Portal vein thrombosis (PVT) is a critical complication in liver cirrhosis (LC), significantly worsening portal hypertension and accelerating the progression to decompensation. Early identification of at-risk patients is paramount for improving prognosis. This review synthesizes current evidence, categorizing the risk factors for PVT-LC into four interconnected domains: hemodynamic disturbances, the severity of cirrhosis, vascular endothelial injury with hypercoagulable states, and thrombophilic genetic factors. By comprehensively delineating these elements and their predictive indicators, we provide a foundational framework for constructing clinically applicable prediction models to guide timely intervention.
Introduction
Liver cirrhosis represents the end-stage of chronic liver disease, with PVT emerging as a common and severe complication. Historically underdiagnosed, advances in imaging have revealed a PVT incidence ranging from 10% in compensated cirrhosis to over 25% in liver transplant candidates. PVT exacerbates portal hypertension, leading to refractory ascites, variceal bleeding, and hepatic encephalopathy. Its often insidious onset means many patients miss the optimal treatment window, underscoring the urgent need for proactive risk stratification and early prediction.
1. Hemodynamic Disturbance
Hemodynamic alterations in the portal system are a cornerstone of PVT pathogenesis. Decreased portal vein velocity (PVV), particularly below 15 cm/s, is one of the most robust predictors, as it promotes blood stasis per Virchow's triad. Portal vein dilation (PVD > 14.5 mm) further reduces flow velocity and can cause valve insufficiency and vortex formation, prolonging contact between clotting factors and the endothelium. Beyond the portal vein, splenic vein dilation and decreased velocity are critical, especially post-splenectomy, where thrombosis often initiates in the splenic vein before extending to the portal system.
2. Vascular Endothelial Injury and Hypercoagulable State
This category encompasses iatrogenic, inflammatory, and metabolic insults that damage the endothelium and promote coagulation.
Iatrogenic Interventions: Splenectomy is a major risk factor (increasing risk ≥10-fold), mediated by reduced portal flow, surgical trauma, and a post-operative rebound thrombocytosis. Endoscopic therapies for varices (ligation and sclerotherapy) also elevate PVT risk, likely by obstructing collateral flow and causing mechanical endothelial injury.
Endotoxemia and Inflammation: Systemic inflammation, often from bacterial translocation, can activate neutrophils and cytokines, damaging endothelium and triggering coagulation. Novel markers like the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) show predictive promise. Emerging players include phosphatidylserine-positive microparticles (PS+MPs) and neutrophil extracellular traps (NETs), which create a pro-thrombotic milieu.
Metabolic Syndrome: Diabetes mellitus is a well-established risk factor, inducing PVT through endothelial dysfunction and a hypercoagulable state. The roles of hypertension and abdominal obesity are also being explored.
Coagulation-Anticoagulation-Fibrinolysis (CAF) Biomarkers: The hypercoagulable state in cirrhosis is uniquely reflected in specific biomarkers. Elevated D-dimer (>0.87 μg/mL) is a key independent predictor. Rather than platelet count, markers of platelet activation like mean platelet volume (MPV) and P-selectin (CD62P) are more relevant. An imbalance between pro-coagulant factor VIII and anticoagulant protein C, as well as a disrupted von Willebrand factor (vWF)/ADAMTS-13 ratio, are also significant predictive indicators.
3. Severity of Liver Cirrhosis
The risk of PVT escalates with the progression of LC.
Portal Hypertension (PH) and its Complications: The severity of PH is a fundamental driver of PVT. A hepatic venous pressure gradient (HVPG) ≥ 16-20 mmHg is a strong predictor. Complications like ascites, variceal hemorrhage, and hepatic encephalopathy are all confirmed risk factors, with their presence indicating a higher likelihood of PVT.
Liver Metabolic Function and Scoring Systems: Laboratory markers of declining liver function, such as low albumin, are associated with PVT. Composite scoring systems are highly useful; both Child-Turcotte-Pugh (CTP) class B/C and higher Model for End-Stage Liver Disease (MELD) scores are independent predictors of PVT, reflecting the liver's deteriorating ability to maintain coagulation balance.
4. Mutations in Thrombophilic Genetic Factors (THRGFs)
A subset of cirrhotic patients with PVT carries inherited pro-thrombotic mutations. Established genes include Factor V Leiden, prothrombin G20210A, and MTHFR C677T. The JAK2 V617F mutation is also significant, often indicating an underlying myeloproliferative neoplasm. A critical highlight is the ethnic variation in these factors; while FV Leiden and G20210A are common in Caucasians, mutations in genes like PROC (Protein C) may be more relevant in Asian populations. This necessitates the development of population-specific genetic screening algorithms.
Clinical Decision-Making and Conclusions
The review culminates in a practical risk stratification framework (Table 4) and a clinical algorithm for early screening (Fig. 3). High-risk factors (e.g., splenectomy history, low PVV) and medium-risk factors (e.g., diabetes, high D-dimer, CTP B/C) are identified, guiding the frequency of ultrasound surveillance and consideration of anticoagulation.
In conclusion, PVT in cirrhosis arises from a complex interplay of hemodynamic, cirrhotic severity, hypercoagulable, and genetic factors. These elements are not isolated but interact and reinforce each other (Fig. 4). Future research must focus on validating novel biomarkers, establishing precise cutoff values for predictive indicators, and constructing integrated models that can be seamlessly applied in clinical practice to enable pre-emptive management and improve patient outcomes.
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The study was recently published in the Journal of Clinical and Translational Hepatology .
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