Systemic Inflammation and Subclinical Hepatic Synthetic Dysfunction Following Doxorubicin-Cyclophosphamide...

Doxorubicin-cyclophosphamide (AC) chemotherapy induces hepatotoxicity through oxidative stress and inflammatory pathway activation, but prospective African data are lacking and conventional liver tests may miss subclinical injury. We evaluated changes in liver enzymes, hepatic synthetic markers, and high-sensitivity C-reactive protein (hs-CRP) after AC chemotherapy in Ethiopian women with breast cancer.

This prospective cohort study enrolled consecutive women (≥ 18 years) with breast cancer scheduled for four cycles of adjuvant/neoadjuvant AC (doxorubicin 60 mg/m²+ cyclophosphamide 600 mg/m²) at Tikur Anbessa Specialized Hospital (Addis Ababa, Ethiopia) from January 2024 through December 2025. Exclusion criteria included chronic liver disease, viral hepatitis, diabetes, and pregnancy/lactation. Serum AST, ALT, ALP, total protein, albumin, and hs-CRP were measured at baseline and 2-4 weeks following the fourth cycle. Paired t-tests/Wilcoxon tests, multivariable regression, and interaction testing were performed with Benjamini-Hochberg adjustment.

Among 43 enrolled patients, 39 (90.7%) completed paired assessments (mean age 43.5 ± 12.3 years; 43.6% premenopausal; 53.5% stage I-II). AC chemotherapy induced an 81% hs-CRP increase (baseline: 3.2 ± 2.1 mg/L; post-AC: 5.8 ± 3.4 mg/L; Δ = +2.6 mg/L; p < 0.001; d = 0.92). Also, 46% experienced significant albumin decline (≥ 0.3 g/dL), and 18% developed frank hypoalbuminemia (< 3.5 g/dL), despite stable AST, ALT, and ALP. ΔHs-CRP correlated inversely with Δalbumin (r = -0.34, p = 0.04). Age ≥ 56 years predicted greater hs-CRP increase (β = +1.8 mg/L; p = 0.03); postmenopausal status predicted lower post-AC albumin (β = -0.3 g/dL; p = 0.04). No grade ≥ 3 hepatotoxicity occurred.

AC chemotherapy was associated with marked systemic inflammation and biomarker changes consistent with subclinical hepatic synthetic impairment in nearly half of patients, not captured by conventional liver panels. Because albumin is also influenced by nutritional and inflammatory factors, this finding is a signal warranting closer monitoring, particularly in older and postmenopausal women, rather than proof of hepatocellular injury. These inexpensive biomarkers should be incorporated into monitoring protocols in resource-limited settings.