Introduction
Portal vein thrombosis (PVT) is common in cirrhotic patients. The prevalence ranges from 1%, at earlier stages to 30% in candidates for liver transplantation. The ADAM (a disintegrin-like and metalloproteinase) proteins, with their subfamily of ADAMTS -13 (A Disintegrin and Metalloprotease with Thrombospondin-13) are produced exclusively by hepatic stellate cells and play an important regulatory role in coagulation. The ADAMTS-13 protein is an enzyme, Willebrand factor cleaving protease. In vascular injury, von Willebrand factor (VWF) together with platelets initiates formation of thrombus. Functional deficiency of ADAMTS-13 results in presence of unusually large VWF multimers in plasma, which promotes platelet aggregation and thrombus formation.
Aims & Methods
The aim was to investigate the relation of serum level of ADAMTS -13 and portal vein thrombosis in patients with HCV related liver cirrhosis.The study was carried out on 56 Egyptian patients with HCV related liver cirrhosis (LC) (LC group: 28 cirrhotic patient without PVT and LC+PVT group: 28 cirrhotic patient with cirrhosis and PVT) and 28 healthy volunteers as controls from Menoufia University Hospitals (Egypt). The study was conducted in period from March 2020 to April 2021. They underwent history taking, physical examination and laboratory investigations (CBC, liver profile {ALT, AST, serum albumin, bilirubin, INR}, urea, creatinine, HBsAg, HCV Ab and serum ADAMTS-13 assay). Abdominal ultrasound with Doppler of portal vein (PV) was done for all patients and controls. Triphasic CT of the liver was done for patients with PVT to exclude hepatocellular carcinoma (HCC). Child-Pugh score, MELD score, AST/Platelet ratio index (APRI score) and FIB-4 were calculated for all patients. Patients on anticoagulant therapy, age less than 18 years, inflammatory or bleeding events in previous 2 months, history of personal unprovoked thromboembolism (familial in first‑degree relatives), etiology of liver cirrhosis other than HCV and HCC are excluded from the study.
Results
Serum ADAMTS-13 (ng/ml) was significantly lower in LC+PVT group (0.66±0.44) than in LC (0.92±0.99) and control group (0.96±0.92) (P=0.0001 for both) but there was no significant difference between LC group and controls (P=0.2). ADAMTS13 at cutoff level 1.62 ng/ml have 71.4% sensitivity and 62.5% specificity for prediction of PVT. In LC+PVT group, level of serum creatinine (mg/dl) (1.5±0.5) and INR (1.7±0.6) were significantly higher than LC group (creatinine 1.28±0.37) (INR 1.29±0.34) (P=0.03 and 0.001 respectively). There was no significant difference between LC+PVT group and LC group as regard, history of encephalopathy, history of gastrointestinal bleeding, presence of ascites, CBC, liver profile (ALT, AST, serum albumin, bilirubin), urea, APRI score, FIB-4, and MELD score (P˃0.05). Regression analysis showed that ADAMTS 13 level and advanced degree of Child-Pugh score predict occurrence of PVT by 1.26 and 4.66 fold respectively. In LC+PVT group, there was a positive correlation between ADAMTS 13 level and INR (r=0.41, P=0.03) but there was no correlation with other parameters (age, platelet count, Hb, albumin, AST, ALT, bilirubin, urea, creatinine and INR, APRI score, FIB-4, MELD score and Child-Pugh score (P˃0.05). In LC group, there was a positive correlation between ADAMTS 13 and Child-Pugh score (r=0.41, P=0.03) and MELD score (r=0.46, P=0.02).
Conclusion
Low levels of ADAMTS-13 are associated with pathogenesis of PVT in liver cirrhosis. ADAMTS-13 concentration is potential biochemical marker in diagnostic strategy of PVT in patients with cirrhosis.
References
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