Antithrombotic Therapy in Non-Neoplastic Chronic Portal Venous Thrombosis in Cirrhosis: Evaluation of Recanalization and Safety.

Abstract INTRODUCTION: Non-neoplastic chronic portal vein thrombosis (PVT) has become a more frecuent diagnosis in the course of liver cirrhosis, with reported prevalences of 4,4% to 15,8%. PVT can motivate life-threatening complications due to worsening portal hypertension. The role of anticoagulation in patients with chronic PVT is not well established, and is considered challenging in cirrhotic patients. OBJECTIVE: To analyze the response to antithrombotic therapy in 12 patients with chronic PVT associated with cirrhosis, and to assess its tolerance and safety. PATIENTS AND METHODS: 12 consecutive patients with liver cirrhosis and chronic PVT were treated with antithrombotic therapy from 2005 to 2006. PVT was diagnosed by imaging procedures, and was classified as complete or partial according to absence or reduction of blood flow in the portal trunk, branches, superior mesenteric and splenic veins. Hepatocellular carcinoma and known thrombophilic risks were ruled out. Cirrhosis was scored according to Child-Pugh’s classification. History of hemorrhagic episodes was assessed. Therapy was started with 15 days of therapeutic doses of low molecular weight heparin (LMWH) (enoxaparin) adjusted according to baseline hipocoagulability (Table 1), followed by either prophylactic doses (0,5mg/kg/day) of LMWH or acenocoumarol (target INR 2–3), during 6 months. Response was evaluated after 3 and 6 months. RESULTS: From the 12 patients studied, 9 (75%) were males with a median age of 52 years old (range 35–72). Cirrhosis was due to alcoholism (41%), virus (33%), mixed in one patient and other causes in two patients. Two (16%) patients belonged to Child Pugh’s class A, 6 (50%) to class B and 4 (33%) to class C. Six patients (50%) had previous hemorrhagic episodes due to esophageal varices. PVT involved the portal trunk and/or branches in 91% of the cases, and in 1 patient coexisted with splenic and mesenteric vein thrombosis. Complete thrombosis was seen in 4 patients and partial in 8. From the 12 patients, 8 (66%) responded to antithrombotic therapy after 6 months, with a complete recanalization in 7 patients (87%). Interestingly, the moderate hipocoagulability level subgroup showed an 88% of response (Table2). After an overall follow-up of 6 months, none of the 12 patients presented hemorrhagic complications and none showed platelets counts below baseline values. Acenocoumarol and LMWH were well tolerated in all cases, with only one patient with intolerance to the subcutaneous injections. CONCLUSIONS: Antithrombotic therapy in chronic PVT in cirrhotic patients showed a high response rate (66%) in our study, with a complete recanalization in 87% of the cases. Adjusted dose scheme according to level of hypocoagulability seems to be effective and safe, since 80% of the subgroup of moderate hypocoagulability responded with no haemorrhagic complications. Table 1. Ranges of baseline coagulation study and adjusted therapeutic doses of LMWH. N, Normal range, LH, Low hypocoagulability; MH, Moderate hypocoagulability. Table 2. Responses rates according to baseline hypocoagulability.

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Antithrombotic Therapy in Non-Neoplastic Chronic Portal Venous Thrombosis in Cirrhosis: Recanalization and Liver Function Evaluation,

Blood ◽

10.1182/blood.v118.21.3358.3358 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3358-3358 ◽

Cited By ~ 4

Author(s):

Leyre Bento ◽

Ana Rodriguez Huerta ◽

Cristina Pascual ◽

Gloria Pérez Rus ◽

Vega Catalina ◽

...

Keyword(s):

Liver Cirrhosis ◽

Liver Function ◽

Antithrombotic Therapy ◽

Conflicts Of Interest ◽

Anticoagulation Therapy ◽

Splenic Vein ◽

Liver Function Tests ◽

Vein Thrombosis ◽

Function Tests ◽

Portal Trunk

Abstract Abstract 3358 INTRODUCTION: Non-neoplastic chronic portal vein thrombosis (PVT) is a frecuent diagnosis in the course of liver cirrhosis, with reported prevalences of 0.6% to 15,8%. PVT can motivate life-threatening complications due to worsening portal hypertension, so anticoagulation therapy is challenging in these patients. OBJECTIVE: To analyze the response to antithrombotic therapy and changes in liver function tests in 28 patients with chronic PVT associated with cirrhosis. PATIENTS AND METHODS: 28 consecutive patients with liver cirrhosis and chronic PVT were treated with antithrombotic therapy from 2004 to 2009. Hepatocellular carcinoma and known thrombophilic risks were ruled out. Therapy consisted in 15 days of therapeutic doses of low molecular weight heparin (LMWH) (enoxaparin) adjusted according to baseline coagulability (Table 1), followed by either prophylactic doses (40mg/day) of LMWH or acenocoumarol (target INR 2–3), during 6 months. Response was evaluated after 6 months. If recanalization was complete, therapy was suspended. If recanalization was partial or no recanalization was observed, therapy was continued until response. RESULTS: From the 28 patients studied, 19 (68%) were males with a median age of 53 years (range 35–77). Cirrhosis was due to alcoholism (25%), virus (54%), mixed in 1 patient and other causes in 3 patients. PVT involved the portal trunk and/or branches in 19/28 (68%) patients, mesenteric vein in 2 patients and portal trunk and/or branches, mesenteric and/or splenic vein thrombosis coexisted in 7 patients. 19/28 (68%) of the patients had moderate or moderate-severe hypocoagulability range. Complete and partial thrombosis was seen in 18 and 10 patients at diagnosis, respectively. From the 28 patients, 18 (64%) responded to antithrombotic therapy after 6 months, with a complete recanalization in 13 patients 13/18 (72%) and partial in 5/18 patients (28%). None of the 28 patients presented hemorrhagic complications and none showed platelets counts below baseline values. 17 from the 18 patients who responded, showed altered liver function tests before therapy. After 6 months, 8/17 (47%) improved liver function (only one patient had received antiviral therapy). After a median follow up of 42 months (range 7–67), 15/18 (83%) patients continued showing complete or partial response while 3 patients progressed. Of note, 3 patients of this group could proceed to further liver transplantation. CONCLUSIONS: Antithrombotic therapy in chronic PVT in cirrhotic patients resulted in a high response rate (64%) in our study, with a complete recanalization in 72% of the cases. Adjusted dose scheme according to level of hypocoagulability seems to be effective and safe, since 63% of the subgroups of moderate and moderate-severe hypocoagulability responded with no haemorrhagic complications. Disclosures: No relevant conflicts of interest to declare.

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Cardiomyopathy in Cirrhotic Patients and Its Relationship with the Severity of Cirrhosis

10.53350/pjmhs2115102779 ◽

2021 ◽

Vol 15 (10) ◽

pp. 2779-2782

Author(s):

Saira Khalid ◽

Nasir Shah ◽

Yasir Abbas Zaidi ◽

Muhammad Saleem Hasan ◽

Saqib Jahangir ◽

...

Keyword(s):

Liver Cirrhosis ◽

Severe Disease ◽

P Value ◽

Cirrhotic Cardiomyopathy ◽

Male Predominance ◽

Class A ◽

Class B ◽

Cirrhotic Patients ◽

The Mean ◽

Class C

Study Objectives: To determine the frequency of cirrhotic cardiomyopathy in patients with liver cirrhosis and to compare it across varying grades of cirrhosis on Child Turcotte Pugh classification. Study Design and Settings: It was a descriptive cross-sectional study carried at Department of Medicine, Lahore General Hospital Lahore over 1 year from Jan 2018 to Dec 2018. Patients and Methods: The present research involved 100 male and female patients aged between 16-70 years having liver cirrhosis diagnosed at least 6 months ago. These patients underwent echocardiographic screening of cardiomyopathy which was diagnosed by the presence of diastolic dysfunction (i.e. increased E/A ratio>1). An informed written consent was obtained from every patient. Results of the Study: There was a male predominance (M:F, 1.6:1) among cirrhotic patients with a mean age of 51.9±9.8 years. The mean BMI was 26.5±3.7 Kg/m2 while the mean duration of cirrhosis was 22.0±10.9 months. Majority (49.0%) of the patients belonged to CTP Class C followed by Class-B (39.0%) and Class-A (12.0%). Cirrhotic cardiomyopathy was observed in 41.0% patients with cirrhosis. There was statistically insignificant difference in the observed frequency of cirrhotic cardiomyopathy among various subgroups of cirrhotic patients depending upon patient’s age (p-value=0.928), gender (p-value=0.997), BMI (p-value=0.983) and duration of disease (p-value=0.782). However, it increased considerably with worsening of disease on CTP Classification; Class-A vs. Class-B vs. Class-C (8.3% vs. 35.9% vs. 53.1%; p-value=0.013). Conclusion: Cirrhotic cardiomyopathy was observed in a substantial proportion of cirrhotic patients and was more frequent in patients with more severe disease which warrants routine echocardiographic screening of cirrhotic patients so that timely recognition and anticipated treatment of this complication may improve the case outcome in future medical practice. Keywords: Cirrhosis, Cardiomyopathy, Child Turcotte Pugh Class

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Correlation between Hepatic Vein Wave form Changes on Doppler Ultrasound and the Severity of Diseases in Cirrhotic Patients

Journal of Medicine ◽

10.3329/jom.v22i2.56698 ◽

2021 ◽

Vol 22 (2) ◽

pp. 100-106

Author(s):

Tarana Yasmin ◽

Sohely Sultana ◽

Mahmuda Nusrat Ima ◽

Md Quamrul Islam ◽

Shyamal Kumar Roy ◽

...

Keyword(s):

Liver Cirrhosis ◽

Doppler Ultrasound ◽

Hepatic Vein ◽

Wave Form ◽

Venous Blood Flow ◽

Class A ◽

Class B ◽

Pugh Class ◽

Cirrhotic Patients ◽

Class C

Background: Cirrhosis is a common problem and is a leading cause of chronic liver disease. Early diagnosis with assessment of severity of diseases may help prevent the associated complications and patients’ sufferings. Now a days Hepatic venous Doppler can be a tool for diagnosis of cirrhosis and to assess correlation between waveform changes and severity of diseases. Objective: The purposes of this study was to determine the significance of hepatic vein waveform changes on doppler ultrasound in cirrhotic patients and to correlate with liver dysfunction. Materials and methods: This study was carried out in the department of Radiology and Imaging of Enam Medical College and Hospital during January 2017 to May 2018. Doppler waveforms were obtained from right hepatic vein in all the cases and classified as triphasic, biphasic and monophasic. Waveform comparisons were made among patients with differing grades of cirrhosis. Child- Pugh class was used to assess severity of cirrhosis. Doppler sonography was done in 80 patients suspecting of having liver cirrhosis. Data on clinical findings, B mode sonographic findings and hepatic vein doppler ultrasound findings were collected and documented in structured forms. Analysis was done using SPSS - 20. Results: Total of 80 patients who met the inclusion criteria are included in the study with mean age of 45.37±7.64 (range 25-75) years. Among these 57 (71%) were males while 23(29%) were females. On the basis of hepatic function 25 (31%) patients presented in Child-Pugh Class A, 31(39%) with Class B and 24(30%) patients had Class C. Hepatic venous waveform was triphasic in 22 (27.5%), biphasic in 28(35%), and monophasic in 30 (37.5%) cases. Our study revealed 88% (21) of Child- Pugh Class C, 23% (7) of Class B and 8% (2) of class A patients had monophasic HV waveform. The hepatic venous waveform progressively changed from triphasic to biphasic to monophasic with advancing grade of cirrhosis. The relationship of these waveforms change had significant relation with hepatic dysfunction (p < 0.022). Conclusion: Hepatic vein wave form changes reflects the change in hepatic circulation associated with progression of liver cirrhosis. It can be used as a new parameter in the assessment of severity of liver cirrhosis. Thus, alteration in hepatic venous blood flow pattern on doppler ultrasound can be a useful noninvasive tool for evaluating diseases severity in patients with cirrhosis. J MEDICINE 2021; 22: 100-106

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Correlation of global longitudinal strain with disease severity in liver cirrhosis

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.155 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

Y Dimitroglou ◽

C Aggeli ◽

A Alexopoulou ◽

T Alexopoulos ◽

D Patsourakos ◽

...

Keyword(s):

Liver Cirrhosis ◽

Disease Severity ◽

Longitudinal Strain ◽

Global Longitudinal Strain ◽

Left Ventricular ◽

Class A ◽

Class B ◽

Pugh Class ◽

Cirrhotic Patients ◽

Class C

Abstract Funding Acknowledgements Type of funding sources: None. Introduction/purpose Cirrhotic cardiomyopathy is characterized by high cardiac output, reduced peripheral resistance and diastolic dysfunction and has been correlated with cirrhosis severity and prognosis. Global longitudinal strain (GLS) is a sensitive marker of cardiac dysfunction which is considered relatively independent of preload and afterload conditions and thus may be of high diagnostic significance in this special population. We sought to investigate alterations of GLS relating to disease severity in cirrhotic patients. Methods Echocardiographic analysis of 51 consecutive cirrhotic patients was performed. Images were acquired and analyzed off-line. GLS was calculated with a semi-automatic way using dedicated software. Clinical and biochemical examination were used to assess severity of liver disease by calculating Child-Pugh class (class C patients have more severe disease than class B and A patients) and MELD-Na score (increased score as the disease progresses). Results Mean age was 58.4 ± 8.7 years, 38 (74.5%) were males. Among patients, 22 (43.1%) were Child-Pugh class A, 17 (33.3%) Child-Pugh B and 12 (23.5%) Child-Pugh C and mean MELD-Na score was 15.3 ± 7.5. Mean left ventricular end-systolic volume (LVEDV) was 117 ± 29ml, mean stroke volume (SV) 72.5 ± 19.9ml , mean left ventricular ejection fraction (LVEF) 61.0 ± 5.0%, mean systolic blood pressure (SBP) 128 ± 13mmHg, mean ratio of peak transmitral to peak annular (septal) velocity during early diastole (E/e’ ratio) 10.4 ± 4.5, mean left atrial volume index (LAVI) 37.4 ± 11.8 ml/cm2 and mean GLS -21.6 ± 2.6%. GLS of Child-Pugh class A patients (-20.3 ± 2.4) was higher (less negative) than GLS of Child-Pugh class B (-22.2 ± 2.2) and class C (-23.0 ± 2.8) patients. Difference between groups B and C was non-significant (figure). Severity of cirrhosis as determined by higher MELD-Na score correlated with LAVI (r = 0.592, p < 0.001), SV (r = 0.554, p < 0.001), GLS (r=-0.441, p = 0.001) and LVEDV (r = 0.428, p = 0.002). GLS correlated with SV (r=-0.369, p = 0.008) but not with preload (LVEDV), or afterload (SBP). In a linear regression model, GLS was independently associated with Meld-Na score when adjusting for age, SBP, LVEDV and NASH etiology [B=-0.139 (-0.252; -0.025), p = 0.018]. Conclusions GLS is lower (more negative) in patients with liver cirrhosis as disease progresses a relation not affected by preload and afterload conditions. Further research works are required to explain the underlying pathophysiology and to assess prognostic significance of reduced GLS values in patients with advanced cirrhosis. Abstract Figure. GLS stratified by Child-Pugh score

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

Blood ◽

10.1182/blood-2019-131226 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5860-5860

Author(s):

Omar Ali Alaber ◽

Apoorva Krishna Chandar ◽

Basma Ali Dahash ◽

Sohi N Mistry ◽

Stanley Martin Cohen ◽

...

Keyword(s):

Liver Cirrhosis ◽

Portal Vein ◽

Portal Vein Thrombosis ◽

Current Evidence ◽

National Database ◽

Insurance Status ◽

Vein Thrombosis ◽

Cirrhotic Patients ◽

Newer Anticoagulants ◽

First Time

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

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Anticoagulant Treatment for Splanchnic Vein Thrombosis in Liver Cirrhosis: A Systematic Review and Meta-Analysis

Thrombosis and Haemostasis ◽

10.1055/s-0040-1722192 ◽

2021 ◽

Author(s):

Emanuele Valeriani ◽

Marcello Di Nisio ◽

Nicoletta Riva ◽

Omri Cohen ◽

Ettore Porreca ◽

...

Keyword(s):

Systematic Review ◽

Liver Cirrhosis ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Meta Analysis ◽

Anticoagulant Treatment ◽

Splanchnic Vein Thrombosis ◽

Vein Thrombosis ◽

Cirrhotic Patients ◽

Overall Mortality

Abstract Background Splanchnic vein thrombosis (SVT) is a common complication in patients with liver cirrhosis. The aim of this study was to evaluate the efficacy and safety of anticoagulant therapy for SVT in cirrhotic patients. Methods In this systematic review and meta-analysis, studies reporting on SVT recanalization and progression, recurrent venous thromboembolism (VTE), major bleeding, and overall mortality were searched in MEDLINE, EMBASE, and ClinicalTrial.gov up to December 2019. Pooled proportions and risk ratios (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Results A total of 1,475 patients were included in 26 studies (23 observational and 3 randomized controlled trials). In patients receiving anticoagulant therapy, SVT recanalization occurred in 68% (95% CI, 62–74; 571/842 patients; 22 studies), SVT progression in 6% (95% CI, 4–9; 25/748 patients; 22 studies), recurrent VTE in 10% (95% CI, 4–22; 48/399 patients; 7 studies), major bleeding in 6% (95% CI, 4–10; 58/785 patients; 18 studies), and overall mortality in 9% (95% CI, 6–14; 68/787 patients; 17 studies). Anticoagulant treatment was associated with higher SVT recanalization (RR 3.19; 95% CI, 1.42–7.17), lower thrombosis progression (RR 0.28; 95% CI, 0.15–0.52), major bleeding (RR 0.52; 95% CI, 0.28–0.97), and overall mortality (RR 0.42; 95% CI, 0.24–0.73) compared with no treatment. Conclusion Anticoagulant therapy seems to improve vein recanalization and to reduce SVT progression, major bleeding, and overall mortality in cirrhotic patients with SVT. The incidence of recurrent VTE during anticoagulation remains substantial.

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Correlation of Grading of Esophageal Varices with Child Turcotte Pugh Class in Patients of Liver Cirrhosis

Journal of Nepalgunj Medical College ◽

10.3126/jngmc.v16i2.24879 ◽

2018 ◽

Vol 16 (2) ◽

pp. 50-53

Author(s):

Anil Shrestha ◽

Dipendra Khadka ◽

Richa Shrestha

Keyword(s):

Liver Cirrhosis ◽

Esophageal Varices ◽

Upper Gastrointestinal Endoscopy ◽

Cross Sectional ◽

Class A ◽

Red Color ◽

Class B ◽

Pugh Class ◽

Cirrhotic Patients ◽

Small Varices

Background: Majority of cirrhotic patients develop varices over their lifetime and it is anticipated that roughly one third of varices will develop bleeding. Child Turcotte Pugh (CTP) class predicts the risk of variceal bleeding and has been used as a prognostic tool inpatients of liver cirrhosis. Objective: To correlate grade of esophageal varices in Upper Gastrointestinal endoscopy with Child Turcotte Pugh class in patients of liver cirrhosis. Material and method: This is a cross sectional descriptive study conducted in thedepartment of medicine of NGMCTH, Kohalpur between December 2017 to November 2018. A total of 97 patients were included inthe study who were diagnosed as cirrhosis of liver clinically and radio logically. Patient were classified into CTP class A, B and According to CTP score. UGI endoscopy was performed and endoscopic grading of esophageal varices were correlated with CTP classand the data were recorded and analysed. Result: Mean of patients was 50 years. Among 97 patients, 30 (30.9%) were in CTP class A,30 (30.9%) in CTP class B and 37 (38.1%) were in CTP class C. 25 (25.8%) had small varices, 50 (51.5%) had large varices with red colorsign, 20 (20.6%) had large varices without red color sign and 2 (2.1%) had no varices. Most of the patients in CTP class B and C hadlarge varices with red color sign whereas CTP class A had small varices. Conclusion: The cirrhotic patients in CTP class B and C havelarge varices with red color sign and have more chances of bleeding. Hence, routine screening is indicated to determine the presenceof varices. Porphylactic therapy after identifying large varices will decrease the incidence of bleeding leading to reduction inmortality rate.

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