Prevalence of chronic venous insufficiency and deep vein thrombosis in cirrhotic patients.

Summary: People with cirrhosis of the liver are at risk for complications that can worsen their quality of life and increase morbidity and mortality. Contrary to previous beliefs, cirrhosis does not protect against the development of thromboembolic events, and cirrhotic patients may have higher rates of deep vein thrombosis (DVT). Background and aims: The study of chronic venous disease and its impact on patients with cirrhosis is unknown in the literature and may be an important fact since this condition also had impact on quality of life and morbidity. The aim of this study is to evaluate the prevalence of DVT (Deep Venous thrombosis) in outpatients with cirrhosis and the degree of chronic venous insufficiency, evaluating possible correlations between clinical and laboratory aspects of cirrhotic patients with these pathologies. Methods: Patients with cirrhosis were evaluated in the outpatient clinic of the Liver Transplantation and Hepatology Service of HC-FMUSP from November 2018 to November 2022, with clinical evaluation, venous disease questionnaires, data collection of imaging and laboratory tests, and venous color Doppler ultrasound. The information was analyzed by the University of São Paulo (USP) Statistics Department. Results: There was a prevalence of 7.6% of DVT in studied patients, VCSS score 6.73 and severe CEAP classification (C4-6) 32.1%. There was no association of DVT with qualitative variables by the Fisher test such as Child Turcotte Pugh Scale (CTP) (p = 0.890), dichotomized INR values (p = 0.804), etiology of cirrhosis (p = 0.650) and chronic kidney disease (p > 0.999), nor with quantitative variables by t-student's such as age (p = 0.974), Body Mass Index (BMI) (p = 0.997), MELD score (p = 0.555), Albumin (p = 0.150) and Platelets (p = 0.403). We found that as the severity of ascites increases, there is an increase in the proportion of patients classified in the category indicating more severe clinical manifestations of chronic venous disease (C4 to C6). The mean age (54 years) was higher in patients with DVT than in those without. The mean BMI of patients without DVT (25.7 kg/m2) is lower than that of patients with DVT (27.0 kg/m2). The prevalence of DVT is higher in patients with thrombophilia (20.0%) than in those without (7.0%). This suggests an association between the two variables. The descriptive measures of the MELD score, the cirrhosis scale used for liver transplant waiting lists, did not indicate an association of this scale with the occurrence of DVT. Conclusion: The incidence of VTE (Venous Thromboembolic Events) and CVD (Chronic Venous Disease) within the sample surpassed that of the general population; nevertheless, more studies are required to validate these results. Concerning venous thromboembolism, no correlation was observed between the variables within the sample and the augmented risk of VTE. Regarding chronic venous disease, studies have shown that edema and orthostatism are correlated with increased severity of CVD on the VCSS scales. Statistical dispersion methods suggest that patients with higher BMI and more severe liver disease (according to the Child-Pugh score) are more likely to experience worsening of CVD. About chronic venous disease, studies have shown that edema and orthostatism are correlated with increased severity of CVD on the VCSS scales.

Venous thromboembolism in in-hospital cirrhotic patients: A systematic review.

Introduction: Patients with liver cirrhosis are at a higher risk of hospitalization. The present review aimed to assess the risk of thromboembolism and its burden on hospitalized cirrhotic patients. Materials and methods: A systematic review (PROSPERO: CRD42021256869) was conducted in PubMed, Embase, Cochrane, Lilacs, and a manual search of references. It evaluated studies that compare cirrhotic patients with venous thromboembolism (VTE) with cirrhotic patients without VTE or studies that compare cirrhotic patients with non-cirrhotic patients. No restrictions were set for the date of publication or language. The last search was conducted in June 2021. Results: After selection, 17 studies were included from an initial search of 5,323 articles. The chronic liver disease etiologies comprise viral, alcohol, autoimmune, NASH (non-alcoholic steatohepatitis), cryptogenic, hemochromatosis, cholestasis, and drug-related. The included studies were conflicted regarding the outcomes of VTE, pulmonary embolism, or bleeding. Patients with cirrhosis associated with VTE had prolonged length of hospital stay, and patients with cirrhosis were at higher risk of portal thrombosis. Conclusion: In-hospital cirrhotic patients are a heterogeneous group of patients that may present both thrombosis and bleeding risk. Clinicians should take extra caution to apply both prophylactic and therapeutic anticoagulation strategies. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021256869].

Clinical Validation of a Novel Scoring System Based on Donor and Recipient Risk Factors for Predicting Outcomes in Liver Transplantation.

BACKGROUND Adequate donor and recipient matching in liver transplantation is crucial to improve patient survival. Our objective was to propose and validate a new model for predicting outcomes using donor and recipient scoring criteria. MATERIAL AND METHODS We retrospectively analyzed data of all patients (n=932) who underwent liver transplantation (n=1106) from January 2006 to December 2018. For score standardization, 30% (n=280) of patients were randomly selected for analysis and divided into 3 categories: ≤4 points, 5 to 8 points, and >8 points. Scoring system validation was performed on a dataset with 70% (n=652) of the patients. RESULTS Survival of the stratified group (30%) was significant (P<0.001). Scores of 4 to 8 points presented lower risk of death (1.74 [CI 0.97-3.13; P=0.062]), while >8 points presented higher risk (2.74 [CI 1.36-5.57; P=0.005]). In the validation score (70%), global survival was significant (P<0.0016); patients with scores of 4 to 8 points had lower risk of death (1.16 [CI 1.16-2.38; P=0.005]); and scores >8 points (2.22 [CI 1.40-3.50; P<0.001]), retransplant, fulminant hepatitis, previous large abdominal/biliary tree surgery, MELD score, and serum creatinine before liver transplantation >1.5 mg/dL (P<0.05) presented higher risk. Individual recipient factors with 4 to 8 points had a lower risk of death (2.29 [CI 1.82-2.87; P<0.0001]) than those with scores >8 points (4.02 [CI 2.22-7.26; P<0.0001]). CONCLUSIONS A novel prognostic-based scoring system using donor and recipient characteristics was proposed and clinically validated. Two-factor scoring indicated the superiority of the predictability outcome and improved prediction of higher mortality.

Prognostic Factors Evaluation for Liver Transplant Mismatching: A New Way of Selecting and Allocating Organs.

BACKGROUND: Liver transplant (LT) is the standard therapy for end-stage liver disease. Advances in surgical techniques and immunosuppression protocols improved the results of LT by increasing long-term survival. Nevertheless, an adequate match between the donor and recipient is paramount for avoiding futile liver transplants. We aimed to identify the prognostic factors in donor-recipient LT matching. METHODS: Retrospective analysis of adult LT was conducted from January 2006 to December 2018, which included the following transplant modalities: deceased donor LT (DDLT), living donor LT (LDLT), combined liver-kidney transplant (CLKT), and domino LT (DLT). RESULTS: Among 1101 patients who underwent LT, 958 patients underwent DDLT, 92 patients underwent LDLT, 45 patients underwent CLKT, and 6 patients underwent DLT. The overall survival (OS) in 1, 5, and 10 years were 89%, 83%, and 82%, respectively. For DDLT, OS in 1, 5, and 10 years were 91%, 84%, and 82%, respectively. For LDLT, OS in 1, 5, and 10 years were 89%, 72%, and 69%, respectively. For CKLT, OS in 1, 5, and 10 years were 90%, 71%, and 71%, respectively. None of the DLT patients died. For DDLT, the factors that affected OS were the presence of fulminant liver failure (odds ratio [OR], 2.23; 95% CI, 1.18-4.18; P = .001), hemodialysis before LT (OR, 2.12; 95% CI, 1.27-3.5; P = .004), retransplant (OR, 4.74; 95% CI, 2.75-8.17; P = .000), and recipient age >60 years (OR, 1.86; 95% CI, 1.27-2.73; P = .001). For hospitalization before LT (due to an acute-on-chronic liver failure), the OR was 2.10 (95% CI, 1.29-3.42; P = .003). Donor intensive care unit time >7 days (OR, 1.46; 95% CI, 1.04-2.06; P = .02) was also associated with overall mortality. CONCLUSIONS: We identified prognostic factors in donor-recipient LT matching. Furthermore, we demonstrated that an adequate organ allocation with donor-recipient selection might increase graft survival and reduce waiting list mortality.

Relationship of Anatomic Variations and Arterial Reconstruction of the Hepatic Artery: Prevalence and Effect on Orthotopic Liver Transplantation.

BACKGROUND: Identifying anatomic variations of the hepatic artery is essential in liver transplantation. The artery supply is crucial for the procedure's success, and, in some cases of anatomic variations, they need reconstruction. Hepatic artery thrombosis is a severe vascular complication. This study evaluated the prevalence of anatomic variations and correlated arterial reconstructions with hepatic artery thrombosis. METHODS: We performed a retrospective analysis of medical records, adult patients undergoing liver transplant, donor's arterial anatomy, arterial reconstructions, and thrombosis after transplant from January 2019 to December 2020. RESULTS: Among 226 cases, 71% had normal anatomy. All these patients met Michel's classification subtypes, of which 161 (71%) were class I, which is the most common. The second most common variation was class II, with 25 donors (11%), followed by class III, with 17 donors (7.5%). Anatomic artery variations were a risk factor for hepatic artery thrombosis development (odds ratio [OR], 7.2; 95% confidence interval [CI], 2.1-22.5; P = .002). In the same way, the artery reconstruction was associated with hepatic artery thrombosis arising with postoperative time (OR, 18.0; 95% CI, 4.9-57.5; P < .001). Global hepatic artery thrombosis occurred in 11 cases (4.87%). CONCLUSION: Anatomic hepatic artery variations are frequent and do not make liver transplant unfeasible. However, variations that require reconstruction may raise the risk of thrombosis.

Experimental Clinical Model of Liver Transplantation in Large White Pigs Without Venovenous Bypass: Pre-, Intra-, and Maintenance Care.

BACKGROUND: Liver transplantation in an animal model is challenging due to hemodynamics and intraoperative anesthetic care. Several models are described in the literature employing different techniques such as venovenous bypass or aortic cross-clamping to maintain hemodynamic stability, although few groups keep the animal alive in the postoperative period. This study aims to evaluate a liver transplantation clinical model in pigs without venovenous bypass or aortic cross-clamping. METHODS: Male pigs weighing 20 to 35 kg underwent liver transplantation surgery without using venovenous bypass or aorta cross-clamping. Protocols were approved by the Animal Care and Use Committee of the University of São Paulo, Brazil. RESULTS: Ten LTs were performed. Cold ischemia and warm ischemia were 119 ± 33.28 minutes and 26 ± 9.6 minutes, respectively. Hemodynamic changes were significantly higher after the postrevasculazation phase: heart rate (P < .001), medium arterial pressure (P < .001), and cardiac output (P = .03). Hypotension was treated with intravenous fluids and, in some cases, with vasoactive drugs especially during the post-reperfusion period. No animals died during the procedure and almost survival until the first postoperative day. Serum aspartate aminotransferase and lactate increased their values in the post-reperfusion phase. CONCLUSIONS: Practice-based on laboratory animals improves surgical skills and the development of experimental models aimed at new advances in this field. Perfecting our technique on the swine model, we could move forward to create a small-for-size model, test new therapeutic strategies, and define the boundaries for safely performing an enlarged liver resection or a partial liver graft transplant.

Small-for-Size Syndrome: Systemic Review in a Porcine Experimental Model.

BACKGROUND: The small-for-size syndrome (SFSS) is characterized by prolonged hyperbilirubinemia, coagulopathy, and/or encephalopathy caused by a small liver graft that cannot sustain the metabolic demands of the recipient after a partial liver transplant (PLT). Models of PLT in pigs are excellent for studying this syndrome. This review aimed to identify the different porcine models of SFSS in the literature and compare their technical aspects and therapeutics methods focused on portal inflow modulation (PIM). METHODS: We performed a systematic review of the porcine experimental model and SFSS. The MEDLINE-PubMed, EMBASE, Cochrane Library, LILACS, and SciELO databases were electronically searched and updated until June 20, 2021. The MeSH terms used were ''ORGAN SIZE'' AND ''LIVER TRANSPLANTATION". RESULTS: Thirteen SFSS porcine models were reported. Four were performed with portocaval shunt to PIM and 3 with mesocaval shunt to PIM. A few studies focused on clinical therapeutics to PIM; a study described somatostatin infusion to avoid SFSS. Initially, studies on PIM showed its potentially beneficial effects without mentioning the minimum portal flow that permits liver regeneration. However, an excessive portal diversion could be detrimental to this process. CONCLUSIONS: The use of porcine models on SFSS resulted in a better understanding of its pathophysiology and led to the establishment of various types of portal modulation, surgical techniques with different complexities, and pharmaceutical strategies such as somatostatin, making clear that without reducing the portal vein pressure the outcomes are poor. With the improvement of these techniques, SFSS can be avoided.