Anticoagulación de la trombosis venosa portal en la cirrosis

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Budd-Chiari syndrome with short-length stenosis: still room for the angioplasty and wait-and-see strategy

We read with interest the study in The Lancet Gastroenterology & Hepatology by Qiuhe Wang and colleagues. 1 This randomised controlled trial aimed to elucidate whether routine stenting plus angioplasty was superior to angioplasty alone for preventing restenosis in patients with Budd-Chiari syndrome with short-length stenosis. The authors found that patients treated with angioplasty plus routine stenting had a lower incidence of restenosis than did patients treated with angioplasty alone, with no differences in survival. Based on these findings, the authors suggested that stenting combined with angioplasty should be used as a first-line invasive treatment in patients with Budd-Chiari syndrome with short-length stenosis

Reliability of the estimation of total hepatic blood flow by doppler ultrasound in patients with cirrhotic portal hypertension

BACKGROUND & AIMS: Hepatic blood flow (HBF) is best estimated by the Fick's method during indocyanine green constant infusion (ICG-HBF) on hepatic vein catheterization. We investigated the consistency and agreement of HBF measured by Doppler ultrasound (US-HBF) as compared with ICG-HBF in portal hypertensive patients with cirrhosis. METHODS: In 50 patients observed for HVPG measurement (56% compensated; Child score 7 ± 2; HVPG 16.6 ± 6.0 mmHg; varices in 75%) US-HBF (Sequoia-512-Acuson; 4.5-7 MHz convex probe; US-HBF = hepatic artery blood flow+portal vein blood flow) and ICG-HBF (Fick's method after an equilibration period of at least 45 min of ICG bolus of 5 mg + constant rate infusion of 0.2 mg/min). Intraclass correlation coefficient (ICC) for consistency and absolute agreement between US-HBF and ICG-HBF were calculated. RESULTS: Mean ICG-HBF and US-HBF were similar, being respectively 1004 ± 543 ml/min and 994 ± 494 ml/min (p = 0.661 vs. ICG-HBF). However, results in individual patients disclosed marked differences between the two methods (386 ± 415 ml/min) and showed only moderate consistency (ICC 0.456; p < 0.0001), absolute agreement (ICC 0.461; p < 0.0001) and linear correlation (R = 0.464; p < 0.0001). The discrepancy between the two methods was maximal in patients with poor liver function, high HBF by any technique and more arterialized liver circulation. Hepatic artery blood flow ≥40% of US-HBF indicated, with 90% specificity, a discrepancy ≥20% between US-HBF and ICG-HBF. CONCLUSIONS: HBF estimations by Doppler-ultrasound and ICG are significantly correlated, but their discrepancy in individual cases is high. Estimation of HBF by Doppler-US should be considered unreliable in patients with poor hepatic function and large liver arterialization

Pyogenic granuloma in the jejunum successfully removed by single-balloon enteroscopy

Pyogenic granuloma is a non-infectious and non-granulomatous lesion. Its location in the small bowel is very rare. We present a 46 year-old woman with a chronic liver disorder that had a severe chronic anemia with occult blood losses. Upper endoscopy and colonoscopy were normal. A small bowel capsule endoscopy showed a pyogenic granuloma in jejunum that was resected endoscopically with single balloon enteroscopy with no major complications. The patient recovered from anemia and six months latter capsule endoscopy did not show lesions

A new prognostic algorithm based on stage of cirrhosis and HVPG to improve risk-stratification after variceal bleeding

Background & Aims: HVPG decrease ≥20% or ≤12mmHg (“responders”) indicates good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed at simplifying risk‐stratification after variceal bleeding using clinical data and HVPG. Methods: 193 cirrhotic patients (62% with ascites and/or hepatic encephalopathy, HE) included within 7‐days of bleeding had HVPG measured before and at 1‐3 months of treatment with propranolol/nadolol plus endoscopic band ligation. End‐points: Rebleeding and rebleeding/transplantation‐free survival for 4‐years. Another cohort (n=231) served as validation set. Results: During follow‐up 45 patients had variceal bleeding and 61 died. HVPG‐responders (n=71) had lower rebleeding‐risk (10% vs 34%, p=0.001) and better survival than 122 non‐responders (61% vs 39%, p=0.001). Patients with/HE (n=120) had lower survival than patients without (40% vs 63%, p=0.005). Among patients with ascites/HE, those with baseline HVPG≤16mmHg (n=16) had low rebleeding‐risk (13%). By contrast, among patients with ascites/HE and baseline HVPG>16mmHg, only HVPG‐responders (n=32) had good prognosis, with lower rebleeding‐risk and better survival than non‐responders (n=72) (respective proportions: 7% vs 39%,p=0.018; 56% vs 30% p=0.010). These findings allowed developing a new algorithm for risk‐stratification in which HVPG‐response was only measured in patients with ascites and/or HE and baseline HVPG>16mmHg. This algorithm reduced the grey‐zone (high‐risk patients not dying on follow‐up) from 46% to 35% and decreased by 42% the HVPG measurements required. The validation cohort confirmed these results. Conclusion: Restricting HVPG measurements to patients with ascites/HE and measuring HVPG‐response only if baseline HVPG>16mmHg improves detection of high‐risk patients while markedly reducing the number of HVPG measurements required

Elastography, spleen size, and platelet count identify portal hypertension in patients with compensated cirrhosis

BACKGROUND & AIMS: Noninvasive methods are needed to identify clinically significant portal hypertension (CSPH) and esophageal varices (EVs) in patients with compensated cirrhosis. We looked for markers of the presence of CSPH and EVs in patients with cirrhosis. METHODS: We performed a cross-sectional study that included a training set of 117 patients with compensated cirrhosis, confirmed by histology, from a tertiary referral center. Spleen diameter was measured by ultrasound, and liver stiffness (LS) was measured by transient elastography; endoscopy was used as the standard for detection of EVs, and measurements of hepatic venous pressure gradient were used as the standard for identifying CSPH. We assessed the ability of platelet count, spleen diameter, LS, and combinations of these factors (ie, ratio of platelet count to spleen size, and LS × spleen size/platelet count [LSPS]) to identify patients with CSPH and EV. The analysis included 2 new statistical models: the PH risk score and the varices risk score. Results were validated using an independent series of 56 patients with compensated patients from another center. RESULTS: LS was the best single noninvasive variable for identifying patients with CSPH (area under the receiver operating characteristic, 0.883; 95% confidence interval [CI], 0.824-0.943; P < .0001). The area under the receiver operating characteristic value increased when LS was combined with platelet count and spleen size, either as LSPS (0.918; 95% CI, 0.872-0.965; P < .0001) or PH risk score (0.935; 95% CI, 0.893-0.977; P < .0001). More than 80% of patients were accurately classified using LSPS and PH risk score. Analyses of the varices risk score and LSPS were superior to all other noninvasive tests for identifying patients with EVs (area under the receiver operating characteristic, 0.909; 95% CI, 0.841-0.954 and 0.882; 95% CI, 0.810-0.935, respectively); they correctly classified 85% of patients in the training set and 75% in the validation set. CONCLUSIONS: Combined data on LS, spleen diameter, and platelet count can be used to identify patients with compensated cirrhosis most likely to have CSPH and EV

Terutroban, A TP-receptor antagonist, reduces portal pressure in cirrhotic rats

Increased production of vasoconstrictive prostanoids, such as thromboxane A2 (TXA2 ), contributes to endothelial dysfunction and increased hepatic vascular tone in cirrhosis. TXA2 induces vasoconstriction by way of activation of the thromboxane-A2 /prostaglandin-endoperoxide (TP) receptor. This study investigated whether terutroban, a specific TP receptor blocker, decreases hepatic vascular tone and portal pressure in rats with cirrhosis due to carbon tetrachloride (CCl4 ) or bile duct ligation (BDL). Hepatic and systemic hemodynamics, endothelial dysfunction, liver fibrosis, hepatic Rho-kinase activity (a marker of hepatic stellate cell contraction), and the endothelial nitric oxide synthase (eNOS) signaling pathway were measured in CCl4 and BDL cirrhotic rats treated with terutroban (30 mg/kg/day) or its vehicle for 2 weeks. Terutroban reduced portal pressure in both models without producing significant changes in portal blood flow, suggesting a reduction in hepatic vascular resistance. Terutroban did not significantly change arterial pressure in CCl4 -cirrhotic rats but decreased it significantly in BDL-cirrhotic rats. In livers from CCl4 and BDL-cirrhotic terutroban-treated rats, endothelial dysfunction was improved and Rho-kinase activity was significantly reduced. In CCl4 -cirrhotic rats, terutroban reduced liver fibrosis and decreased alpha smooth muscle actin (α-SMA), collagen-I, and transforming growth factor beta messenger RNA (mRNA) expression without significant changes in the eNOS pathway. In contrast, no change in liver fibrosis was observed in BDL-cirrhotic rats but an increase in the eNOS pathway. CONCLUSION: Our data indicate that TP-receptor blockade with terutroban decreases portal pressure in cirrhosis. This effect is due to decreased hepatic resistance, which in CCl4 -cirrhotic rats was linked to decreased hepatic fibrosis, but not in BDL rats, in which the main mediator appeared to be an enhanced eNOS-dependent vasodilatation, which was not liver-selective, as it was associated with decreased arterial pressure. The potential use of terutroban for portal hypertension requires further investigation

Current knowledge in pathophysiology and management of Budd-Chiari syndrome and non-cirrhotic non-tumoral splanchnic vein thrombosis

Budd-Chiari Syndrome (BCS) and non-cirrhotic non-tumoral portal vein thrombosis (NCPVT) are two rare disorders, with several similarities that are categorized under the term splanchnic vein thrombosis. Both disorders are frequently associated with an underlying pro-thrombotic disorder. They can cause severe portal hypertension and usually affect oung patients, negatively influencing life expectancy when the diagnosis and treatment is not done at an early stage. Yet, they have specific features that require individual considerations. The current review will focus on the available knowledge on pathophysiology, diagnosis and management of both entities. BCS is defined as the obstruction of hepatic venous outflow regardless of its causative mechanism or level of obstruction. This obstruction can be traced to the small hepatic venules up to the entrance of the inferior vein cava (IVC) into the right atrium. Hepatic outflow obstruction related to cardiac disease, pericardial disease or sinusoidal obstruction syndrome have different pathophysiological and clinical implications and are excluded from this definition. BCS is classified as primary when the obstruction originates in the vein and thrombosis is the main cause, or secondary when the vein is externally compressed (abscess, tumor). The focus of this review is on primary BCS. NCPVT refers to the presence of a thrombus in the main portal vein trunk and/or the left or right intrahepatic portal vein branches that may extend to the splenic vein and/or the superior or inferior mesenteric veins. Isolated splenic or mesenteric vein thrombosis are out of the scope of this review.Copyright © 2019. Published by Elsevier B.V

PPARa activation improves endothelial dysfunction and reduces fibrosis and portal pressure in cirrhotic rats

Background & Aims: Peroxisome proliferator-activated receptor a (PPARa) is a transcription factor activated by ligands that regulates genes related to vascular tone, oxidative stress, and fibrogenesis, pathways implicated in the development of cirrhosis and portal hypertension. This study aims at evaluating the effects of PPARa activation with fenofibrate on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl4-cirrhotic rats. Methods: Mean arterial pressure (MAP), portal pressure (PP), and portal blood flow (PBF) were measured in cirrhotic rats treated with oral fenofibrate (25 mg/kg/day, n = 10) or its vehicle (n = 12) for 7 days. The liver was then perfused and dose-relaxation curves to acetylcholine (Ach) were performed. We also evaluated Sirius Red staining of liver sections, collagen-I mRNA expression, and smooth muscle actin (a-SMA) protein expression, cyclo-oxygenase-1 (COX-1) protein expression, and cGMP levels in liver homogenates, and TXB2 production in perfusates. Nitric oxide (NO) bioavailability and eNOS activation were measured in hepatic endothelial cells (HEC) isolated from cirrhotic rat livers. Results: CCl4 cirrhotic rats treated with fenofibrate had a significantly lower PP (29%) and higher MAP than those treated with vehicle. These effects were associated with a significant reduction in hepatic fibrosis and improved vasodilatory response to acetylcholine. Moreover, a reduction in COX-1 expression and TXB2 production in rats receiving fenofibrate and a significant increase in NO bioavailability in HEC with fenofibrate were observed. Conclusions: PPARa activation markedly reduced PP and liver fibrosis and improved hepatic endothelial dysfunction in cirrhotic rats, suggesting it may represent a new therapeutic strategy for portal hypertension in cirrhosis

Congenital antithrombin deficiency in patients with splanchnic vein thrombosis

Splanchnic vein thromboses (SVT) are a rare condition that can be life-threatening. The most severe thrombophilia associated to SVT is antithrombin (AT) deficiency, usually caused by SERPINC1 mutations. Although transitory AT deficiencies and congenital disorders of the N-glycosylation pathways (CDG) have been recently reported as causes of AT deficiency, the current AT clinical screening still only includes anti-FXa activity. This study aims to 1) improve the detection of antithrombin deficiency in SVT and 2) characterize the features of antithrombin deficiency associated with SVT.The study was performed in 2 cohorts: 1) 89 SVT patients with different underlying etiologies but in whom AT deficiency had been ruled out by classical diagnostic methods; and 2) 271 unrelated patients with confirmed AT deficiency and venous thrombosis. Antithrombin was evaluated by functional (anti-FXa and anti-FIIa) and immunological methods (ELISA, crossed immunoelectrophoresis, western blot), and SERPINC1 sequencing was performed.In 4/89 patients (4.5%) additional alterations in AT were found (two had SERPINC1 mutations, one had a specific variant causing transient AT deficiency and one patient had CDG). In 11 of the 271 patients (4.1%) with AT deficiency and thrombosis, thrombosis was located at the splanchnic venous territory.AT deficiency may be underdiagnosed by current clinical screening techniques. Therefore, a comprehensive AT evaluation should be considered in cases of rethrombosis or doubtful interpretation of anti-FXa activity levels. SVT is a relatively common localization of the thrombotic event in patients with congenital AT deficiency.© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd