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RESEARCH ARTICLE |
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| Year : 2003 | Volume
: 19
| Issue : 2 | Page : 117-119 |
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Total PSA and free PSA in patients with severe liver dysfunction
Rama Devi Mittal1, Mahendra Kumar Singh2, Charles Selvaraju1, Gourdas Choudhuri2
1 Department of Urology, SGPGIMS, Lucknow, India
2 Department of Gastroenterology, SGPGIMS, Lucknow, India
Correspondence Address:
Rama Devi Mittal
Department of Urology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow 226 014
India
 Source of Support: None, Conflict of Interest: None  | Check |
 Abstract | | |
Objectives: To evaluate the effect of liver diseases in patients, on serum free prostate specific antigen (JPSA) levels, total prostate specific antigen (tPSA) levels and fPSA/tPSA ratios.
Methods: Serum concentrations of total and free as well as JPSA/tPSA were determined in 20 men with histologically confirmed liver cirrhosis, 15 men with chronic hepatitis and 20 healthy men.
Results: The serum levels of total PSA in liver cirrhosis as well as in chronic hepatitis were significantly lower than those observed in control. Free PSA remained unchanged.
Conclusions: Our study suggests that despite severe liver dysfunction the tPSA, fPSA as well as the ratio of fPSA/ tPSA were not elevated as it was hypothesized that liver impairment might affect the PSA levels, as liver is a site for PSA metabolism.
Keywords: Total PSA, free PSA, liver cirrhosis. chronic hepatitis.
How to cite this article:
Mittal RD, Singh MK, Selvaraju C, Choudhuri G. Total PSA and free PSA in patients with severe liver dysfunction. Indian J Urol 2003;19:117-9 |
| Introduction | |  |
Prostate specific antigen (PSA) is a single chain 33kD glycoprotein serine protease. It is the most useful marker currently available in the field of oncology and has revolutionized the early detection, management and follow-up of patients with prostate cancer. [1] It exists in multiple forms in serum covalently bound to αl-antichymotrypsin inhibitor, which is the immuno-detectable form. Majority (7090%) of total PSA (tPSA) is covalently linked and encapsulated by β-macroglobulin and not detectable by current immunoassays. The tPSA not bound to protein is called free PSA. [2],[3] Recent studies have investigated the utility of assaying the free to total PSA ratio in the detection of prostate cancer and its usefulness in discriminating between prostate cancer and benign hypertrophy (BPH), the ratio being lower in prostate cancer and higher in BPH. Liver is believed to be the main site for PSA metabolism. [4] Hence liver disease might cause an artificial increase in serum levels of tPSA and fPSA.
There are very few reports of both free and total PSA levels in patients with severe liver dysfunction. [5] Hence the present study was undertaken to evaluate the serum concentration of total and free PSA in North Indian patients with diseased liver and the possible influence of liver function, if any, on serum PSA and metabolism of PSA.
| Patients and Methods | | |
All patients coming to our hospital to the department of Gastroenterology with liver dysfunction were selected for the study. Serum fPSA and tPSA were measured in 20 men with histological confirmed cirrhosis (LC), 15 chronic hepatitis (CH) and 20 normal healthy controls (NC). All these patients were free of any renal impairment or prostate disease. The age ranges in cirrhosis group were between 30-50 (mean 47) and 36-65 (mean 50) from chronic hepatitis and 40-70 (mean 52) in the control group. Prior to this study informed consent was taken from the patients. Standard urological evaluation, urine analysis, serum fPSA and tPSA determination and liver function tests such as total protein, albumin, total bilirubin, glutamic oxaloacetic transaminase (SGOT), and glutamic pyruvic transaminase (SGPT) and alkaline phosphatase were assayed in all the 3 groups by Technicon autoanalyzer RA-2000 using Bayers reagents. Both free and total PSA were measured by enzyme-linked immunoassay using diagnostic kits Medicorp (Quebec Canada). The total and free PSA assay were based on solid two-site immuno-enzymatic sandwich assay. The statistical analyses were done using ANOVA. Data were expressed as mean +SE. Student's t test [6] was used to compare the means between 2 groups of patients with that of control. P<0.05 was considered statistically significant.
| Results | | |
The age distribution and levels of total protein, albumin, bilirubin, serum glutamic oxaloacetic transaminase, serum pyruvic transaminase, alkaline phosphatase are summarized in [Table - 1]. Free PSA, total PSA and fPSA/tPSA levels are depicted in [Figure - 1]a, b and c respectively. As shown in [Figure - 1]b serum levels of tPSA in liver cirrhosis, chronic hepatitis patients were significantly lower than those in the control group (p<0.01 and 0.05 respectively). Free PSA was slightly lower in patients with cirrhosis and chronic hepatitis (0.23 + 0.02; 0.29 + 0.03) than control (0.31 + 0.02), but these differences were not statistically significant [Figure - 1]b. The ratio of fPSA and tPSA (fPSA/ tPSA) amongst the 3 groups were unchanged [Figure - 1]c.
| Discussion | | |
It is assumed that there may be several disease states where serum PSA levels may be affected. [7],[8] Sasagawa et al [9] examined serum levels of free and total PSA and in patients with end stage renal disease and reported no changes in PSA levels. Agha et al [4] suggest that liver may be the most likely site of PSA metabolism and cause changes in the levels of PSA as evident from our observations too, by the significant low levels of total PSA in liver cirrhosis as well as chronic hepatitis patients as compared to normal men. It is known that male patients with cirrhosis have higher estrogen and lower testosterone levels [10] than normal men, so lower levels of tPSA observed by us prove our anticipation, assuming a significant reserve in the liver for PSA metabolism. Our study also suggests that the cut-off value of serum PSA in liver dysfunction is lower than that of control. So it would be worthwhile to pursue further studies in patients with prostatic disease.
Serum fPSA and ratio of fPSA/tPSA were similar amongst the three groups. It is well established that fPSA/ tPSA ratio is useful when the total PSA level is between 4-10 ng/ml. Since in our study the tPSA in all patients and control subjects is below 4 ng/ml, the fPSA/tPSA ratio does not alter in hepatic dysfunction. Moreover, total protein, bilirubin and the hepatic enzymes had no effect on tPSA or fPSA/tPSA ratios, thereby corroborating the earlier report. [11] Our hypothesis at the commencement of the experiment was that liver impairment might cause drastic elevation in PSA levels. The liver, however, with its limited reserve could maintain serum fPSA/tPSA within the normal range. The result that total PSA in liver cirrhosis and chronic hepatitis were significantly lower than the controls suggests a lower cut-off value. A study in PSA metabolic modifications induced by liver cirrhosis in patients with high PSA levels as observed in our study (4 patients, unpublished observations) would be also relevant and needs investigation with larger number of patients.
The liver thus demonstrates significant reserve for the hepatic metabolism of serum PSA (both free and complex forms). The implication is that the potential utility of serum PSA and fPSA/tPSA ratio as tumor markers for possible concomitant prostate cancer persists even in patients with liver cirrhosis and/or chronic hepatitis induced impairment. It is not clear though, whether levels of total PSA, free PSA and fPSA/tPSA in patients with both liver disease and prostate cancer will have any relationship and whether the diagnosis and treatment of prostate cancer in such patients will alter their prognosis or survival, is yet to be established and needs further study.
| References | | |
| 1. | Nash AF, Melezinek I. The role of prostate specific measurement in the detection and management of prostate cancer. EndocrineRelated Cancer 2000; 7: 37-51.  [PUBMED] [FULLTEXT] |
| 2. | Lilija H. Christensson A, Dahlen U et al. Prostate specific antigen in serum occurs predominantly in complex with alpha-antichymo trypsin. Clin Chem 1991; 37: 1618-1625. |
| 3. | Oesterling JE, Jacobson SJ, Klee GG et al. Free, complex and total serum prostate specific antigen : The establishment of appropriate reference ranges for their concentrations and ratios. J Urol 1995; 154: 1090-1095. |
| 4. | Agha AH, Schechter E, Roy JB, Culkin DJ. Prostate specific antigen is metabolized in the liver. J Urol 1996; 155: 1332-1335. [PUBMED] [FULLTEXT] |
| 5. | Williams PB, Eastman JA, Culkin DJ, et al. Influence of hepatic function on serum levels of prostate specific antigen. J Urol 1997; 158: 1867-1869. |
| 6. | Darlington RB. Radicals and squares: statistical methods for the behavioral sciences. Logan Hill Press, New York, pp. 229-503. |
| 7. | Kabalin IN, Hornberger JC. Prostate specific antigen is not excreted by human kidney or eliminated by routine haemodialysis. Urology 1991; 37: 308-316. |
| 8. | Monath JR, Burkart JM, Freedman BL et al. Urology 1993; 42: 398-400. |
| 9. | Sasagawa I, Kubta Y, Hoyami S et al. Serum levels of total and free prostate specific antigen in haemodialysis males. J Urol 1988; 160: 83-85. |
| 10. | Chopra IJ, Tulchinsky D, Greenway FL. Estrogen-androgen imbalance in hepatic cirrhosis studied in 13 male patients. Ann Intern Med 1973; 79: 198-203. [PUBMED] |
| 11. | Kilic S. Guntekin E, Danisman A et al. Serum free and total prostate specific antigen levels in patients with liver disease. Urology 1998:52:825-828. |
[Figure - 1]
[Table - 1]
| This article has been cited by | | 1 |
The investigation of total PSA, free PSA, and free/total PSA ratio in patients with liver cirrhosis patients according to child-pugh score |
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| Inci, M. and Rifaioglu, M.M. and Inci, M. and Celik, M. and Demir, M. and Ulutas, T. and Davarci, M. and Motor, V.K. and Davran, R. and Gokce, C. | | Urology. 2013; 81(3): 617-622 | | [Pubmed] | |
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