Anticoagulation Therapy And Early Prediction For Portal Vein Thrombosis In Cirrhotic Patients With Hepatitis B

Background and aimsCirrhosis is considered to be the end-stage liver disease.Decompensated cirrhosis often appears portal hypertension,which can result in severe complications,such as gastroesophageal bleeding,hepatic encephalopathy,and spontaneous bacterial peritonitis.Patients with cirrhosis have a high incidence of portal vein thrombosis(PVT).PVT is defined as the formation of a thrombus in the portal vein.The thrombus can include variable portions from mesenteric veins to splenic vein.Clinical manifestations of PVT with live cirrhosis vary from asymptomatic to deadly complication.PVT also precludes liver transplantation(LT)in some medical centres,and when performed,increases the difficulty and the surgical complexity of LT.Optimal management of PVT with cirrhosis remains unclear.In patients with concomitant PVT and liver cirrhosis,anticoagulation and transjugular intrahepatic portosystemic shunting(TIPS)may provide a chance of repermeation.Up to now,no randomized controlled trial has been reported and most conclusions about PVT treatment come from case series.Enoxaparin was used to treat PVT in patients with liver cirrhosis,however,there is no paper about optimal dosage of enoxaparin in the management of PVT with cirrhosis.Although anticoagulation and TIPS has been reported to be effective for PVT in cirrhosis,non-recanalization was observed in many patients.Furthermore,the rate of rethrombosis after recanalization is high when anticoagulation was stopped.It has been reported that early initiation of anticoagulation after the development of PVT was the predictive factor for recanalization.In another study,none of the patients who received prophylactic anticoagulation developed PVT during the follow-up period.Since early and prophylactic anticoagulation retatment is encouraging,patients waiting for LT need detection for PVT to achieve the opportunity of liver transplantation.In addition,it is necessary to identify the patients who should receive anticoagulation for the prevention of PVT in cirrhosis.Therefore,the optimal and efficient modalities for PVT monitoring should be established as soon as possible.Recent study showed that the risk of PVT was significantly associated with the platelet count,while the conclusion is opposite in other paper.Furthermore,the function of platelet seems play a more important role during PVT development.It has been shown that the reduced portal flow velocity was related to the occurrence of PVT in cirrhotic patients,however,this view is not supported by two studies.Whether thrombophilic genotype is significantly associated with PVT for cirrhosis remains controversial.Moreover,other authors also reported predictive variable for PVT in cirrhosis,including sclerotherapy,trauma,surgical operation,obesity,and so on,while some conclusions are arguable.Since most of the above-mentioned conclusions are insufficient due to limited data and poor-quality evidence,the predictive value of various factors for PVT required further investigations.In currently,it has been in dispute on the relationship between PVT and genetic thrombophilic defects,which are costly in general.In view of this,it is necessary to explore the optimum predictive factors for PVT in cirrhosis,so as to ensure maximum cost-effectiveness.There have been reports about the relationship between PVT of cirrhosis and basic laboratory tests,such as prothrombin time(PT),platelet count,fibrinogen(FIB)and D-dimer,while the results remain controversial.It is difficult for single coagulation parameter to evaluate the whole coagulation state.Disseminated intravascular coagulation score(DIC score),intergrating routine coagulation parameter mentioned-above,deserves to be investigated in coagulation of cirrhosis.The DIC score was determined using the International Society on Thrombosis and Haemostasis(ISTH)scoring system,based on readily available coagulation parameters:platelet count,Fibrin-related marker,PT and FIB.In a prospective study of 272 adult patients with newly diagnosed acute myeloid leukemia,the calculated DIC score predicted significantly arterial venous thrombosis.Yet,the prognostic value of the DIG score in patients with cirrhosis is uncertain.On the basis of findings above,in the part 1 of the study,we aim to evaluate the efficacy and safety of anticoagulation therapy with different doses of enoxaparin for PVT in cirrhotic patients with hepatitis B;Furthermore,we also evaluated the prognostic value of DIC score as a novel predictor for PVT in cirrhosis with hepatitis B in the part 2 of the study.MethodsPart 1Sixty-five patients with hepatitis B related cirrhosis and acute PVT were treated by different doses of enoxaparin.All the patients were assigned randomly into two groups,one group to receive enoxaparin 1.0mg/kg subcutaneous every 12 hours,the other group to enoxaparin 1.5 mg/kg subcutaneous every 24 hours.Clinical,biochemical evaluation,Doppler ultrasound and contrast-enhanced computed tomography were performed during the anticoagulation treatment.Part 2109 cirrhotic patients with hepatitis B were included.Clinical data,laboratory tests and imaging examinations of the patients at baseline time and every three months.All patients were followed up until study end point(occurrence of PVT within 12 months,or 12 months after baseline time).We evaluated the predictive value of DIC score in the PVT formation for cirrhosis.ResultsPart1Among the 65 patients,51 patients(78.5%)obtained complete/partial recanalization of PVT after 6 months of anticoagulation therapy.Child-Pugh scores were lower in the 51 patients obtained complete/partial recanalization than those in the 14 no responders(P<0.01).No patients presented variceal bleeding during anticoagulation therapy in two groups.The rates of non-variceal bleeding from using 1.5 mg/kg every 24 hours(23.5%)were higher than 1.0mg/kg every 12 hours(6.4%).Part 2Of the 109 patients,14 patients(12.8%)developed PVT as the PVT group,whereas no PVT was observed in 95 patients(87.2%)as the PVT group.By the study end point,there was a significant increase in D-dimer,Child-Pugh score and DIC score(all P<0.001)as well as a significant lower in portal flow velocity(P<0.001).According to ROC analysis,area under curve(AUC)was calculated in every variable.Among these factors,DIC score showed the optimum diagnostic performance in predicting the PVT development in cirrhotic patients.DIC score had the largest AUC of 0.845,followed by Child-Pugh Score of 0.778,D-dimer of 0.732,and portal vein velocity of 0.709.Conclusions1.Anticoagulation therapy with two doses of enoxaparin for PVT in hepatitis B patients with cirrhosis is efficient and safe.2.1.0mg/kg enoxaparin subcutaneous every 12 hours is the better anticoagulation regimen in treatment of PVT in cirrhotic patients.3.The incidence of portal vein thrombosis in cirrhotic patients with hepatitis B is12.8%.4.Among the routine laboratory parameters and imaging examinations,the DIC score is a useful tool in assessing PVT risk in patients with hepatitis B-related cirrhosis and shows good cost-effectiveness.