Measurement of des-gamma-carboxy prothrombin levels in hemodialysis patients positive for anti-hepatitis virus C antibody.
BACKGROUND
The prevalence of anti-hepatitis virus C (HCV) antibody is much higher in hemodialysis (HD) patients than in the normal population. Recently, blood des-gamma-carboxy prothrombin (PIVKA-II) has been demonstrated as a sensitive marker for the early detection of hepatocellular carcinoma (HCC). In this study, we measured blood PIVKA-II in HD patients positive for anti-HCV antibody or hepatitis B virus surface (HBs) antigen to examine if HD therapy may affect the measurement of PIVKA-II.


METHODS
Ninety-four stable HD patients who had anti-HCV antibodies (n = 86) or HBs antigen (n = 8) without any evidence of HCC were enrolled in the study (age: 60 +/- 11 years, duration of HD: 17 +/- 10 years, male/female = 63/31). Five patients had liver cirrhosis and another 5 patients received warfarin treatment. We simultaneously measured serum PIVKA-II and alpha-fetoprotein (AFP), and compared the association between these markers and HCV RNA titer and laboratory parameters.


RESULTS
Serum PIVKA-II became positive (> or = 40 mAU/ml) in only 5.6% (5/89) of patients without warfarin administration, ranging from 47 to 71 mAU/ml. Seventy out of 89 patients (78.7%) were below 20 mAU/ml. Serum PIVKA-II did not correlate with biochemical parameters including HCV RNA, while serum AFP was significantly correlated with serum AST (r = 0.21, p < 0.05), gamma-GTP (r = 0.21, p < 0.01) and platelet counts (r = -0.29, p < 0.01), respectively. In contrast, 5 patients receiving warfarin had an extremely high PIVKA-II value ranging from 1,930 to 19,900 mAU/ml. PIVKA-II was significantly and inversely correlated with the thrombotest value (r = -0.72, p = 0.01).


CONCLUSIONS
The positivity of blood PIVKA-II in HD patients with hepatitis viremia was identical to that in patients without renal failure. Warfarin treatment dramatically increased serum PIVKA-II more than 1,000 mAU/ml. These findings suggested that HD treatment itself did not affect the measurement of PIVKA-II, but vitamin K deficiency can readily influence the PIVKA-II level in dialysis patients.
Kato
A
A
First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan. a.kato@scchr.jp
Yasuda
H
H
Togawa
A
A
Yamamoto
T
T
Yonemura
K
K
Maruyama
T
T
Maruyama
Y
Y
Hishida
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D000925:Anticoagulants / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D005260:Female; D006526:Hepatitis C / Q000097:blood / Q000175:diagnosis / Q000628:therapy; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood* / Q000187:drug effects; D011516:Prothrombin / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D006435:Renal Dialysis; D013223:Statistics as Topic; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use; D000509:alpha-Fetoproteins / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
D000925:Anticoagulants; D015415:Biomarkers; D018937:Hepatitis C Antibodies; D011498:Protein Precursors; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D014859:Warfarin; D012313:RNA; D011516:Prothrombin; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase