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  232 Journal of the College of Physicians and Surgeons Pakistan 2014, Vol. 24(4): 232-235 INTRODUCTION Cancer antigen-125 (CA-125), also known as mucin-16(MUC-16), is the most commonly used tumour marker todetect ovarian cancer. 1 Its level in serum is used tomonitor the response to chemotherapy, relapse, anddisease progression in ovarian cancer patients.However, its role for screening and early detection of ovarian cancer is limited due to a low sensitivity andspecificity. 1 CA-125 was first detected by Bast et al  . in1981 using a murine monoclonal antibody purifiedfollowing immunization of mice with a human ovariancancer cell line. 1,2 The cut-off value for CA-125 levels is35 U/L. 3 CA-125 level is not only elevated in ovariancancer but many malignant and benign conditions suchas pregnancy, cardiovascular and liver diseases cangive rise to elevated CA-125 levels. 3-5 Liver cirrhosis is among the leading causes of death asit may result in serious complications like ascites,hepatic encephalopathy and variceal haemorrhage. 6 It isone of the most common disorders associated withincreased levels of serum CA-125. 7 In acute and chronichepatitis, CA-125 can be elevated in 2 - 22% patients,and 20 - 100% with cirrhosis may have its high levels. 7  Asignificant correlation has been detected betweenCA-125 levels and the presence of ascites in cirrhoticpatients. 2 Some studies have shown that in patients withchronic liver disease, the presence of ascites appears toplay a key role in the mechanism responsible for theincreased levels of CA-125. 7 In cirrhosis, higher CA-125 levels have been detected inpatients with ascites than in those without ascites; atrates of 83 - 100% and 20 - 38%, respectively. 2 It hasbeen suggested that a correlation is present betweenascites and increased CA-125 levels, and it can be usedas a tool in detection of ascites. 2 The authors havepreviously reported association of CA-125 withcirrhosis, 8 however, no work has been done todetermine the correlation of CA-125 levels in patientswith cirrhosis and the severity of disease and ascites.The aim of this study was to evaluate CA-125 levels inpatients with liver cirrhosis and the probable relationbetween the high levels and the amount of ascites in thepresent setup. METHODOLOGY This study included 130 patients admitted to theDepartment of Gastroenterology, Shifa InternationalHospital, Islamabad, Pakistan, from March 2012 toFebruary 2013. Patients aged 18 years and above withdiagnosis of liver cirrhosis of any etiology were includedin the study. CTscan abdomen was used to exclude thepatients with ovarian cancer. The study was approved bythe Ethics Committee of the Hospital and informedconsent was obtained from all study participants.Cirrhosis was confirmed by clinical, biochemical andultrasonographic (USG) findings. ORIGINALARTICLE Cancer Antigen-125 as a Marker of Ascites in Patients with Liver Cirrhosis Muhammad Omar Qureshi, Faisal Saud Dar and Nasir Khokhar A BSTRACT Objective: To evaluate the correlation between Cancer Antigen-25 (CA-125) levels with the amount of ascites in patientswith liver cirrhosis. Study Design: Observational, analytical study. Place and Duration of Study: Shifa International Hospital, Islamabad, from March 2012 to February 2013. Methodology:  Atotal of 130 patients with liver cirrhosis (with and without ascites) had serum CA-125 levels measured.The amount of ascites was classified according to physical examination and ultrasound (USG) findings. CA-125 levelswere compared and correlated with amount of ascites. Results: Majority of patients (57%) had hepatitis C virus and 60% were in class Child Pugh C. There was moderatecorrelation between amount of ascites and CA-125 levels (r = 0.642, p < 0.001) with significant raised levels of CA-125 inpatients with ascites (p < 0.001). Conclusion: There was a moderate correlation between CA-125 levels and presence and amount of ascites. Key Words: CA-125. Ascites. Cirrhosis.  Department of Gastroenterology, Shifa International Hospital, Islamabad.Correspondence: Prof. Nasir Khokhar, Department of Gastroenterology, Shifa International Hospital, H-8/4, Islamabad. E-mail: drnkhokhar@yahoo.com Received: March 07, 2013; Accepted: November 05, 2013.  Physical examination, USG and liver function tests(LFTs), albumin, INR, biochemistry and CA-125 levelswere performed on all patients. The samples werestudied on the same day. CA-125 level was measuredby immulyte OM-MAmethod. For CA-125 levels, valuesless than 35 U/Lwere taken as normal. It was further divided as between 35 - 100, 100 - 500, 500 - 1000 andabove 1000 U/L.The amount of ascites was classified according tophysical examination and USG findings into: (1) noascites, (2) mild ascites defined as the amount that canbe recognized only by USG around liver and betweenintestinal loops, but not by physical examination, (3)moderate ascites, indicated an amount not causingdistension in the abdomen, palpable liver and spleen,and easily visualized on USG; and (4) severe ascites,indicated by distension in the abdomen and visualizationon USG. 9 The demographic characteristics of the patientand etiology of liver disease were noted. The severity of liver disease was assessed according to Child-Pughscore. Atotal score from 5-6, 7-9 and 10-15 wasclassified as class A, B and C, respectively. 10 The data was collected on purpose-designed proformaand analyzed using Statistical Package for SocialSciences (SPSS) Version 17. Frequency and percentageof different variables were determined. Chi-square testwas used to assess categorical variables and Studentt-test for continuous variables. Spearman's rankcorrelation analysis was used to determine thecorrelation between CA-125 levels and the amount of ascites. Avalue of p < 0.05 indicated significance. RESULTS Baseline characteristics of study population are shownin Table I. Out of a total 130 patients, 57% had HCV ascause of their cirrhosis, and 60% were in Child class Cand had mean MELD score of 16.7 ±5.2. Twenty twopatients had no ascites. Mean CA-125 level was 429.5 ±201 U/L.There was a moderate correlation between CA-125levels and amount of ascites (Table II). Out of 22patients with no ascites, 14 had normal CA-125 levelsand rest had mild elevations only. Out of 41 patients withtense ascites, only 3 had normal CA-125 levels and 12had CA-125 levels above 1000 (Table II).There were significantly increased CA-125 levels inpatients with ascites as compared with no ascites(Table III). DISCUSSION Cancer antigen-125 is the most frequently used marker for detection of ovarian cancer. 11  About 90% of womenwith advanced ovarian cancer have elevated levels of CA-125 in their blood, making CA-125 a useful tool for detecting ovarian cancer. 12 Cancer antigen-125 may beelevated in the blood of some patients with specifictypes of malignancies 4 or other benign conditions, such Cancer antigen-125 as a marker of ascites in patients with liver cirrhosis Table I: Baseline characteristics of study population. CharacteristicsValue (%)Gender Male74 (56.9%)Female56 (43.07%) Age (years)52 ±9.4Cause of cirrhosis HCV74 (56.9%)HBV6 (4.61%)Others50 (38.4%)Child class A7 (5.38%)B45 (34.61%)C78 (60%)MELD score (mean + SD)16.7 ±5.2 CA-125 levels Mean429.5 ±201Normal18 (13.84%)35 - 10019 (14.61%) 100 - 50053 (40.7%)500 - 100028 (21.5%) Above 100012 (9.23%) Ascites  Absent22 (16.9%) Present108 (83%)Other complicationsPSE56 (43%)GI bleed61 (47%)SBP16 (12.3%)Journal of the College of Physicians and Surgeons Pakistan 2014, Vol. 24(4): 232-235  233 Table II: CA-125 levels and severity of ascites. Severity of ascitesCA-125 levels severity (U/L)TotalSignificanceNormal35 - 100100 - 500500 - 1000> 1000No14620022p < 0.001Mild01093022r = 0.642Moderate132813045Severe3014121241Total1819532812130 Spearman rank correlation showed strong correlation between CA-125 Levels and severity of ascites (r =0.642) (p < 0.001). Table III: CA-125 levels in patients with ascites and no ascites. CLD with no ascitesCLD with ascitesp-valueTotal number of patients22 108 Number of patients with CA-1258 (36%)104 (96.2%)< 0.001levels greater than normalMean CA-125 levels32 ±17438 ±208< 0.001Range 10 - 101 U/L17 - 3048-  as acute leukemia, non-Hodgkin lymphoma, ascites,and pericarditis. 13,14 Interestingly, CA-125 has recentlybeen shown to increase in patients with chroniccongestive heart failure. 15,16 Elevation of CA-125 levels has been reported in patientswith liver disease and its elevation is common in patientswith liver cirrhosis. 7 It is related to the presence of ascites, and possibly to the insufficiency of liver function,but not to the etiology of cirrhosis and ascites. 2 SerumCA-125 probably comes from ascites. 17 The precise srcin of CA-125 in patients with ascites hasnot been defined yet, but there are several theories.Kabawat et al  . 18 detected CA-125 in all kinds of coelomic epithelium derived from the same srcin aspericardium, pleura and mesothelial cells lining theperitoneum. Mezger et al  :1069-83. Muhammad Omar Qureshi, Faisal Saud Dar and Nasir Khokhar  234 Journal of the College of Physicians and Surgeons Pakistan 2014, Vol. 24(4): 232-235  12.Gupta D, Lis CG. Pretreatment serum albumin as a predictor of cancer survival: a systematic review of the epidemiologicalliterature. Nutr J 2010; 9 :69.13.Camera A, Villa MR, Rocco S, De Novellis T, Costantini S,Pezzullo L, et al  . Increased CA-125 serum levels in patientswith advanced acute leukemia with serosal involvement. Cancer 2000; 88 :75-8.14.Zacharos ID, Efstathiou SP, Petreli E, Georgiou G, Tsioulos DI,Mastorantonakis SE, et al  . The prognostic significance of CA-125 in patients with non-Hodgkin's lymphoma. Eur J Haematol  2002; 69 :221-6.15.Kouris NT, Zacharos ID, Kontogianni DD, Goranitou GS, SifakiMD, Grassos HE. The significance of CA-125 levels in patientswith chronic congestive heart failure. Correlation with clinicaland echocardiographic parameters. Eur J Heart Fail 2005; 7 :199-203.16.Fagiano P, D'Aloia A, Brentana L, Bignotti T, Fiorina C, VizzardiE, et al  . Serum levels of different tumor markers in patients withchronic heart failure. Eur J Heart Fail 2005; 7 :57-61.17.Xiao WB, Liu YL. Elevation of serum and ascites cancer antigen-125 levels in patients with liver cirrhosis. J Gastroenterol Hepatol 2003; 18 :1315-6.18.Kabawat SE, Bast RC Jr, Bhan AK, Welch WR, Knapp RC,Colvin RB. Tissue distribution of a coelomic-epithelium-relatedantigen recognized by the monoclonal antibody OC125. Int J Gynecol Pathol 1983; 2 :275-85.19.Mezger J, Lamerz R, Arnholdt H, Huhn D, Wilmanns W.Tumor-marker in der diagnostik von aszites- und pleura-punktaten. Onkologie 1986; 9 :11-6.20.Xu J, Liu J, Guo JX, Ma HB, Zhao J, Liu AX, et al. Evaluationon clinical value of serum CA-125 level in hepatitis cirrhosis. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2010; 24 :334-6.21.Kim YS, Kim DY, Ryu KH, Song JH, Kim MS, Jung HS, et al  .Clinical significance of serum CA-125 in patients with chronicliver diseases. Korean J Gastroenterol 2003; 42 :409-14.22.Deschênes M, Michel RP, Alpert E, Barkun JS, Metrakos P,Tchervenkov J. Elevation of CA-125 level is due to abdominaldistension in liver transplantation candidates. Transplantation 2001; 72 :1519-22. Cancer antigen-125 as a marker of ascites in patients with liver cirrhosisJournal of the College of Physicians and Surgeons Pakistan 2014, Vol. 24(4): 232-235  235
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