Publications by authors named "Vincenzo La Mura"

53 Publications

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

J Hepatol 2021 Jul 30. Epub 2021 Jul 30.

Gastroenterology Unit, ASL Latina, Department of Translational and Precision Medicine, "Sapienza" University of Rome, Italy.

Background & Aims: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model.

Methods: In total, 776 patients who underwent 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: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. 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 the 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 to update the MELD.

Conclusions: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed.

Lay Summary: While the discriminative performance of the model for end-stage liver disease (MELD) score 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 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.
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http://dx.doi.org/10.1016/j.jhep.2021.07.018DOI Listing
July 2021

Combined approach for embolization of otherwise unmanageable gastric varices.

Ann Gastroenterol 2021 Jul-Aug;34(4):510-515. Epub 2021 Mar 23.

Radiology Department, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan (Anna Maria Ierardi, Gianpaolo Carrafiello).

Background: This study aimed to determine the feasibility, safety and effectiveness of combined percutaneous transhepatic obliteration (PTO) and balloon-occluded retrograde transvenous obliteration (BRTO) therapy for the treatment of patients with high-risk bleeding gastric varices.

Methods: Ten patients were retrospectively reviewed. All the patients presented gastric varices, according to the Sarin classification, at high risk of bleeding, and not otherwise manageable. Patients with portal vein thrombosis were excluded. All patients were treated with a combination of PTO and BRTO. In all cases the gastric varices were embolized with glue, combined with coils or not, with an occlusion balloon inflated into the shunt. In 7 cases, embolization was immediate; in the remaining 3 the balloon remained inflated for 4 h and in 2 of them embolization of the shunt was required. Technical success was defined as complete obliteration of the gastric varices observed during a contrast-enhanced computed tomography study and endoscopy within 1 month following treatment. Clinical success was defined as absence of bleeding of gastric varices during the follow-up period. Major and minor complications during the follow up were recorded.

Results: Twelve sessions of combined PTO and BRTO procedures were performed in 10 patients; in 2 patients a new combined treatment was required during the follow up. Technical and clinical success was 100%. Neither major nor minor procedure-related complications were observed.

Conclusion: Combined PTO and BRTO therapy is safe and effective for the treatment of gastric varices that cannot be managed otherwise.
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http://dx.doi.org/10.20524/aog.2021.0616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276367PMC
March 2021

Decompensation in Direct-Acting Antiviral Cured Hepatitis C Virus Compensated Patients With Clinically Significant Portal Hypertension: Too Rare to Warrant Universal Β-Blocker Therapy.

Am J Gastroenterol 2021 06;116(6):1342-1344

Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy.

Nonselective β-blockers improve decompensation-free survival in viremic hepatitis C virus compensated cirrhotic patients with clinically significant portal hypertension, but their protective role after sustained virological response by direct-acting antiviral (DAA) is undefined. We evaluated the incidence of decompensation in DAA-cured Child-A patients without high-risk varices. During the 49-month (12-60) follow-up, only one of 148 patients decompensated (ascites), with a 4-year cumulative risk of 1%, but decompensation was associated with hepatocellular carcinoma. The risk of decompensation in DAA cured hepatitis C virus compensated Child-A cirrhotic patients with clinically significant portal hypertension but without high-risk varices is negligible; thus, questioning the need for nonselective β-blocker treatment in this setting (see Visual abstract, Supplemental Digital Content, 1, http://links.lww.com/AJG/B861). JOURNAL/ajgast/04.03/00000434-202106000-00035/inline-graphic1/v/2021-05-28T144026Z/r/image-tiff.
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http://dx.doi.org/10.14309/ajg.0000000000001158DOI Listing
June 2021

Deep vein thrombosis in COVID-19 patients in general wards: prevalence and association with clinical and laboratory variables.

Radiol Med 2021 May 19;126(5):722-728. Epub 2021 Jan 19.

Department of Medicine and Surgery (DiMeC), Unit of Radiology, University of Parma, Parma, Italy.

Background: Preliminary reports suggest a hypercoagulable state in COVID-19. Deep vein thrombosis (DVT) is perceived as a frequent finding in hospitalized COVID-19 patients, but data describing the prevalence of DVT are lacking.

Objectives: We aimed to report the prevalence of DVT in COVID-19 patients in general wards, blinded to symptoms/signs of disease, using lower extremities duplex ultrasound (LEDUS) in random patients. We tested the association of DVT with clinical, laboratory and inflammatory markers and also reported on the secondary endpoint of in-hospital mortality.

Patients/methods: n  = 263 COVID-19 patients were screened with LEDUS between March 01, 2020 and April 05, 2020 out of the overall n = 1012 admitted with COVID-19.

Results: DVT was detected in n = 67 screened patients (25.5%), n = 41 patients (15.6%) died during the index hospitalization. Multiple logistic regression demonstrated that only C-reactive protein (odds ratio 1.009, 95% CI 1.004-1.013, p < 0.001) was independently associated with the presence of DVT at LEDUS. Both age (odds ratio 1.101, 95% CI 1.054-1.150, p < 0.001) and C-reactive protein (odds ratio 1.012, 95% CI 1.006-1.018, p < 0.001) were instead significantly independently associated with in-hospital mortality.

Conclusions: The main study finding is that DVT prevalence in COVID-19 patients admitted to general wards is 25.5%, suggesting it may be reasonable to screen COVID-19 patients for this potentially severe but treatable complication, and that inflammation, measured with serum C-reactive protein, is the main variable associated with the presence of DVT, where all other clinical or laboratory variables, age or D-dimer included, are instead not independently associated with DVT.
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http://dx.doi.org/10.1007/s11547-020-01312-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815188PMC
May 2021

Acute Portal Vein Thrombosis in SARS-CoV-2 Infection: A Case Report.

Am J Gastroenterol 2020 07;115(7):1140-1142

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, U.O.C. Medicina Generale Emostasi e Trombosi, University of Milan, Milan, Italy.

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http://dx.doi.org/10.14309/ajg.0000000000000711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273956PMC
July 2020

The Role of Spleen and Liver Elastography and Color-Doppler Ultrasound in the Assessment of Transjugular Intrahepatic Portosystemic Shunt Function.

Ultrasound Med Biol 2020 07 8;46(7):1641-1650. Epub 2020 May 8.

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, UOC Gastroenterologia ed Endoscopia, Milan, Italy. Electronic address:

The reference standard for assessing transjugular intrahepatic portosystemic shunt (TIPS) function is venography with portosystemic pressure gradient (PPG) measurement. This procedure is invasive and expensive; thus, we assessed the feasibility, reproducibility and diagnostic accuracy of color-Doppler ultrasound (CDUS) and spleen and liver stiffness (LS) measurements for identifying TIPS dysfunction. Twenty-four patients (15 undergoing TIPS placement and nine undergoing TIPS revision) consecutively underwent CDUS examination and LS and spleen stiffness (SS) determination by transient elastography (TE) and point shear-wave elastography (pSWE). All parameters were taken before TIPS placement/revision (1-15 d before) and 24 h after, just before revision by venography. pSWE inter-observer agreement was assessed by intra-class correlation coefficient (ICC). CDUS and elastographic data were correlated (Pearson coefficient) with pressure gradients (hepatic venous pressure gradient [HVPG], PPG). Main determinants of TIPS dysfunction were investigated by linear regression. Forty-nine paired examinations were performed in total: 49 (100%) SS reliable measurements by pSWE and 38 (88%) by TE. The ICC for pSWE values was 0.90 (95% confidence interval [CI] 0.81‒0.94). SS values significantly correlated with HVPG and PPG (R = 0.51, p = 0.01). The area under the Receiver-Operating Characteristic (AUROC) curve of SS for diagnosing TIPS dysfunction was 0.86 (95% CI 0.70‒0.96) using a 25 kPa cutoff. At multivariate analysis, the flow direction of the intrahepatic portal vein branches and SS values were independently associated to TIPS dysfunction. The intrahepatic portal vein branches flow direction and SS value are two simple, highly sensitive parameters accurately excluding TIPS dysfunction. SS measurement by pSWE is feasible, reproducible and both positively and significantly correlates with HVPG and PPG values.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.04.007DOI Listing
July 2020

AB0, von Willebrand factor/factor VIII and portal vein thrombosis in decompensated cirrhosis: Too late to unmask the culprit?

Liver Int 2020 07 18;40(7):1788-1789. Epub 2020 May 18.

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, CRC "A. M. and A. Migliavacca" Center for Liver Disease, Milan, Italy.

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http://dx.doi.org/10.1111/liv.14493DOI Listing
July 2020

Reply.

Hepatology 2020 10;72(4):1494-1495

Division of Gastroenterology, University of Alberta, CEGIIR, Edmonton, AB, Canada.

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http://dx.doi.org/10.1002/hep.31253DOI Listing
October 2020

A Prognostic Strategy Based on Stage of Cirrhosis and HVPG to Improve Risk Stratification After Variceal Bleeding.

Hepatology 2020 10 6;72(4):1353-1365. Epub 2020 Jul 6.

Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Background And Aims: A hepatic venous pressure gradient (HVPG) decrease of 20% or more (or ≤12 mm Hg) indicates a good prognosis during propranolol/nadolol treatment but requires two HVPG measurements. We aimed to simplify the risk stratification after variceal bleeding using clinical data and HVPG.

Methods: A total of 193 patients with cirrhosis (62% with ascites and/or hepatic encephalopathy [HE]) who were within 7 days of bleeding had their HVPG measured before and at 1-3 months of treatment with propranolol/nadolol plus endoscopic band ligation. The endpoints were rebleeding and rebleeding/transplantation-free survival for 4 years. Another cohort (n = 231) served as the validation set.

Results: During follow-up, 45 patients had variceal bleeding and 61 died. The HVPG responders (n = 71) had lower rebleeding risk (10% vs. 34%, P = 0.001) and better survival than the 122 nonresponders (61% vs. 39%, P = 0.001). Patients with HE (n = 120) had lower survival than patients without HE (40% vs. 63%, P = 0.005). Among the patients with ascites/HE, those with baseline HVPG ≤ 16 mm Hg (n = 16) had a low rebleeding risk (13%). In contrast, among patients with ascites/HE and baseline HVPG > 16 mm Hg, only the HVPG responders (n = 32) had a good prognosis, with lower rebleeding risk and better survival than the nonresponders (n = 72) (respective proportions: 7% vs. 39%, P = 0.018; 56% vs. 30% P = 0.010). These findings allowed us to develop a strategy for risk stratification in which HVPG response was measured only in patients with ascites and/or HE and baseline HVPG > 16 mm Hg. This method reduced the "gray zone" (i.e., high-risk patients who had not died on follow-up) from 46% to 35% and decreased the HVPG measurements required by 42%. The validation cohort confirmed these results.

Conclusions: Restricting HVPG measurements to patients with ascites/HE and measuring HVPG response only if the patient's baseline HVPG is over 16 mm Hg improves detection of high-risk patients while markedly reducing the number of HVPG measurements required.
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http://dx.doi.org/10.1002/hep.31125DOI Listing
October 2020

Total area of spontaneous portosystemic shunts independently predicts hepatic encephalopathy and mortality in liver cirrhosis.

J Hepatol 2020 06 15;72(6):1140-1150. Epub 2020 Jan 15.

Department of Radiology, University of Bonn, Bonn, Germany.

Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.

Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.

Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02-2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA.

Conclusion: This study suggests that TSA >83 mm increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.

Lay Summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.
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http://dx.doi.org/10.1016/j.jhep.2019.12.021DOI Listing
June 2020

Prevalence, features and predictive factors of liver nodules in Fontan surgery patients: The VALDIG Fonliver prospective cohort.

J Hepatol 2020 04 11;72(4):702-710. Epub 2019 Nov 11.

Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERehd, Universidad de Alcalá, Madrid, Spain. Electronic address:

Background & Aims: Fontan surgery is used to treat a variety of congenital heart malformations, and may lead to advanced chronic liver disease in the long-term. This study examines the prevalence, characteristics and predictors of liver nodules in patients following Fontan surgery.

Methods: This was a prospective, cross-sectional, observational study conducted at 8 European centres. Consecutive patients who had undergone Fontan surgery underwent blood tests, abdominal ultrasonography (US), transient elastography (Fibroscan®), echocardiography, haemodynamic assessments, and abdominal MRI/CT scan. The primary outcome measure was liver nodules detected in the MRI/CT scan. Predictors of liver nodules were identified by multivariate logistic regression.

Results: One hundred and fifty-two patients were enrolled (mean age 27.3 years). The mean time elapsed from surgery to inclusion was 18.3 years. Liver nodule prevalences were 29.6% (95% CI 23-37%) on US and 47.7% (95% CI 39-56%) on MRI/CT. Nodules were usually hyperechoic (76.5%), round-shaped (>80%), hyperenhancing in the arterial phase (92%) and located in the liver periphery (75%). The sensitivity and specificity of US were 50% (95% CI 38-62%) and 85.3% (95% CI 75-92%), respectively. Inter-imaging test agreement was low (adjusted kappa: 0.34). In the multivariate analysis, time since surgery >10 years was the single independent predictor of liver nodules (odds ratio 4.18; p = 0.040). Hepatocellular carcinoma was histologically diagnosed in 2 of the 8 patients with hypervascular liver nodules displaying washout.

Conclusion: While liver nodules are frequent in Fontan patients, they may go unnoticed in US. Liver nodules are usually hyperechoic, hypervascular and predominantly peripheral. This population is at risk of hepatocellular carcinoma, the diagnosis of which requires confirmatory biopsy.

Lay Summary: Fontan surgery is the standard of care for many patients with univentricular congenital cardiopathies. Recent advances have improved the survival of Fontan patients, and nowadays most of them reach adulthood. In this setting, Fontan-associated liver disease (FALD) is increasingly recognised, and has become a significant prognostic factor. Liver nodules are considered a component of FALD yet their prevalence, imaging features and predictors have hardly been evaluated. In this study, we observed that liver nodules are frequent, typically hyperechoic, hypervascular and predominantly peripheral in patients with FALD. This population is at risk of hepatocellular carcinoma, the diagnosis of which must be confirmed by biopsy.
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http://dx.doi.org/10.1016/j.jhep.2019.10.027DOI Listing
April 2020

Lowering Portal Pressure Improves Outcomes of Patients With Cirrhosis, With or Without Ascites: A Meta-Analysis.

Clin Gastroenterol Hepatol 2020 02 5;18(2):313-327.e6. Epub 2019 Jun 5.

Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut; Section of Digestive Diseases, VA Connecticut Healthcare System, West Haven, Connecticut. Electronic address:

Background & Aims: In unselected patients with cirrhosis, those with reductions in hepatic venous pressure gradient (HVPG) to below a defined threshold (responders) have a reduced risk of variceal hemorrhage (VH) and death. We performed a meta-analysis to compare this effect in patients with vs without ascites.

Methods: We collected data from 15 studies of primary or secondary prophylaxis of VH that reported data on VH and death in responders vs nonresponders. We included studies in which data on ascites at baseline and on other relevant outcomes during follow-up evaluation were available. We performed separate meta-analyses for patients with vs without ascites.

Results: Of the 1113 patients included in the studies, 968 patients (87%) had been treated with nonselective β-blockers. In 993 patients (89%), HVPG response was defined as a decrease of more than 20% from baseline (>10% in 11% of patients) or to less than 12 mm Hg. In the 661 patients without ascites, responders (n = 329; 50%) had significantly lower odds of events (ascites, VH, or encephalopathy) than nonresponders (odds ratio [OR], 0.35; 95% CI, 0.22-0.56). Odds of death or liver transplantation were also significantly lower among responders than nonresponders (OR, 0.50, 95% CI, 0.32-0.78). In the 452 patients with ascites, responders (n = 188; 42%) had significantly lower odds of events (VH, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome) than nonresponders (OR, 0.27; 95% CI, 0.16-0.43). Overall, odds of death or liver transplantation were lower among responders (OR, 0.47; 95% CI, 0.29-0.75). No heterogeneity was observed among studies.

Conclusions: In a meta-analysis of clinical trials, we found that patients with cirrhosis with and without ascites who respond to treatment with nonselective β-blockers (based on reductions in HVPG) have a reduced risk of events, death, or liver transplantation.
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http://dx.doi.org/10.1016/j.cgh.2019.05.050DOI Listing
February 2020

Evaluation of three "beyond Baveno VI" criteria to safely spare endoscopies in compensated advanced chronic liver disease.

Dig Liver Dis 2019 08 11;51(8):1135-1140. Epub 2019 Jan 11.

CRC "A. M. e A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.

Background: Liver stiffness measurement (LSM) <20 kPa and platelet count >150,000/mm exclude varices needing treatment (VNT) in viral compensated advanced chronic liver disease (cACLD), saving-up to 20-25% endoscopies (Baveno VI criteria). Refinements of such criteria to further reduce endoscopies and an approach without LSM (Platelet 150/MELD 6) were later proposed.

Aims: To assess LSM 25/platelet 125, LSM 25/platelet 110 (Expanded-Baveno VI) and Platelet 150/MELD 6 accuracy versus Baveno VI criteria, and the impact of platelet count variability on criteria accuracy in all-etiologies cACLD.

Methods: cACLD patients undergoing screening endoscopy with laboratory data within 6 months and LSM within one year.

Results: Of 442 patients, 31% had varices (7% with VNT). Baveno VI criteria had 100% sensitivity (Se) and negative predictive value (NPV) and spared 19.5% endoscopies. "LSM 25/platelet 125" and "Expanded-Baveno VI" criteria maintained such accuracy, sparing 15% and 24% more endoscopies, respectively (p < 0.001). Platelet 150/MELD 6 was less accurate, misclassifying 10% VNT. Platelet count variability exceeded 8% and one VNT patient was misclassified with both "Expanded-Baveno VI" and "LSM 25/platelet 125" criteria considering the previous platelet count.

Conclusions: Both "Expanded-Baveno VI" and "LSM 25/platelet 125" criteria are accurate in cACLD, but the former are more advantageous. Platelet 150/MELD 6 proved inadequate.
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http://dx.doi.org/10.1016/j.dld.2018.12.025DOI Listing
August 2019

Metabolomics discloses potential biomarkers to predict the acute HVPG response to propranolol in patients with cirrhosis.

Liver Int 2019 04 10;39(4):705-713. Epub 2019 Feb 10.

Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Background: In cirrhosis, a decrease in hepatic venous pressure gradient (HVPG) > 10% after acute iv propranolol (HVPG response) is associated with a lower risk of decompensation and death. Only a part of patients are HVPG responders and there are no accurate non-invasive markers to identify them. We aimed at discovering metabolomic biomarkers of HVPG responders to propranolol.

Methods: Sixty-six patients with cirrhosis and HVPG ≥ 10 mm Hg in whom the acute HVPG response to propranolol was assessed, were prospectively included. A targeted metabolomic serum analysis using ultrahigh-performance liquid chromatography coupled to mass spectrometry was performed. Different combinations of 2-3 metabolites identifying HVPG responders (HVPG reduction > 10%) were obtained by stepwise logistic regression. The best of these model (AUROC, Akaike criterion) underwent internal cross-validation and cut-offs to classify responders/non-responders was proposed.

Results: A total of 41/66 (62%) patients were HVPG responders. Three hundred and eighty-nine metabolites were detected and 177 were finally eligible. Eighteen metabolites were associated to the HVPG response at univariate analysis; at multivariable analysis, a model including a phosphatidylcholine (PC(P-16:0/22:6)) and a free fatty acid (20:2(n-6), eicosadienoic acid) performed well for HVPG response, with an AUROC of 0.801 (0.761 at internal validation). The cut-off 0.629 was the most efficient for overall classification (49/66 patients correctly classified). Two cut-off values allowed identifying responders (0.688, PPV 84%) and non-responders (0.384, NPV 82%) with undetermined values for 17/66 patients. Clinical variables did not add to the model.

Conclusions: The combination of two metabolites helps at identifying HVPG responders to acute propranolol. It could be a useful non-invasive test to classify the HVPG response to propranolol.
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http://dx.doi.org/10.1111/liv.14042DOI Listing
April 2019

Renin-angiotensin-aldosterone system in cirrhosis: There's room to try!

Dig Liver Dis 2019 02 23;51(2):297-298. Epub 2018 Aug 23.

IRCCS Ca' Granda, Maggiore Hospital Foundation, Unit of General Medicine - Hemostasis and Thrombosis, Milan, Italy; CRC "A.M. e A. Migliavacca" Center for the Study of Liver Disease, Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.

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http://dx.doi.org/10.1016/j.dld.2018.07.038DOI Listing
February 2019

Reply.

Clin Gastroenterol Hepatol 2019 03 13;17(4):798-799. Epub 2018 Sep 13.

Centro di Ricerca Coordinata "A.M. e A. Migliavacca per lo Studio e la Cura delle Malattie del Fegato", Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.

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http://dx.doi.org/10.1016/j.cgh.2018.09.011DOI Listing
March 2019

Coagulation, Microenvironment and Liver Fibrosis.

Cells 2018 07 24;7(8). Epub 2018 Jul 24.

Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, UOC Medicina Generale-Emostasi e Trombosi, 20122 Milano, Italy.

Fibrosis is the main consequence of any kind of chronic liver damage. Coagulation and thrombin generation are crucial in the physiological response to tissue injury; however, the inappropriate and uncontrolled activation of coagulation cascade may lead to fibrosis development due to the involvement of several cellular types and biochemical pathways in response to thrombin generation. In the liver, hepatic stellate cells and sinusoidal endothelial cells orchestrate fibrogenic response to chronic damage. Thrombin interacts with these cytotypes mainly through protease-activated receptors (PARs), which are expressed by endothelium, platelets and hepatic stellate cells. This review focuses on the impact of coagulation in liver fibrogenesis, describes receptors and pathways involved and explores the potential antifibrotic properties of drugs active in hemostasis in studies with cells, animal models of liver damage and humans.
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http://dx.doi.org/10.3390/cells7080085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115868PMC
July 2018

Multimodality treatment of hepatocellular carcinoma: How field practice complies with international recommendations.

Liver Int 2018 09 15;38(9):1624-1634. Epub 2018 Jul 15.

Division of Gastroenterology and Hepatology, CRC "A.M. and A. Migliavacca" Center for the study of Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.

Background: Management of hepatocellular carcinoma (HCC) is framed within standardized protocols released by Scientific Societies, whose applicability and efficacy in field practice need refining.

Aim: We evaluated the applicability and effectiveness of guidelines for the treatment of HCC of the American Association for the Study of the Liver (AASLD).

Methods: 370 consecutive cirrhotic patients with de novo HCC in different stages, 253 BCLC A, 66 BCLC B, 51 BCLC C received treatment through a multidisciplinary team (MDT) decision and were followed until death or end of follow-up.

Results: Treatment was adherent to AASLD recommendations in 205 (81%) BCLC A patients, 36 (54%) BCLC B, and 27 (53%) BCLC C. Radiological complete response was achieved in 165 (45%) patients after the first-line treatment, in 22 (19%) after a second-line and in 9 (23%) after a third-line treatment. Adherence to AASLD recommendation allowed a lower yearly mean mortality rate in BCLC A patients compared with other treatment (5.0% vs 10.4% P = .004), whereas upward treatment stage migration compared with the standard of care was associated with reduced yearly mortality in BCLC B (8.6% vs 20.7%, P = .029) and BCLC C (42.6% vs 59.0%, P = .04) patients.

Conclusions: HCC multimodality treatment including other than first-line therapy is common in clinical practice and impact on the achievement of complete response. Personalized treatment was able to provide survival benefits to patients whose profile is not accounted for by international recommendations, which need to be amended.
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http://dx.doi.org/10.1111/liv.13888DOI Listing
September 2018

Association Between Portosystemic Shunts and Increased Complications and Mortality in Patients With Cirrhosis.

Gastroenterology 2018 05 31;154(6):1694-1705.e4. Epub 2018 Jan 31.

Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada.

Background & Aims: Spontaneous portosystemic shunts (SPSS) have been associated with hepatic encephalopathy (HE). Little is known about their prevalence among patients with cirrhosis or clinical effects. We investigated the prevalence and characteristics of SPSS in patients with cirrhosis and their outcomes.

Methods: We performed a retrospective study of 1729 patients with cirrhosis who underwent abdominal computed tomography or magnetic resonance imaging analysis from 2010 through 2015 at 14 centers in Canada and Europe. We collected data on demographic features, etiology of liver disease, comorbidities, complications, treatments, laboratory and clinical parameters, Model for End-Stage Liver Disease (MELD) score, and endoscopy findings. Abdominal images were reviewed by a radiologist (or a hepatologist trained by a radiologist) and searched for the presence of SPSS, defined as spontaneous communications between the portal venous system or splanchnic veins and the systemic venous system, excluding gastroesophageal varices. Patients were assigned to groups with large SPSS (L-SPSS, ≥8 mm), small SPSS (S-SPSS, <8 mm), or without SPSS (W-SPSS). The main outcomes were the incidence of complications of cirrhosis and mortality according to the presence of SPSS. Secondary measurements were the prevalence of SPSS in patients with cirrhosis and their radiologic features.

Results: L-SPSS were identified in 488 (28%) patients, S-SPSS in 548 (32%) patients, and no shunt (W-SPSS) in 693 (40%) patients. The most common L-SPSS was splenorenal (46% of L-SPSS). The presence and size of SPSS increased with liver dysfunction: among patients with MELD scores of 6-9, 14% had L-SPSS and 28% had S-SPSS; among patients with MELD scores of 10-13, 30% had L-SPSS and 34% had S-SPSS; among patients with MELD scores of 14 or higher, 40% had L-SPSS and 32% had S-SPSS (P < .001 for multiple comparison among MELD groups). HE was reported in 48% of patients with L-SPSS, 34% of patients with S-SPSS, and 20% of patients W-SPSS (P < .001 for multiple comparison among SPSS groups). Recurrent or persistent HE was reported in 52% of patients with L-SPSS, 44% of patients with S-SPSS, and 37% of patients W-SPSS (P = .007 for multiple comparison among SPSS groups). Patients with SPSS also had a larger number of portal hypertension-related complications (bleeding or ascites) than those W-SPSS. Quality of life and transplantation-free survival were lower in patients with SPSS vs without. SPSS were an independent factor associated with death or liver transplantation (hazard ratio, 1.26; 95% confidence interval, 1.06-1.49) (P = .008) in multivariate analysis. When patients were stratified by MELD score, SPSS were associated with HE independently of liver function: among patients with MELD scores of 6-9, HE was reported in 23% with L-SPSS, 12% with S-SPSS, and 5% with W-SPSS (P < .001 for multiple comparison among SPSS groups); among those with MELD scores of 10-13, HE was reported in 48% with L-SPSS, 33% with S-SPSS, and 23% with W-SPSS (P < .001 for multiple comparison among SPSS groups); among patients with MELD scores of 14 or more, HE was reported in 59% with L-SPSS, 57% with S-SPSS, and 48% with W-SPSS (P = .043 for multiple comparison among SPSS groups). Patients with SPSS and MELD scores of 6-9 were at higher risk for ascites (40.5% vs 23%; P < .001) and bleeding (15% vs 9%; P = .038) than patients W-SPSS and had lower odds of transplant-free survival (hazard ratio 1.71; 95% confidence interval, 1.16-2.51) (P = .006).

Conclusions: In a retrospective analysis of almost 2000 patients, we found 60% to have SPSS; prevalence increases with deterioration of liver function. SPSS increase risk for HE and with a chronic course. In patients with preserved liver function, SPSS increase risk for complications and death. ClinicalTrials.gov ID NCT02692430.
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http://dx.doi.org/10.1053/j.gastro.2018.01.028DOI Listing
May 2018

Intrahepatic vascular changes in non-alcoholic fatty liver disease: Potential role of insulin-resistance and endothelial dysfunction.

World J Gastroenterol 2017 Oct;23(37):6777-6787

Internal Medicine, IRCCS San Donato, Department of Biomedical Sciences for Health, University of Milan, 20097 San Donato Milanese, Italy.

Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, anti-inflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.
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http://dx.doi.org/10.3748/wjg.v23.i37.6777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645612PMC
October 2017

Harmful and Beneficial Effects of Anticoagulants in Patients With Cirrhosis and Portal Vein Thrombosis.

Clin Gastroenterol Hepatol 2018 07 21;16(7):1146-1152.e4. Epub 2017 Oct 21.

A. M. and A. Migliavacca-Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.

Background & Aims: Vitamin K antagonists (VKAs) promote recanalization of portal vein thrombosis (PVT) in patients with cirrhosis. However, the benefit of PVT recanalization might be offset by major and minor bleeding associated with use of anticoagulants. We evaluated harmful and beneficial effects of VKA in patients with PVT and cirrhosis.

Methods: We performed a retrospective study of 63 consecutive patients with cirrhosis given anticoagulants for the first detection of non-neoplastic PVT from 2003 to 2015 in Italy. We collected data on bleeding events in these patients and compared them with those from patients without cirrhosis with venous thromboembolism (VTE) (n = 160) for up to 4 years. Time in the therapeutic range, based on the international normalized ratio, was used to determine the quality of anticoagulation. We also collected data from 139 patients with cirrhosis who did not receive VKAs (controls), to analyze portal hypertension-related events. We performed survival analyses to determine the effects of VKA in patients with PVT vs controls.

Results: The group with VTE and the group with PVT were comparable in age, sex, and time in the therapeutic range, but patients with VTE received VKAs for a longer time period (31.1 ± 16.9 mo vs 23.3 ± 16.2 mo; P = .002). The incidence of major or minor bleeding was higher in patients with PVT than patients with VTE (major, 24% vs 7%; P = .012; minor, 29% vs 19%; P = .024). Patients with PVT had a higher rate of major bleeding from the upper-gastrointestinal tract than patients with VTE (P = .019), but there were no significant differences in other types of major bleeding (P = .376). Patients with PVT and controls had the same rate of upper-gastrointestinal bleeding. Complete recanalization in patients with PVT receiving VKA (n = 31) was independently associated with increased portal hypertension-related event-free and transplantation-free survival times.

Conclusions: In a retrospective analysis of 63 patients with cirrhosis given anticoagulants for PVT, we found VKA use to increase risk of minor bleeding, compared with patients without cirrhosis given VKA. However, this risk is offset by the ability of VKA to increase portal hypertension-related, event-free, and transplantation-free survival of patients with PVT recanalization. Portal hypertension, rather than anticoagulants, could account for the difference in risk of major bleeding between patients with PVT vs patients with VTE.
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http://dx.doi.org/10.1016/j.cgh.2017.10.016DOI Listing
July 2018

Reply to the diagnostic conundrum of bacterial infections in cirrhotic patients.

Liver Int 2017 09;37(9):1412

Medicina Interna, IRCCS San Donato, Università degli studi di Milano, San Donato Milanese, Milano, Italy.

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http://dx.doi.org/10.1111/liv.13474DOI Listing
September 2017

Erratum to: HBV and HCV infection in type 2 diabetes mellitus: a survey in three diabetes units in different Italian areas.

Acta Diabetol 2017 09;54(9):887

Unit of Metabolic Diseases and Clinical Dietetics, "Alma Mater Studiorum" University of Bologna, Policlinico S. Orsola, Via Massarenti, 9, 40138, Bologna, Italy.

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http://dx.doi.org/10.1007/s00592-017-1032-8DOI Listing
September 2017

Determinants of esophageal varices bleeding in patients with advanced hepatocellular carcinoma treated with sorafenib.

United European Gastroenterol J 2016 Jun 30;4(3):363-70. Epub 2015 Oct 30.

A.M. & A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy.

Background And Aims: Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC), yet treatment safety may be challenged by portal hypertension. We therefore assessed the prevalence, risk factors and clinical consequences of esophageal varices (EVs) in sorafenib-treated patients with HCC.

Methods: Starting in 2008, all compensated patients with advanced or intermediate HCC not eligible for other therapies were consecutively enrolled in a prospective evaluation of sorafenib therapy, all with pretreatment by upper-gastrointestinal endoscopy (UGE).

Results: A total of 150 patients received sorafenib for 4.6 (95% CI, 3.3-5.6) months. At baseline, 61 (41%) patients were EV free (group A), 78 (52%) had EVs (61 small EVs (group B), 17 medium/large EVs (group C)) and 11 (7%) previously endoscopically treated EVs (group D). Propranolol was given to all patients with medium/large EVs and those with previous bleeding. Twelve patients (8%) bled from EVs after 36 (18-260) days of sorafenib. During sorafenib, bleeding occurred in six of 26 group B patients with neoplastic portal vein thrombosis (nPVT), three of nine group C patients with nPVT, two of five group D patients with nPVT and one of six without nPVT (p < 0.0001), nPVT being the strongest independent predictor of bleeding by multivariate analysis (HR = 15.4, 95% CI 1.84-129.6).

Conclusion: UGE screening is worthwhile in HCC patients allocated to sorafenib since it identifies patients with EVs at risk of bleeding during therapy, particularly those with nPVT.
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http://dx.doi.org/10.1177/2050640615615041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924436PMC
June 2016

The impact of infection by multidrug-resistant agents in patients with cirrhosis. A multicenter prospective study.

Liver Int 2017 01 22;37(1):71-79. Epub 2016 Jul 22.

Unità di Gastroenterologia e Microbiologia, Ospedale Predabissi, Melegnano, Italy.

Background & Aims: Bacterial strains resistant to antibiotics are a serious clinical challenge. We assessed the antibiotic susceptibility of bacteria isolated from infections in patients with cirrhosis by a multicentre investigation.

Results: Three hundred and thirteen culture-positive infections (173 community acquired [CA] and 140 hospital acquired [HA]) were identified in 308 patients. Urinary tract infections, spontaneous bacterial peritonitis and bacteremias were the most frequent. Quinolone-resistant Gram-negative isolates were 48%, 44% were extended-spectrum beta-lactamase producers and 9% carbapenem resistant. In 83/313 culture-positive infections (27%), multidrug-resistant agents (MDRA) were isolated. This prevalence did not differ between CA and HA infections. MDRA were identified in 17 of 37 patients on quinolone prophylaxis, and in 46 of 166 not on prophylaxis (45% vs 27%; P<.03). In 287 cases an empiric antibiotic therapy was undertaken, in 37 (12.9%) this therapy failed. The in-hospital mortality rate of this subset of patients was significantly higher compared to patients who received an effective broad(er)-spectrum therapy (P=.038). During a 3-month follow-up, 56/203 culture-positive patients (27.6%) died, 24/63 who have had MDRA-related infections (38%) and 32/140 who have had antibiotic-susceptible infections (22.8%) (P=.025). Multivariate analysis disclosed MDRA infection, age, hepatocellular carcinoma, bilirubin, international normalized ratio and the occurrence of portal hypertension-related complications independent predictors of death.

Conclusions: Infection by MDRA is frequent in patients with cirrhosis and the prognosis is severe, especially in patients unresponsive to empiric antibiotic therapy.
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http://dx.doi.org/10.1111/liv.13195DOI Listing
January 2017

Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis.

Liver Int 2016 09 31;36(9):1322-30. Epub 2016 Mar 31.

Division of Gastroenterology and Hepatology, IRCCS Ca' Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy.

Background & Aims: Portal vein thrombosis (PVT) is frequently observed in cirrhosis and may be a clinically important complication. In vitro assays for endogenous thrombin potential (ETP) demonstrated that in cirrhosis plasma has intrinsic resistance to the anticoagulant action of thrombomodulin (TM-R). This study retrospectively explores the association of TM-R with de novo PVT and its clinical impact on cirrhosis.

Methods: Fifty-three patients with cirrhosis were tested for ETP-ratio with/without thrombomodulin. Clinical, endoscopic variables, presence/absence of PVT by Doppler-US and/or CT examination were collected at baseline and up to 4 years from baseline. The de novo PVT was the primary clinical end-point. Portal hypertension (PHT)-related complications and transplantation free survival were secondary end-points. ETP-ratio higher than the 95° percentile of the distribution in 173 healthy controls defined TM-R.

Results: During 48 months of follow-up, 11 patients developed de novo PVT, with preference for the 36 patients with TM-R after adjusting for Child-Pugh class (HR: 8.354; 90%CI:1.475 - 47.305; P = 0.009). Seventeen patients experienced PHT-related complications, 23 either died or underwent liver transplantation. PHT complications and transplantation free survival were associated with TM-R, but were independently predicted by Child-Pugh class, only. Same results were obtained by considering the MELD score.

Conclusions: Owing to PVT results from the pro-coagulant imbalance occurring in patients with advanced cirrhosis, TM-R might serve as a predictor and could possibly be a biological mediator of adverse outcome in patients with advanced cirrhosis.
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http://dx.doi.org/10.1111/liv.13087DOI Listing
September 2016

Therapeutic and clinical aspects of portal vein thrombosis in patients with cirrhosis.

World J Hepatol 2015 Dec;7(29):2906-12

Massimo Primignani, Giulia Tosetti, U.O. Gastroenterologia ed Epatologia, IRCCS-Ca' Granda, Ospedale Maggiore Policlinico, 20122 Milano, Italy.

Portal vein thrombosis (PVT) is a frequent complication in cirrhosis, particularly in advanced stages of the disease. As for general venous thromboembolism, risk factors for PVT are slow blood flow, vessel wall damage and hypercoagulability, all features of advanced cirrhosis. Actually, the old dogma of a hemorrhagic tendency in cirrhosis has been challenged by new laboratory tools and the clinical evidence that venous thrombosis also occurs in cirrhosis. The impaired hepatic synthesis of both pro- and anticoagulants leads to a rebalanced hemostasis, more liable to be tipped towards thrombosis or even bleeding. Conventional anticoagulant drugs (low molecular weight heparin or vitamin K antagonists) may be used in cirrhosis patients with PVT, particularly in those eligible for liver transplantation, to prevent thrombosis progression thus permitting/facilitating liver transplant. However, several doubts exist on the level of anticoagulation achieved as estimated by coagulation tests, on the efficacy of treatment monitoring and on the correct timing for discontinuation in non-transplant candidates, while in transplant candidates there is expert consensus on continuing anticoagulation until transplantation. The recent introduction of direct acting oral anticoagulant drugs (DOACs) in other clinical settings generates much interest on their possible application in patients with cirrhosis and PVT. However, DOACs were not evaluated yet in patients with liver disease and cannot be recommended for the present time.
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http://dx.doi.org/10.4254/wjh.v7.i29.2906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678377PMC
December 2015

Therapy of the refractory ascites: Total paracentesis vs. TIPS.

Gastroenterol Hepatol 2016 Aug-Sep;39(7):477-80. Epub 2015 Nov 18.

Policlinico IRCCS San Donato, Department of Internal Medicine and Hepatology, University of Milan, Italy. Electronic address:

This revision was aimed to report the evidences on the treatment of patients with cirrhosis and refractory ascites. Mainly, we wished to explore which of the predicting variables could be used to prefer large-volume paracentesis or TIPS.
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http://dx.doi.org/10.1016/j.gastrohep.2015.07.011DOI Listing
December 2017

Prognosis of acute variceal bleeding: Is being on beta-blockers an aggravating factor? A short-term survival analysis.

Hepatology 2015 Dec 17;62(6):1840-6. Epub 2015 Oct 17.

Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic-IDIBAPS, University of Barcelona and Centro de Investigación, Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain.

Unlabelled: Nonselective beta-blockers (NSBB) are widely used because they have been proved effective in the prophylaxis of acute variceal bleeding (AVB). However, a significant proportion of patients still experience AVB while on treatment with NSBB, and its impact on prognosis of AVB is unknown. The present study was aimed at assessing the effect of being on prophylactic therapy with NSBB on 5-day failure and 6-week mortality of patients with cirrhosis admitted with AVB. Included were 142 patients: 49 were receiving prophylactic therapy with NSBB (NSBB group) and 93 were not (control group). There were some differences in the baseline characteristics between the groups: higher proportion of alcoholic etiology and active alcoholism (37% versus 10%), higher platelet count, and lower hematocrit at admission in the control group. However, the severity of AVB and initial treatment were similar. Five-day failure occurred in 20% of patients (14% in NSBB versus 24% in controls, P = 0.27). The adjusted odds ratio for 5-day failure under NSBB was 2.46 (95% confidence interval 0.53-11.37, P = 0.25). Nineteen patients (13%) died, and two had liver transplantation within 6 weeks. The probability of survival at 6 weeks was 96% in the NSBB group and 82% in the control group (P = 0.02). After adjusting by propensity score and Model for End-Stage Liver Disease score, the NSBB adjusted odds ratio for 6-week mortality was 0.38 (95% confidence interval 0.05-2.63, P = 0.32). The estimated association between NSBB with both 5-day failure and 6-week mortality was homogenous across all Model for End-Stage Liver Disease spectrums.

Conclusion: Prophylactic NSBB treatment is not a negative prognostic indicator for the short-term survival of patients with cirrhosis admitted with AVB.
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http://dx.doi.org/10.1002/hep.28151DOI Listing
December 2015

Treatment of Spontaneous Bacterial Peritonitis.

Dig Dis 2015 6;33(4):582-5. Epub 2015 Jul 6.

Department of Internal Medicine, Policlinico IRCCS San Donato, University of Milan, San Donato Milanese, Italy.

Spontaneous bacterial peritonitis (SBP) is an infection of patients with cirrhosis and ascites. This peculiarity is due to the frequent intestinal translocation that allows bacteria to cross the intestinal barrier, colonizing the ascitic fluid. In cirrhosis, SBP is inferior only to urinary tract infections. It is prevalently sustained by Gram-negative bacteria such as Escherichia coli and Klebsiella. Risk factors for developing SBP are advanced age, refractory ascites, variceal bleeding, renal failure, low albumin levels (below 2.5 g/ml), bilirubin over 4 mg/dl, Child-Pugh class C and a previous diagnosis of SBP. Thus, this is an indication for a long-term antibiotic prophylaxis with norfloxacin. Renal failure - especially the hepatorenal syndrome - complicates SBP in about 20% of cases independently of the efficacy of the antibiotic therapy. The mortality of these patients is about 90%. Infusion of albumin significantly reduces the incidence of hepatorenal syndrome and consequently the risk of death. Long-term quinolonic prophylaxis as well as increased antibiotic therapies are causing the emergence of multidrug-resistant agents as frequent causes of SBP. In such cases, the antibiotic sensitivity to quinolones is low, and European recommendations suggest a second-line antibiotic therapy, including meropenem or piperacillin plus tazobactam. Collection of blood, urine and ascitic fluid for cultures is important for bacterial recognition, possibly before starting an empirical antibiotic therapy. Indeed, the probability of positive cultures rapidly vanishes when they are performed during already implemented antibiotic administration. It is important to know that a failure of the first-line therapy is associated with an increased probability of death.
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http://dx.doi.org/10.1159/000375358DOI Listing
April 2016
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