive procedure. Testing of the viral genome in peripheral blood mononuclear cells (PBMCs) has been suggested to uncover occult infections not detected by serologic methods or virus determination in serum . In this study, we aimed to investigate for the first time the prevalence of OBI in large cohorts of CHD patients and KTxR with additional testing of HBV DNA in PBMCs.…”

Hepatitis B virus (HBV) variants fluctuate in paired plasma and peripheral blood mononuclear cells among patient cohorts during different chronic hepatitis B (CHB) disease phases

“…HBsAg negative) HBV between family members who carried a unique genotype and vaccine escape mutant strains within the PBMC site . Similarly, unique HBV strains in the PBMC compartment have been found in patients with HIV positive, even leading to occult HBV reactivation and fulminant hepatic failure in one patient . In the woodchuck model, it was demonstrated that at low replication rates, the virus is predisposed to invade the PBMC compartment leading to occult viral infection and even primary hepatocellular carcinoma in 20% of infected animals .…”

An estimation of the prevalence of occult HBV infection in Western Europe and in Northern America: A meta‐analysis

“…The main characteristics of the 34 studies included in the meta-analysis are summarized in Tables 1 and 2; 6 26,29,42,45,51,53 evaluated the prevalence of OBI in subjects without chronic liver disease, 30 5,7,[22][23][24][25][26][27][28][30][31][32][33][34][35][36][37][38][39][40][41][43][44][45][46][47][48][49][50]52 in those with chronic liver disease and 2 26,45 in both. All were cross-sectional studies, but 3 7,46,50 were cohort studies.…”