Circulating D-dimer level may predict tumor burden in chronic hepatitis C related hepatocellular carcinoma

Abstract

Introduction: Coagulation and fibrinolysis activation has been implicated in angiogenesis, tumor cell invasion, tumor progression and metastatic spread. D-dimer is a biomarker that globally indicates the activation of hemostasis and fibrinolysis. Aim: To study the correlation of circulating D-dimer level with the tumor grade in HCV related HCC. Methods: HCC was diagnosed by non- invasive method in cirrhotic patients according to EASL criteria using contrast enhanced abdominal CT and or MRI. After metastatic work up, HCC grade was described as grade one if it was within Milan criteria (one nodule <5cm or up to 3 nodules; the largest is <3cm without vascular invasion or extra- hepatic involvement); grade two if it was beyond Milan criteria but non –metastatic & grade three if it was metastatic (vascular invasion, lymph node metastasis, distant metastasis). BCLC staging depending on HCC burden, Child -Turcotte-Pugh (CTP) class and ECOG performance status (PST), was done for all studied cases. Chromic HCV was diagnosed by 4th generation ELIZA for HCV antibody and confirmed by quantitative PCR for HCV RNA. Circulating D dimer level, serum AFP level, liver biochemical tests, serum creatinine & complete blood count were measured for all studied cases. Patients with history of previous treatment for HCC; recent benign thrombo-embolic disorder or renal impairment were excluded. Results: Fifty chronic HCV related HCC cases; 43 males and 7 females with age 62.2±7.4 years were enrolled. Circulating D-dimer level was significantly higher in HCC grade 2 and 3 than HCC grade 1 [(400-800) versus (0-400 ng/ml), p=0.001] & in BCLC stage D than BCLC stage C HCC [(400-800) versus (0-700 ng/ml), p=0.021].There was significant positive correlation between circulating D-dimer level and HCC size and HCC grade (r =0.35, p = 0.012, r =0.33, p = 0.016 respectively). There was also significant positive correlation between circulating D-dimer level and both serum AFP level (r =0.45, p=0.001) and ECOG performance status (r =0.4, p = 0.002). Serum level of circulating D-dimer at cut off level ≥300 ng/ml can predict HCC grade beyond Milan criteria (G2& 3) with PPV of 77.1%, NPV of 73.3%, AUC= 0.8 and p <0.0005.Also, serum AFP level at cut off ≥394.5 can predict HCC grades beyond Milan criteria with PPV of 89.3%, NPV of 72.7%, AUC= 0.81 and P<0.0005. Conclusion: In HCV related HCC, circulating D-dimer level was positively correlated with HCC grade and largest tumor size with higher level in HCC grades 2&3 as well as BCLC stage D. Cut off level of circulating D-dimer level of ≥300 ng/ml can predict HCC grades beyond Milan criteria.