Nationwide Survey Finds Only One-Third of Spanish Microbiology Labs Perform Quantitative HBsAg Testing
核心洞察
A nationwide GEHEP-SEIMC (搜索) survey of 118 Spanish clinical microbiology laboratories (77.1% response rate) found only 37.4% perform quantitative HBsAg (搜索) (qHBsAg) testing.
Lack of clinical demand (57.1%) was the most frequently cited barrier, and 86.0% of non-performing centers did not refer samples externally for quantification.
Hospital size was significantly associated with implementation (p=0.041), with 62.5% of hospitals with ≥1000 beds testing versus none with <200 beds.
A nationwide survey conducted by the Spanish Group for the Study of Viral Hepatitis (GEHEP-SEIMC (搜索)) has found that only about one-third of Spanish clinical microbiology laboratories currently perform quantitative hepatitis B surface antigen (qHBsAg) testing, despite the biomarker's endorsement in major international guidelines for monitoring chronic hepatitis B virus (HBV) infection. The cross-sectional, descriptive study, which surveyed 118 hospital-based clinical microbiology laboratories between March and May 2025, represents the first comprehensive national assessment of qHBsAg implementation in Spain.
The survey achieved a response rate of 77.1% (91 of 118 invited laboratories). Among respondents, only 37.4% (34/91) reported performing qHBsAg testing in their center. Of the 57 centers not performing the assay, 86.0% (49/57) reported not referring samples to an external laboratory for quantification, raising concerns that patients may be deprived of a biomarker now endorsed by international guidelines.
Barriers to Implementation
Lack of clinical demand emerged as the most frequently cited barrier to qHBsAg implementation, reported by 57.1% of non-performing centers. This was followed by lack of equipment (5.4%) and lack of resources (3.6%), often reported in combination. A smaller proportion of laboratories cited lack of necessity (1.8%), while 7.1% reported other reasons, including awaiting reagent availability or planning to implement the assay in the near future.
The authors note that qHBsAg "gained interest during the interferon era but later fell into relative disuse, which, together with its limited presence in some clinical practice guidelines, has likely contributed to its weak implementation." They emphasize that the limited uptake "reflects the insufficient integration of qHBsAg into hepatology and infectious disease care pathways," suggesting a need for stronger alignment between clinical specialties and microbiology services, as well as educational initiatives.
Hospital Size and Geographic Variation
Hospital size, measured by number of beds, was significantly associated with qHBsAg implementation (Pearson's χ²=8.26; df=3; p=0.041). No hospital with fewer than 200 beds reported performing qHBsAg, compared with 23.3% of hospitals with 200–500 beds, 44.9% of hospitals with 500–1000 beds, and 62.5% of hospitals with ≥1000 beds. Post hoc pairwise comparisons did not remain statistically significant after Bonferroni correction, likely reflecting limited subgroup sample sizes.
Geographic distribution of responses encompassed all autonomous communities, with implementation rates varying widely from 0% in some regions (including the Canary Islands, Extremadura, and La Rioja) to 100% in others (Asturias, Cantabria, Navarra, and the Balearic Islands). However, no statistically significant differences were found across regions, with low sample sizes in several areas limiting the power of this analysis.
Testing Practices and Assay Platforms
Among centers performing qHBsAg, the most common practice (57.6%) was reflex quantification after a positive qualitative HBsAg screening result. A further 27.3% performed quantification only upon specific clinician request, while 15.2% used the quantitative assay as the initial screening test. Proactive reporting of qHBsAg results—defined as active communication of quantitative results to clinicians through inclusion in the laboratory report—was reported by 69.7% of laboratories, and 81.8% reported diluting samples exceeding the assay's upper limit of quantification to obtain an exact value.
The commercial assays most frequently used were the Abbott Alinity HBsAg Quantitative Assay (搜索) (55.9%), Diasorin Liaison XL Murex HBsAg Quant (搜索) (26.5%), Roche Elecsys HBsAg II Quant (搜索) (11.8%), and Siemens ADVIA Centaur Quantitative HBsAg assay (搜索) (5.8%). All were chemiluminescent immunoassays, differing mainly in platform and signal detection method.
Patient-Level Data
Marked heterogeneity was observed across centers regarding the number of HBsAg-positive patients detected and quantified. Some hospitals reported more than 3000–4000 positive cases over the past five years, whereas others reported only a few dozen, reflecting differences in hospital size and the timing of qHBsAg implementation.
Over the past five years, a total of 14,576 qHBsAg determinations were reported. The largest proportion corresponded to values >3000 IU/mL, accounting for 29.5% (n=4306), followed by values <100 IU/mL, representing 27.3% (n=3972). Intermediate categories were less frequent: 16.0% (n=2339) fell within 1000–3000 IU/mL, 16.5% (n=2410) within 250–1000 IU/mL, and 10.6% (n=1549) within 100–250 IU/mL. In the most recent year, 40.7% (n=197) of quantified determinations were <100 IU/mL, 27.1% (n=131) were >3000 IU/mL, 12.2% (n=59) between 1000 and 3000 IU/mL, 11.6% (n=56) between 250 and 1000 IU/mL, and 8.5% (n=41) between 100 and 250 IU/mL.
Clinical Significance and Guideline Context
The study underscores the clinical value of qHBsAg as a biomarker. Serum qHBsAg reflects, to varying degrees, transcriptional activity from intrahepatic cccDNA as well as expression from integrated HBV DNA, and should therefore be interpreted as an indirect—rather than exclusive—marker of viral transcriptional activity. Loss of HBsAg is widely used as a surrogate endpoint for functional cure in chronic HBV infection, though it does not necessarily indicate sterilizing cure.
The most recent European Association for the Study of the Liver (EASL) Clinical Practice Guidelines (2025) explicitly recommend annual quantification of HBsAg in HBsAg-positive patients, both in HBeAg-positive and HBeAg-negative phases, as part of standard monitoring. The authors note that qHBsAg has greater applicability than emerging biomarkers such as HBV RNA or HBcrAg, which "remain limited by lack of standardization and clinical availability."
The authors emphasize that ensuring widespread availability of qHBsAg testing is critical "not only for current clinical decision-making but also to prepare healthcare systems for the potential arrival of new therapeutic agents for hepatitis B, where reliable biomarkers will play a central role in evaluating treatment response and functional cure endpoints."
Study Limitations
The authors acknowledge several limitations. The voluntary nature of the survey implies a limited sample size relative to all microbiology laboratories in Spain, and the sampling frame reflects the GEHEP-SEIMC (搜索) laboratory network, which may not capture laboratories outside this distribution list. As an online self-administered survey, responses may be subject to recall and reporting biases, and self-selection bias must be considered, as laboratories already performing qHBsAg may have been more likely to respond, potentially overestimating uptake. The survey also did not capture patient-level serologic panels (anti-HBs, anti-HBc), HBV DNA results, or confirmatory/neutralization testing practices in cases of discordant HBsAg reactivity.
Despite these limitations, the authors conclude that the survey "provides valuable insights and establishes a foundation for future structured evaluations," and that the results "should be interpreted as a baseline assessment to inform harmonization efforts and future evaluations linking testing availability to clinical decision-making."