【Veterinary Research】Persistent SAA Elevation After Clinical Remission of Feline Upper Respiratory Tract Disease: Two Case Reports With Adjunctive Huaier Administration

The article was published in Open Veterinary Journal, an international peer-reviewed journal covering a broad range of topics in veterinary medicine and animal health. The journal is indexed in PubMed/MEDLINE, Scopus, and Web of Science. The reported 2025 Journal Impact Factor is 1.6, and the journal is classified within Q2 in its relevant category.

Case 1: Longitudinal Changes in SAA

A 13-year-old spayed female Abyssinian had an SAA concentration of 148.7 mg/L at the initial presentation.

The reported upper respiratory clinical signs resolved within 6 days. However, despite the absence of apparent clinical signs, SAA concentrations remained above the reference range for more than 500 days, generally fluctuating between approximately 20 and 60 mg/L.

Adjunctive Huaier administration was initiated on Day 584. SAA concentrations subsequently declined over time and reached 3.75 mg/L on Day 696, which was within the reference range.

No recurrence of the reported upper respiratory clinical signs was observed through Day 1,411, and subsequent SAA measurements were reported to remain within the reference range during follow-up.

The prolonged period of elevated SAA before Huaier administration followed by subsequent normalization is noteworthy as a temporal observation. However, because this was a single uncontrolled case, it cannot be determined whether Huaier administration contributed to the decline in SAA. Spontaneous fluctuation or resolution of inflammatory activity and other unmeasured factors cannot be excluded.

Case 2: Clinical Course Following Recurrence and Initiation of Huaier

A 13-year-old neutered male domestic cat had an SAA concentration of 214.1 mg/L at the initial presentation.

Although the clinical signs subsequently resolved, SAA concentrations remained persistently elevated, generally at approximately 50–70 mg/L.

On Day 328, upper respiratory tract disease recurred and SAA increased to 198.12 mg/L. At that time, antimicrobial and other treatments were resumed, and adjunctive Huaier administration was initiated concurrently.

The clinical signs resolved by Day 335. On Day 376, SAA had decreased to 5.11 mg/L, representing the first reported value within the reference range during the observation period.

Subsequent SAA measurements were reported to remain within the reference range through Day 780.

Because Huaier administration was initiated concurrently with antimicrobial and other treatments, the contribution of Huaier to the subsequent decline in SAA cannot be separated from the effects of the other interventions or from the natural course of the disease.

Potential Clinical Relevance in Veterinary Medicine

Clinical Interpretation of Persistent SAA Elevation

These two cases illustrate that resolution of observable clinical signs in cats with upper respiratory tract disease may not necessarily occur at the same time as normalization of SAA concentrations.

Persistent SAA elevation following apparent clinical remission may be compatible with ongoing inflammatory activity or another unresolved inflammatory process. However, SAA is a nonspecific biomarker, and an elevated SAA concentration alone cannot establish the presence, location, or cause of a specific inflammatory disease process.

Serial measurement of SAA may therefore provide additional information about changes in systemic inflammatory activity in individual cats, particularly when clinical signs and laboratory findings do not appear to change in parallel.

However, these two cases do not establish the optimal duration, frequency, or clinical utility of serial SAA monitoring, and SAA results should be interpreted in conjunction with the overall clinical assessment.

Temporal Relationship Between Huaier Administration and SAA

In both cases, SAA concentrations subsequently entered the reference range after adjunctive Huaier administration was introduced.

This temporal sequence may warrant further investigation, particularly in Case 1, in which SAA had remained above the reference range for more than 500 days before Huaier administration.

However, temporal association alone does not demonstrate causation.

In Case 1, spontaneous changes in inflammatory activity and other unidentified factors cannot be excluded.

In Case 2, interpretation is particularly limited because Huaier administration was initiated concurrently with antimicrobial and other treatments. The relative contribution of each intervention therefore cannot be determined.

Accordingly, the present observations should not be interpreted as evidence that Huaier normalizes SAA concentrations or treats persistent inflammatory activity in cats.

Interpretation of the Proposed IL-6-Related Mechanism

Experimental and preclinical studies involving Huaier-derived components have described effects on several immune- and inflammation-related signaling pathways, including pathways associated with cytokines such as interleukin-6 (IL-6).

IL-6 is involved in the hepatic acute-phase response and can contribute to the regulation of SAA production.

However, IL-6 and other relevant cytokines were not directly measured in either of the two cats.

Therefore, an IL-6-mediated mechanism cannot be demonstrated from these cases. Any proposed relationship between Huaier administration, IL-6-related signaling, and the subsequent changes in SAA should be regarded as a biological hypothesis rather than an established mechanism.

Further experimental and clinical studies would be required to determine whether Huaier has a reproducible effect on cytokine signaling or SAA concentrations in cats.

Several important limitations should be considered when interpreting these findings.

The most important limitations are the inclusion of only two cases and the absence of an untreated, placebo, or other concurrent control group.

As a result, the observed reductions in SAA cannot be causally attributed to Huaier administration, and no reliable estimate of treatment effect can be calculated.

Spontaneous resolution or fluctuation of inflammatory activity cannot be excluded. Unrecognized concurrent disease, environmental factors, changes in management, or other unidentified variables may also have influenced SAA concentrations.

Interpretation of Case 2 is particularly limited because Huaier administration was initiated at the same time that antimicrobial and other treatments were resumed. It is therefore not possible to distinguish a potential contribution of Huaier from the effects of these other interventions or from the natural clinical course.

In addition, SAA is a nonspecific acute-phase protein. Persistent elevation may be compatible with ongoing inflammatory activity, but SAA concentration alone cannot establish the presence, location, or underlying cause of inflammation.

Relevant cytokines, including IL-6, were not directly measured. Consequently, the proposed involvement of cytokine-related signaling pathways is based on biological plausibility and previous experimental findings rather than direct evidence from these cats.

The cases also do not establish whether normalization of SAA itself is associated with improved long-term clinical outcomes.

For these reasons, the present findings should be regarded as preliminary, hypothesis-generating clinical observations rather than evidence of therapeutic efficacy.

Larger prospective studies with appropriate control groups, predefined outcome measures, standardized treatment protocols, and serial assessment of SAA and relevant inflammatory mediators would be required to determine whether Huaier has a reproducible effect on inflammatory biomarkers or clinical outcomes in cats with upper respiratory tract disease.

▼ Case summaries related to this paper
CASE 1
CASE 2

• Serum amyloid A (SAA): A major acute-phase protein in cats that is commonly used as a sensitive, but nonspecific, biomarker of systemic inflammatory activity. Increased SAA concentrations may occur in association with a variety of inflammatory, infectious, neoplastic, and other disease processes.
• IL-6 (interleukin-6): A cytokine involved in the regulation of immune and inflammatory responses and in the hepatic acute-phase response, including stimulation of SAA production. In the present cases, IL-6 concentrations were not directly measured.

Link to the full article：https://openveterinaryjournal.com/?mno=308316