A mutation of the start codon in the X region of hepatitis B virus DNA in a patient with non-B, non-C chronic hepatitis

Abstract

There are cases of hepatitis involving occult hepatitis B virus (HBV) infection in which, even though the HB surface antigen (HBsAg) is negative, HBV-DNA is detected by a polymerase chain reaction (PCR). We conducted a sequence analysis of the entire HBV region in a case of non-B non-C chronic hepatitis in a 46-yearold female. A diagnosis of non-B non-C chronic hepatitis was made. Although HBV markers, such as HBs antibody (anti-HBs), anti-HBc, HBeAg and anti-HBe, were negative, HBV-DNA was positive. Nested PCR was performed to amplify the precore region of HBV-DNA and all remaining regions by long nested PCR. Sequence analysis of the two obtained bands was conducted by direct sequencing. Compared with the control strains, the ATG (Methionine) start codon in the X region had mutated to GTG (Valine). It is assumed that a mutation at the start codon in the X region may be the reason why HBV markers are negative in some cases of hepatitis that involve occult HBV infection.

Mutations associated with occult hepatitis B in HIV‐positive South Africans

“…While this represented 2.2 kb of the 3.2 kb genome, the X and preC/C ORFs were not analyzed. As occult‐associated mutations have previously been identified in both of these ORFs [Kao et al, ; Chaudhuri et al, ; Candotti et al, ; Chen et al, ; Fujise et al, ], the total number of occult‐associated mutations through the HBV genome is likely underestimated. Additionally, we were most interested in the dominant viral variant in each patient.…”

“…Occult‐associated mutations—those that appear exclusively or with higher frequency in occult HBV infections as compared to chronic HBV infection—have been identified throughout the HBV genome. While occult‐associated mutations have been identified in the X preCore/Core, and Pol regions most studies to date have focused on mutations within the PreS/S reading frame [Hou et al, ; Chan et al, ; Kao et al, ; Chaudhuri et al, ; Jeantet et al, ; Wagner et al, ; Khattab et al, ; Pogány et al, ; Datta et al, ; Awerkiew et al, ; Banerjee et al, ; Araujo et al, ; Candotti et al, ; Gonza et al, ; Henke‐Gendo et al, ; Miyagawa et al, ; Vivekanandan et al, ; Bremer et al, ; Chen et al, ; Kumar et al, ; Song et al, ; Tamori et al, ; Cheung et al, ; El Chaar et al, ; Martin et al, , Martin et al, ; Hamkar et al, ; Motta et al, ; Thedja et al, ; Xu et al, ; Yuan et al, ; Fujise et al, ; Launay et al, ; Mello et al, ; Bes et al, ; Shahmoradi et al, ; Svicher et al, ; Cassini et al, ; Kim et al, ]. In several studies, the functional importance of these mutations has been evaluated [Schories et al, ; Hass et al, ; Martin et al, ; Svicher et al, ].…”

Potential Mutations Associated With Occult Hepatitis B Virus Status

“…X ORF produces the X protein (HBx) and although the exact function of HBx during HBV replication is still unclear, multiple studies suggest that HBx is necessary for viral replication in vivo and in vitro ( 30 , 37 - 40 ). Mutations in the X region can involve the regulatory elements that control replication, like the basal core promoter and the enhancer II.…”

Occult Hepatitis B Virus Infection

“…[6][7][8][9][10]21]. Yapılan bazı çalışmalarda ise özellikle seronegatif OHB oluşumunda HBV X geninde mutasyonların etkisini düşündüren sonuçlar elde edilmiştir [38]. OHB farklı bazı klinik tablolarla karşımıza çıkabilir.…”

“…OHB ile ilişkili son klinik durum ise bütün HBV serolojik belirteç-lerin negatif olduğu seronegatif OHB durumudur. Seronegatif OHB'nun sıklığı ve oluşma mekanizması tam olarak bilinmemekle birlikte bazı çalışmalarda oluşumunda HBV X geninde mutasyonların etkisini düşündüren sonuçlar elde edilmiştir [38]. Özel-likle diğer klinik durumlarda (iyileşme sonrası, kaçak mutantlar ve izole antiHBc IgG pozitifliği) antiHBc IgG taranması ile transfüzyona bağlı HBV bulaşı önlenebilmesine rağmen, seronegatif OHB'de bunun mümkün olmaması klinik olarak önem arz etmektedir.…”