Individuals with cirrhosis maintain a delicate balance between pro- and anticoagulation, which can lead to a state of hypercoagulability. This hypercoagulable condition not only exacerbates liver fibrosis but also increases the risk of venous thrombosis, particularly portal vein thrombosis (PVT). PVT has detrimental effects on liver function, complicates the success of liver transplantation, and negatively impacts the survival rate of patients with cirrhosis. Currently, multiple studies have confirmed that individuals with cirrhosis responded well to treatment with novel direct oral anticoagulants (DOACs), showing both safety and efficacy. Furthermore, the use of DOACs as a preventive measure in patients with cirrhosis following surgery has been shown to lower the occurrence of portal vein thrombosis and postpone the progression of liver fibrosis.

Acute portal vein thrombosis is characterized by nonspecific abdominal pain, causing severe morbidity and mortality. Prompt diagnosis is crucial to avoid short-term complications such as intestinal infarction, sepsis, and death. The therapeutic goal is to prevent thrombus extension into the mesenteric veins and intestinal ischemia complications. Systemic anticoagulation is the standard treatment. However, endovascular treatments such as thrombolysis, thrombectomy, balloon angioplasty, stent placement, and transjugular intrahepatic portosystemic shunt placement have been performed in patients who are refractory to anticoagulation therapy or at a high risk of intestinal ischemia. This review discusses the clinical and diagnostic considerations in acute portal vein thrombosis, focusing on current endovascular treatments that are effective and safe. However, prospective data are required to compare endovascular treatment techniques and assess their outcomes.

Background: Portal hypertension is a major complication of chronic liver diseases, leading to serious issues such as esophageal variceal bleeding. The increase in portal vein pressure is driven by both an organic component and a functional component, including tonic contraction of hepatic stellate cells. These processes result in a pathological rise in intrahepatic vascular resistance, stemming from partial impairment of hepatic microcirculation, which is further exacerbated by abnormalities in extrahepatic vessels, including increased portal blood flow. Objectives: This review aims to provide a comprehensive overview of the evolving pharmacological therapies for portal hypertension, with consideration and discussion of pathophysiological mechanisms, clinical complications, and pharmacogenetic considerations, highlighting potential directions for future research. Methods: A review of recent literature was performed to evaluate current knowledge and potential therapeutic strategies in portal hypertension. Results: For over 35 years, non-selective beta-blockers have been the cornerstone therapy for portal hypertension by reducing portal vein inflow as an extrahepatic target, effectively preventing decompensation and variceal hemorrhages. However, since not all patients exhibit an adequate response to non-selective beta-blockers (NSBBs), and some may not tolerate NSBBs, alternative or adjunctive therapies that enhance the effects of NSBBs on portal pressure are being investigated in preclinical and early clinical studies. Conclusions: A better understanding of pharmacogenetic factors and pathophysiological mechanisms could lead to more individualized and effective treatments for portal hypertension. These insights highlight potential directions for future research.

Portal vein thrombosis (PVT) is one of the common complications of cirrhosis. The incidence of PVT correlates with liver disease severity-higher incidence in patients with Child-Turcotte-Pugh (CTP) C, large spontaneous portosystemic shunts, hepatofugal portal flow, and in the presence of hepatocellular carcinoma. PVT may worsen ascites, increase the risk and poor control of variceal bleeding. The occurrence of PVT may increase morbidity and lower survival after a liver transplant. Using statins prevents the occurrence of PVT, whereas beta-blockers may aggravate its occurrence. Cross-sectional imaging is mandatory for the precise diagnosis and classification of PVT. Symptomatic, occlusive PVT and candidacy for liver transplantation are the main indications for anticoagulation. Vitamin K antagonists, low-molecular-weight heparin, and newer anticoagulants are effective and safe in cirrhosis. Direct-acting oral anticoagulants are agents of choice in early cirrhosis (CTP A, B). The duration of anticoagulant therapy, predictors of response, and management of complications of cirrhosis while on therapy require in-depth knowledge and individualized treatment. Transjugular intrahepatic porto-systemic shunt can be considered in nonresponsive cases or when anticoagulants are contraindicated. This manuscript reviews the latest updated knowledge about managing PVT in cirrhosis.

With the growth of the older adult population, the number of older adults waitlisted for and undergoing kidney and liver transplantation has increased. Transplantation is an important and definitive treatment for this population. We present a contemporary review of the unique preoperative, intraoperative, and postoperative issues that patients older than 65 y face when they undergo kidney or liver transplantation. We focus on geriatric syndromes that are common in older patients listed for kidney or liver transplantation including frailty, sarcopenia, and cognitive dysfunction; discuss important considerations for older transplant recipients, which may impact preoperative risk stratification; and describe unique challenges in intraoperative and postoperative management for older patients. Intraoperative challenges in the older adult include using evidence-based best anesthetic practices, maintaining adequate perfusion pressure, and using minimally invasive surgical techniques. Postoperative concerns include controlling acute postoperative pain; preventing cardiovascular complications and delirium; optimizing immunosuppression; preventing perioperative kidney injury; and avoiding nephrotoxicity and rehabilitation. Future studies are needed throughout the perioperative period to identify interventions that will improve patients' preoperative physiologic status, prevent postoperative medical complications, and improve medical and patient-centered outcomes in this vulnerable patient population.

The incidence of splanchnic vein thrombosis (SVT) is reported to be <25 times lower than that of deep vein thrombosis and pulmonary emboli, which occur in 70 to 270/100,000 cases in the general population. Current guidelines recommend initial treatment with therapeutic low-molecular-weight heparin followed by a transition to a vitamin K antagonist (VKA) or a direct oral anticoagulant (DOAC) in patients with cirrhosis who develop SVT without severe liver dysfunction. This, however, is based on observational data. This study aimed to evaluate the efficacy and safety of anticoagulant therapy in patients with cirrhosis who present with SVT and receive either a DOAC or a VKA.

This multicenter retrospective cohort study was conducted from December 2021 to November 2022. Patients between the ages of 18 and 75 years with cirrhosis and acute SVT who received either a VKA or a DOAC between July 2019 and July 2021 were eligible for inclusion. The primary outcome was the efficacy of treatment, defined as a new thrombotic event. The secondary outcome was the safety of treatment, defined as the development of major bleeding. Readmission data were followed up at 6 and 10 months. Bivariate analysis was conducted to assess the relationship between the medication groups and each outcome and summarized as odds ratios (ORs) with 95% confidence intervals (CIs). Statistical significance was set at 5% for all of the comparisons.

A total of 80 patients from 50 hospitals were included in this study. Sixty-one patients (59.02% male) received DOACs and 19 (57.89% male) received a VKA. Of the patients who received DOACs, 41 (67.21%) received apixaban, one (1.64%) received dabigatran, and 19 (31.15%) received rivaroxaban. The results from the bivariate analysis revealed no significant differences between DOACs and warfarin for both the efficacy (OR 1.46, 95% CI 0.44-4.84, P = 0.53) and safety outcomes (OR 1.03, 95% CI 0.04-26.43, P = 1) at 10 months.

The use of DOACs in patients with cirrhosis who present with SVT may be efficacious and safe compared with warfarin. The findings from our study may inform power analyses for well-conducted randomized trials to confirm these findings.

Comparing direct oral anticoagulants (DOACs) and warfarin's efficacy and safety in patients with nonvalvular atrial fibrillation (AF) and liver cirrhosis (LC).

Evidence of the pharmacodynamics of DOACs is limited in patients with AF and LC.

A retrospective cohort study was conducted in the largest hospital system in Taiwan, involving patients with AF and LC for the years 2012 to 2021. Hazards of thromboembolic events (ischemic stroke, transient ischemic attack, and systemic embolism), intracranial hemorrhage, gastrointestinal, major bleeding, and all-cause mortality were investigated with a new-user, active comparator design. Inverse probability of treatment weighting was applied to balance potential confounders between treatment groups.

In total, 478 DOAC users and 247 warfarin users were included. DOACs and warfarin demonstrated similar trends in preventing thromboembolic events, namely ischemic stroke [adjusted hazard ratio (aHR), 1.05 (95% CI: 0.42-2.61)], transient ischemic attack [aHR, 1.36 (95% CI: 0.18-10.31)], and systemic embolism [aHR, 0.49 (95% CI: 0.14-1.70)]. DOAC use was associated with a similar risk of intracranial hemorrhage [aHR, 0.65 (95% CI: 0.26-1.59)] and gastrointestinal bleeding [aHR, 0.64 (95% CI: 0.39-1.03)], a decreased risk of major bleeding [aHR, 0.64 (95% CI: 0.42-0.99)], and a reduction in mortality [aHR, 0.73 (95% CI: 0.54-0.99)]. DOAC users exhibited a significant reduction in major bleeding risk in patients with Child-Pugh class A (aHR, 0.48; 95% CI: 0.33-0.70).

DOACs showed potential safety advantages over warfarin for patients with nonvalvular AF and LC, particularly in reducing major bleeding risk in those with Child-Pugh class A.

Non-vitamin K antagonist oral anticoagulants have shown similar efficacy and lower bleeding rates than vitamin K antagonists for venous thromboembolism. However, this has not been proven in mesenteric vein thrombosis. This study aimed to compare the clinical outcomes of vitamin K antagonists and non-vitamin K antagonist oral anticoagulants.

Between January 2014 and July 2022, mesenteric vein thrombosis was diagnosed on computed tomography in 225 patients in a tertiary hospital. Among them, a total of 44 patients who underwent long-term anticoagulation therapy over 3 months were enrolled in this study. Patients were divided into two groups based on the anticoagulant used: vitamin K antagonists (Group 1, n = 21) and non-vitamin K antagonist oral anticoagulants (Group 2, n = 23). The efficacy outcomes were symptom recurrence and thrombus resolution on follow-up computed tomography, and the safety outcome was bleeding complications.

The median age of the patients was 56 years (range, 46-68 years), and 52% were men. The most common risk factors were unprovoked intra-abdominal infections (30%). The median duration of anticoagulation therapy was 13 months (20 months in Group 1 vs 6 months in Group 2; P = .076). Of the 44 patients, 17 (39%) received the standard treatment. The median follow-up period was longer in Group 1 than in Group 2 (57 vs 28 months; P = .048). No recurrence of mesenteric vein thrombosis-related symptoms were observed in either group. The median duration of follow-up computed tomography was 31 months (42 months in Group 1 vs 18 months in Group 2; P = .064). Computed tomography revealed complete thrombus resolution, partial resolution, and no changes in 71%, 19%, and 10%, respectively (P = .075). Regarding bleeding complications, varix bleeding and melena developed in two patients in Group 2, and anticoagulation treatment thereafter ceased.

Despite the short follow-up duration in the non-vitamin K antagonist oral anticoagulants group, there was no clinically significant difference in the thrombus resolution rate or bleeding complications when compared with the vitamin K antagonists group. Although research on the long-term effects of non-vitamin K antagonist oral anticoagulants in patients is limited, non-vitamin K antagonist oral anticoagulants can be considered an alternative to conventional treatments.

Portal vein thrombosis (PVT) poses significant therapeutic challenges due to its complex pathophysiology and diverse clinical presentations. Recent advancements have spurred the development of new therapeutic approaches to enhance treatment efficacy and safety. This review synthesized emerging therapies for PVT based on a comprehensive literature search across major databases such as PubMed, EMBASE, and Web of Science, among others, focusing on studies published in the last decade. Anticoagulation therapy, particularly with novel oral anticoagulants (NOACs), emerged as beneficial in personalized treatment regimens. Innovative surgical techniques and improved risk stratification methods were identified as crucial in the perioperative management of PVT. Additionally, advances in cell therapy and medical treatments for hepatocellular carcinoma in the context of PVT were explored. Promising outcomes were observed with modalities such as Yttrium 90 and liver transplantation combined with thrombectomy, particularly in complex PVT cases associated with hepatocellular carcinoma, albeit on a limited scale. The reviewed literature indicates a shift towards individualized treatment approaches for PVT, integrating novel anticoagulants, refined risk assessment tools, and tailored interventional strategies. While these emerging therapies show potential for enhanced efficacy and safety, further research is essential to validate findings across broader patient populations and establish standardized treatment protocols.

The popularity of direct oral anticoagulants (DOACs) is increasing among patients with cirrhosis. Cirrhosis has a major impact on the pharmacokinetics of drugs, potentially increasing adverse events. Safe use of drugs in cirrhosis requires a diligent risk-benefit analysis. The aim of this study is to develop practice recommendations for safe use of DOACs in cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data.

We conducted a systematic literature search to identify studies on pharmacokinetics, pharmacodynamics and safety of DOACs in cirrhosis. Data were collected and presented in summary tables by severity of cirrhosis using the Child-Turcotte-Pugh (CTP) classification. A multidisciplinary expert panel evaluated the results and classified the DOACs according to safety.

Fifty four studies were included. All DOACs were classified as 'no additional risks known' for CTP A. For CTP B, apixaban, dabigatran and edoxaban were classified as 'no additional risks known'. Apixaban and edoxaban showed fewer adverse events in patients with cirrhosis, while dabigatran may be less impacted by severity of cirrhosis based on its pharmacokinetic profile. Rivaroxaban was classified as 'unsafe' in CTP B and C based on significant pharmacokinetic alterations. Due to lack of data, apixaban, dabigatran and edoxaban were classified as 'unknown' for CTP C.

DOACs can be used in patients with CTP A cirrhosis, and apixaban, dabigatran and edoxaban can also be used in CTP B. It is recommended to avoid rivaroxaban in CTP B and C. There is insufficient evidence to support safe use of other DOACs in CTP C cirrhosis.

Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child-Pugh class C cirrhosis (CPC).

We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM).

Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3-year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs.

Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin.

Background: Portal vein thrombosis (PVT) is a rare disease with an estimated incidence of 2 to 4 cases per 100,000 inhabitants. The most common predisposing conditions for PVT are chronic liver diseases (cirrhosis), primary or secondary hepatobiliary malignancy, major infectious or inflammatory abdominal disease, or myeloproliferative disorders. Methods: PVT can be classified on the basis of the anatomical site, the degree of venous occlusion, and the timing and type of presentation. The main differential diagnosis of PVT, both acute and chronic, is malignant portal vein invasion, most frequently by hepatocarcinoma, or constriction (typically by pancreatic cancer or cholangiocarcinoma). Results: The management of PVT is based on anticoagulation and the treatment of predisposing conditions. The aim of anticoagulation in acute thrombosis is to prevent the extension of the clot and enable the recanalization of the vein to avoid the development of complications, such as intestinal infarction and portal hypertension. Conclusions: The treatment with anticoagulant therapy favors the reduction of portal hypertension, and this allows for a decrease in the risk of bleeding, especially in patients with esophageal varices. The anticoagulant treatment is generally recommended for at least three to six months. Prosecution of anticoagulation is advised until recanalization or lifelong if the patient has an underlying permanent pro-coagulant condition that cannot be corrected or if there is thrombosis extending to the mesenteric veins.

Splanchnic vein thrombosis (SVT), a thrombosis which involves the portal, mesenteric, and splenic veins, and the Budd-Chiari syndrome, represents an uncommon type of venous thromboembolism (VTE). Like with deep vein thrombosis of the lower extremities and pulmonary embolism, ample evidence suggests a significant association between SVT and cancer, particularly intra-abdominal solid malignancies (e.g. hepatobiliary and pancreatic cancers) and myeloproliferative neoplasms (MPN). Clinical symptoms of SVT in cancer patients can be ambiguous, and frequently attributed to the primary cancer itself. Alternatively, SVT may be asymptomatic and detected incidentally during cancer staging or follow-up evaluations. SVT can also precede the diagnosis of cancer and has been associated with poorer outcomes in patients with liver or pancreatic cancers. Therefore, an unprovoked SVT warrants a thorough evaluation for an underlying malignancy or MPN. Cancer-associated SVT carries a high risk of VTE extension, recurrence and bleeding. Extended anticoagulant treatment is often required in the absence of a high bleeding risk. Guidelines suggest treatment with either low molecular weight heparin (LMWH) or direct oral anticoagulants (DOACs), although available data on the safety and effectiveness of DOACs in these patients is limited. This comprehensive review outlines the epidemiology, pathogenesis, risk factors, and diagnosis of cancer-associated SVT and underscores the importance of comprehensive patient evaluation and evidence-based management.

Limited evidence is available on management of splanchnic vein thrombosis (SVT).

This study aimed to evaluate safety and efficacy of direct oral anticoagulants (DOACs) for SVT treatment.

Studies were systematically searched in the PubMed, Web of Science, and Scopus databases according to PRISMA guidelines. We assessed any recanalization, full recanalization, recurrence, mortality, and major bleeding as outcomes of interest. Results were reported as weighted mean prevalence (WMP) with 95% CI. Subgroup analyses and meta-regressions have been performed to address heterogeneity and adjust for potential confounders.

We included a total of 16 studies (17 datasets) on 648 patients with SVT treated with DOACs. We found any recanalization in 60.3% (95% CI: 41.8%-76.3%; I2 = 84.9%; P < .001) and full recanalization in 51.7% (95% CI: 36.0%-67.0%; I2 = 87.4%; P < .001). Recurrent venous thromboembolism occurred in 2.8% (95% CI: 1.4%-5.9%; I2 = 0%; P = .787) and death in 3.4% (95% CI: 1.6%-7.3%; I2 = 13.2%; P = .318) of patients. Major bleeding was reported by 5.8% (95% CI: 3.7%-8.9%; I2 = 29.2%; P = .125) of patients. Results were consistent when separately analyzing prospective studies, retrospective studies, studies on cirrhotic patients, and studies enrolling patients with portal vein thrombosis. Meta-regression analyses showed that an increasing age and cancer impacted the rate of recanalization. Cirrhosis was associated with a higher rate of major bleeding and mortality.

The results of the present study, mostly based on observational studies, suggest good safety and efficacy profiles of DOACs in patients with SVT. Randomized studies are needed to corroborate our findings.

This systematic review aimed to evaluate the comparative effectiveness and safety of direct oral anticoagulants (DOACs) compared to traditional anticoagulation (vitamin K antagonists or low-molecular-weight heparins) in cirrhotic patients with portal vein thrombosis (PVT).

We conducted a literature search in PubMed and Embase databases up to May 2024. Studies were selected according to the PICOS criteria, focusing on cirrhotic patients with PVT treated with DOACs (dabigatran, rivaroxaban, apixaban, or edoxaban) compared to traditional anticoagulation.

Our systematic review included four observational studies conducted in Japan, China, and the United States, involving a total of 223 patients with cirrhosis and PVT. The included studies collectively suggested that anticoagulation therapy, including DOACs, was associated with improved recanalization rates and reduced progression of PVT in patients with liver cirrhosis, without a significant increase in bleeding complications. Specifically, edoxaban demonstrated superior effectiveness in reducing PVT volume compared to traditional anticoagulation, while maintaining a favorable safety profile.

DOACs may provide a promising therapeutic option for PVT in cirrhotic patients. Further research is needed to confirm the potential benefits and risks of DOACs in this population.

In patients with atrial fibrillation (AF) and stroke risk factors, randomized trials have demonstrated that anticoagulation decreases the risk of ischemic stroke. However, all trials to date have excluded patients with significant liver disease, leaving guidelines to extrapolate recommendations. We aim to evaluate the impact of anticoagulation on safety events in patients with AF and cirrhosis.

In this retrospective cohort study, we obtained de-identified health record data to extract anticoagulation strategy, comorbidities, prescriptions, lab values, and procedures for a cohort of patients with cirrhosis who develop AF. After selecting a propensity matched population to match patients with various anticoagulation strategies, we tracked data on outcomes for death, transfusion requirements, hospital and ICU admissions. After propensity score weighting and multivariable adjustment, anticoagulation strategy was associated with increased hospital admission count (OR = 1.74 per admission, P < .001), binary risk of hospital admission (OR = 1.54, P = .010) and risk of ICU admission (OR = 1.41, P = .047). We detected no significant differences in mortality, transfusion of blood products, or average length of stay. Direct oral anticoagulant (DOAC) prescriptions were associated with increased binary risk of hospital admission compared to warfarin prescriptions. In a third comparison, DOAC strategy alone was associated with increased hospital admission count (OR = 1.41 per admission, P < .001) and binary risk of hospital admission (OR = 1.52, P = .038) compared to no anticoagulation strategy.

Anticoagulation strategy in patients with cirrhosis and AF was associated with increased rate of hospital admission and ICU admission but not associated with increased risk of mortality or transfusion requirement.

Splanchnic vein thrombosis includes Budd-Chiari syndrome and portal vein thrombosis. These diseases share common features: (i) they are rare diseases and (ii) they can lead to portal hypertension and its complications. Budd-Chiari syndrome and portal vein thrombosis in the absence of underlying liver disease share many risk factors, the most common being myeloproliferative neoplasms. A rapid and comprehensive workup for thrombosis risk factors is necessary in these patients. Long-term anticoagulation is indicated in most patients. Portal vein thrombosis can also develop in patients with cirrhosis, and is associated with a worse course of cirrhosis. Indications for anticoagulation in patients with cirrhosis are increasing. Transjugular intrahepatic portosystemic shunt is a second-line procedure in this setting. Because of the rarity of these diseases, high-level evidence studies are rare. However, collaborative studies have provided a better understanding of their natural history and allowed to improve the management of these patients. This review focuses on the causes, diagnosis, and management of patients with Budd-Chiari syndrome, patients with portal vein thrombosis without underlying liver disease, and patients with cirrhosis and portal vein thrombosis.

The management of a patient in the peri-transplantation period is highly challenging, and it is even more difficult while the patient is on the transplantation waitlist. Keeping the patient alive during this period involves managing the complications of liver disease and preventing the disease's progression. Based on the pre-transplantation etiology and type of liver failure, there is a difference in the management protocol. The current review is divided into different sections, which include: the management of underlying cirrhosis and complications of portal hypertension, treatment and identification of infections, portal vein thrombosis management, and particular emphasis on the management of patients of hepatocellular carcinoma and acute liver failure in the transplantation waitlist. The review highlights special concerns in the management of patients in the Asian subcontinent also. The review also addresses the issue of delisting from the transplant waitlist to see that futility does not overtake the utility of organs. The treatment modalities are primarily expressed in tabular format for quick reference. The following review integrates the vast issues in this period concisely so that the management during this crucial period is taken care of in the best possible way.

Little to no data exist to guide treatment decision in patients with venous thromboembolism (VTE) and chronic liver disease.

To assess the effectiveness and safety of direct oral anticoagulants (DOACs)-individually and as a class-vs warfarin and between 2 DOACs in patients with acute VTE and chronic liver disease.

We conducted a retrospective, US claims-based, propensity score-matched cohort study in adults with acute VTE and chronic liver disease who had newly initiated oral anticoagulants between 2011 and 2017. The primary outcome was a composite of hospitalization for recurrent VTE and hospitalization for major bleeding.

The cohorts included 2361 DOAC-warfarin, 895 apixaban-warfarin, 2161 rivaroxaban-warfarin, and 895 apixaban-rivaroxaban matched pairs. Lower risk of the primary outcome was seen with DOACs (hazard ratio [HR], 0.72; 95% CI, 0.61-0.85), apixaban (HR, 0.48; 95% CI, 0.35-0.66) or rivaroxaban (HR, 0.73; 95% CI, 0.61-0.88) vs warfarin but not apixaban-rivaroxaban (HR, 0.68; 95% CI, 0.43-1.08). The HRs of hospitalization for major bleeding were 0.69 (95% CI, 0.57-0.84) for DOAC-warfarin, 0.43 (95% CI, 0.30-0.63) for apixaban-warfarin, 0.72 (95% CI, 0.58-0.89) for rivaroxaban-warfarin, and 0.60 (95% CI, 0.35-1.06) for apixaban-rivaroxaban. Recurrent VTE risk was lower with apixaban (HR, 0.47; 95% CI, 0.26-0.86), but not DOACs (HR, 0.81; 95% CI, 0.59-1.12) or rivaroxaban vs warfarin (HR, 0.81; 95% CI, 0.57-1.14) or apixaban-rivaroxaban (HR, 0.92; 95% CI, 0.42-2.02).

While the magnitude of clinical benefit varied across individual DOACs, in adults with acute VTE and chronic liver disease, oral factor Xa inhibitors (as a class or individually) were associated with lower risk of recurrent VTE and major bleeding.

A 59-year-old female with Child-Pugh class B cirrhosis attributed to nonalcoholic steatohepatitis complicated by hepatic encephalopathy, portal hypertension with esophageal varices, and thrombocytopenia is seen for management of an acute segmental right lower lobe pulmonary embolism in a clinic. She is hemodynamically stable. Complete blood count is notable for hemoglobin 11.6  g/dL and platelets 80 K/μL. Prothrombin time is 12.6 seconds; partial thromboplastin time, 33.7 seconds; and fibrinogen, 221  mg/dL. She was referred to discuss if a direct oral anticoagulant (DOAC) can be used for anticoagulation. What would you suggest?

Rebalanced hemostasis describes the precarious balance of procoagulant and antithrombotic proteins in patients with severe liver failure. This review is aimed to discuss currently available coagulation monitoring tests and pertinent decision-making process for plasma coagulation factor replacements during liver transplantation (LT).

Contemporary viscoelastic coagulation monitoring systems have demonstrated advantages over conventional coagulation tests in assessing the patient's coagulation status and tailoring hemostatic interventions. There is increasing interest in the use of prothrombin complex and fibrinogen concentrates, but it remains to be proven if purified factor concentrates are more efficacious and safer than allogeneic hemostatic components. Furthermore, the decision to use antifibrinolytic therapy necessitates careful considerations given the risks of venous thromboembolism in severe liver failure.

Perioperative hemostatic management and thromboprophylaxis for LT patients is likely to be more precise and patient-specific through a better understanding and monitoring of rebalanced coagulation. Further research is needed to refine the application of these tools and develop more standardized protocols for coagulation management in LT.

 Direct oral anticoagulants (DOACs) are effective for the management of thromboembolic disorders. However, bleeding remains a major concern in cirrhotic patients receiving DOACs.

 PubMed, EMBASE, and Cochrane Library databases were searched. The incidence of bleeding episodes in cirrhotic patients receiving DOACs was pooled. Odds ratios (ORs) were calculated to compare the incidence of bleeding episodes in cirrhotic patients who received DOACs versus those who received conventional anticoagulants and did not receive anticoagulants.

 Twenty-nine studies were included. All bleeding, major bleeding, fatal bleeding, gastrointestinal bleeding, and intracranial hemorrhage episodes were observed in 310/2,469, 100/1,388, 2/611, 166/1,886, and 5/1,147 cirrhotic patients receiving DOACs, respectively. Their pooled incidences were 13, 6, 0, 8, and 0%, respectively. They became higher in subgroup analyses of studies with advanced age, a longer treatment duration, and Child-Turcotte-Pugh class C. Compared with conventional anticoagulants, DOACs were associated with lower incidences of all bleeding (OR = 0.71, 95% confidence interval [CI] = 0.52-0.98) and major bleeding (OR = 0.55, 95% CI = 0.37-0.83) in cirrhotic patients, but not those of fatal bleeding (OR = 0.21, 95% CI = 0.04-1.28), gastrointestinal bleeding (OR = 0.78, 95% CI = 0.52-1.17), or intracranial hemorrhage (OR = 0.36, 95% CI = 0.12-1.12). The incidences of all bleeding (OR = 1.04, 95% CI = 0.22-4.79) and major bleeding (OR = 0.96, 95% CI = 0.26-3.61) did not significantly differ between cirrhotic patients with portal vein thrombosis (PVT) who received DOACs and those who did not receive anticoagulants.

 DOACs carry a low risk of bleeding in liver cirrhosis. Age, treatment duration, and Child-Turcotte-Pugh class may be associated with bleeding in cirrhotic patients receiving DOACs. The risk of bleeding is not increased by DOACs in cirrhotic patients with PVT.

Splanchnic vein thrombosis (SVT) is a manifestation of venous thromboembolism in an unusual site. Portal, mesenteric, and splenic veins are the most common vessels involved in SVT which occurs mainly in patients with liver cirrhosis, although non-cirrhotic patients could be affected as well. Thrombosis of hepatic veins, also known as Budd-Chiari syndrome, is another manifestation of SVT. Prompt diagnosis and intervention are mandatory in order to increase the recalization rate and reduce the risk of thrombus progression and hypertensive complications. Traditional anticoagulation with heparin and vitamin-K antagonists is the treatment of choice in these cases. However, recent studies have shown promising results on the efficacy and safety of direct oral anticoagulants (DOACs) in this setting. Available results are mainly based on retrospective studies with small sample size, but first clinical trials have been published in the last years. This manuscript aims to provide an updated overview of the current evidence regarding the role of DOACs for SVT in both cirrhotic and non-cirrhotic patients.

Chronic liver disease (CLD) is a highly prevalent condition. There is burgeoning recognition that there are many people with subclinical liver disease that may nonetheless be clinically significant. CLD has a variety of systemic aberrations relevant to stroke, including thrombocytopenia, coagulopathy, elevated liver enzymes, and altered drug metabolism. There is a growing body of literature on the intersection of CLD and stroke. Despite this, there have been few efforts to synthesize these data, and stroke guidelines provide scant guidance on this topic. To fill this gap, this multidisciplinary review provides a contemporary overview of CLD for the vascular neurologist while appraising data regarding the impact of CLD on stroke risk, mechanisms, and outcomes. Finally, the review addresses acute and chronic treatment considerations for patients with stroke-ischemic and hemorrhagic-and CLD.

Vascular liver disorders (VLDs) comprise a wide spectrum of clinical-pathological entities that primarily affect the hepatic vascular system of both cirrhotic and non-cirrhotic patients. VLDs more frequently involve the portal and the hepatic veins, as well as liver sinusoids, resulting in an imbalance of liver homeostasis with serious consequences, such as the development of portal hypertension and liver fibrosis. Surprisingly, many VLDs are characterized by a prothrombotic phenotype. The molecular mechanisms that cause thrombosis in VLD are only partially explained by the alteration in the Virchow's triad (hypercoagulability, blood stasis, and endothelial damage) and nowadays their pathogenesis is incompletely described and understood. Studies about this topic have been hampered by the low incidence of VLDs in the general population and by the absence of suitable animal models. Recently, the role of coagulation imbalance in liver disease has been postulated as one of the main mechanisms linked to fibrogenesis, so a novel interest in vascular alterations of the liver has been renewed. This review provides a detailed analysis of the current knowledge of molecular mechanisms of VLD. We also focus on the promising role of anticoagulation as a strategy to prevent liver complications and to improve the outcome of these patients.

Vascular, autoimmune hepatitis, and malignant causes of acute-on-chronic liver failure are rare but important to consider and investigate in patients with underlying liver disease who present with acute deterioration and other more common etiologies have been excluded. Vascular processes including Budd-Chiari syndrome and portal vein thrombosis require imaging for diagnosis and anticoagulation is the mainstay of therapy. Patients may require advanced interventional therapy including transjugular intrahepatic portosystemic shunt or consideration of liver transplantation. Autoimmune hepatitis is a complex disease entity that requires a high degree of clinical suspicion and can present heterogeneously.

Much has evolved over the past 25 years regarding our understanding of the coagulopathy of liver disease. Paradoxically, this form of coagulopathy is relatively hypercoagulability despite the common clinical impression of a hemorrhagic tendency. The latter is largely driven by portal-mesenteric venous pressure (ie, portal hypertension) and has little to do with hemostatic pathways. It cannot be emphasized enough that the INR does not offer a meaningful measure in this situation and may lead to interventions such as fresh frozen plasma that can actually worsen portal pressure and hence pressure-driven bleeding. With regard to procedure-related bleeding, we point out substantial differences in the definition of high-risk procedures and propose a new operational definition dependent on the applicability of local hemostatic measures, although this requires further investigation. The common occurrence of venous thrombosis in these patients requires careful consideration of hemostatic pathways and overall risk and benefit of intervention. The decision regarding anticoagulation therapy needs to be driven not only by a global assessment including history of non-portal hypertensive-related bleeding, but also by fall risk which can result in head trauma in patients prone to encephalopathy. This is probably best estimated by frailty but has yet to be adequately investigated. In the background of these concerns, several superimposed and complex conditions including infections and renal dysfunction should be taken into account. Inherited forms of thrombophilia in the setting of cirrhosis perhaps do not outweigh the thrombophilia inherent to liver disease but warrant further consideration.

Portal vein thrombosis (PVT) leads to significant morbidity and mortality burden in patients with cirrhosis. An improved understanding of the utility of anticoagulation in patients with PVT will aid clinical decision making and inform future research. This meta-analysis aimed to evaluate the association between anticoagulation therapy and clinical outcomes in the context of treatment for PVT in cirrhosis.

Pubmed, Embase, and Web of Science were searched from inception to February 13, 2022, for studies comparing the use of anticoagulation to other modalities as treatment for PVT in cirrhosis. Pooled odds ratios (OR) were calculated using a random-effects model for PVT improvement, recanalization, progression, bleeding events, and all-cause mortality in treatment studies.

We identified 944 records, of which 16 studies (n = 1126) examining anticoagulation as PVT treatment were included for subsequent analysis. Anticoagulation as PVT treatment was associated with PVT improvement (OR 3.64; 95% CI 2.56-5.17), PVT recanalization (OR 3.73; 95% CI 2.45-5.68), decreased PVT progression (OR 0.38; 95% CI 0.23-0.63), and decreased all-cause mortality (OR 0.47; 95% CI 0.29-0.75). The use of anticoagulation was not associated with bleeding events (OR 0.80; 95% CI 0.39-1.66). All analyses demonstrated low heterogeneity.

These results support the use of anticoagulation in cirrhosis as treatment for PVT. These findings may inform the clinical management of PVT and highlight the need for further studies such as large randomized controlled trials characterizing the safety and efficacy of anticoagulation for PVT in cirrhosis.

Portal Vein Thrombosis (PVT), a common complication of advanced liver disease, is defined as an obstruction of the portal vein due to thrombus formation that can extend to the superior mesenteric and splenic veins. It was believed that PVT occurred predominantly due to prothrombotic potential. However, recent studies have shown that decreased blood flow related to portal hypertension appears to increase PVT risk as per Virchow's triad. It is well known that there is a higher incidence of PVTs in cirrhosis with a higher MELD and Child Pugh score. The controversy for management of PVTs in cirrhotics lies in the individualized assessment of risks versus benefits of anticoagulation, since these patients have a complex hemostatic profile with both bleeding and procoagulant propensities. In this review, we will systematically compile the etiology, pathophysiology, clinical features, and management of portal vein thrombosis in cirrhosis.

The expression splanchnic vein thrombosis encompasses Budd-Chiari syndrome and portal vein thrombosis. These disorders have common characteristics: they are both rare diseases which can cause portal hypertension and its complications. Budd-Chiari syndrome and portal vein thrombosis in the absence of underlying liver disease share many risk factors, among which myeloproliferative neoplasms represent the most common; a rapid comprehensive work-up for risk factors of thrombosis is needed in these patients. Long-term anticoagulation is indicated in most patients. Portal vein thrombosis can also develop in patients with cirrhosis and in those with porto-sinusoidal vascular liver disease. The presence and nature of underlying liver disease impacts the management of portal vein thrombosis. Indications for anticoagulation in patients with cirrhosis are growing, while transjugular intrahepatic portosystemic shunt is now a second-line option. Due to the rarity of these diseases, studies yielding high-grade evidence are scarce. However, collaborative studies have provided new insight into the management of these patients. This article focuses on the causes, diagnosis, and management of patients with Budd-Chiari syndrome, portal vein thrombosis without underlying liver disease, or cirrhosis with non-malignant portal vein thrombosis.

Atrial fibrillation is frequently diagnosed in patients with liver cirrhosis, especially in those with non-alcoholic steatohepatitis or alcoholic etiology. Anticoagulant treatment is recommended for thromboembolic protection in patients with atrial fibrillation. Considering the impaired coagulation balance in liver cirrhosis, predisposing patients to bleed or thrombotic events, the anticoagulant treatment is still a matter of debate. Although patients with liver cirrhosis were excluded from the pivotal studies that confirmed the efficacy and safety of the anticoagulant treatment in patients with atrial fibrillation, data from real-life cohorts demonstrated that the anticoagulant treatment in patients with liver cirrhosis could be safe. This review aimed to evaluate the recent data regarding the safety and efficacy of anticoagulant treatment in patients with decompensated liver cirrhosis. Direct oral anticoagulants are safer than warfarin in patients with compensated liver cirrhosis. In Child-Pugh class C liver cirrhosis, direct oral anticoagulants are contraindicated. New bleeding and ischemic risk scores should be developed especially for patients with liver cirrhosis, and biomarkers for bleeding complications should be implemented in clinical practice to personalize this treatment in a very difficult population represented by decompensated liver cirrhosis patients.

The benefit-risk profile of direct oral anticoagulants (DOACs) compared with warfarin, and between DOACs in patients with atrial fibrillation (AF) and chronic liver disease is unclear.

We conducted a new-user, retrospective cohort study of patients with AF and chronic liver disease who were enrolled in a large, US-based administrative database between January 1, 2011, and December 31, 2017. We assessed the effectiveness and safety of DOACs (as a class and individually) compared with warfarin, and between DOACs in patients with AF and chronic liver disease. The primary outcomes were hospitalization for ischemic stroke/systemic embolism and hospitalization for major bleeding. Inverse probability treatment weights were used to balance the treatment groups on measured confounders.

Overall, 10 209 participants were included, with 4421 (43.2%) on warfarin, 2721 (26.7%) apixaban, 2211 (21.7%) rivaroxaban, and 851 (8.3%) dabigatran. The incidence rates per 100 person-years for ischemic stroke/systemic embolism were 2.2, 1.4, 2.6, and 4.4 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. The incidence rates per 100 person-years for major bleeding were 7.9, 6.5, 9.1, and 15.0 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. After inverse probability treatment weights, the risk of hospitalization for ischemic stroke/systemic embolism was significantly lower between DOACs as a class (hazard ratio [HR], 0.64 [95% CI, 0.46-0.90]) or apixaban (HR, 0.40 [95% CI, 0.19-0.82]) compared with warfarin, but not significantly different between rivaroxaban versus warfarin (HR, 0.76 [95% CI, 0.47-1.21]) or rivaroxaban versus apixaban (HR, 1.73 [95% CI, 0.91-3.29]). Compared with warfarin, the risk of hospitalization for major bleeding was lower with DOACs as a class (HR, 0.69 [95% CI, 0.58-0.82]), apixaban (HR, 0.60 [95% CI, 0.46-0.78]), and rivaroxaban (HR, 0.79 [95% CI, 0.62-1.0]). However, the risk of hospitalization for major bleeding was higher for rivaroxaban versus apixaban (HR, 1.59 [95% CI, 1.18-2.14]).

Among patients with AF and chronic liver disease, DOACs as a class were associated with lower risks of hospitalization for ischemic stroke/systemic embolism and major bleeding versus warfarin. However, the incidence of clinical outcomes among patients with AF and chronic liver disease varied between individual DOACs and warfarin, and in head-to-head DOAC comparisons.

Portal vein thrombosis (PVT) is a common complication of cirrhosis and can be a cause or consequence of liver disease progression. It is unclear whether PVT treatment is affecting clinical outcomes in cirrhotics.

This is a multicenter study of cirrhotics with PVT, initially retrospectively and thereafter prospectively registered in a data base. We studied the impact of PVT treatment on this population for efficacy, safety and the impact on survival. In survival analysis Mantel-Cox and Wilcoxon-Breslow-Gehan tests were used. A P value of <0.05, was considered significant. For statistical computations the STATA 12.1 was used.

Seventy-six patients were included (76% decompensated, median MELD score 12 and Child-Pugh score 7), 47% with concomitant HCC. Fifty-one patients with PVT were treated with Vitamin-K antagonists or Low-Molecular-Weight Heparin. Patients were followed up for at least 6 months after PVT diagnosis, or until death or transplantation. PV patency after 6 months was not statistically different between patients receiving or not anticoagulation (complete-partial recanalization 27.4% of treated vs. 20% of untreated, P=0.21). Median survival was statistically worse between patients treated with anticoagulation than those untreated (10 vs. 15 months, P=0.036). Less portal hypertensive bleeding and less decompensation rates were found in treated cirrhotics vs. untreated (45.8% vs. 54.2%, P=0.003 and 78% vs. 80.9%, P=0.78, respectively). Patients with HCC had worse survival when treated vs. untreated (P=0.047).

In our cohort of cirrhotics with PVT, treatment was feasible with acceptable side effects, but without meaningful clinical benefits.

Liver cirrhosis (LC) is associated with portal venous thrombosis (PVT) in roughly 20% of cirrhotic patients but the underlying mechanism is still unclear. Low-grade endotoxemia by lipopolysaccharides (LPS), a component of outer gut microbiota membrane, is detectable in the portal circulation of LC and could predispose to PVT. LPS may translocate into systemic circulation upon microbiota dysbiosis-induced gut barrier dysfunction, that is a prerequisite for enhanced gut permeability and ensuing endotoxemia. Experimental and clinical studies provided evidence that LPS behaves a pro-thrombotic molecule so promoting clotting and platelet activation. Experiments conducted in the portal circulation of cirrhotic patients showed the existence of LPS-related enhanced thrombin generation as well as endothelial dysfunction, venous stasis, and platelet activation. The review will analyze 1) the pro-thrombotic role of endotoxemia in the context of LC 2) the biological plausibility linking endotoxemia with PVT and 3) the potentially interventional tools to lower endotoxemia and eventually hypercoagulation.

BACKGROUND: In patients with noncirrhotic chronic portal vein thrombosis (PVT), the benefit of long-term anticoagulation is unknown. We assessed the effects of rivaroxaban on the risk of venous thromboembolism and portal hypertension-related bleeding in such patients. METHODS: In this multicenter, controlled trial, we randomly assigned patients with noncirrhotic chronic PVT without major risk factors for thrombosis to receive either rivaroxaban 15 mg/day or no anticoagulation. The primary end point was 2-year thrombosis-free survival. Secondary end points included the occurrence of site-specific thromboses and major bleeding events. RESULTS: A total of 111 participants were enrolled in the trial, with a mean age of 50.4±13.2 years; 58% of participants were men. An unplanned interim analysis was requested by the independent data safety monitoring board (DSMB) after 10 thrombotic events occurred. The thrombosis incidence rate was 0 per 100 person-years in the rivaroxaban group and 19.71 per 100 person-years (95% confidence interval, 7.49 to 31.92) in the no anticoagulation group (log-rank P=0.0008) after a median follow-up of 11.8 months. Based on the interim analysis, the DSMB recommended switching patients from the no anticoagulation group to anticoagulation. After a median follow-up of 30.3 months (intraquartile range, 24.3 to 47.8), major bleeding occurred in two patients receiving rivaroxaban and in one patient not receiving anticoagulation. No deaths occurred. CONCLUSIONS: After a median follow-up of 11.8 months, among patients with noncirrhotic chronic PVT without major risk factors for thrombosis, daily rivaroxaban reduced the incidence of venous thromboembolism and did not increase major bleeding events. (Funded by grants from the French Ministry of Health and the Association de Malades des Vaisseaux du foie; ClinicalTrials.gov number, NCT02555111.)

Portal vein thrombosis constitutes the most common thrombotic event in patients with cirrhosis, with increased rates in the setting of advanced liver disease. Despite being a well-known complication of cirrhosis, the contribution of portal vein thrombosis to hepatic decompensation and overall mortality is still a matter of debate. The incorporation of direct oral anticoagulants and new radiological techniques for portal vein recanalization have expanded our therapeutic arsenal. However, the lack of large prospective observational studies and randomized trials explain the heterogenous diagnostic and therapeutic recommendations of current guidelines. This article seeks to make a comprehensive review of the pathophysiology, clinical features, diagnosis, and treatment of portal vein thrombosis in patients with cirrhosis.

Direct oral anticoagulants (DOACs), such as apixaban, edoxaban, rivaroxaban, or dabigatran, are an effective treatment for atrial fibrillation (AF) and deep venous thromboembolism. We hope to evaluate the safety of DOACs versus warfarin/low molecular weight heparin (LMWH) in improving bleeding events in patients with different severity of the liver disease.

We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the effects of DOACs in patients with liver cirrhosis. A random-effects model or fixed-effects model was selected to pool risk ratios (RR) and 95% confidence intervals (CI).

A total of 18 studies involving 41,447 participants was included in this meta-analysis. Compare with warfarin/ LMWH, the use of DOACs significantly reduced the incidence of all bleeding (RR: 0.76; 95%CI: 0.66 to 0.87), major bleeding (RR: 0.51; 95%CI: 0.28 to 0.91), intracranial hemorrhage (RR: 0.50; 95%CI: 0.31 to 0.81), and gastrointestinal bleeding (RR: 0.76, 95% CI: 0.60 to 0.97), and all-cause death in patients with liver disease (RR: 0.77; 95%CI: 0.62 to 0.95). Similar results were observed in atrial fibrillation patients with liver disease and cirrhosis subgroups. Furthermore, the pooled estimates of the Child-Turcotte-Pugh (CTP) class indicated that DOACs reduced the incidence of all bleeding (RR: 0.61; 95%CI: 0.45 to 0.82), gastrointestinal bleeding (RR 0.55; 95%CI: 0.37 to 0.83), and all-cause death (RR: 0.62; 95%CI: 0.49 to 0.79) in patients with mild to moderate cirrhosis.

Our study demonstrates that DOACs significantly reduce the risk of bleeding in patients with liver disease compared with warfarin/LMWH.

In an aging population with cardiovascular comorbidities, anticoagulant (AC), antiplatelet (AP), and nonsteroidal anti-inflammatory drug (NSAID) use are increasing. It remains unclear whether these agents pose increased bleeding risk in cirrhosis. This study aimed to assess the association between these medications and bleeding and portal hypertension complications in cirrhosis.

The IMS PharMetrics database was used to identify privately insured adults diagnosed with cirrhosis from 2007 to 2015, stratified as compensated or decompensated based on the presence of portal hypertensive complications 1 year before cirrhosis diagnosis. Bleeding or decompensation outcomes were assessed 6 to 18 months after cirrhosis diagnosis using a landmark analysis design. Multivariable Cox proportional hazards regression modeling assessed associations between AC, AP, and NSAID drug exposures and outcomes adjusting for covariates.

A total of 18,070 cirrhosis patients were analyzed; 57% male; 74% ages 50 to 64 years; 34% with a prior decompensation. Overall, 377 (2%) had claims for ACs; 385 (2%) APs; and 1231 (7%) NSAIDs. APs were associated with increased bleeding [adjusted hazard ratio (aHR)=1.31; 95% confidence interval (CI): 1.00, 1.72] and decompensation events (aHR=1.44; 95% CI: 1.06, 1.95) in a 9-month landmark analysis. NSAIDs were significantly associated with bleeding events (aHR=1.29; 95% CI: 1.06, 1.57) on 3-month landmark analysis. No statistically significant associations were seen between ACs and bleeding or decompensation outcomes in adjusted analyses.

AP use was associated with increased bleeding and decompensation events among privately insured patients with cirrhosis. NSAID use was associated with significant early bleeding, but not decompensations. Lastly ACs were not associated with bleeding or decompensation outcomes.

Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting.

To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation.

This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation.

A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group (P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population (P = 0.55). No fatal bleeding or thromboembolic events occurred.

DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.

The clinical utility of anticoagulation for patients with cirrhosis and asymptomatic portal vein thrombosis (PVT) is widely debated. Complex hemostatic derangements in cirrhosis that increase risk of both bleeding and thrombosis, as well as a lack of randomized controlled data, limit conclusive assessments regarding optimal management of anticoagulation in this setting. In this review, we summarize the relevant literature pertaining to PVT in cirrhosis, including the effect of untreated PVT on the natural progression of liver disease and the overall impact of anticoagulation on clot burden and other relevant clinical outcomes. Apart from patients who are symptomatic or listed for liver transplantation, data supporting anticoagulation for the treatment of PVT is limited and without clear consensus guidelines. In patients with cirrhosis without PVT, emerging evidence for the role of prophylactic anticoagulation to mitigate the progression of fibrosis suggests an optimal risk-benefit tradeoff with decreased rates of liver decompensation and mortality, without a heightened risk of bleeding. In summation, as our understanding of the role of both prophylactic and therapeutic anticoagulation in cirrhosis continues to evolve, ongoing risk stratification of patients with asymptomatic PVT demands further attention.

Advanced chronic liver disease is considered a reversible condition after removal of the primary aetiological factor. This has led to a paradigm shift in which portal hypertension (PH) is a reversible complication of cirrhosis. The pharmacologic management of PH is centered on finding targets to modify the natural history of cirrhosis and PH.

This paper offers an overview of the use of pharmacological strategies in early clinical development that modify PH. Papers included were selected from searching clinical trials sites and PubMed from the last 10 years.

A paradigm shift has generated a new concept of PH in cirrhosis as a reversible complication of a potentially curable disease. Decreasing portal pressure to prevent decompensation and further complications of cirrhosis that may lead liver transplantation or death is a goal. Therapeutic strategies also aspire achieve total or partial regression of fibrosis thus eliminating the need for treatment or screening of PH.

Patients with cirrhosis frequently acquire complex changes in their haemostatic system including a decreased platelet count and decreased levels of various haemostatic proteins. Although historically patients with cirrhosis were thought to have a haemostasis-related bleeding tendency, it is now widely accepted that the haemostatic system of patients with cirrhosis remains in balance as a result of simultaneous changes in pro- and anti-haemostatic systems. The concept of rebalanced haemostasis has led to changes in clinical management, although firm evidence from well-designed clinical studies is largely lacking. For example, many invasive procedures in patients with cirrhosis and a prolonged prothrombin time are now performed without prophylaxis with fresh frozen plasma. Conversely, clinicians have become more aware of the need for anti-thrombotic therapy, even in those patients with abnormal routine coagulation tests. This paper will outline recent advances in pathogenesis, prevention and treatment of both bleeding and thrombotic complications in patients with cirrhosis. Among other topics, we will discuss the haemostatic status of acutely ill patients with cirrhosis, the various causes of bleeding in patients with cirrhosis, and how best to prevent or treat bleeding. In addition, we will discuss the hypercoagulable features of patients with cirrhosis, new insights into the pathogenesis of portal vein thrombosis, and how best to prevent or treat thromboses.

Patients with cirrhosis of the liver are at high risk of developing portal vein thrombosis (PVT), which has a complex, multifactorial cause. The condition may present with a myriad of symptoms and can occasionally cause severe complications. Contrast-enhanced computed tomography (CT) is the gold standard for the diagnosis of PVT. There are uncertainties regarding the effect on PVT and its treatment outcome in patients with cirrhosis. The main challenge for managing PVT in cirrhosis is analyzing the risk of hemorrhage compared to the risk of thrombus extension leading to complications. All current knowledge regarding non-tumor PVT in cirrhosis, including epidemiology, risk factors, classification, clinical presentation, diagnosis, impact on natural history, and treatment, is discussed in the present article.

Evidence for direct oral anticoagulants (DOACs) in patients with cirrhosis is limited. Few patients with Child-Turcotte-Pugh (CTP) class B and C cirrhosis have been studied.

To compare major bleeding rates in patients with cirrhosis receiving a DOAC versus warfarin.

A retrospective cohort study was conducted in adults with cirrhosis receiving a DOAC versus warfarin for venous thromboembolism, portal-vein thrombosis, or atrial fibrillation. The primary outcome was the rate of major bleeding. Secondary outcomes included time to major bleeding, clinically relevant nonmajor bleeding, all bleeding, gastrointestinal bleeding, intracranial bleeding, and new thromboembolic events. The study was approved by the Ochsner Health System Institutional Review Board.

A total of 44 patients receiving a DOAC and 41 patients receiving warfarin were included. Major bleeding occurred in 4 patients receiving a DOAC and 6 patients receiving warfarin (9.1% vs 14.6%; P = 0.881). Rates of major bleeding were similar in 24 DOAC and 17 warfarin patients with CTP Class B (4.2% vs 17.6%; P = 0.37) and 8 DOAC and 9 warfarin patients with CTP Class C (37.5% vs 11.1%; P = 0.41) cirrhosis. Secondary bleeding and efficacy outcomes were similar between cohorts. The study was limited by a small sample size.

Treatment with DOACs in patients with cirrhosis was associated with a similar rate of major bleeding compared with warfarin. Inclusion of CTP class C patients in future studies remains valuable to evaluate safety and efficacy of DOACs in this population.