{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:56:17Z","timestamp":1791186977299,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Doxorubicin\u2010cyclophosphamide (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\u2010sensitivity C\u2010reactive protein (hs\u2010CRP) after AC chemotherapy in Ethiopian women with breast cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective cohort study enrolled consecutive women (\u2265\u200918 years) with breast cancer scheduled for four cycles of adjuvant\/neoadjuvant AC (doxorubicin 60\u2009mg\/m\n                      <jats:sup>2\u2009<\/jats:sup>\n                      +\u2009cyclophosphamide 600\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) 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\u2010CRP were measured at baseline and 2\u20134 weeks following the fourth cycle. Paired\n                      <jats:italic>t<\/jats:italic>\n                      \u2010tests\/Wilcoxon tests, multivariable regression, and interaction testing were performed with Benjamini\u2013Hochberg adjustment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 43 enrolled patients, 39 (90.7%) completed paired assessments (mean age 43.5\u2009\u00b1\u200912.3 years; 43.6% premenopausal; 53.5% stage I\u2013II). AC chemotherapy induced an 81% hs\u2010CRP increase (baseline: 3.2\u2009\u00b1\u20092.1\u2009mg\/L; post\u2010AC: 5.8\u2009\u00b1\u20093.4\u2009mg\/L; \u0394\u2009=\u2009+2.6\u2009mg\/L;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001;\n                      <jats:italic>d<\/jats:italic>\n                      \u2009=\u20090.92). Also, 46% experienced significant albumin decline (\u2265\u20090.3\u2009g\/dL), and 18% developed frank hypoalbuminemia (&lt;\u20093.5\u2009g\/dL), despite stable AST, ALT, and ALP. \u0394Hs\u2010CRP correlated inversely with \u0394albumin (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.34,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). Age \u2265\u200956 years predicted greater hs\u2010CRP increase (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009+1.8\u2009mg\/L;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03); postmenopausal status predicted lower post\u2010AC albumin (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u2009\u22120.3\u2009g\/dL;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). No grade \u2265\u20093 hepatotoxicity occurred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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\u2010limited settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hsr2.73236","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:01:17Z","timestamp":1789113677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Inflammation and Subclinical Hepatic Synthetic Dysfunction Following Doxorubicin\u2010Cyclophosphamide Chemotherapy in Ethiopian Women With Breast Cancer: A Prospective Cohort Study"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7283-6409","authenticated-orcid":false,"given":"Tamrat","family":"Nida","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, School of Biomedicine, College of Health Sciences Addis Ababa University Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2196-6835","authenticated-orcid":false,"given":"Abdisa Tufa","family":"Bedada","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, School of Biomedicine, College of Health Sciences Addis Ababa University Addis Ababa Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_13_3_1","article-title":"Patterns of Breast Cancer Presentation and Management in Ethiopia: A Multicenter Study","volume":"8","author":"Tigeneh W.","year":"2022","journal-title":"JCO Global Oncology"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JGO.17.00175"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0439-8"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00285-4"},{"issue":"1","key":"e_1_2_13_7_1","first-page":"32","article-title":"Chemotherapy\u2010Induced Cardiotoxicity and Hepatotoxicity: Shared Mechanisms and Clinical Implications","volume":"20","author":"Florescu M.","year":"2023","journal-title":"Current Heart Failure Reports"},{"issue":"2","key":"e_1_2_13_8_1","first-page":"95","article-title":"Hepatotoxicity Secondary to Chemotherapy","volume":"2","author":"Grigorian A.","year":"2014","journal-title":"Journal of Clinical and Translational Hepatology"},{"key":"e_1_2_13_9_1","article-title":"Toxic Effects and Molecular Mechanism of Doxorubicin on Different Organs: An Update","volume":"918","author":"Renu K.","year":"2022","journal-title":"European Journal of Pharmacology"},{"issue":"1","key":"e_1_2_13_10_1","first-page":"4","article-title":"Effects of Doxorubicin on the Liver: A Systematic Review","volume":"43","author":"Prathumsap N.","year":"2023","journal-title":"Journal of Applied Toxicology"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2014.10.002"},{"key":"e_1_2_13_12_1","unstructured":"National Cancer Institute \u201cCommon Terminology Criteria for Adverse Events (CTCAE) Version 5.0 \u201d published 2017 https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/ctc.htm."},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-014-0182-7"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29802"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.01.028"},{"key":"e_1_2_13_16_1","first-page":"1465","article-title":"Prevalence and Factors Associated With Hepatitis B Virus Infection Among Patients With Cancer in Uganda: A Cross\u2010Sectional Study","volume":"7","author":"Ocama P.","year":"2021","journal-title":"JCO Global Oncology"},{"issue":"3","key":"e_1_2_13_17_1","first-page":"155","article-title":"Elevated C\u2010Reactive Protein in the Diagnosis, Prognosis, and Cause of Cancer","volume":"58","author":"Allin K. 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