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• W2019707844 abstract "In 2006, we treated an elderly hepatitis B core antibody-positive (HBcAb+) patient affected by diffuse large B-cell lymphoma who achieved complete remission following six courses of R-CVP (rituximab, cyclophosphamide, prednisone, vincristine). Awareness regarding the proper management of hepatitis B surface antigen-negative (HBsAg−) patients undergoing chemotherapy was not as diffuse as it is now, so the patient was not considered as a candidate for lamivudine prophylaxis or for hepatitis B virus (HBV) vaccination. After 1 year of follow-up, aspartate transaminase and alanine transaminase levels had increased, to 116 and 139 IU/l, respectively. In spite of persistently undetectable HBsAg by three [Vitros (Johnson & Johnson Medical S.p.A. Pomezia, Italy), Monolisa Ultra (Biorad Laboratories S.r.l. Segrate (MI), Italy) and EIAgen (Adaltis Italia S.p.A. Casalecchio sul Reno (BO), Italy)] of five assays (AXSYM and ARCHITECT, both from Abbott S.r.l., Roma, Italy) used, a high viral load (1·7 × 107 IU/ml) was found. Viral sequencing by Trugene® HBV genotyping kit (Siemens Medical Solutions Diagnostics Srl, Milano, Italy) revealed a genotype D and the presence of the G145R mutation. This is the most common mutation observed in the ‘a’ determinant (from aa 121 to 169) of the surface antigen, capable of generating the ‘escape’ mutant under immunological pressure (passive or active). Of interest, T126T/I, T131A, C139Y and E/D144G mutations were also observed. Antiviral treatment with lamivudine, 100 mg qd, was then started, followed by rapid clinical and virological benefit. In a recent review article, Marzano et al (2007) stated that “in […] anti-core (HBsAg negative) patients (classified as ‘potential occult carriers’) undergoing [oncological] or mild haematological therapies […], HBsAg monitoring every 1–3 months is advised”. Marzano et al (2007) did not recommend HBV–DNA assay either before starting chemotherapy in ‘potential occult carriers’ because of its insufficient sensitivity, or during the follow up for high cost and lack of data about correct timings. However, no suggestions were given regarding which commercial assays should be used for HBsAg detection, though this was a crucial issue in our experience. In haematological chemotherapy regimens classified as ‘mild’, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) or CHOP 21 (cyclophosphamide, doxorubicin, vincristine, prednisone, every 3 weeks), no prophylaxis is indicated. Nevertheless, as properly reminded in another review (Lalazar et al, 2007), these regimens also contain drugs (steroids and anthracyclines) considered as ‘high risk’ for reactivation, so that anti-core patients are advised to undergo HBV vaccination even before ‘mild’ therapies. Concern is rising in the scientific community regarding currently employed assays, which can fail to detect certain variations of the ‘a’ determinant region (Moerman et al, 2004) leading to false negative results with serious consequences, in both missing hepatitis B reactivation in oncological patients, and not excluding potentially hazardous blood donations (Jongerius et al, 1998; Locarnini, 1998; Coleman et al, 1999; Hunt et al, 2000; Ijaz et al, 2001; Echevarria & Avellon, 2006; Roque-Afonso et al, 2007). Our mistake in the identification of a potential ‘HBV occult carrier’, who was therefore treated with an immunosuppressant chemotherapeutic regimen without a correct prophylaxis, outlines the potential risk of using HBsAg detection as the ‘gold standard’ screening test in oncological HBcAb+ patients. Commercially available HBsAg detection assays should be ideally chosen to target invariant epitopes of the surface antigen itself, in order to minimize the danger of obtaining a false negative result. When physicians are not confident on the assay performance, it is perhaps advisable to vaccinate onco-haematological, anti-core positive patients before beginning chemotherapy or to screen for hepatitis B reactivation by periodically monitoring seric HBV–DNA rather than by searching for the appearance of HBsAg." @default.
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• W2019707844 date "2009-02-19" @default.
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• W2019707844 title "From a medical mistake to a clinical warning: the case of HBV mutant virus reactivation in haematological patients" @default.
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• W2019707844 doi "https://doi.org/10.1111/j.1365-2141.2008.07539.x" @default.
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