Pro-coagulant imbalance in patients with chronic liver disease

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Assessing spleen stiffness by point shear‐wave elastography: Is it feasible and reproducible in patients with chronic liver disease? Is it useful to predict portal hypertension?

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Baveno-VII criteria to predict decompensation and initiate non-selective beta-blocker in compensated advanced chronic liver disease patients

Background/Aims The utility of Baveno-VII criteria of clinically significant portal hypertension (CSPH) to predict decompensation in compensated advanced chronic liver disease (cACLD) patient needs validation. We aim to validate the performance of CSPH criteria to predict the risk of decompensation in an international real-world cohort of cACLD patients. Methods cACLD patients were stratified into three categories (CSPH excluded, grey zone, and CSPH). The risks of decompensation across different CSPH categories were estimated using competing risk regression for clustered data, with death and hepatocellular carcinoma as competing events. The performance of “treating definite CSPH” strategy to prevent decompensation using non-selective beta-blocker (NSBB) was compared against other strategies in decision curve analysis. Results One thousand one hundred fifty-nine cACLD patients (36.8% had CSPH) were included; 7.2% experienced decompensation over a median follow-up of 40 months. Non-invasive assessment of CSPH predicts a 5-fold higher risk of liver decompensation in cACLD patients (subdistribution hazard ratio, 5.5; 95% confidence interval, 4.0–7.4). “Probable CSPH” is suboptimal to predict decompensation risk in cACLD patients. CSPH exclusion criteria reliably exclude cACLD patients at risk of decompensation, regardless of etiology. Among the grey zone, the decompensation risk was negligible among viral-related cACLD, but was substantially higher among the non-viral cACLD group. Decision curve analysis showed that “treating definite CSPH” strategy is superior to “treating all varices” or “treating probable CSPH” strategy to prevent decompensation using NSBB. Conclusions Non-invasive assessment of CSPH may stratify decompensation risk and the need for NSBB in cACLD patients

Etiology, management, and outcome of the Budd-Chiari syndrome

Background: The Budd-Chiari syndrome (BCS) is hepatic venous outflow obstruction. What is known about the syndrome is based on small studies of prevalent cases. Objective: To characterize the causes and treatment of incident BCS. Design: Consecutive case series of patients with incident BCS, enrolled from October 2003 to October 2005 and followed until May 2006. Setting: Academic and nonacademic hospitals in France, Spain, Italy, Great Britain, Germany, Belgium, the Netherlands, Portugal, and Switzerland. Patients: Persons older than 16 years with definite hepatic outflow obstruction diagnosed by imaging. Persons with hepatic outflow obstruction due to heart failure, sinusoidal obstruction syndrome, cancer, or liver transplantation were excluded. Measurements: Signs and symptoms; laboratory and imaging findings; diagnosis; treatment; and overall, transplantation-free, and intervention-free survival. Results: 163 incident cases of BCS were identified. Median follow-up was 17 months (range, 0.1 to 31 months). Most patients (84%) had at least 1 thrombotic risk factor, and many (46%) had more than 1; the most common was myeloproliferative disorders (49% of 103 tested patients). Patients were mainly treated with anticoagulation (140 patients [86%]), transjugular intrahepatic portosystemic shunting (56 patients [34%]), or liver transplantation (20 patients [12%]), and 80 patients (49%) were managed noninvasively. Only 3 patients underwent surgical shunting. The survival rate was 87% (95% CI, 82% to 93%) at 1 year and 82% (CI, 75% to 88%) at 2 years. Limitation: Treatment was not standardized across all centers, and data on important clinical variables were missing for some patients. Conclusion: Most patients with BCS have at least 1 thrombotic risk factor, and many have more than 1; myeloproliferative disorders are most common. One- and 2-year survival rates are good with contemporary management, which includes noninvasive therapies (anticoagulation and diuretics) and invasive techniques. Transjugular intrahepatic portosystemic shunting seems to have replaced surgical shunting as the most common invasive therapeutic procedure. Primary Funding Source: Fifth Framework Programme of the European Commission

Somatic calreticulin mutations in patients with Budd-Chiari syndrome and portal vein thrombosis

Carta a l'editorWe studied the role of the recently identified CALR mutations in 141 patients with Budd-Chiari Syndrome (BCS) or portal vein thrombosis (PVT) in a large multinational cohort. A CALR mutation was present in one of the 141 patients (0.7%). This patient was previously diagnosed with primary myelofibrosis. This results in CALR positivity in one out of 44 (2.3%) patients with myeloproliferative neoplasm (MPN), and in one of 11 (9.1%) JAK2V617F negative patients diagnosed with MPN. We suggest that analysis of CALR mutations should be performed in JAK2V617F negative BCS and PVT patients..

Use of albumin infusion for cirrhosis-related complications: An international position statement

BACKGROUND & AIMS: Numerous studies have evaluated the role of human albumin (HA) in managing various liver cirrhosis-related complications. However, their conclusions remain partially controversial, probably because HA was evaluated in different settings, including indications, patient characteristics, and dosage and duration of therapy. METHODS: Thirty-three investigators from 19 countries with expertise in the management of liver cirrhosis-related complications were invited to organise an International Special Interest Group. A three-round Delphi consensus process was conducted to complete the international position statement on the use of HA for treatment of liver cirrhosis-related complications. RESULTS: Twelve clinically significant position statements were proposed. Short-term infusion of HA should be recommended for the management of hepatorenal syndrome, large volume paracentesis, and spontaneous bacterial peritonitis in liver cirrhosis. Its effects on the prevention or treatment of other liver cirrhosis-related complications should be further elucidated. Long-term HA administration can be considered in specific settings. Pulmonary oedema should be closely monitored as a potential adverse effect in cirrhotic patients receiving HA infusion. CONCLUSIONS: Based on the currently available evidence, the international position statement suggests the potential benefits of HA for the management of multiple liver cirrhosis-related complications and summarises its safety profile. However, its optimal timing and infusion strategy remain to be further elucidated. IMPACT AND IMPLICATIONS: Thirty-three investigators from 19 countries proposed 12 position statements on the use of human albumin (HA) infusion in liver cirrhosis-related complications. Based on current evidence, short-term HA infusion should be recommended for the management of HRS, LVP, and SBP; whereas, long-term HA administration can be considered in the setting where budget and logistical issues can be resolved. However, pulmonary oedema should be closely monitored in cirrhotic patients who receive HA infusion

Congenital extrahepatic portosystemic shunts (Abernethy malformation): An international observational study

Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology

Bakground & aims Although discrimination of the model for end stage liver disease (MELD) is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discrimination and calibration performance of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intra-hepatic portosystemic shunt (TIPS); classic MELD-Mayo; MELD-UNOS, used by United Network for Organ Sharing (UNOS). Recalibration and model updating were also explored. Methods 776 patients submitted to elective TIPS (TIPS cohort), and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. Results Major patient characteristics in TIPS/non-TIPS cohorts were: viral etiology 402/188, alcoholic 185/130, NASH 65/33; mean follow-up± SD 25±9/19±21months; 3-6-12 month mortality were respectively, 57-102-142/31-47-99. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post-hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used for a MELD updating. Conclusions In this validation study the MELD performance was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for a MELD updating are proposed. Lay summary While discrimination performance of the Model for End Stage Liver Disease (MELD) is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in two independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis and propose a validated model recalibration. Candidate variables for a MELD updating are proposed

Preemptive-TIPS improves outcome in high-risk variceal bleeding : An observational study

Objective Patients admitted with acute variceal bleeding (AVB) and Child Pugh C score (CP\u2010C) or Child Pugh B plus active bleeding at endoscopy (CP\u2010B+AB) are at high risk for treatment failure, rebleeding and mortality. Preemptive TIPS (p\u2010TIPS) has been shown to improve survival in these patients but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high\u2010risk patients. Design Multicenter, international, observational study including 671 patients from 34 centers admitted for AVB and high\u2010risk of treatment failure. Patients were managed according to current guidelines and use of drugs and endoscopic therapy (D+E) or preemptive TIPS (p\u2010TIPS) was based on individual center policy. Results p\u2010TIPS in the setting of AVB is associated with a lower mortality in Child C patients compared to D+E (1 year mortality 22% vs 47% in D+E group; P=0.002). Mortality rate in CP\u2010B+AB patients was low and p\u2010TIPS did not improve it. In CP\u2010C and CP\u2010B +AB patients, p\u2010TIPS reduces treatment failure and rebleeding (1 year CIF\u2010probability of remaining free of the composite endpoint: 92% vs 74% in the D+E group; P=0.017), development of \u201cde novo\u201d or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion p\u2010TIPS must be the treatment of choice in CP\u2010C patients with AVB. Due to the strong benefit in preventing further bleeding and ascites, p\u2010TIPS could be a good treatment strategy for CP\u2010B+AB patients