Portal Vein Thrombosis In Liver Cirrhosis Research Articles

Understanding the pathogenesis of portal vein thrombosis in liver cirrhosis: We are still on the way.

Portal vein thrombosis (PVT) is a common complication of liver cirrhosis. In this issue of the Journal of Clinical Ultrasound: Sonography and other Imaging Techniques, a systematic review and meta‐analysis by Giri et al assessed the role of portal system hemodynamics for predicting the presence and development of PVT in liver cirrhosis.

Impact of Portal Vein Thrombosis on Endoscopic Variceal Band Ligation in Liver Cirrhosis

Background. Portal vein (PV) thrombosis (PVT) is a common complication of liver cirrhosis and can refer to thrombosis within the PV that can extend to its left or right branches and in some cases to the superior mesenteric vein or the splenic vein (Chawla and Bodh, 2015). For severe PVT patients, there are possibilities of increasing PV resistance and reduction of the blood flow though PV towards liver, which exacerbate liver function damage meanwhile elevating the gastrointestinal variceal bleeding risk. Endoscopic Variceal band ligation (EVL) is often used to prevent esophageal variceal bleeding; postoperative complications such as severe gastrointestinal bleeding and bleeding-related death, fever, retrosternal pain, and esophageal stenosis may appear. There was absence of the research which evaluated the impact of PVT in liver cirrhosis on the complication of endoscopic Variceal band ligation for now. We herein aimed to compare cirrhosis patients with and without PVT of recent complications after EVL. Method. We established the retrospective investigation on 144 consecutive cirrhosis patients (excluding patients with hepatocellular carcinoma and who received portal vein-systemic circulation devascularization or shunt surgery, splenectomy, hepatectomy, liver transplantation, transjugular intrahepatic portal vein stent shunt (TIPS), endoscopic varices Variceal ligation, or sclerotherapy before) who have received first endoscopic esophageal varices band ligation in Gastrointestinal Endoscopy Center of the First Affiliated Hospital, College of Medicine, ZheJiang University, between January 2014 and December 2017. Portal vein Doppler ultrasonography, liver computerized tomography (CT), and angiography or liver-enhanced magnetic resonance imaging (MRI) were applied to evaluate the portal vein thrombosis of each patient before EVL. There were 18 patients confirmed with portal vein thrombosis while the other 126 patients without PVT. The primary end point for this research is the upper gastrointestinal hemorrhage and related death occurred from the date of ligation until leaving hospital, and the secondary end point is the appearance of postoperative fever and retrosternal pain. Results. There are no significant differences of gastrointestinal bleeding, bleeding-related death, fever, or retrosternal pain after EVL and the length of hospital stays between cirrhotic patients with or without PVT ( P = 0.34 , 0.51 , 0.58 , 0.61 , 0.88 ). Conclusion. Liver cirrhosis with portal vein thrombosis did not increase incidence of recent complications of the endoscopic Variceal band ligation.

Consensus for management of portal vein thrombosis in liver cirrhosis (2020, Shanghai).

Portal vein thrombosis (PVT) is a common and severe complication of liver cirrhosis. So far, there have been few consensuses or practice guidelines on the management of PVT in liver cirrhosis. In this expert consensus, we systematically review the epidemiology, risk factors, imaging examinations, diagnosis, assessment of disease severity, and treatment strategy of PVT in liver cirrhosis, based on the most recent evidence and expert opinions, to further standardize the diagnosis and treatment of the disease in clinical practice.

Anticoagulation Favors Thrombus Recanalization and Survival in Patients With Liver Cirrhosis and Portal Vein Thrombosis: Results of a Meta-Analysis.

IntroductionBenefit and risk of anticoagulation in cirrhotic patients with portal vein thrombosis (PVT) remain controversial, especially in those with asymptomatic PVT and in non-liver transplant candidates. Furthermore, the predictors of portal vein recanalization and bleeding events after anticoagulation are critical for making clinical decisions, but still unclear. We conducted a meta-analysis to investigate the outcomes of anticoagulation for PVT in liver cirrhosis and explore the predictors of portal vein recanalization and bleeding events after anticoagulation.MethodsAll studies regarding anticoagulation for PVT in liver cirrhosis were searched via PubMed, EMBASE, and Cochrane Library databases. Thrombotic outcomes, bleeding events, and survival were compared between anticoagulation and non-anticoagulation groups. Predictors of portal vein recanalization and bleeding events were pooled. Risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated.ResultsThirty-three studies including 1696 cirrhotic patients with PVT were included. Anticoagulation significantly increased portal vein recanalization (RR = 2.61; 95% CI 1.99–3.43; P < 0.00001) and overall survival (RR = 1.11; 95% CI 1.03–1.21; P = 0.01) and decreased thrombus progression (RR = 0.26; 95% CI 0.14–0.49; P < 0.0001). Anticoagulation did not significantly influence overall bleeding (RR = 0.78; 95% CI 0.47–1.30; P = 0.34). Early initiation of anticoagulation (RR = 1.58; 95% CI 1.21–2.07; P = 0.0007) significantly increased portal vein recanalization. Child-Pugh class B and C (RR = 0.77; 95% CI 0.62–0.95; P = 0.02) and higher MELD score (MD = − 1.48; 95% CI − 2.20–0.76; P < 0.0001) were significantly associated with decreased portal vein recanalization. No predictor significantly associated with bleeding events was identified.ConclusionsEarly initiation of anticoagulation should be supported in liver cirrhosis with PVT. Predictors of portal vein recanalization should be taken into consideration to identify those who may not benefit from anticoagulation.RegistrationThe work was registered in PROSPERO with registration no. CRD42020157142.Electronic supplementary materialThe online version of this article (10.1007/s12325-020-01550-4) contains supplementary material, which is available to authorized users.

Correlational study on portal vein thrombosis of liver cirrhosis

Objective: To study the relevant factors influencing the portal vein thrombosis (PVT) in patients with liver cirrhosis, and the effect of PVT formation on the complications and clinical manifestations of liver cirrhosis. And further investigate the treatment of PVT. Methods: 199 cirrhotic cases with portal vein thrombosis who were hospitalized from January 1, 2014 to October 31, 2018 were selected as PVT group. 199 cirrhotic cases without portal vein thrombosis during the same period were randomly selected as control group to collect the relevant clinical data. Univariate analysis and logistic regression model analysis were carried out on the factors that may affect the formation of PVT, and the complications of cirrhotic patients with PVT were statistically analyzed. According to different data, statistical analysis was performed by t-test, Z- test, χ2 test or Fisher's exact probability method. Results: Univariate analysis results showed that there were statistical differences (P < 0.05) between the two groups on the parts of etiologies of cirrhosis, portal vein width, white blood cells, red blood cells, hemoglobin, platelets, alanine transaminase, aspartate transaminase, alkaline phosphatase, γ - glutamyltransferase, cholinesterase (CHE), blood sugar, total cholesterol, triglyceride, prothrombin time, fibrinogen and thrombin time. Logistic regression model analysis results showed that alcoholic cirrhosis [OR = 3.125 (95% confidence interval, 1.414-6.906), P = 0.005], and portal vein widening [OR = 5.814 (95% confidence interval, 2.746-12.307), P < 0.001] were independent influencing factors of PVT formation in cirrhosis. PVT formation in cirrhosis made patients more susceptible to leukopenia [OR = 1.594 (95% confidence interval, 1.015-2.502), P = 0.043] and CHE reduction [OR = 4.267 (95% confidence interval, 2.313-7.869) P < 0.001]. Gastroesophageal variceal bleeding, ascites, pleural effusion, esophageal varices, severe gastroesophageal varices, and hospitalization length were significantly elevated in PVT group than the control group, and the difference was statistically significant (P < 0.05). Conclusion: Alcoholic cirrhosis and portal vein widening are the factors influencing the formation of PVT in liver cirrhosis. Patients with PVT in liver cirrhosis are more susceptible to leukopenia and CHE reduction. The formation of PVT makes patients with liver cirrhosis more susceptible to rupture and bleeding of gastroesophageal varices, severe gastroesophageal varices, ascites, and pleural effusion and other clinical manifestations, thereby prolonging the length of hospital stay.

Anticoagulation Increases Bleeding Rates in Portal Vein Thrombosis: A National Database Study

Introduction: Liver cirrhosis is being increasingly recognized as a hypercoagulable state, mainly due to disproportionate reduction in antithrombotic factors (protein C, S and anti-thrombin III). Portal vein thrombosis (PVT) is a frequent sequala of liver cirrhosis that can lead to numerous complications and potential exclusion from transplant lists, at least until the resolution of the thrombus. The current evidence for anticoagulation (AC) for PVT in liver cirrhosis is limited to small retrospective studies. Major liver societies recommend limited anticoagulation with enoxaparin based on expert opinion (Category C). We sought to examine the incidence of bleeding after AC in cirrhotic patients with PVT. Methods: Data were obtained from a commercial de-identified database (Explorys, IBM, Inc.) that integrates electronic health records from 27 major integrated U.S. healthcare systems from 1999 to July 2019. Cases were defined as adult patients aged &gt;=18 years having a new Systematized Nomenclature of Medicine Clinical Terms (SNOMED) diagnosis of PVT, had been anticoagulated for the first time following PVT and had experienced bleeding for the first time following AC. Controls were adults who had a diagnosis of PVT and did not get AC. We included older anticoagulants (warfarin and enoxaparin) as well as newer anticoagulants (apixaban, fondaparinux and rivaroxaban). We compared the incidence of bleeding (defined as bleeding from any site) in those with PVT who received AC to those with PVT who did not receive AC. In addition, we also compared the incidence of bleeding between older and newer anticoagulants, and also examined whether there were differences in gender, race, and insurance status for those who bled while on AC. Analysis comprised of calculating odds ratios (OR) and confidence intervals (CI) for the OR. Results: A total of 213,810 patients had liver cirrhosis and out of those, 7,570 (3.5%) patients had PVT. Four hundred and ten cases out of 1,430 patients who received AC bled for the first time whereas 980 cases out of 3,880 patients who did not receive AC bled for the first time. Cases on AC had 1.18 times higher odds of bleeding when compared to controls who did not receive AC (CI = 1.04 - 1.36). Newer AC were less likely to increase bleeding when compared to older AC (OR = 0.6, CI = 0.4 - 0.9). Females were significantly more likely to be first time bleeders on AC when compared to male first-time bleeders on AC (Table 1). However, race and insurance status did not seem to affect bleeding rates (Table 1). Conclusion: Anticoagulation for PVT in liver cirrhosis increases bleeding events. Newer AC were significantly less likely to increase bleeding when compared to older AC. Females were more likely to bleed on newer AC than males, but race and insurance status did not affect bleeding rates. Limitations of the study include the retrospective nature of the analysis that relied on diagnosis coding, and smaller numbers in our subgroup analyses which limits generalizability. Clinicians should be aware of the significant risk of bleeding when prescribing AC, particularly older AC to cirrhotic patients with PVT. Disclosures No relevant conflicts of interest to declare.

Advances in the study of gastroesophageal varices with portal vein thrombosis in liver cirrhosis

Portal vein thrombosis (PVT) is one of the serious complications in the decompensated stage of liver cirrhosis, which is often accompanied by the aggravation of liver cirrhosis and other complications and in severe cases; it may induce gastroesophageal variceal hemorrhage and endanger the lives of patients. Furthermore, the most common complication in decompensated stage of cirrhosis is history of gastroesophageal variceal hemorrhage and the formation of PVT that may be a risk factor to promote each other. Presently, there are guidelines for diagnosis and treatment of gastroesophageal variceal hemorrhage in liver cirrhosis, but there is still a lack of in-depth understanding of cirrhosis complicated with PVT. This paper summarizes advances in the study of gastroesophageal variceal hemorrhage complicated with PVT in liver cirrhosis in order to enhance the understanding of risk factors for diagnosis and treatment.

Anticoagulant therapy in patients with liver cirrhosis and portal vein thrombosis: insights for the clinician.

Portal vein thrombosis (PVT) is a frequent complication in the natural history of patients with liver cirrhosis (LC). The prevalence of PVT in LC is highly variable, ranging from 0.6% to 25% according to different reports. The impact of PVT on the natural history of LC is unclear, but it seems to negatively affect the prognosis of patients undergoing liver transplantation (LT) by increasing post-LT mortality and delaying waiting time. The antithrombotic treatment of PVT is still challenging as PVT may often remain asymptomatic and incidentally diagnosed, and a spontaneous partial/total regression of PVT is observed in an important proportion of patients, even in the absence of anticoagulation. Recent evidence suggested that the anticoagulant treatment for PVT may favorably affect both ischemic and bleeding outcomes in LC patients. Anticoagulant therapies so far available include unfractioned heparin, low molecular weight heparins (LMWHs) and fondaparinux for acute treatment, and LMWHs and vitamin K antagonists (VKAs) for long-term treatment. No robust data currently support the use of direct oral anticoagulants (DOACs) in patients with LC and PVT, as the safety and efficacy of DOACs in this setting is still unclear. This review summarizes current evidence for the evaluation and management of patients with LC and PVT.

Anticoagulation Treatment with Low Molecular-Weight Heparin for Portal Vein Thrombosis in Liver Cirrhosis: Efficacy and Risk of Hemorrhagic Complications

▪Introduction: Portal vein thrombosis (PVT) is a well-known complication caused by disturbed portal flows and hemostatic imbalances in liver cirrhosis (LC). Low molecular-weight heparin (LMWH) can be used as a treatment of PVT, but knowledge the about efficacy and safety of LMWH for LC patients remains limited. The aim of this study is therefore to investigate the clinical outcomes of cirrhotic patients with PVT treated with LMWH.Method: From September of 2013 to December of 2015, LC patients who had PVT were treated with therapeutic doses of LMWH, dalteparin or enoxaparin for six months. Patients with severely decompensated LC, a history of major bleeding in the last six months, and/or impaired renal function were excluded.Results: Ninety patients were enrolled. The median age was 63.5 years (range 38-65), and male patients numbered 66 (73.3%). The most common cause of LC was hepatitis B virus infection (55 patients, 61.1%), followed by alcohol abuse (12 patients, 13.3%). Fifty-eight patients (64.4%) had hepatocellular carcinoma. Half of the patients had Child-Pugh class A cirrhosis, and 41 patients (45.6%) had class B cirrhosis. Thirty patients had thrombocytopenia with platelet counts less than 50,000/mm3. All patients had thrombus in the main trunk or in branches of the portal vein. Splenic vein involvement was confirmed in four patients, and 25 patients had superior mesenteric vein thrombus. PVT was newly discovered in 30 patients (33.3%), previously established but recently progressed was found in 43 (47.8%), and chronic but stable thrombus was noted in 17 (18.9%). The median time from the initial diagnosis of PVT to the start of anticoagulation therapy was 8.7 months (range: 0-125.9 months). Dalteparin was prescribed to 81 patients (90.0%) and enoxaparin to 9 (10.0%). The median duration of treatment was 5.8 months (range: 1-34.6 months). The overall rate of recanalization was 58.9%. Complete recanalization was reported in 16 patients (17.8%) and partial recanalization in 37 (41.1%). Patients with a favorable Child-Pugh class and recently diagnosed thrombus showed significantly better responses (Table 1). Concomitant hepatocellular carcinoma had no effect on the recanalization rate. In the patients who responded to anticoagulation therapy, the post-treatment laboratory findings including serum bilirubin and albumin were slightly improved compared to the pre-treatment state. At the time of the analysis, 48 patients (53.3%) had finished six months of the initial LMWH treatment as scheduled, while treatments for five patients were ongoing. The relapse rate of PVT was 56.6%, and the median time from the cessation of anticoagulation to relapse was 4.2 months (range: 1.4-7.0 months). Eight patients (8.9%) suspended their use of LMWH due to adverse events. The most common adverse event was bleeding, which was reported in 13 patients (14.4%). A history of variceal bleeding was a significant risk factor for hemorrhagic complications. Patients denoted as Child-Pugh Classes B or C showed a higher incidence rate compared to those designated as Class A. Two patients died due to fatal bleeding events, which were in these cases intractable duodenal variceal bleeding and intracranial hemorrhage.Conclusion: Anticoagulation therapy using LMWH for PVT in LC is effective, with a recanalization rate of 59.6%. Advanced LC and a delayed start of anticoagulation since the initial diagnosis of PVT disrupted the recanalization effect of LMWH. Long-term maintenance of anticoagulation should be considered owing to the high recurrence rates, but much care is necessary with regard to hemorrhagic complications in patients with a past history of variceal bleeding. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Non-Malignant Portal Vein Thrombosis in Liver Cirrhosis: Diagnosis and Treatment

Portal vein thrombosis (PVT) is considered a common complication of liver cirrhosis. Its prevalence increases with liver disease severity, reaching 25% in patients awaiting liver transplantation (LT). The majority of patients with cirrhosis are diagnosed incidentally with PVT during routine ultrasound in their cirrhosis follow-up. Doppler ultrasound is the recommended first-line investigation. Computed tomography or magnetic resonance angiography are the best methods to assess the extent of the PVT. The natural history of PVT in liver cirrhosis is not very well defined, but in the context of LT the deleterious effects of PVT are better known. There are no consensus guidelines about the treatment of PVT in cirrhotic patients and although anticoagulation is considered as the first-line therapy, the evidence regarding this treatment is based on a small series of patients. Nonetheless, it seems that anticoagulation therapy is useful in cirrhotic patients with PVT, particularly in patients who are candidates for a LT, in order to maximise the recanalisation rate and prevent thrombus progression. This treatment must be administered as soon as possible following a prophylactic treatment to avoid variceal bleeding, otherwise it seems to have a broad safety profile. A transjugular intrahepatic portosystemic shunt would be the alternative procedure for patients with no response to anticoagulation therapy or where portal hypertension complications occur.

Associations of antiphospholipid antibodies with splanchnic vein thrombosis: a systematic review with meta-analysis.

Splanchnic vein thrombosis (SVT) refers to Budd-Chiari syndrome (BCS) and portal vein system thrombosis (PVST). Current practice guidelines have recommended the routine screening for antiphospholipid antibodies (APAs) in patients with SVT. A systematic review and meta-analysis of observational studies was performed to explore the association between APAs and SVT. The PubMed, EMBASE, and ScienceDirect databases were searched for all relevant papers, in which the prevalence of positive APAs or levels of APAs should be compared between BCS or noncirrhotic PVST patients versus healthy controls, or between cirrhotic patients with portal vein thrombosis (PVT) versus those without PVT. Fourteen studies were eligible. Only 1 study evaluated the role of APAs in BCS patients and found that positive immunoglobulin (Ig) G anticardiolipin antibody (aCL) was more frequently observed in BCS patients than in healthy controls; however, the associations of other APAs with BCS were not evaluated. Positive IgG aCL was more frequently observed in noncirrhotic patients with PVST than in healthy controls; however, other APAs, such as IgM aCL, lupus anticoagulants (LAs), anti-β2-glycoprotein-I antibody (aβ2GPI), and aβ2GPI-oxidized low-density lipoprotein antibody (ox-LDL) were not associated with noncirrhotic PVST. Positive unclassified aCL was more frequently observed in cirrhotic patients with PVT than in those without PVT; however, the association of IgG aCL and IgM aCL with the development of PVT in liver cirrhosis remained inconsistent among studies. The risk of BCS and noncirrhotic PVST might be increased by positive IgG aCL but not IgM aCL, LA, aβ2GPI, or aβ2GPI ox-LDL. However, the evidence regarding APAs in BCS originated from only 1 study. The association between APAs and PVT in liver cirrhosis was unclear.

Role of D-dimer in the Development of Portal Vein Thrombosis in Liver Cirrhosis: A Meta-analysis.

Background and Aims:A meta-analysis was performed to explore the role of the D-dimer in the development of portal vein thrombosis (PVT) in liver cirrhosis.Methods:All papers were searched via PubMed, EMBASE, China National Knowledge Infrastructure, Wan Fang, and VIP databases. A standardized mean difference (SMD) with 95% confidence interval (CI) was pooled.Results:Overall, 284 studies were initially identified, of which 21 were included. Cirrhotic patients with PVT had a significantly higher D-dimer concentration than those without PVT (pooled SMD = 1.249, 95%CI = 0.740–1.758). After the portal hypertension-related surgery, cirrhotic patients with PVT had a similar preoperative D-dimer concentration to those without PVT (pooled SMD = 0.820, 95%CI = −0.122–0.286), but a higher postoperative value of D-dimer concentration than those without PVT (pooled SMD = 2.505, 95%CI = 0.975–4.036). Notably, the D-dimer concentration at the 1st postoperative day was similar between cirrhotic patients with and without PVT (pooled SMD = 0.137, 95%CI = −0.827–1.101), but that at the 7th post-operative day was higher in cirrhotic patients with PVT than in those without PVT (pooled SMD = 1.224, 95%CI = 0.277–2.171).Conclusion:D-dimer might be regarded as a diagnostic marker for PVT in liver cirrhosis. In addition, postoperative D-dimer testing is worthwhile for the diagnosis of PVT after portal hypertension-related surgery.

Management of portal vein thrombosis in liver cirrhosis

Portal vein thrombosis (PVT) is a fairly common complication of liver cirrhosis. Importantly, occlusive PVT might influence the prognosis of patients with cirrhosis. Evidence from a randomized controlled trial has shown that anticoagulation can prevent the occurrence of PVT in patients with cirrhosis without prior PVT. Evidence from several case series has also demonstrated that anticoagulation can achieve portal vein recanalization in patients with cirrhosis and PVT. Early initiation of anticoagulation therapy and absence of previous portal hypertensive bleeding might be positively associated with a high rate of portal vein recanalization after anticoagulation. However, the possibility of spontaneous resolution of partial PVT questions the necessity of anticoagulation for the treatment of partial PVT. In addition, a relatively low recanalization rate of complete PVT after anticoagulation therapy suggests its limited usefulness in patients with complete PVT. Successful insertion of a transjugular intrahepatic portosystemic shunt (TIPS) not only recanalizes the thrombosed portal vein, but also relieves the symptomatic portal hypertension. However, the technical difficulty of TIPS potentially limits its widespread application, and the risk and benefits should be fully balanced. Notably, current recommendations regarding the management of PVT in liver cirrhosis are insufficient owing to low-quality evidence.

Effect of Antithrombin, Protein C and Protein S on Portal Vein Thrombosis in Liver Cirrhosis: A Meta-analysis

BackgroundThe effects of antithrombin (AT), protein C (PC) and protein S (PS) on the pathogenesis of portal vein thrombosis (PVT) in liver cirrhosis remain controversial in different studies. In this study, a systematic review and meta-analysis to examine this issue were performed. MethodsPubMed database was employed to identify all studies in which AT, PC and PS concentrations were measured in both cirrhotic patients with and without PVT. A standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to evaluate the effect of AT, PC and PS on PVT. Data were pooled using both fixed-effect and random-effect models. Only the pooled data using random-effect model were considered appropriate, when significant heterogeneity was observed. ResultsNine studies involving 160 cirrhotic patients with PVT and 428 cirrhotic patients without PVT were eligible. AT and PC concentrations were similar between PVT and non-PVT groups (AT: SMD=−0.21, 95% CI=−0.56 to 0.14, P=0.24; PC: SMD=−0.23, 95% CI=−0.55 to 0.09, P=0.16). But PS concentration was significantly lower in the PVT group than in the non-PVT group (SMD=−0.29, 95% CI=−0.49 to −0.08, P=0.006). Subgroup analyses were further conducted in 4 studies in which baseline liver function was similar between cirrhotic patients with and without PVT, showing similar AT, PC and PS concentrations between the 2 groups (AT: SMD=−0.10, 95% CI=−0.36 to 0.16, P=0.57; PC: SMD=−0.18, 95% CI=−0.62 to 0.25, P=0.41; PS: SMD=−0.10, 95% CI=−0.59 to 0.39, P=0.69). ConclusionsAT, PC and PS concentrations might not be associated with the pathogenesis of PVT in liver cirrhosis, especially when the impact of liver function was excluded.