Core Tip: Chronic hepatitis C virus infection is increasingly recognized as a systemic condition that promotes thrombosis through inflammation, endothelial dysfunction, and coagulation imbalance. This minireview highlights how hepatitis C contributes to portal vein thrombosis, venous thromboembolism, and cardiovascular disease. Direct-acting antiviral therapy not only clears the virus but also reduces systemic inflammation and thrombotic risk, though patients with advanced fibrosis remain vulnerable. The review emphasizes the urgent need for hepatitis C-specific thrombotic risk assessment tools and biomarker-guided strategies to improve prevention and management.
INTRODUCTION
Hepatitis C virus (HCV) infection is a pervasive yet under-treated and commonly undiagnosed chronic illness. Characterized by a prolonged chronic stage, it can lead to both hepatic and extrahepatic health issues. According to the World Health Organization, chronic HCV infection affects an estimated 57 million individuals globally[ 1 ], and these individuals have a 25%-32% increased risk of cardiovascular complications - including coronary artery disease, stroke, and peripheral vascular disease - compared to uninfected controls, independent of traditional risk factors[ 2 , 3 ]. In the United States, an estimated 3.7 million individuals are affected by this virus, making it the most common blood-borne infection in the country as well as the most common cause of end-stage liver disease, prompting liver transplant[ 4 ]. Worldwide, however, fewer than 5% of individuals infected with HCV have been diagnosed, and under 1% have undergone treatment. Nevertheless, the World Health Organization has been implementing different approaches to reduce HCV incidence rates, including broader screening efforts, improved access to appropriate healthcare services, and the implementation of effective and efficient direct-acting antiviral (DAA) therapies[ 5 ].
HCV, identified in 1989, is a positive-sense, single-stranded RNA virus classified within the Flaviviridae family. The HCV life cycle is intricately associated with hepatocyte lipid metabolism[ 6 ]. Viral replication induces extensive rearrangements of intracellular membranes, resulting in the formation of a specialized cytoplasmic structure termed the “membranous web”. Additionally, HCV assembly is closely linked to the biogenesis of very-low-density lipoproteins, with viral propagation dependent on lipid metabolic pathways. These pathways include cholesterol transfer via lipoprotein receptors during cellular entry, lipid-mediated regulation of viral genome replication, and the involvement of both cytosolic and luminal lipid droplets in viral particle formation[ 7 ].
In the United States, around 60% of acute HCV infections are linked to injection drug use, with additional risk factors including men who have sex with men [particularly those with human immunodeficiency virus (HIV)], perinatal transmission, tattoo placement, vertical transmission, hemodialysis, occupation in healthcare, and exposure to blood products prior to 1992[ 4 ]. Medical and cosmetic procedures pose a lower risk when appropriate infection-control practices are followed. Most individuals with acute HCV infection are asymptomatic, though some may develop symptoms such as jaundice, fatigue, and abdominal pain within a few weeks of exposure[ 5 ].
Chronic HCV infection is defined by the persistence of the viral RNA for over six months and is often clinically silent, although some patients exhibit gastrointestinal, neuropsychiatric, and algesic manifestations. Long-term complications of chronic HCV include hepatic fibrosis, cirrhosis, hepatocellular decompensation, and hepatocellular carcinoma, with 20%-30% of infected individuals developing cirrhosis over a 25-year to 30-year period. Established risk factors for cirrhosis include male sex, age over 50 years, co-infection with hepatitis B or HIV, immunosuppressive therapy, alcohol consumption, obesity, and nonalcoholic steatohepatitis[ 8 ]. Up to 74% of patients experience extrahepatic manifestations that negatively impact quality of life, including an increased prevalence of diabetes mellitus and cardiovascular disease, many of which may be ameliorated through DAA therapy[ 5 ].
Although traditional existing literature often characterizes cirrhosis as a hypocoagulable state, emerging evidence supports the concept of a precariously rebalanced hemostatic system, rather than a primary bleeding diathesis. Additionally, extrahepatic manifestations of HCV - particularly those involving vascular and coagulation pathways - are increasingly acknowledged for their clinical relevance, paralleling growing interest in the systemic effects of chronic HCV infection[ 9 ]. Chronic HCV infection promotes a pro-inflammatory state that results in increased levels of thrombogenicity. Consequently, this inflammatory state is linked to an elevated risk of cardiovascular complications and related adverse events. The purpose of this review article is to explore the interplay of thrombotic risk in hepatitis C with hepatic and cardiovascular dysfunction and to assess the novel shift from the traditional view of cirrhosis as an anticoagulated state to a fragile rebalanced hemostasis.
EPIDEMIOLOGY OF THROMBOTIC RISK IN HCV
HCV infection, long recognized for its hepatotropic nature and progression to cirrhosis, is now increasingly acknowledged as a systemic disease with significant thrombotic potential. While cirrhosis is classically associated with thrombocytopenia and reduced synthesis of coagulation factors, recent evidence suggests that liver disease - particularly when caused by HCV - can promote a prothrombotic state. A combination of chronic inflammation, endothelial dysfunction, direct activation of the coagulation cascade, enhancement of platelet aggregation, and HCV-driven suppression of endogenous anticoagulant pathways contributes to an increased risk of both venous and arterial thrombotic events, including portal vein thrombosis (PVT), deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke[ 10 ]. Understanding the underlying mechanisms and prevalence of these events is critical for guiding clinical suspicion and management in HCV-infected populations.
Thrombotic complications in HCV infection are believed to result from a constellation of interrelated mechanisms. Chronic inflammation is thought to enhance procoagulant activity by promoting activation of the coagulation cascade via inflammatory cytokines. A meta-analysis shows that in patients with HCV infection, this thrombotic tendency may be further amplified by endothelial dysfunction, which is partly driven by oxidative stress associated with persistent inflammation[ 11 ]. Furthermore, dysregulation of fibrinolysis and enhanced thrombin generation - partially mediated by tissue factor expression on virally infected endothelium - contribute to a prothrombotic state. The presence of antiphospholipid antibodies, frequently observed in HCV-infected patients, may further promote hypercoagulability. Additionally, circulating immune complexes, particularly in the context of mixed cryoglobulinemia, have been implicated in triggering vascular inflammation and thrombotic phenomena[ 10 ].
PVT is a significant complication in HCV-related cirrhosis. In a cohort of 1000 Egyptian cirrhotic patients, PVT was identified in 21.6% of cases, with complete portal vein occlusion observed in 70.4% of those affected. Clinically, half of these patients experienced at least one episode of portal hypertensive bleeding, while others presented with abdominal pain or jaundice. The presence of PVT was significantly associated with advanced liver disease, ascites, male sex, and focal hepatic lesions[ 11 ]. These data reflect the substantial thrombotic burden in HCV cirrhosis and reinforce the need for routine vascular imaging and risk stratification in this population.
Beyond the portal circulation, HCV infection has been linked to systemic venous thromboembolism (VTE), including PE and DVT. A retrospective cohort study showed an increased incidence of PE and DVT in patients aged 64 years or younger and in those without traditional risk factors or comorbidities, suggesting HCV itself may serve as an independent prothrombotic trigger[ 12 ]. Several mechanisms may account for this association. Chronic systemic inflammation in HCV can cause vasculopathy and impaired blood flow. Additionally, the prothrombotic state often observed in chronic liver disease includes a reduction in natural anticoagulants - such as antithrombin III, protein C, and protein S - alongside elevated levels of procoagulant factors, including factor VIII and von Willebrand factor. These alterations collectively shift the hemostatic balance toward hypercoagulability, increasing the risk of thrombotic events[ 13 ]. These findings suggest that HCV should be considered a potential underlying etiology in cases of VTE of unknown origin[ 12 ].
Chronic HCV infection is also associated with an increased risk of thrombotic cardiovascular and cerebrovascular events, including coronary artery disease, acute coronary syndromes, and ischemic stroke. The underlying mechanisms are multifactorial but primarily stem from persistent systemic inflammation, which promotes endothelial dysfunction, accelerates atherosclerotic plaque formation, and enhances thrombin generation - processes that occur independently of serum lipid levels. HCV-infected individuals are also susceptible to cardiomyopathies, such as dilated and hypertrophic forms, which carry poor prognoses and may contribute to intracardiac thrombosis due to disrupted blood flow in the heart and stasis of blood in chambers. Lipid-lowering therapies have been shown to reduce the incidence of myocardial infarction in this population, likely due to their anti-inflammatory and antithrombotic properties rather than effects on lipid profiles alone[ 14 ]. These findings further support the systemic thrombotic risk posed by chronic HCV infection.
Chronic HCV infection elevates thrombotic and cardiovascular risk through mechanisms that are distinct from, but also overlap with, those of traditional risk factors such as diabetes, dyslipidemia, and hypertension[ 15 ]. The unique contribution of HCV lies in its ability to act as a nontraditional, modifiable risk factor for thrombosis, independent of metabolic syndrome, and to potentiate cardiovascular risk even in the absence of classic risk factors[ 16 ]. Viral eradication with DAAs reverses many of these pathogenic processes, underscoring the importance of HCV-specific mechanisms in cardiovascular risk[ 17 ].
HEPATIC DYSFUNCTION AND COAGULATION IMBALANCE
Hemostatic alterations are frequently encountered in patients with cirrhosis. Historically, the bleeding tendency observed in this population was attributed to impaired hepatic synthesis of procoagulant factors and thrombocytopenia, which were also thought to confer relative protection against thrombotic events. Consequently, invasive diagnostic and therapeutic procedures were traditionally considered to pose a high risk for bleeding in this population. However, emerging evidence has challenged this paradigm, demonstrating concurrent reductions in anticoagulant factors. These parallel changes result in a rebalanced, yet inherently unstable, hemostatic system. As a result, patients with cirrhosis remain vulnerable to both hemorrhagic and thrombotic complications, depending on the clinical context and precipitating factors[ 18 ].
In cirrhosis, reduced activity of several procoagulant factors is offset by increased levels of factor VIII, synthesized by liver sinusoidal endothelial cells, along with decreased concentrations of natural anticoagulants. As mentioned previously, chronic liver disease is frequently associated with a prothrombotic state characterized by a decline in natural anticoagulant proteins, including antithrombin III, protein C, and protein S, along with elevated concentrations of procoagulant factors such as factor VIII and von Willebrand factor. This imbalance in the hemostatic system promotes a hypercoagulable state, thereby heightening the risk of thrombotic complications[ 11 ]. Additional prothrombotic influences include alterations in circulating microparticles, cell-free DNA, and neutrophil extracellular traps. Together, these changes promote a shift toward a pro-coagulant state[ 18 ].
Fibrinolytic balance is also disrupted in cirrhosis. Elevated levels of tissue-type and urokinase-type plasminogen activators, combined with reductions in α2-antiplasmin, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor, are somewhat counterbalanced by decreased plasminogen availability and reduced fibrin clot permeability. The net impact of these opposing forces on fibrinolysis remains uncertain. Nonetheless, current evidence supports the concept that patients with cirrhosis exhibit a rebalanced, yet procoagulant-leaning, hemostatic profile[ 18 ].
Cirrhosis develops because of chronic hepatic inflammation, leading to progressive replacement of normal parenchyma with fibrotic tissue and regenerative nodules. This distortion of hepatic structures increases the resistance in the vasculature, which results in the development of portal hypertension. The interplay between portal hypertension and the procoagulant shift of cirrhosis may contribute to the risk of PVT, a frequent and clinically significant complication in advanced liver disease. Variceal bleeding is a life-threatening sequela of cirrhosis and is primarily driven by portal hypertension[ 19 ]. The most common sites of bleeding are esophageal and gastric varices, while rectal variceal bleeding occurs less frequently[ 20 ]. This phenomenon may seem paradoxical considering the procoagulant state that these patients are in, but it is important to note that variceal bleeding is primarily driven by portal pressure and not related to failure of the hemostatic system[ 21 ].
In the context of chronic hepatitis C, impaired hepatic synthesis of thrombopoietin contributes to the development of thrombocytopenia[ 22 ]. Thrombopoietin, a key regulator of thrombopoiesis, is predominantly produced by hepatocytes. It exerts its effects by binding to receptors on megakaryocyte progenitors and mature megakaryocytes, initiating signaling pathways that drive their proliferation and maturation. Nevertheless, reductions in platelet count are compensated by increased levels of the platelet adhesive protein von Willebrand factor, while decreases in procoagulant and antifibrinolytic proteins are offset by parallel declines in anticoagulant and profibrinolytic factors[ 18 ]. These findings emphasize the delicate equilibrium between platelet production and coagulation factors in preserving vascular integrity despite liver impairment.
INFLAMMATION, CRYOGLOBULINEMIA, AND ENDOTHELIAL DYSFUNCTION
The liver is an essential part of the immune system through surveillance and maintenance of homeostasis. It is responsible for metabolizing gut pathogen-derived molecules, including lipopolysaccharides, as noted in a cross-sectional study[ 23 ]. When the liver is not functioning properly due to chronic inflammation and fibrosis caused by chronic HCV infection, it fails to adequately clear lipopolysaccharides, allowing this pathogenic molecule to accumulate and stimulate the immune system to release interleukin-6 (IL-6) and other pro-inflammatory molecules. This persistent stimulation of the immune system will eventually result in immune senescence and T cell exhaustion. T cells will express inhibitory markers and T cell immunoglobulins, which represent T cell exhaustion, as well as CD-57 expression and killer cell lectin-like receptor subfamily G, which represent senescent T cells[ 24 ]. This exhaustion results from the extensive proliferation of the T cells, which is caused by the pro-inflammatory byproducts of impaired liver function and immune system dysfunction, as mentioned in a longitudinal study[ 24 ]. This chronic systemic inflammatory state will cause increased incidence of extrahepatic manifestations, including cardiovascular and cerebrovascular disease[ 25 ].
Furthermore, HCV is a lymphotropic virus that promotes B-cell proliferation. This can cause the development of lymphoproliferative disorders, such as cryoglobulinemic vasculitis, non-Hodgkin lymphoma, and monoclonal gammopathies (Waldenstrom’s macroglobulinemia, multiple myeloma, monoclonal gammopathy of undetermined significance)[ 25 , 26 ]. Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 °C and then redissolve at body temperature[ 26 ]. These immune complexes deposit within small and medium-sized vessels, leading to vascular injury, resulting in skin and organ involvement[ 26 ]. This phenomenon is known as cryoglobulinemic vasculitis, which presents with a wide array of presentations, including purpura, Raynaud’s phenomenon, skin ulceration, arthralgia, and many other systemic manifestations[ 26 ].
In the setting of HCV-induced cirrhosis and the development of lymphotropic disorders, there is an increased production of reactive oxygen species within diseased cells. In patients with HCV, elevated reactive oxygen species, antioxidants, and glutathione levels have been identified, especially within lymphocytes, which increases the correlation between HCV and oxidative stress. Additionally, patients with chronic hepatitis C have lower levels of antioxidant defense enzymes, including superoxide dismutase, glutathione reductase, and glutathione peroxidase. This oxidative stress perpetuates the cycle of worsening viral infection and thus viral-associated disorders, specifically through the upregulation of the genome translation of HCV, placing stress on other organelles (endoplasmic reticulum) that are normally protective against reactive oxygen species[ 27 ]. Elevated oxidative stress within the body from HCV promotes steatosis, fibrosis, and cirrhosis in the liver, leading to proinflammatory markers that favor insulin resistance and the accumulation of fatty acids, as noted in a prospective cohort study. These deposits within the walls of arteries increase the incidence of atherosclerosis. Endothelial dysfunction (in this case caused by atherosclerosis) causes systemic manifestations such as peripheral artery disease, coronary artery disease, stroke, etc .[ 28 ]. Endothelial activation upregulates vascular endothelial growth factor, an independent risk factor for stroke and coronary artery disease and a recognized extrahepatic manifestation of HCV infection[ 28 ]. During viremia, endothelial cells - which normally regulate coagulation - remain persistently activated, promoting a procoagulant state and correlating positively with thrombus formation[ 29 ]. Figure 1 illustrates these pathways, highlighting how chronic endothelial activation links HCV infection to increased vascular risk.
IMPACT OF DAA THERAPY
DAA therapy is essential for preventing further manifestations of chronic HCV. DAAs improve endothelial dysfunction and its sequelae (atherosclerosis and thrombogenesis)[ 28 ]. This improvement occurs through the reduction and reversal of systemic inflammation, which drives liver injury and lymphotropic disease. By decreasing this proinflammatory, hypercoagulable state, DAAs help reduce oxidative stress, endothelial activation, and thrombogenesis[ 28 ].
Sustained virological response (SVR) refers to the absence of detectable HCV RNA after completion of DAA treatment and correlates with treatment success. SVR is directly associated with decreased mortality, reduced liver damage, and less severe extrahepatic manifestations. DAAs decrease systemic inflammation and hypercoagulability, thereby lowering the risk of atherosclerosis and thrombosis[ 28 ]. According to an observational study, SVR is positively correlated with improved endothelial function, which can be demonstrated clinically by an elevated ankle-brachial index one year after DAA therapy[ 28 ]. The ankle-brachial index is a clinical test used to assess the severity of peripheral artery disease caused by atherosclerosis.
DAA therapy and prolonged SVR are strongly associated with reduced endothelial dysfunction, decreased vascular damage, and improved cardiovascular outcomes, including lower rates of thrombotic events such as stroke and coronary artery disease[ 28 ]. However, patients with extensive fibrosis remain at elevated risk for HCV sequelae despite virologic cure with DAAs[ 30 ]. This includes both hepatocellular carcinoma secondary to fibrosis and extrahepatic manifestations such as lymphotropic disorders, atherosclerosis, and thrombotic complications[ 30 ]. A large cohort study of HIV-infected veterans receiving highly active antiretroviral therapy showed that HCV seropositivity was independently associated with an increased risk of mortality. This demonstrates that although DAA therapy lowers cardiovascular disease incidence, the risk remains higher than in uninfected populations[ 31 ].
Furthermore, patients with advanced fibrosis despite viral clearance via DAAs continue to experience higher rates of cardiovascular events and thrombotic complications than those without fibrosis or the general population. HCV infection and interferon-based treatments cause continuous epigenetic alterations, including DNA methylation and histone modifications, in hepatocytes and vascular cells. These changes persist following viral clearance and are linked to impaired immune function and a continued risk of vascular and neoplastic complications[ 32 ]. Patients with advanced fibrosis may also experience persistent low-level inflammation, changes in cytokine levels, and immune system imbalances, which together promote a tendency for blood clot formation[ 33 ]. Additionally, chronic HCV infection causes endothelial dysfunction and vascular remodeling that may persist despite viral clearance, especially in patients with established fibrosis or cirrhosis[ 34 ]. Therefore, individuals with advanced liver fibrosis who achieve HCV eradication through DAAs remain at a persistent, though attenuated, risk of cardiovascular and prothrombotic complications. This risk is attributable to irreversible vascular injury, enduring epigenetic modifications, and sustained immune activation.
PATHOPHYSIOLOGICAL MECHANISMS: A MULTIFACTORIAL MODEL
Several studies disagree on whether there is a correlation between HCV viral load and liver disease severity. It has been speculated that higher HCV titers are observed in patients with active hepatitis infection, which is more strongly correlated with increased liver damage and inflammation[ 35 ]. Prolonged infection may further elevate viral load, as seen in chronic hepatitis[ 35 ]. However, other retrospective cohort studies suggest that liver disease severity is independent of viral load and that there are similar incidences of HCV-related liver disease in patients with both high and low viral load levels[ 36 ]. Elevated viral load does increase the severity of the infection itself, but does not result in progression of hepatic dysfunction[ 36 ]. This is important to delineate that the severity of liver injury associated with HCV is less likely to be caused directly by the HCV itself, but by the immune system-mediated damage that we have presented here. In these cases, liver injury is thought to result directly from systemic inflammation and the viral-induced cytopathic effects of an overactive immune response, particularly through HCV-specific T-cell activation ( Figure 2 )[ 36 , 37 ]. Additionally, other confounding risk factors may be more relevant to the increased risk of HCV-related chronic liver disease and the development of hepatocellular carcinoma, including age of HCV infection, gender, alcohol use, and coinfection with HBV and HIV[ 37 ].
UNRESOLVED QUESTIONS AND RESEARCH GAPS
Although several studies and meta-analyses have demonstrated a significant association between chronic HCV infection and thrombotic events[ 11 , 38 ], these associations have not been proven to be causal. Chronic HCV infection induces a prothrombotic state by promoting systemic inflammation, endothelial dysfunction, and alterations in coagulation pathways. Direct viral effects and immune-mediated injury led to increased expression of endothelial adhesion molecules, local vascular inflammation, and enhanced production of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), all of which contribute to endothelial activation and a procoagulant environment[ 39 ].
A multicenter retrospective cohort study demonstrated that individuals with chronic hepatitis C treated with DAAs experienced reduced rates of cardiovascular events compared to untreated patients, with the most notable reduction observed in VTE[ 40 ]. Similarly, Jeong et al [ 41 ] reported a reduced incidence of stroke following antiviral therapy. While such studies support a potential causal link between HCV eradication and reduced thrombotic risk, further research is needed to definitively establish causality, as confounding factors such as comorbid conditions may influence outcomes[ 38 ]. Prospective cohort studies and Mendelian randomization analyses are warranted to address this gap.
Currently, there are no established risk assessment scores specifically developed or validated for evaluating thrombotic risk in HCV infection. Existing tools, such as the CHA 2 DS 2 -VASc score, have limited applicability in this population, as mentioned in a comparative study[ 42 ]. Given the dynamic alterations in coagulation balance seen in cirrhosis, with simultaneous procoagulant and anticoagulant changes[ 43 ], there is a need for liver-specific thrombotic risk tools that integrate hepatic function ( e.g. , model for end-stage liver disease, Child-Pugh, platelet dynamics). Such tools could guide decisions regarding surveillance imaging and the use of prophylactic anticoagulation.
For hospitalized patients, the American Gastroenterological Association recommends general VTE risk assessment models, such as the Padua prediction score[ 44 , 45 ] and the International Medical Prevention Registry on Venous Thromboembolism VTE risk assessment model[ 46 ], to guide anticoagulation decisions[ 47 ]. However, no validated risk stratification tools currently exist for patients outside the hospital setting, underscoring the need for an HCV-specific risk assessment model.
Genetic predisposition and comorbidities also play significant roles in the development of thrombotic events in patients with HCV. Poujol-Robert et al [ 48 ] noted that genetic thrombophilias - such as protein C deficiency, elevated factor VIII, and hyperhomocysteinemia - are more frequently observed in HCV patients with advanced cirrhosis, and their coexistence markedly increases the risk of intrahepatic and systemic thrombotic events. A case-control study notes that prothrombotic genetic factors were also associated with extensive fibrosis and early cirrhosis, suggesting a synergistic effect between genetic predisposition and HCV-related hepatic injury in promoting thrombosis[ 48 ].
Comorbidities such as diabetes mellitus, chronic kidney disease, HIV, and cardiovascular disease are common in HCV-infected individuals and further amplify thrombotic risk. Diabetes mellitus is frequent in HCV and independently promotes vascular inflammation, endothelial activation, and atherosclerosis, thereby increasing thrombotic risk. HCV itself induces insulin resistance and metabolic disturbances, compounding this effect[ 49 ]. HIV infection has been associated with chronic immune activation, elevated levels of procoagulant markers ( e.g. , D-dimer, factor VIII), and reduced natural anticoagulants, which together create a hypercoagulable state[ 50 ]. As noted in a meta-analysis, patients with HCV/HIV co-infection have higher rates of thrombotic and cardiovascular events compared with either infection alone[ 50 , 51 ].
CONCLUSION
Chronic HCV infection is increasingly recognized as a prothrombotic condition. In clinical practice, thrombotic risk assessment in HCV largely relies on identifying conventional risk factors and applying clinical judgment, as no HCV-specific risk score exists. Epidemiological data indicate that older age and male sex, which are non-modifiable factors, significantly increase the risk of VTE in HCV-infected patients, suggesting these variables may be incorporated into future scoring tools[ 38 ]. Furthermore, HCV infection has been associated with elevated inflammatory markers such as C-reactive protein (CRP)[ 52 ], TNF-α, IL-6, and endothelial dysfunction markers[ 16 ], all of which are linked to cardiovascular disease and may have predictive value in risk modeling. IL-6 is a proinflammatory cytokine that facilitates lymphocyte activation and proliferation, as well as the induction of hepatic synthesis of acute-phase reactants. TNF-α is another proinflammatory cytokine that promotes hepatic synthesis of acute-phase proteins, which in turn leads to activation of lymphocytes and endothelial cells. TNF-mediated signaling pathways are upregulated and activated in chronic hepatitis C, with TNF-α mRNA being widely expressed at elevated levels in hepatocytes, Kupffer cells, and infiltrating mononuclear cells of HCV patients. CRP is an acute-phase protein primarily synthesized by hepatocytes, with its production regulated mainly by both IL-6 and TNF-α. Elevated CRP levels are linked to underlying atherosclerosis and thus are an established marker for assessing cardiovascular disease risk in the general population. It also correlates with survival and mortality in both non-hepatitis C and cirrhotic hepatitis C patients. However, CRP levels are frequently lower than expected in chronic HCV infections, despite elevated IL-6 concentrations. This paradox is likely attributable to HCV-induced inhibition of hepatic CRP synthesis. Multiple studies have demonstrated that individuals with HCV exhibit reduced CRP levels compared to uninfected controls, even in the context of increased IL-6 and advanced liver fibrosis[ 53 , 54 ].
Currently, risk assessment in HCV-positive patients is performed using general VTE and cardiovascular risk models, as no HCV-specific tools exist. Standard VTE risk assessment in hospitalized patients relies on validated models such as the Padua prediction score[ 45 ], which incorporates age, comorbidities, and immobility but does not include HCV status as an independent variable. For cardiovascular risk, traditional calculators are used, though these may underestimate risk in HCV populations due to the additional inflammatory and metabolic burden of infection. Future directions include developing risk tools that integrate HCV-specific factors and biomarkers of inflammation and endothelial dysfunction[ 16 ]. Such models could be incorporated into clinical guidelines to inform decisions on anticoagulation initiation and duration.
Historically, cirrhosis was considered a “naturally anticoagulated” state due to thrombocytopenia and reduced hepatic synthesis of clotting factors. This paradigm has shifted with recognition of a rebalanced but fragile hemostatic system, where declines in anticoagulant proteins ( e.g. , antithrombin III, protein C, protein S) and increases in procoagulant drivers ( e.g. , factor VIII, Willebrand factor) create vulnerability to both thrombosis and bleeding[ 18 ].
Modern guidelines recommend weighing thrombotic risk ( e.g. , atrial fibrillation, VTE, PVT) against bleeding risk, which is elevated in cirrhosis due to coagulopathy and thrombocytopenia[ 47 ]. A systematic review and meta-analysis found that PVT recanalization rates were significantly higher in anticoagulated patients compared with untreated patients (71% vs 42%, P < 0.0001), with no increase in overall bleeding risk and a reduced risk of variceal hemorrhage ( P = 0.04; Figure 3 ).
The severity of liver disease (Child-Turcotte-Pugh class), presence of clinically significant coagulopathy or thrombocytopenia, and indication for anticoagulation ( e.g. , CHAD 2 S 2 -VASc score in atrial fibrillation) should all be considered. In compensated cirrhosis (Child-Pugh A or B) with a clear indication, anticoagulation is generally favored, while in advanced cirrhosis (Child-Pugh C), bleeding risk may outweigh benefits, requiring individualized decision-making[ 47 ].
Despite reduced antithrombin III levels in cirrhosis, low-molecular-weight heparin (LMWH) remains the preferred agent[ 55 ]. Direct oral anticoagulants (DOACs) are effective and may be superior to warfarin for treating PVT in compensated cirrhosis[ 56 ]. The choice of anticoagulant is influenced by hepatic metabolism and the degree of liver dysfunction. DOACs are generally safe in Child-Pugh A and select Child-Pugh B cirrhosis but are contraindicated in Child-Pugh C due to impaired hepatic clearance and increased drug exposure[ 57 ]. Thus, anticoagulant choice (DOAC, LMWH, or vitamin K antagonist) should be individualized based on liver function, renal function, and patient preference[ 58 ].
Patients with cirrhosis are at elevated risk for VTE, with PVT occurring in approximately 8% annually among those on the liver transplant waitlist[ 59 ]. Anticoagulation, particularly in patients with more extensive mesenteric thrombosis, is associated with improved one-year outcomes[ 60 ]. Despite this, thromboprophylaxis - pharmacologic or mechanical - is often underutilized[ 61 ]. In a single-center, non-blinded randomized controlled trial, prophylactic LMWH reduced the risk of PVT (relative risk 0.05; P = 0.048) without increasing bleeding or mortality[ 60 ]. While bleeding concerns are prominent in advanced cirrhosis, studies suggest that upper gastrointestinal bleeding outcomes are more closely tied to the severity of organ failure and comorbidities than to anticoagulation itself[ 62 ].
Development of risk stratification tools would better equip clinicians to safely offer anticoagulation and thromboprophylaxis to select patients, even in advanced cirrhosis. A risk stratification tool for patients with HCV infection should integrate clinical, hemostatic, and inflammatory biomarkers to assess the ongoing risk of thrombogenesis. Perhaps interventional trials centered around anticoagulation in DAA-treated patients and untreated patients could shed light on this matter. The primary objectives of these trials would involve systematic monitoring of major bleeding episodes and thromboembolic events at 12-month intervals. Additionally, the studies would evaluate longitudinal changes in key coagulation biomarkers, including factor VIII, protein C, von Willebrand factor, and D-dimer levels. Endothelial function would be assessed through flow-mediated dilation measurements, and the incidence of PVT would be carefully documented to elucidate the vascular complications associated with the patient population under investigation. The potential mechanisms and clinical benefits of anticoagulation in HCV cirrhosis are summarized in Figure 3 .
Future studies are needed to clarify the mechanistic and clinical links between HCV and thrombogenesis, with particular focus on the role of biomarkers and prospective clinical trials. Key priorities include large, prospective cohort studies that longitudinally measure inflammatory, endothelial, and coagulation biomarkers ( e.g. , CRP, IL-6, D-dimer, thrombin generation markers, and markers of endothelial dysfunction) in HCV populations, to assess their predictive value for venous and arterial thrombotic events, and their changes with antiviral therapy and HCV clearance[ 16 , 63 ].
There is also a need for prospective trials evaluating whether biomarker-guided risk stratification can improve outcomes by identifying high-risk HCV patients for targeted preventive interventions[ 16 , 63 ]. Mechanistic studies are warranted to dissect the pathways by which HCV-induced inflammation, immune activation, and endothelial injury drive hypercoagulability, and to determine whether distinct biomarker profiles are associated with specific thrombotic phenotypes[ 46 ]. Finally, randomized controlled trials are required to test whether interventions such as DAA therapy or anticoagulation reduce thrombotic risk in biomarker-defined high-risk populations[ 63 ]. Current evidence highlights the importance of integrating biomarker research with prospective clinical trials to advance risk prediction and management of thrombosis in HCV infection[ 16 , 63 ].
All in all, these novel scientific findings necessitate the translation of evidence into clinical practice, outlining specific responsibilities for physicians. Key clinical recommendations for hepatologists, cardiologists, and primary care providers include: Implementing universal HCV screening for all adults and high-risk populations, initiating DAA therapy promptly in all patients with confirmed chronic HCV infection, especially those with coexisting cardiovascular disease, evaluating and managing conventional cardiovascular risk factors in individuals with HCV, and fostering multidisciplinary collaboration to identify extrahepatic manifestations and enhance cardiovascular risk mitigation strategies[ 64 ]. With the increasing ability of primary care providers to manage HCV treatment, access to care has expanded, enabling earlier intervention - an essential step in reducing both hepatic and thrombotic complications[ 65 ].
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding Author's Membership in Professional Societies: American Society for Gastrointestinal Endoscopy.
Specialty type: Virology
Country of origin: United States
Peer-review report’s classification
Scientific Quality: Grade B, Grade B
Novelty: Grade B, Grade C
Creativity or Innovation: Grade B, Grade C
Scientific Significance: Grade B, Grade B
P-Reviewer: Baltacı S, MD, Türkiye; Zhang JL, MD, PhD, Academic Fellow, FASCRS, China S-Editor: Hu XY L-Editor: A P-Editor: Xu ZH
1 Martinello M Solomon SS Terrault NA Dore GJ Hepatitis C Lancet 2023 402 1085 1096 37741678 10.1016/S0140-6736(23)01320-X
2 Pothineni NV Delongchamp R Vallurupalli S Ding Z Dai Y Hagedorn CH Mehta JL Impact of hepatitis C seropositivity on the risk of coronary heart disease events Am J Cardiol 2014 114 1841 1845 25438910 10.1016/j.amjcard.2014.09.020 PMC4372470
3 Wang W Chen C Re VL 3rd Chang SH Wilson DL Park H Association between treatment of hepatitis C virus and risk of cardiovascular disease among insured patients with the virus in the United States Pharmacoepidemiol Drug Saf 2023 32 1142 1151 37278688 10.1002/pds.5651 PMC10655016
4 Westerhoff M Ahn J Chronic Hepatitis C and Direct Acting Antivirals Surg Pathol Clin 2018 11 287 296 29751875 10.1016/j.path.2018.02.002
5 Maness DL Riley E Studebaker G Hepatitis C: Diagnosis and Management Am Fam Physician 2021 104 626 635 34913652
6 Zeisel MB Felmlee DJ Baumert TF Hepatitis C virus entry Curr Top Microbiol Immunol 2013 369 87 112 23463198 10.1007/978-3-642-27340-7_4
7 Dubuisson J Cosset FL Virology and cell biology of the hepatitis C virus life cycle: an update J Hepatol 2014 61 S3 S13 25443344 10.1016/j.jhep.2014.06.031
8 Malnick S Maor Y Melzer E Tal S Chronic hepatitis C in the aged: much ado about nothing or nothing to do? Drugs Aging 2014 31 339 347 24664397 10.1007/s40266-014-0170-8
9 Zanetto A Northup P Roberts L Senzolo M Haemostasis in cirrhosis: Understanding destabilising factors during acute decompensation J Hepatol 2023 78 1037 1047 36708812 10.1016/j.jhep.2023.01.010
10 González-Reimers E Quintero-Platt G Martín-González C Pérez-Hernández O Romero-Acevedo L Santolaria-Fernández F Thrombin activation and liver inflammation in advanced hepatitis C virus infection World J Gastroenterol 2016 22 4427 4437 27182154 10.3748/wjg.v22.i18.4427 PMC4858626
11 Wijarnpreecha K Thongprayoon C Panjawatanan P Ungprasert P Hepatitis C Virus Infection and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis Ann Hepatol 2017 16 514 520 28611268 10.5604/01.3001.0010.0279
12 Wang CC Chang CT Lin CL Lin IC Kao CH Hepatitis C Virus Infection Associated With an Increased Risk of Deep Vein Thrombosis: A Population-Based Cohort Study Medicine (Baltimore) 2015 94 e1585 26402820 10.1097/MD.0000000000001585 PMC4635760
13 Galli L Gerdes VE Guasti L Squizzato A Thrombosis Associated with Viral Hepatitis J Clin Transl Hepatol 2014 2 234 239 26357629 10.14218/JCTH.2014.00031 PMC4521234
14 Iorga RA Bacalbasa N Bratu OG Ionita Radu F Diaconu CC The impact of infection with hepatitis C virus on cardiovascular risk Am J Cardiovasc Dis 2020 10 201 206 32923102 PMC7486524
15 Goossens N Negro F Cardiovascular Manifestations of Hepatitis C Virus Clin Liver Dis 2017 21 465 473 28689586 10.1016/j.cld.2017.03.003
16 Babiker A Hassan M Muhammed S Taylor G Poonia B Shah A Bagchi S Inflammatory and cardiovascular diseases biomarkers in chronic hepatitis C virus infection: A review Clin Cardiol 2020 43 222 234 31785111 10.1002/clc.23299 PMC7068107
17 Ampuero J Romero-Gómez M Assessing cardiovascular risk in hepatitis C: An unmet need World J Hepatol 2015 7 2214 2219 26380047 10.4254/wjh.v7.i19.2214 PMC4561776
18 Under the auspices of the Italian Association for the Study of Liver Diseases (AISF) and the Italian Society of Internal Medicine (SIMI) Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference Dig Liver Dis 2016 48 455 467 27012444 10.1016/j.dld.2016.02.008
19 Ginès P Krag A Abraldes JG Solà E Fabrellas N Kamath PS Liver cirrhosis Lancet 2021 398 1359 1376 34543610 10.1016/S0140-6736(21)01374-X
20 Liu YB Chen MK Epidemiology of liver cirrhosis and associated complications: Current knowledge and future directions World J Gastroenterol 2022 28 5910 5930 36405106 10.3748/wjg.v28.i41.5910 PMC9669831
21 Lisman T Caldwell SH Intagliata NM Haemostatic alterations and management of haemostasis in patients with cirrhosis J Hepatol 2022 76 1291 1305 35589251 10.1016/j.jhep.2021.11.004
22 Dahal S Upadhyay S Banjade R Dhakal P Khanal N Bhatt VR Thrombocytopenia in Patients with Chronic Hepatitis C Virus Infection Mediterr J Hematol Infect Dis 2017 9 e2017019 28293407 10.4084/MJHID.2017.019 PMC5333732
23 Shmagel KV Saidakova EV Shmagel NG Korolevskaya LB Chereshnev VA Robinson J Grivel JC Douek DC Margolis L Anthony DD Lederman MM Systemic inflammation and liver damage in HIV/hepatitis C virus coinfection HIV Med 2016 17 581 589 27187749 10.1111/hiv.12357 PMC4987156
24 Shive CL Kowal CM Desotelle AF Nguyen Y Carbone S Kostadinova L Davitkov P O'Mara M Reihs A Siddiqui H Wilson BM Anthony DD Endotoxemia Associated with Liver Disease Correlates with Systemic Inflammation and T Cell Exhaustion in Hepatitis C Virus Infection Cells 2023 12 2034 37626844 10.3390/cells12162034 PMC10453378
25 Rosenthal E Cacoub P Extrahepatic manifestations in chronic hepatitis C virus carriers Lupus 2015 24 469 482 25801890 10.1177/0961203314556140
26 Dammacco F Lauletta G Vacca A The wide spectrum of cryoglobulinemic vasculitis and an overview of therapeutic advancements Clin Exp Med 2023 23 255 272 35348938 10.1007/s10238-022-00808-1 PMC8960698
27 Ivanov AV Bartosch B Smirnova OA Isaguliants MG Kochetkov SN HCV and oxidative stress in the liver Viruses 2013 5 439 469 23358390 10.3390/v5020439 PMC3640510
28 Muñoz-Hernández R Ampuero J Millán R Gil-Gómez A Rojas Á Macher HC Gallego-Durán R Gato S Montero-Vallejo R Rico MC Maya-Miles D Sánchez-Torrijos Y Soria IC Stiefel P Romero-Gómez M Hepatitis C Virus Clearance by Direct-Acting Antivirals Agents Improves Endothelial Dysfunction and Subclinical Atherosclerosis: HEPCAR Study Clin Transl Gastroenterol 2020 11 e00203 32955194 10.14309/ctg.0000000000000203 PMC7431267
29 Blüm P Pircher J Merkle M Czermak T Ribeiro A Mannell H Krötz F Hennrich A Spannagl M Köppel S Gaitzsch E Wörnle M Arterial thrombosis in the context of HCV-associated vascular disease can be prevented by protein C Cell Mol Immunol 2017 14 986 996 27086952 10.1038/cmi.2016.10 PMC5719134
30 Lee YA Friedman SL Reversal, maintenance or progression: what happens to the liver after a virologic cure of hepatitis C? Antiviral Res 2014 107 23 30 24726738 10.1016/j.antiviral.2014.03.012 PMC4050744
31 Backus LI Phillips BR Boothroyd DB Mole LA Burgess J Rigsby MO Chang SW Effects of hepatitis C virus coinfection on survival in veterans with HIV treated with highly active antiretroviral therapy J Acquir Immune Defic Syndr 2005 39 613 619 16044016
32 Hlady RA Zhao X El Khoury LY Luna A Pham K Wu Q Lee JH Pyrsopoulos NT Liu C Robertson KD Interferon drives HCV scarring of the epigenome and creates targetable vulnerabilities following viral clearance Hepatology 2022 75 983 996 34387871 10.1002/hep.32111 PMC9416882
33 Sigon G D'Ambrosio R Clerici M Pisano G Chantarangkul V Sollazzi R Lombardi R Peyvandi F Lampertico P Fargion S Tripodi A Fracanzani AL Procoagulant imbalance influences cardiovascular and liver damage in chronic hepatitis C independently of steatosis Liver Int 2019 39 2309 2316 31419372 10.1111/liv.14213
34 Elkhattib I Raafat KW Elsayed B Elnaggar M Chronic hepatitis C and the risk for atherosclerotic and cardiomyopathic heart disease World J Hepatol 2025 17 108678 40901587 10.4254/wjh.v17.i8.108678 PMC12400435
35 Kato N Yokosuka O Hosoda K Ito Y Ohto M Omata M Quantification of hepatitis C virus by competitive reverse transcription-polymerase chain reaction: increase of the virus in advanced liver disease Hepatology 1993 18 16 20 8392026
36 Noh R Lee DH Kwon BW Kim YH Kim SB Song IH Clinical Impact of Viral Load on the Development of Hepatocellular Carcinoma and Liver-Related Mortality in Patients with Hepatitis C Virus Infection Gastroenterol Res Pract 2016 2016 7476231 27656205 10.1155/2016/7476231 PMC5021494
37 Anand BS Velez M Assessment of correlation between serum titers of hepatitis C virus and severity of liver disease World J Gastroenterol 2004 10 2409 2411 15285030 10.3748/wjg.v10.i16.2409 PMC4576299
38 Ambrosino P Tarantino L Criscuolo L Nasto A Celentano A Di Minno MN The risk of venous thromboembolism in patients with hepatitis C. A systematic review and meta-analysis Thromb Haemost 2016 116 958 966 27411407 10.1160/TH16-03-0185
39 Pircher J Czermak T Merkle M Mannell H Krötz F Ribeiro A Vielhauer V Nadjiri J Gaitzsch E Niemeyer M Porubsky S Gröne HJ Wörnle M Hepatitis C virus induced endothelial inflammatory response depends on the functional expression of TNFα receptor subtype 2 PLoS One 2014 9 e113351 25419735 10.1371/journal.pone.0113351 PMC4242623
40 Wu VC Huang CH Wang CL Lin MH Kuo TY Chang CH Wu M Chen SW Chang SH Chu PH Wu CS Lin YS Cardiovascular outcomes in hepatitis C virus infected patients treated with direct acting antiviral therapy: a retrospective multi-institutional study Eur Heart J Cardiovasc Pharmacother 2023 9 507 514 37170917 10.1093/ehjcvp/pvad030
41 Jeong D Wong S Karim ME Manges AR Makuza JD Velásquez García HA Adu PA Binka M Yu A Bartlett SR Krajden M Janjua NZ Direct-Acting Antivirals and Risk of Hepatitis C Extrahepatic Manifestations JAMA Netw Open 2025 8 e2514631 40498486 10.1001/jamanetworkopen.2025.14631 PMC12159775
42 Lip GY Nieuwlaat R Pisters R Lane DA Crijns HJ Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation Chest 2010 137 263 272 19762550 10.1378/chest.09-1584
43 Intagliata NM Davitkov P Allen AM Falck-Ytter YT Stine JG AGA Technical Review on Coagulation in Cirrhosis Gastroenterology 2021 161 1630 1656 34579937 10.1053/j.gastro.2021.09.004
44 Barbar S Noventa F Rossetto V Ferrari A Brandolin B Perlati M De Bon E Tormene D Pagnan A Prandoni P A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score J Thromb Haemost 2010 8 2450 2457 20738765 10.1111/j.1538-7836.2010.04044.x
45 Bogari H Patanwala AE Cosgrove R Katz M Risk-assessment and pharmacological prophylaxis of venous thromboembolism in hospitalized patients with chronic liver disease Thromb Res 2014 134 1220 1223 25294587 10.1016/j.thromres.2014.09.031
46 Rosenberg D Eichorn A Alarcon M McCullagh L McGinn T Spyropoulos AC External validation of the risk assessment model of the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) for medical patients in a tertiary health system J Am Heart Assoc 2014 3 e001152 25404191 10.1161/JAHA.114.001152 PMC4338701
47 O'Shea RS Davitkov P Ko CW Rajasekhar A Su GL Sultan S Allen AM Falck-Ytter Y AGA Clinical Practice Guideline on the Management of Coagulation Disorders in Patients With Cirrhosis Gastroenterology 2021 161 1615 1627.e1 34579936 10.1053/j.gastro.2021.08.015
48 Poujol-Robert A Rosmorduc O Serfaty L Coulet F Poupon R Robert A Genetic and acquired thrombotic factors in chronic hepatitis C Am J Gastroenterol 2004 99 527 531 15056097 10.1111/j.1572-0241.2004.04092.x
49 Negro F Facts and fictions of HCV and comorbidities: steatosis, diabetes mellitus, and cardiovascular diseases J Hepatol 2014 61 S69 S78 25443347 10.1016/j.jhep.2014.08.003
50 Perkins MV Joseph SB Dittmer DP Mackman N Cardiovascular Disease and Thrombosis in HIV Infection Arterioscler Thromb Vasc Biol 2023 43 175 191 36453273 10.1161/ATVBAHA.122.318232 PMC10165851
51 Fernández-Montero JV Barreiro P de Mendoza C Labarga P Soriano V Hepatitis C virus coinfection independently increases the risk of cardiovascular disease in HIV-positive patients J Viral Hepat 2016 23 47 52 26390144 10.1111/jvh.12447
52 Roed T Kristoffersen US Knudsen A Wiinberg N Lebech AM Almdal T Thomsen RW Kjær A Weis N Increased prevalence of coronary artery disease risk markers in patients with chronic hepatitis C--a cross-sectional study Vasc Health Risk Manag 2014 10 55 62 24482574 10.2147/VHRM.S53557 PMC3905100
53 Shah S Ma Y Scherzer R Huhn G French AL Plankey M Peters MG Grunfeld C Tien PC Association of HIV, hepatitis C virus and liver fibrosis severity with interleukin-6 and C-reactive protein levels AIDS 2015 29 1325 1333 25870985 10.1097/QAD.0000000000000654 PMC4478137
54 Salter ML Lau B Mehta SH Go VF Leng S Kirk GD Correlates of elevated interleukin-6 and C-reactive protein in persons with or at high risk for HCV and HIV infections J Acquir Immune Defic Syndr 2013 64 488 495 23978997 10.1097/QAI.0b013e3182a7ee2e PMC3848037
55 Senzolo M Rodriguez-Castro KI Rossetto V Radu C Gavasso S Carraro P Zerbinati P Sartori MT Simioni P Increased anticoagulant response to low-molecular-weight heparin in plasma from patients with advanced cirrhosis J Thromb Haemost 2012 10 1823 1829 22712870 10.1111/j.1538-7836.2012.04824.x
56 Nagaoki Y Aikata H Daijyo K Teraoka Y Shinohara F Nakamura Y Hatooka M Morio K Nakahara T Kawaoka T Tsuge M Hiramatsu A Imamura M Kawakami Y Ochi H Chayama K Efficacy and safety of edoxaban for treatment of portal vein thrombosis following danaparoid sodium in patients with liver cirrhosis Hepatol Res 2018 48 51 58 28342265 10.1111/hepr.12895
57 Joglar JA Chung MK Armbruster AL Benjamin EJ Chyou JY Cronin EM Deswal A Eckhardt LL Goldberger ZD Gopinathannair R Gorenek B Hess PL Hlatky M Hogan G Ibeh C Indik JH Kido K Kusumoto F Link MS Linta KT Marcus GM McCarthy PM Patel N Patton KK Perez MV Piccini JP Russo AM Sanders P Streur MM Thomas KL Times S Tisdale JE Valente AM Van Wagoner DR Peer Review Committee Members 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines Circulation 2024 149 e1 e156 38033089 10.1161/CIR.0000000000001193 PMC11095842
58 Davis JPE Lim JK Francis FF Ahn J AGA Clinical Practice Update on Management of Portal Vein Thrombosis in Patients With Cirrhosis: Expert Review Gastroenterology 2025 168 396 404.e1 39708000 10.1053/j.gastro.2024.10.038
59 Francoz C Belghiti J Vilgrain V Sommacale D Paradis V Condat B Denninger MH Sauvanet A Valla D Durand F Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation Gut 2005 54 691 697 15831918 10.1136/gut.2004.042796 PMC1774501
60 Villa E Cammà C Marietta M Luongo M Critelli R Colopi S Tata C Zecchini R Gitto S Petta S Lei B Bernabucci V Vukotic R De Maria N Schepis F Karampatou A Caporali C Simoni L Del Buono M Zambotto B Turola E Fornaciari G Schianchi S Ferrari A Valla D Enoxaparin prevents portal vein thrombosis and liver decompensation in patients with advanced cirrhosis Gastroenterology 2012 143 1253 1260.e4 22819864 10.1053/j.gastro.2012.07.018
61 Smith CB Hurdle AC Kemp LO Sands C Twilla JD Evaluation of venous thromboembolism prophylaxis in patients with chronic liver disease J Hosp Med 2013 8 569 573 24101541 10.1002/jhm.2086
62 Cerini F Gonzalez JM Torres F Puente Á Casas M Vinaixa C Berenguer M Ardevol A Augustin S Llop E Senosiaín M Villanueva C de la Peña J Bañares R Genescá J Sopeña J Albillos A Bosch J Hernández-Gea V Garcia-Pagán JC Impact of anticoagulation on upper-gastrointestinal bleeding in cirrhosis. A retrospective multicenter study Hepatology 2015 62 575 583 25773591 10.1002/hep.27783
63 Nielsen NS Jespersen S Gaardbo JC Arnbjerg CJ Clausen MR Kjær M Gerstoft J Ballegaard V Ostrowski SR Nielsen SD Impaired Platelet Aggregation and Rebalanced Hemostasis in Patients with Chronic Hepatitis C Virus Infection Int J Mol Sci 2017 18 1016 28481325 10.3390/ijms18051016 PMC5454929
64 Vassalle C Petta S Pepe A Craxi A Bondin M Cacoub P Expert opinion on managing chronic HCV in patients with cardiovascular disease Antivir Ther 2018 23 35 46 30451152 10.3851/IMP3248
65 Benjaram S Kapur S McKay A Almujarkesh MK Carter KS Picardal A Levine D Lohia P Hepatitis C-Everything a Primary Care Physician Needs to Know About Diagnosis, Management, and Follow-Up J Clin Med 2025 14 4801 40649175 10.3390/jcm14134801 PMC12251219