Maria Vega Catalina

Efficacy and Safety of Anticoagulation on Patients With Cirrhosis and Portal Vein Thrombosis

BACKGROUND & AIMS Portal vein thrombosis (PVT) is a frequent event in patients with cirrhosis; it can be treated with anticoagulants, but there are limited data regarding safety and efficacy of this approach. We evaluated this therapy in a large series of patients with cirrhosis and non-neoplastic PVT. METHODS We analyzed data from 55 patients with cirrhosis and PVT, diagnosed from June 2003 to September 2010, who received anticoagulant therapy for acute or subacute thrombosis (n = 31) or progression of previously known PVT (n = 24). Patients with cavernomatous transformation were excluded. Thrombosis was diagnosed, and recanalization was evaluated by using Doppler ultrasound, angio-computed tomography, and/or angio-magnetic resonance imaging analyses. RESULTS Partial or complete recanalization was achieved in 33 patients (60%; complete in 25). Early initiation of anticoagulation was the only factor significantly associated with recanalization. Rethrombosis after complete recanalization occurred in 38.5% of patients after anticoagulation therapy was stopped. Despite similar baseline characteristics, patients who achieved recanalization developed less frequent liver-related events (portal hypertension-related bleeding, ascites, or hepatic encephalopathy) during the follow-up period, but this difference was not statistically significant (P = .1). Five patients developed bleeding complications that were probably related to anticoagulation. A platelet count <50 × 109/L was the only factor significantly associated with higher risk for experiencing a bleeding complication. There were no deaths related to anticoagulation therapy. CONCLUSIONS Anticoagulation is a relatively safe treatment that leads to partial or complete recanalization of the portal venous axis in 60% of patients with cirrhosis and PVT; it should be maintained indefinitely to prevent rethrombosis.

Antiviral therapy decreases hepatic venous pressure gradient in patients with chronic hepatitis C and advanced fibrosis.

BACKGROUNDS:Antiviral therapy (AVT) may improve liver histology in patients with advanced viral hepatitis but its effect on portal pressure remains unknown.AIM:This study was aimed to evaluate the influence of antiviral therapy (AVT) on hepatic venous pressure gradient (HVPG) in hepatitis C virus infected patients with portal hypertension.METHODS:Twenty compensated patients with chronic hepatitis C, fibrosis stage 3 or 4 and HVPG > 5 mmHg received PEG-IFN α2b plus ribavirin. Every patient underwent liver biopsy and portal pressure measurements before and immediately after AT. Biopsies were evaluated according to METAVIR score.RESULTS:HVPG significantly dropped in all but one treated patient, with a mean (SD) reduction of 28.2 (12)% [13.8 (5.6) Vs. 10.2 (3.8) mmHg, p = 0.005]. The percentage of HVPG decrease was significantly greater in patients who achieved a virological end of treatment response [26.2 (12.5)% Vs. 12.7 (8.5)%, p = 0.05] and in those with a decrease of at least 2 points in the grade of inflammation [35.7 (4.5)% Vs. 22.1 (9.5)%, p = 0.015]. Nine out of 11 patients with baseline HVPG ≥ 12 mmHg showed a decrease greater than 20% (3/11) or under the 12 mmHg threshold (6/11).CONCLUSIONS:AVT reduces HVPG in compensated patients with advanced hepatitis C (fibrosis stage 3 or 4) and portal hypertension.

Oral probiotic VSL#3 attenuates the circulatory disturbances of patients with cirrhosis and ascites

The modulation of gut flora constitutes a therapeutic tool in patients with liver disease, but some of its modalities require further investigation. Here, we evaluated the effects of probiotics on the hepatic and systemic haemodynamic alterations of advanced liver disease.

Rebleeding prophylaxis improves outcomes in patients with hepatocellular carcinoma. A multicenter case-control study.

Outcome of variceal bleeding (VB) in patients with hepatocellular carcinoma (HCC) is unknown. We compared outcomes after VB in patients with and without HCC. All patients with HCC and esophageal VB admitted between 2007 and 2010 were included. Follow‐up was prolonged until death, transplantation, or June 2011. For each patient with HCC, a patient without HCC matched by age and Child‐Pugh class was selected. A total of 292 patients were included, 146 with HCC (Barcelona Classification of Liver Cancer class 0‐3 patients, A [in 25], B [in 29], C [in 45], and D [in 41]) and 146 without HCC. No differences were observed regarding previous use of prophylaxis, clinical presentation, endoscopic findings, and initial endoscopic treatment. Five‐day failure was similar (25% in HCC versus 18% in non‐HCC; P = 0.257). HCC patients had greater 6‐week rebleeding rate (16 versus 7%, respectively; P = 0.025) and 6‐week mortality (30% versus 15%; P = 0.003). Fewer patients with HCC received secondary prophylaxis after bleeding (77% versus 89%; P = 0.009), and standard combination therapy was used less frequently (58% versus 70%; P = 0.079). Secondary prophylaxis failure was more frequent (50% versus 31%; P = 0.001) and survival significantly shorter in patients with HCC (median survival: 5 months versus greater than 38 months in patients without HCC; P < 0.001). Lack of prophylaxis increased rebleeding and mortality. On multivariate analysis Child‐Pugh score, presence of HCC, portal vein thrombosis, and lack of secondary prophylaxis were predictors of death. Conclusions: Patients with HCC and VB have worse prognosis than patients with VB without HCC. Secondary prophylaxis offers survival benefit in HCC patients. (Hepatology 2013; 58:2079–2088)

Serum levels of soluble vascular cell adhesion molecule are related to hyperdynamic circulation in patients with liver cirrhosis

Background: In patients with liver cirrhosis, serum levels of soluble vascular cell adhesion molecule‐1 (sVCAM‐1) have been associated with increasing fibrosis and are related to angiogenesis.

Left ventricular systolic function is associated with sympathetic nervous activity and markers of inflammation in cirrhosis

An accurate evaluation of cardiac function in patients with cirrhosis remains a challenge. We used robust echocardiographic indices to characterize left ventricular (LV) systolic function and its relationship to activation of the sympathetic nervous system and inflammation in 59 patients with cirrhosis and 59 age‐matched controls. Additionally, in 11 patients we withdrew beta‐blockers and diuretics and used phenylephrine and albumin infusion to evaluate the response to acute afterload and preload changes (interventional substudy). Measures of systolic LV function such as the ejection intraventricular pressure difference (EIVPD) and the systolic strain rate were higher in patients with cirrhosis than in controls (median [1st‐3rd quartile], 4.0 [3.1‐5.1] versus 2.9 [2.4‐3.6] mm Hg and –1.3 [–1.6 to –1.1] versus –1.2 [–1.6 to –1.1)] s–1, respectively; P < 0.05 for both). EIVPD was related to the severity of liver disease (Model for End‐Stage Liver Disease, rho = 0.45, P < 0.001), the degree of sympathetic nervous system activation (noradrenaline, rho = 0.26, P = 0.05; heart rate variability, rho = –0.43, P = 0.003), and treatment with beta‐blockers (P = 0.001). In the interventional substudy, EIVPD was higher in patients with ascites (6.5 [5.4‐8.5] versus 4.0 [3.9‐5.1] mm Hg, P = 0.045). The decrease in EIVPD induced by phenylephrine was inversely related to baseline systolic function (P < 0.05) and associated with markers of systemic vasodilatation (nitric oxide, rho = –0.66, P = 0.06; diastolic blood pressure, rho = 0.68, P = 0.04) and inflammation (interleukin‐1beta, rho = –0.80, P = 0.009). Conclusion: LV systolic function is enhanced in cirrhosis due to augmented adrenergic tone and modulated by treatment with beta‐blockers; acute afterload stress induces a deeper impairment of systolic function in patients with more advanced degrees of vasodilatation and inflammation; these changes in LV function related to cirrhosis can be assessed using robust echocardiographic methods. (Hepatology 2017;65:2019‐2030).

Systemic inflammation in decompensated cirrhosis

Acute‐on‐chronic liver failure (ACLF) in cirrhosis is characterized by acute decompensation (AD), organ failure(s), and high short‐term mortality. Recently, we have proposed (systemic inflammation [SI] hypothesis) that ACLF is the expression of an acute exacerbation of the SI already present in decompensated cirrhosis. This study was aimed at testing this hypothesis and included 522 patients with decompensated cirrhosis (237 with ACLF) and 40 healthy subjects. SI was assessed by measuring 29 cytokines and the redox state of circulating albumin (HNA2), a marker of systemic oxidative stress. Systemic circulatory dysfunction (SCD) was estimated by plasma renin (PRC) and copeptin (PCC) concentrations. Measurements were performed at enrollment (baseline) in all patients and sequentially during hospitalization in 255. The main findings of this study were: (1) Patients with AD without ACLF showed very high baseline levels of inflammatory cytokines, HNA2, PRC, and PCC. Patients with ACLF showed significantly higher levels of these markers than those without ACLF; (2) different cytokine profiles were identified according to the type of ACLF precipitating event (active alcoholism/acute alcoholic hepatitis, bacterial infection, and others); (3) severity of SI and frequency and severity of ACLF at enrollment were strongly associated. The course of SI and the course of ACLF (improvement, no change, or worsening) during hospitalization and short‐term mortality were also strongly associated; and (4) the strength of association of ACLF with SI was higher than with SCD. Conclusion: These data support SI as the primary driver of ACLF in cirrhosis. (Hepatology 2016;64:1249‐1264).