Does CA-125 Always Indicate Ovarian Cancer? A Case of Hepatocellular Carcinoma with Elevated CA-125

Does CA-125 Always Indicate Ovarian Cancer? 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A Case of Hepatocellular Carcinoma with Elevated CA-125 Alaa Abdulrahman Mamieh, Hiba Hatim Eltayeb, Mariam Acharadze, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8167042/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Cancer antigen 125 (CA-125) is frequently utilized as a tumor marker for diagnosing epithelial ovarian cancer (EOC), particularly in postmenopausal women presenting with non-specific abdominal symptoms such as ascites and bloating. Nonetheless, its restricted specificity may present some diagnostic difficulties, as increased levels can also arise in numerous benign and non-gynecological disorders. We report the case of a 69-year-old postmenopausal woman who exhibited abdominal distension, dyspnea, and increased CA-125 levels, initially indicating a potential ovarian cancer. Subsequent examinations identified hepatocellular carcinoma (HCC) as a consequence of chronic hepatitis C infection, with no indications of gynecologic cancer. This example underscores the necessity of evaluating alternate etiologies for increased CA-125 readings, particularly in those with predispositions to liver disease. A comprehensive clinical assessment, bolstered by imaging and laboratory analyses, is crucial to prevent misdiagnosis and guarantee suitable management. Cancer antigen 125 (CA-125) Ovarian Cancer (OC) hepatocellular carcinoma (HCC) Tumor marker Figures Figure 1 Figure 2 Introduction Tumor marker, or biomarker, are bioactive compounds that are produced, secreted, or shed by tumor cells in bodily fluids or tissues. For a biomarker to be clinically valuable, it must demonstrate high sensitivity and specificity, gain widespread acceptance among patients, and provide strong predictive value for both diagnosis and prognosis. Furthermore, its effectiveness must be validated through prospective clinical trials. However, no biomarker currently meets all of these ideal criteria [ 1 , 2 ]. Among the biomarkers studied, cancer antigen 125 (CA125), is a transmembrane glycoprotein, released by coelomic epithelial cells, and is involved in metastasis, carcinogenesis, as well as CA-125-targeted treatment. The standard blood concentration of CA-125 varies from 0 to 35 U/ml. Moreover, CA-125 has played a crucial role in monitoring the progression of ovarian cancer and preoperative measurement of CA125 levels is routinely conducted in patients suspected of or diagnosed with ovarian cancer. Nonetheless, its efficacy as well as accuracy in early diagnosis remains contentious as it has high sensitivity but low specificity [ 3 , 4 , 5 ]. Ovarian cancer (OC) is the most fatal gynecological malignancy and the fifth leading cause of cancer-related mortality in women. As there are a few common clinical signs and poor screening methods, less than 40% of women with OC receive an early diagnosis [ 3 , 6 ]. OC is primarily categorized into two types; Epithelial ovarian cancer (EOC) and non-epithelial ovarian cancer, with the former type representing the majority of the cases. EOC accounts for approximately 95% of the cases and ascites is considered one of its primary symptoms [ 7 , 8 ]. Postmenopausal women are particularly vulnerable, as the likelihood of receiving an advanced-stage diagnosis increases with age. This heightened susceptibility is mainly due to the absence of efficient early detection techniques and the limited effectiveness of conventional treatments [ 1 ]. Despite the advancements in treatment, OC remains a significant challenge for oncologists. The disease is frequently diagnosed at an advanced stage, and survival rates have shown only marginal improvement over the past two decades with as low as 20%-40% survival rate for stages III and IV [ 9 , 10 ]. Given these limitations, the discovery of reliable biomarkers for the early diagnosis and management of EOC has become a primary research focus. Numerous biomarkers have been identified in serum, urine, ovarian cyst fluid, ascitic fluid, and other bodily fluids [ 11 ]. Since CA-125 is also produced by other cells, including the peritoneum, endometrial, fallopian tube, amniotic cells, lung, and conjunctiva, it’s not considered a specific marker. This tumor marker may be raised in numerous physiological and pathological diseases such as, endometriosis, fibroids, as well as inflammation-associated conditions such as heart failure and ulcerative colitis [ 12 , 13 , 14 ]. Furthermore, individuals infected with viral hepatitis tend to exhibit significantly higher levels of these biomarkers compared to those without such infections [ 15 ]. We present the case of a 69-year-old postmenopausal woman who presented with abdominal distension, ascites, breathlessness, and markedly elevated CA-125 levels. Due to the heightened prevalence of ovarian cancer in postmenopausal females, malignancy was strongly suspected. However, further imaging and serological evaluations revealed hepatocellular carcinoma (HCC) which was then revealed to be a complication of Hepatitis C viral (HCV) infection. This case report aims to show the diagnostic limitations of CA-125 and its potential elevation in illnesses other than ovarian cancer. Methods The development of this case report was predicated on a thorough clinical assessment and treatment of a single patient who was admitted to our hospital. Comprehensive data collection from the patient's medical history, physical examination, diagnostic workup, therapeutic interventions, and follow-up evaluations were all part of the methodology. To guarantee accuracy, clinical data was carefully examined after being taken out of the patient's electronic medical records. The attending physicians followed standard evidence-based practice when making decisions about diagnosis and treatment. To protect patient confidentiality, all identifying information was anonymized. In addition, a literature review was also conducted using PubMed and Google Scholar. Our search criteria encompassed combinations of "ovarian cancer," "hepatocellular carcinoma," "CA-125," "ascites," and "tumor markers." The review was limited to articles that were published from 2019–2025, in English and are relevant to the search criteria. Case presentation A 69-year-old postmenopausal woman presented to the hospital with complaints of weakness, weight loss, increased abdominal size, breathlessness, and left breast swelling with erythema/redness. The patient has a history of chronic gastritis and takes esomeprazole 40 mg but denies any other medical conditions or surgeries. Her social and family history were unremarkable, and she denies smoking or consuming alcohol. Her bowel movements occur every 1–2 days. Vital signs revealed hypotension: temperature 37.8°C, SpO2 94% (sitting), 89% (lying down), respiratory rate 24 breaths/min, heart rate 83 beats/min, and blood pressure 117/63 mmHg. On physical examination, the patient was alert and oriented to time, place, person, and situation. Inspection revealed a swollen, hyperemic left breast, which was hot to the touch, along with scleral icterus. On lung auscultation, there were diminished vesicular breath sounds, while heart tones were normal and rhythmic. Palpation of the abdomen revealed a soft abdomen with flank and shifting dullness, raising suspicion of ascites. The kidneys were not palpable, and urination was normal with the presence of an inserted urethral catheter. Laboratory results showed Grade II normocytic normochromic anemia and thrombocytopenia as shown in table (1). Serum tumor marker testing as outlined in table (2), revealed a markedly elevated CA-125 level of 278.6 U/mL, while liver function tests indicated hyperbilirubinemia, suggesting hepatic impairment. To further clarify the diagnosis, imaging studies were performed. Abdominal ultrasonography revealed ascites and a macronodular liver pattern, indicative of possible cirrhosis. Breast ultrasonography showed cutaneous and subcutaneous edema with inflammatory changes in the left breast, without evidence of localized masses or pathological lymphadenopathy. A chest radiograph was unremarkable. Serological screening revealed active hepatitis C virus (HCV) infection, indicated by positive anti-HCV antibodies, while hepatitis B surface antigen (HBsAg) and HIV tests were negative as demonstrated in table (3). Table 1 General Blood Analysis Parameter Results Unit Percentage Range WBC 8.54 10 3 µL 4.00–10.00 RBC 2.90 10 12 /l 4.20–5.20 HBG 9.20 g/dL 12.00–16.00 HCT 28.0 % 36.00–46.00 MCV 96.6 FL 80.00–97.00 MCH 31.7 Pg 27.00–33.00 MCHC 32.9 g/dL 32.00–36.00 RDW-CV 19.9 % 11.00–16.00 RDW-SD 69.3 FL 37.00–46.00 PLT 53 10 9 l 150.00–400.00 PDW 13.3 FL 9.00–14.00 MPV 11.3 FL 8.00–12.00 PCT P-LCR 35.8 % 15.00–35.00 PCT 0.06 % 0.17–0.35 Monocytes 0.73 10 3 µL 0.12–1.10 Lymphocytes 0.82 10 3 µL 1.00–4.00 Neutrophils 6.97 10 3 µL 2.00–7.00 Eosinophils 0.02 10 3 µL 0.02–0.50 Basophils 0.00 10 3 µL 0.00–0.10 Lymphocytes 9.6 % 25.00–40.00 Monocytes 8.5 % 3.00–11.00 Neutrophils 81.7 % 50.00–70.00 Basophils 0.00 % 0.00–1.00 Eosinophils 0.2 % 0.50–5.00 IG 0.07 10 3 µL 0.00–0.06 IG 0.8 % 0.00–0.60 Reticulocytes 5.78 % 0.50–2.00 Reticulocyte 0.1676 10 6 µL 0.02–0.11 IRF 25.0 % 0.60–10.50 LFR 75.0 % 90.00–98.00 MFR 15.3 % 0.60–9.00 HFR 9.8 % 0.00–1.70 Ret-He 31.7 pg 32.10–38.80 Table 2 Tumor Marker Analysis Parameter Results Unit Percentage Range AFP < 5.0 ng/mL 0.00–20.00 CEA 1.38 ng/mL 0.00–5.00 CA 19 − 9 17.69 g/dL 0.00–39.00 CA 125 278.6 U/ml 0.00–35.00 CA 15 − 3 25.88 U/ml 0.00–30.00 Table 3 Virology Analysis Parameter Results Reference Range HBsAg (-) negative negative Anti- HCV (+) positive negative Anti- HIV ½ (-) negative negative Anti- Treponema pallidum (total Ig) (-) negative negative Considering the patient’s clinical history, physical examination, and initial test results, the differential diagnosis included decompensated liver cirrhosis secondary to chronic HCV infection, as well as potential ovarian and breast cancers. The absence of suspicious findings on breast imaging ruled out neoplastic processes and supported the diagnosis of a localized skin and soft tissue infection (SSTI). Follow-up contrast-enhanced CT of the abdomen and pelvis excluded ovarian malignancy but confirmed cirrhotic liver morphology and identified a hepatic lesion in segment VII, classified as LI-RADS 4, as illustrated in figures (1 & 2) indicating a high likelihood of hepatocellular carcinoma (HCC). Figure 2. Abdominal CT scan showing the focal parenchymal lesion, categorized as LI-RADS 4, indicating a high probability of hepatocellular carcinoma. The final diagnosis was HCC secondary to HCV-induced cirrhosis, with ascites and concurrent skin and soft tissue infection (SSTI). The patient underwent diagnostic paracentesis, and cytological analysis of the ascitic fluid revealed no malignant cells. Antibiotic therapy was initiated for the identified SSTI of the left breast. After a comprehensive oncological evaluation, the HCC was determined to be advanced and non-resectable, with no curative therapeutic options available. As a result, systemic cancer therapy was not initiated. The patient was enrolled in Georgia’s national hepatitis C management program and began direct-acting antiviral (DAA) therapy. Initial clinical assessments showed symptomatic improvement after the commencement of antiviral treatment. Discussion Our case highlights the diagnostic difficulties in interpreting elevated cancer antigen 125 (CA-125) levels, especially in postmenopausal women. CA-125, which is a high molecular weight glycoprotein, is commonly employed preoperatively as a tumor marker for epithelial ovarian cancer (EOC), or adnexal masses and 80% of females with EOC have elevated CA-125 levels (normal range < 35 U/ml) initially [ 4 , 13 ]. Therefore, at first, our patient’s symptoms of dyspnea, abdominal distension, and the markedly raised CA-125 readings, indicated a strong likelihood of ovarian cancer and/or inflammation which prompted further investigations. Despite being commonly elevated in ovarian cancer, CA-125 lacks specificity and does not conclusively verify the existence of ovarian malignancy [ 5 ]. Despite demonstrating significant sensitivity for epithelial ovarian carcinoma (EOC), CA-125 levels may also be elevated in various non-malignant and non-gynecological conditions, including endometriosis, fibroids, inflammatory disorders, and hepatic diseases such as cirrhosis and viral hepatitis [ 12 , 14 ]. Additionally, CA-125 levels may be affected by an array of demographic and lifestyle factors, such as age, race, menopausal status, gravidity/parity, prior gynecologic surgery, the menstrual phase during blood collection, utilization of oral contraceptive pills (OCP), hormone replacement therapy (HRT), along with smoking history and caffeine intake [ 13 ]. From a pathophysiological view, the connection between elevated CA-125 levels and inflammation is thought to be mediated by pro-inflammatory cytokines and other inflammatory agents. For instance, Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharides are identified as key stimulators of CA-125 synthesis in the body. IL-1 is known as the most potent inducer in the inflammatory response, suggesting a mechanistic link between systemic inflammation and increased CA-125 expression [ 16 ]. In the case of liver diseases, the rise in tumor markers, particularly CA-125, is nonspecific and the causes are still unknown. However, CA125 is sensitive to hepatic disorders and often has elevated serum concentrations in hepatocellular carcinoma patients but the diagnostic accuracy of relying solely on CA-125 tests is constrained [ 17 , 18 ]. Therefore, serum CA-125 testing, in conjunction with imaging modalities, can be utilized in the preliminary screening of women [ 5 ]. One of the common signs that occur in patients with intra-or-extra abdominal tumors is ascites which is a buildup of fluid in the peritoneal cavity. This sign is caused by various etiologies such as; increased capillary permeability, venous pressure, lymphatic blockage, lowered serum protein, and protein exudation and the fluid is usually rich in both extracellular and cellular components [ 2 , 19 ]. About 10% of ascites cases are malignant, with ovarian cancer being the most prevalent type. In addition to intra-abdominal tumors [primary peritoneal cancer] and extra-abdominal tumors [lymphoma, lung, and breast cancer] other prevalent primary malignancies include colorectal, pancreatic, and gastric cancers [ 20 ]. Moreover, ascites is also considered a hallmark of severe cirrhosis and it often coexists with liver decompensation in patients with Hepatocellular Carcinoma (HCC). Therefore, it can act as a marker for both tumor aggressiveness and liver damage [ 21 ]. Moreover, it’s critically important for a comprehensive clinical assessment and a thorough differential diagnosis to be done, especially when the presenting symptoms are non-specific and potentially misleading. The diagnostic approach was confounded by the patient's initial symptoms of dyspnea, ascites, and breast swelling, which are not specific to a single organ system and due to the elevated CA-125 level, the initial clinical impression was further biased towards ovarian malignancy; however, as Hu et al. (2022) have emphasized, non-gynecologic causes of CA-125 elevation should always be taken into account. The patient was a non-smoker with no apparent risk factors, except for a history of chronic hepatitis C, which subsequently proved to be a critical factor in the diagnostic process. Additionally, the patient did not have any gynecologic complaints or a family history of gynecologic malignancies. The patient’s clinical presentation was further complicated by a simultaneous skin and soft tissue infection (SSTI) of the left breast, heightening the suspicion of breast cancer. Subsequent breast imaging and a positive response to antibiotics verified the existence of a non-malignant inflammatory condition. Furthermore, cross-sectional imaging identified a hepatic lesion classified as LI-RADS 4, which was strongly indicative of hepatocellular carcinoma (HCC). The definitive diagnosis of HCC, validated by imaging and laboratory results, was linked to the persistent HCV infection, hence dismissing the preliminary suspicion of ovarian cancer and underscoring the diagnostic difficulties presented by overlapping and atypical clinical characteristics. This case underscores the necessity of exercising caution when interpreting tumor markers, such as CA-125, and the significance of evaluating alternative explanations for their elevation. Before a diagnosis can be made solely on the basis of tumor markers, clinicians must consider the clinical history, physical findings, and comprehensive imaging and serologic testing. Conclusion This case brings attention to the critical requirement for cautious interpretation of elevated CA-125 levels, especially in the context of liver disease where non-malignant conditions may lead to significant marker elevation. It illustrates how dependence on tumor markers alone, without comprehensive clinical correlation, can lead to diagnostic confusion and possibly unnecessary interventions. The case reinforces that CA-125, while useful in specific settings, should not be viewed in isolation but rather as part of a broader diagnostic framework. A multidisciplinary approach that incorporates clinical presentation, imaging findings, and laboratory data is essential for distinguishing between malignant and benign causes, thereby ensuring accurate diagnosis, avoiding overtreatment, and improving overall patient care. Declarations Consent for publication: Written informed consent for publication of personal and clinical details along with any identifiable images was obtained from the patient prior to submission of this manuscript. Data availability: No datasets were generated or analyzed during the current study. Conflict of interest: The authors declare that there are no competing interests. Funding: This review received no funding. Author contributions: Alaa Abdulrahman Mamieh: Conceptualized the study, collected clinical data, performed literature review, and drafted the initial version of the manuscript. Hiba Hatim Eltayeb: Contributed to data analysis, interpretation of findings, and critical revision of the manuscript for important intellectual content. Mariam Acharadze: Validation of clinical information, supervision and preparation of the case documentation. Siavash Hosseinpour Chermahini: Performed final manuscript editing, supervised the overall structure. References Matsas A, Stefanoudakis D, Troupis T, et al. Tumor markers and their diagnostic significance in ovarian cancer. Life. 2023;13(8):1689. 10.3390/life13081689 . Jain T, Ram S, Kumar H, et al. Ascitic and serum levels of tumor biomarkers (CA 72 – 4, CA 19 – 9, CEA, and CA 125) in discrimination of cause of ascites: A prospective study. Arq Gastroenterol. 2022;59(3):198–203. 10.1590/S1678-9946202223038 . 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Available from: https://www.statpearls.com Hu X, Zhang J, Cao Y. Factors associated with serum CA125 level in women without ovarian cancer in the United States: A population-based study. BMC Cancer. 2022;22(1):544. 10.1186/s12885-022-09568-1 . Orbay TM, Moralıoğlu S, Bayrak NA, et al. Massive elevation of CA-125 in chylous ascites. Turk Arch Pediatr. 2023;58(5):555–8. 10.5152/TurkPediatriArs.2023.22084 . Nwaobi AC, Ugbomoiko DO, Egunjobi TO et al. Prevalence and diagnostic impacts of viral hepatitis seromarkers among chronic liver disease patients and their influence on the serum levels of AFP, CA-125, and GGT. Int J Adv Res Biol Sci. 2023;10(2):175–187. Available from: https://www.ijarbs.com Feng Q, Hu X, Zhao J, et al. Female genital tuberculosis presented with primary infertility and persistent CA-125 elevation: A case report. Ann Med Surg. 2022;78:103785. 10.1016/j.amsu.2022.103785 . Tarique S, Ghias M, Abid M et al. Association of CA 125 with degree of fibrosis in chronic liver disease with portal hypertension. Ann King Edward Med Univ. 2021;27(4):486–490. Available from: https://www.annals.edu.pk Bhatti S, Saeed A, Ahuja K et al. Evaluation of tumor markers among patients with hepatitis C infection. Pak Biomed J. 2022;84–87. Available from: https://www.pakbiomedj.com Záveský L, Jandáková E, Weinberger V, et al. Ascites in ovarian cancer: MicroRNA deregulations and their potential roles in ovarian carcinogenesis. Cancer Biomark. 2022;33(1):1–6. 10.3233/CBM-220792 . He J, Zhang HP. Research progress and treatment status of malignant ascites. Front Oncol. 2024;14:1390426. 10.3389/fonc.2024.1390426 . Liao JI, Ho SY, Liu PH, et al. Prognostic prediction for patients with hepatocellular carcinoma and ascites: Role of albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade. Cancers. 2023;15(3):753. 10.3390/cancers15030753 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 05 May, 2026 Reviewers agreed at journal 30 Apr, 2026 Reviewers invited by journal 19 Dec, 2025 Editor assigned by journal 17 Dec, 2025 Editor invited by journal 05 Dec, 2025 Submission checks completed at journal 05 Dec, 2025 First submitted to journal 05 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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1","display":"","copyAsset":false,"role":"figure","size":291443,"visible":true,"origin":"","legend":"\u003cp\u003eAbdominal CT scan demonstrates the liver with cirrhotic morphology adjacent to normal hepatic tissue.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8167042/v1/20c8de438fef2d11a9ba060e.png"},{"id":99318707,"identity":"e45c4f86-39ea-4fcf-9a82-7d25c80e549b","added_by":"auto","created_at":"2025-12-31 16:34:01","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":292480,"visible":true,"origin":"","legend":"\u003cp\u003eAbdominal CT scan showing the focal parenchymal lesion, categorized as LI-RADS 4, indicating a high probability of hepatocellular carcinoma.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8167042/v1/519bd4f951469daeceb3217c.png"},{"id":99323667,"identity":"1f28845e-57d1-446b-8895-75f0449700bc","added_by":"auto","created_at":"2025-12-31 16:45:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1255274,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8167042/v1/8f7d72b1-279b-4d24-90d5-7d196b2f53d1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Does CA-125 Always Indicate Ovarian Cancer? A Case of Hepatocellular Carcinoma with Elevated CA-125","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTumor marker, or biomarker, are bioactive compounds that are produced, secreted, or shed by tumor cells in bodily fluids or tissues. For a biomarker to be clinically valuable, it must demonstrate high sensitivity and specificity, gain widespread acceptance among patients, and provide strong predictive value for both diagnosis and prognosis. Furthermore, its effectiveness must be validated through prospective clinical trials. However, no biomarker currently meets all of these ideal criteria [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong the biomarkers studied, cancer antigen 125 (CA125), is a transmembrane glycoprotein, released by coelomic epithelial cells, and is involved in metastasis, carcinogenesis, as well as CA-125-targeted treatment. The standard blood concentration of CA-125 varies from 0 to 35 U/ml. Moreover, CA-125 has played a crucial role in monitoring the progression of ovarian cancer and preoperative measurement of CA125 levels is routinely conducted in patients suspected of or diagnosed with ovarian cancer. Nonetheless, its efficacy as well as accuracy in early diagnosis remains contentious as it has high sensitivity but low specificity [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOvarian cancer (OC) is the most fatal gynecological malignancy and the fifth leading cause of cancer-related mortality in women. As there are a few common clinical signs and poor screening methods, less than 40% of women with OC receive an early diagnosis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. OC is primarily categorized into two types; Epithelial ovarian cancer (EOC) and non-epithelial ovarian cancer, with the former type representing the majority of the cases. EOC accounts for approximately 95% of the cases and ascites is considered one of its primary symptoms [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Postmenopausal women are particularly vulnerable, as the likelihood of receiving an advanced-stage diagnosis increases with age. This heightened susceptibility is mainly due to the absence of efficient early detection techniques and the limited effectiveness of conventional treatments [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the advancements in treatment, OC remains a significant challenge for oncologists. The disease is frequently diagnosed at an advanced stage, and survival rates have shown only marginal improvement over the past two decades with as low as 20%-40% survival rate for stages III and IV [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Given these limitations, the discovery of reliable biomarkers for the early diagnosis and management of EOC has become a primary research focus. Numerous biomarkers have been identified in serum, urine, ovarian cyst fluid, ascitic fluid, and other bodily fluids [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSince CA-125 is also produced by other cells, including the peritoneum, endometrial, fallopian tube, amniotic cells, lung, and conjunctiva, it\u0026rsquo;s not considered a specific marker. This tumor marker may be raised in numerous physiological and pathological diseases such as, endometriosis, fibroids, as well as inflammation-associated conditions such as heart failure and ulcerative colitis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Furthermore, individuals infected with viral hepatitis tend to exhibit significantly higher levels of these biomarkers compared to those without such infections [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe present the case of a 69-year-old postmenopausal woman who presented with abdominal distension, ascites, breathlessness, and markedly elevated CA-125 levels. Due to the heightened prevalence of ovarian cancer in postmenopausal females, malignancy was strongly suspected. However, further imaging and serological evaluations revealed hepatocellular carcinoma (HCC) which was then revealed to be a complication of Hepatitis C viral (HCV) infection. This case report aims to show the diagnostic limitations of CA-125 and its potential elevation in illnesses other than ovarian cancer.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe development of this case report was predicated on a thorough clinical assessment and treatment of a single patient who was admitted to our hospital. Comprehensive data collection from the patient's medical history, physical examination, diagnostic workup, therapeutic interventions, and follow-up evaluations were all part of the methodology. To guarantee accuracy, clinical data was carefully examined after being taken out of the patient's electronic medical records. The attending physicians followed standard evidence-based practice when making decisions about diagnosis and treatment. To protect patient confidentiality, all identifying information was anonymized. In addition, a literature review was also conducted using PubMed and Google Scholar. Our search criteria encompassed combinations of \"ovarian cancer,\" \"hepatocellular carcinoma,\" \"CA-125,\" \"ascites,\" and \"tumor markers.\" The review was limited to articles that were published from 2019\u0026ndash;2025, in English and are relevant to the search criteria.\u003c/p\u003e "},{"header":"Case presentation","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003cp\u003eA 69-year-old postmenopausal woman presented to the hospital with complaints of weakness, weight loss, increased abdominal size, breathlessness, and left breast swelling with erythema/redness. The patient has a history of chronic gastritis and takes esomeprazole 40 mg but denies any other medical conditions or surgeries. Her social and family history were unremarkable, and she denies smoking or consuming alcohol. Her bowel movements occur every 1\u0026ndash;2 days. Vital signs revealed hypotension: temperature 37.8\u0026deg;C, SpO2 94% (sitting), 89% (lying down), respiratory rate 24 breaths/min, heart rate 83 beats/min, and blood pressure 117/63 mmHg.\u003c/p\u003e \u003cp\u003eOn physical examination, the patient was alert and oriented to time, place, person, and situation. Inspection revealed a swollen, hyperemic left breast, which was hot to the touch, along with scleral icterus. On lung auscultation, there were diminished vesicular breath sounds, while heart tones were normal and rhythmic. Palpation of the abdomen revealed a soft abdomen with flank and shifting dullness, raising suspicion of ascites. The kidneys were not palpable, and urination was normal with the presence of an inserted urethral catheter.\u003c/p\u003e \u003cp\u003eLaboratory results showed Grade II normocytic normochromic anemia and thrombocytopenia as shown in table (1). Serum tumor marker testing as outlined in table (2), revealed a markedly elevated CA-125 level of 278.6 U/mL, while liver function tests indicated hyperbilirubinemia, suggesting hepatic impairment. To further clarify the diagnosis, imaging studies were performed. Abdominal ultrasonography revealed ascites and a macronodular liver pattern, indicative of possible cirrhosis. Breast ultrasonography showed cutaneous and subcutaneous edema with inflammatory changes in the left breast, without evidence of localized masses or pathological lymphadenopathy. A chest radiograph was unremarkable. Serological screening revealed active hepatitis C virus (HCV) infection, indicated by positive anti-HCV antibodies, while hepatitis B surface antigen (HBsAg) and HIV tests were negative as demonstrated in table (3).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eGeneral Blood Analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e 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align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8.00\u0026ndash;12.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePCT P-LCR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15.00\u0026ndash;35.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePCT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.17\u0026ndash;0.35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMonocytes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003csup\u003e3\u003c/sup\u003e\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.12\u0026ndash;1.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymphocytes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003csup\u003e3\u003c/sup\u003e\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00\u0026ndash;4.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeutrophils\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003csup\u003e3\u003c/sup\u003e\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.00\u0026ndash;7.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEosinophils\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003csup\u003e3\u003c/sup\u003e\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02\u0026ndash;0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBasophils\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003csup\u003e3\u003c/sup\u003e\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;0.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymphocytes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25.00\u0026ndash;40.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMonocytes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.00\u0026ndash;11.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeutrophils\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e81.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e50.00\u0026ndash;70.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBasophils\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEosinophils\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.50\u0026ndash;5.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIG\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003csup\u003e3\u003c/sup\u003e\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIG\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReticulocytes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.50\u0026ndash;2.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eReticulocyte\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.1676\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003csup\u003e6\u003c/sup\u003e\u0026micro;L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.02\u0026ndash;0.11\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIRF\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.60\u0026ndash;10.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLFR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e90.00\u0026ndash;98.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMFR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.60\u0026ndash;9.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHFR\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;1.70\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRet-He\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e32.10\u0026ndash;38.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTumor Marker Analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eResults\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnit\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercentage Range\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAFP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eng/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;20.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCEA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eng/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;5.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCA 19\u0026thinsp;\u0026minus;\u0026thinsp;9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;39.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCA 125\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e278.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;35.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCA 15\u0026thinsp;\u0026minus;\u0026thinsp;3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eU/ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.00\u0026ndash;30.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVirology Analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eResults\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eReference Range\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHBsAg\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(-) negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti- HCV\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(+) positive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti- HIV \u0026frac12;\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(-) negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnti- Treponema pallidum (total Ig)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(-) negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003enegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eConsidering the patient\u0026rsquo;s clinical history, physical examination, and initial test results, the differential diagnosis included decompensated liver cirrhosis secondary to chronic HCV infection, as well as potential ovarian and breast cancers. The absence of suspicious findings on breast imaging ruled out neoplastic processes and supported the diagnosis of a localized skin and soft tissue infection (SSTI).\u003c/p\u003e \u003cp\u003eFollow-up contrast-enhanced CT of the abdomen and pelvis excluded ovarian malignancy but confirmed cirrhotic liver morphology and identified a hepatic lesion in segment VII, classified as LI-RADS 4, as illustrated in figures (1 \u0026amp; 2) indicating a high likelihood of hepatocellular carcinoma (HCC).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eFigure 2.\u003c/b\u003e Abdominal CT scan showing the focal parenchymal lesion, categorized as LI-RADS 4, indicating a high probability of hepatocellular carcinoma.\u003c/p\u003e \u003cp\u003eThe final diagnosis was HCC secondary to HCV-induced cirrhosis, with ascites and concurrent skin and soft tissue infection (SSTI). The patient underwent diagnostic paracentesis, and cytological analysis of the ascitic fluid revealed no malignant cells. Antibiotic therapy was initiated for the identified SSTI of the left breast. After a comprehensive oncological evaluation, the HCC was determined to be advanced and non-resectable, with no curative therapeutic options available. As a result, systemic cancer therapy was not initiated. The patient was enrolled in Georgia\u0026rsquo;s national hepatitis C management program and began direct-acting antiviral (DAA) therapy. Initial clinical assessments showed symptomatic improvement after the commencement of antiviral treatment.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur case highlights the diagnostic difficulties in interpreting elevated cancer antigen 125 (CA-125) levels, especially in postmenopausal women. CA-125, which is a high molecular weight glycoprotein, is commonly employed preoperatively as a tumor marker for epithelial ovarian cancer (EOC), or adnexal masses and 80% of females with EOC have elevated CA-125 levels (normal range\u0026thinsp;\u0026lt;\u0026thinsp;35 U/ml) initially [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Therefore, at first, our patient\u0026rsquo;s symptoms of dyspnea, abdominal distension, and the markedly raised CA-125 readings, indicated a strong likelihood of ovarian cancer and/or inflammation which prompted further investigations.\u003c/p\u003e \u003cp\u003eDespite being commonly elevated in ovarian cancer, CA-125 lacks specificity and does not conclusively verify the existence of ovarian malignancy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite demonstrating significant sensitivity for epithelial ovarian carcinoma (EOC), CA-125 levels may also be elevated in various non-malignant and non-gynecological conditions, including endometriosis, fibroids, inflammatory disorders, and hepatic diseases such as cirrhosis and viral hepatitis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Additionally, CA-125 levels may be affected by an array of demographic and lifestyle factors, such as age, race, menopausal status, gravidity/parity, prior gynecologic surgery, the menstrual phase during blood collection, utilization of oral contraceptive pills (OCP), hormone replacement therapy (HRT), along with smoking history and caffeine intake [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFrom a pathophysiological view, the connection between elevated CA-125 levels and inflammation is thought to be mediated by pro-inflammatory cytokines and other inflammatory agents. For instance, Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharides are identified as key stimulators of CA-125 synthesis in the body. IL-1 is known as the most potent inducer in the inflammatory response, suggesting a mechanistic link between systemic inflammation and increased CA-125 expression [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the case of liver diseases, the rise in tumor markers, particularly CA-125, is nonspecific and the causes are still unknown. However, CA125 is sensitive to hepatic disorders and often has elevated serum concentrations in hepatocellular carcinoma patients but the diagnostic accuracy of relying solely on CA-125 tests is constrained [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Therefore, serum CA-125 testing, in conjunction with imaging modalities, can be utilized in the preliminary screening of women [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOne of the common signs that occur in patients with intra-or-extra abdominal tumors is ascites which is a buildup of fluid in the peritoneal cavity. This sign is caused by various etiologies such as; increased capillary permeability, venous pressure, lymphatic blockage, lowered serum protein, and protein exudation and the fluid is usually rich in both extracellular and cellular components [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. About 10% of ascites cases are malignant, with ovarian cancer being the most prevalent type. In addition to intra-abdominal tumors [primary peritoneal cancer] and extra-abdominal tumors [lymphoma, lung, and breast cancer] other prevalent primary malignancies include colorectal, pancreatic, and gastric cancers [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Moreover, ascites is also considered a hallmark of severe cirrhosis and it often coexists with liver decompensation in patients with Hepatocellular Carcinoma (HCC). Therefore, it can act as a marker for both tumor aggressiveness and liver damage [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMoreover, it\u0026rsquo;s critically important for a comprehensive clinical assessment and a thorough differential diagnosis to be done, especially when the presenting symptoms are non-specific and potentially misleading. The diagnostic approach was confounded by the patient's initial symptoms of dyspnea, ascites, and breast swelling, which are not specific to a single organ system and due to the elevated CA-125 level, the initial clinical impression was further biased towards ovarian malignancy; however, as Hu et al. (2022) have emphasized, non-gynecologic causes of CA-125 elevation should always be taken into account. The patient was a non-smoker with no apparent risk factors, except for a history of chronic hepatitis C, which subsequently proved to be a critical factor in the diagnostic process. Additionally, the patient did not have any gynecologic complaints or a family history of gynecologic malignancies.\u003c/p\u003e \u003cp\u003eThe patient\u0026rsquo;s clinical presentation was further complicated by a simultaneous skin and soft tissue infection (SSTI) of the left breast, heightening the suspicion of breast cancer. Subsequent breast imaging and a positive response to antibiotics verified the existence of a non-malignant inflammatory condition. Furthermore, cross-sectional imaging identified a hepatic lesion classified as LI-RADS 4, which was strongly indicative of hepatocellular carcinoma (HCC). The definitive diagnosis of HCC, validated by imaging and laboratory results, was linked to the persistent HCV infection, hence dismissing the preliminary suspicion of ovarian cancer and underscoring the diagnostic difficulties presented by overlapping and atypical clinical characteristics.\u003c/p\u003e \u003cp\u003eThis case underscores the necessity of exercising caution when interpreting tumor markers, such as CA-125, and the significance of evaluating alternative explanations for their elevation. Before a diagnosis can be made solely on the basis of tumor markers, clinicians must consider the clinical history, physical findings, and comprehensive imaging and serologic testing.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case brings attention to the critical requirement for cautious interpretation of elevated CA-125 levels, especially in the context of liver disease where non-malignant conditions may lead to significant marker elevation. It illustrates how dependence on tumor markers alone, without comprehensive clinical correlation, can lead to diagnostic confusion and possibly unnecessary interventions. The case reinforces that CA-125, while useful in specific settings, should not be viewed in isolation but rather as part of a broader diagnostic framework. A multidisciplinary approach that incorporates clinical presentation, imaging findings, and laboratory data is essential for distinguishing between malignant and benign causes, thereby ensuring accurate diagnosis, avoiding overtreatment, and improving overall patient care.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of personal and clinical details along with any identifiable images was obtained from the patient prior to submission of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analyzed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis review received no funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlaa Abdulrahman Mamieh: Conceptualized the study, collected clinical data, performed literature review, and drafted the initial version of the manuscript.\u003c/p\u003e\n\u003cp\u003eHiba Hatim Eltayeb: Contributed to data analysis, interpretation of findings, and critical revision of the manuscript for important intellectual content.\u003c/p\u003e\n\u003cp\u003eMariam Acharadze: Validation of clinical information, supervision and preparation of the case documentation.\u003c/p\u003e\n\u003cp\u003eSiavash Hosseinpour Chermahini: Performed final manuscript editing, supervised the overall structure.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMatsas A, Stefanoudakis D, Troupis T, et al. 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Cancers. 2023;15(3):753. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/cancers15030753\u003c/span\u003e\u003cspan address=\"10.3390/cancers15030753\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cancer antigen 125 (CA-125), Ovarian Cancer (OC), hepatocellular carcinoma (HCC), Tumor marker","lastPublishedDoi":"10.21203/rs.3.rs-8167042/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8167042/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCancer antigen 125 (CA-125) is frequently utilized as a tumor marker for diagnosing epithelial ovarian cancer (EOC), particularly in postmenopausal women presenting with non-specific abdominal symptoms such as ascites and bloating. Nonetheless, its restricted specificity may present some diagnostic difficulties, as increased levels can also arise in numerous benign and non-gynecological disorders. We report the case of a 69-year-old postmenopausal woman who exhibited abdominal distension, dyspnea, and increased CA-125 levels, initially indicating a potential ovarian cancer. Subsequent examinations identified hepatocellular carcinoma (HCC) as a consequence of chronic hepatitis C infection, with no indications of gynecologic cancer. This example underscores the necessity of evaluating alternate etiologies for increased CA-125 readings, particularly in those with predispositions to liver disease. A comprehensive clinical assessment, bolstered by imaging and laboratory analyses, is crucial to prevent misdiagnosis and guarantee suitable management.\u003c/p\u003e","manuscriptTitle":"Does CA-125 Always Indicate Ovarian Cancer? A Case of Hepatocellular Carcinoma with Elevated CA-125","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-30 00:24:06","doi":"10.21203/rs.3.rs-8167042/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-05T10:57:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"212658162078915165139373552112195167508","date":"2026-04-30T09:12:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-19T13:01:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-18T01:52:13+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-05T08:48:24+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-05T08:12:29+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2025-12-05T08:01:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a193fb13-d44b-4eae-bb93-237304ace8eb","owner":[],"postedDate":"December 30th, 2025","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-05T10:57:23+00:00","index":54,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-30T00:24:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-30 00:24:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8167042","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8167042","identity":"rs-8167042","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}