Publications by authors named "Massimo Primignani"

79 Publications

Decompensation in advanced non-alcoholic fatty liver disease may occur at lower hepatic venous pressure gradient levels that in patients with viral disease.

Clin Gastroenterol Hepatol 2021 Oct 21. Epub 2021 Oct 21.

Division of Gastroenterology, Azienda Ospedaliero-Universitaria di Modena and University of Modena and Reggio Emilia, Modena, Italy.

Background & Aims: Portal hypertension (PH) is the strongest predictor of hepatic decompensation and death in patients with cirrhosis. However, its discriminatory accuracy in patients with non-alcoholic fatty liver disease (NAFLD) has been challenged as hepatic vein catheterization may not reflect the real portal vein pressure as accurately as in patients with other etiologies. We aimed to evaluate the relationship between hepatic venous pressure gradient (HVPG) and presence of portal hypertension related decompensation in patients with advanced NAFLD (aNAFLD).

Methods: Multicenter cross-sectional study including 548 patients with aNAFLD and 444 with advanced RNA-positive hepatitis C (aHCV) who had detailed portal hypertension evaluation (HVPG measurement, gastroscopy, and abdominal imaging). We examined the relationship between etiology, HVPG, and decompensation by logistic regression models. We also compared the proportions of compensated/decompensated patients at different HVPG levels.

Results: Both cohorts, aNAFLD and aHVC, had similar baseline age, gender, Child-Pugh score, and MELD. Median HVPG was lower in the aNAFLD cohort (13 vs 15 mmHg) despite similar liver function and higher rates of decompensation in aNAFLD group (32% vs 25% p=0.019) than in the aHCV group. For any of the HVPG cutoff analyzed (<10, 10-12 or 12 mmHg) the prevalence of decompensation was higher in the aNAFLD than in the aHCV group.

Conclusion: Patients with aNAFLD have higher prevalence of portal hypertension related decompensation at any value of HVPG as compared to aHCV patients. Longitudinal studies aiming to identify HVPG thresholds able to predict decompensation and long-term outcomes in aNAFLD population are strongly needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2021.10.023DOI Listing
October 2021

Evolution of Nonmalignant Portal Vein Thrombosis in Liver Cirrhosis: A Pictorial Review.

Clin Transl Gastroenterol 2021 Oct 1;12(10):e00409. Epub 2021 Oct 1.

Liver Cirrhosis Study Group, Department of Gastroenterology, The General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area), Shenyang, China.

Portal vein thrombosis (PVT) is a common complication in liver cirrhosis, especially in advanced cirrhosis. It may be related to a higher risk of liver-related events and liver function deterioration. Imaging examinations can not only provide an accurate diagnosis of PVT, such as the extent of thrombus involvement and the degree of lumen occupied, but also identify the nature of thrombus (i.e., benign/malignant and acute/chronic). Evolution of PVT, mainly including development, recanalization, progression, stability, and recurrence, could also be assessed based on the imaging examinations. This article briefly reviews the pathophysiology, diagnosis, classification, and evolution of PVT with an emphasis on their computed tomography imaging features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14309/ctg.0000000000000409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483868PMC
October 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.07.018DOI Listing
July 2021

Clonal Megakaryocyte Dysplasia with Normal Blood Values Is a Distinct Myeloproliferative Neoplasm.

Acta Haematol 2021 Jul 19:1-8. Epub 2021 Jul 19.

Department of Immunology and Inflammation, Center for Haematology Research, Imperial College London, London, United Kingdom.

Introduction: In 1991, we reported 18 persons with a clinical-pathologic entity and termed atypical myeloproliferative disorder because they did not meet the contemporary diagnostic criteria for a myeloproliferative neoplasm. We sought to gain further knowledge on this disease entity.

Methods: This retrospective cohort study included consecutive subjects registered in the database of the Center for the Study of Myelofibrosis in Pavia, Italy, from 1998 to 2020 (June), and diagnosed with atypical myeloproliferative disorder according to our adjudicated criteria. We studied clinical, histological, cytogenetic, and molecular covariates and risks of thrombosis, disease progression, and death. Data were compared with those of concurrent subjects with prefibrotic myelofibrosis.

Results: Fifteen new subjects with atypical myeloproliferative disorder were identified. Seven were male. Median age was 50 years (IQR, 41-54 years). Thirteen were diagnosed with a synchronous symptomatic or incidentally detected thrombotic event. The bone marrow showed megakaryocyte hyperplasia with dysplasia. JAK2V617F was present in 10 subjects and CALR mutation in one. No other somatic mutations were identified in next generation sequencing. After a median follow-up of 101 months (IQR, 40-160 months), no subject had disease progression or blast transformation. Incidence of post-diagnosis or recurrent thrombosis was 3.9 events (95% confidence interval, 3.5-4.0) and 5.0 events (4.6-5.6) per 100 person-years. Features of subjects with atypical myeloproliferative disorder differed markedly from those of 546 subjects with prefibrotic myelofibrosis.

Conclusion: Our data indicate that these 15 persons have a distinct myeloproliferative neoplasm. We propose naming this new disorder clonal megakaryocyte dysplasia with normal blood values.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000517207DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20524/aog.2021.0616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276367PMC
March 2021

Response to Sharma and Saraya.

Am J Gastroenterol 2021 08;116(8):1756-1757

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14309/ajg.0000000000001290DOI Listing
August 2021

Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis.

J Hepatol 2021 08 12;75(2):342-350. Epub 2021 Jun 12.

Gastroenterology Department, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain.

Background & Aims: Antibiotic prophylaxis reduces the risk of infection and mortality in patients with cirrhosis and acute variceal bleeding (AVB). This study examines the incidence of, and risk factors for, bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis.

Methods: A post hoc analysis was performed using the database of an international, multicenter, observational study designed to examine the role of pre-emptive transjugular intrahepatic portosystemic shunts in patients with cirrhosis and AVB. Data were collected on patients with cirrhosis hospitalized for AVB (n = 2,138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and a retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization.

Results: A total of 1,656 patients out of 1,770 (93.6%) received antibiotic prophylaxis; third-generation cephalosporins (76.2%) and quinolones (19.0%) were used most frequently. Of the patients on antibiotic prophylaxis, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (odds ratio [OR] 3.1; 95% CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95% CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95% CI 1.8-3.8), nasogastric tube placement (OR 1.7; 95% CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95% CI 1.2-4.9).

Conclusion: Bacterial infections develop in almost one-fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.

Lay Summary: Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infections are the most frequent and occur early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2021.03.026DOI Listing
August 2021

Natural history and predictors associated with the evolution of portal venous system thrombosis in liver cirrhosis.

Eur J Gastroenterol Hepatol 2021 Mar 12. Epub 2021 Mar 12.

Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (formerly General Hospital of Shenyang Military Area) Graduate School, China Medical University, Shenyang, China Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Berlin, Germany Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, CRC 'A.M. and A. Migliavacca' Center for Liver Disease, Milan, Italy.

Background: Portal venous system thrombosis (PVST) will progress in some cases, indicating worse outcome and the necessity of antithrombotic treatment, but will spontaneously improve in others. It is crucial to understand the natural history of PVST in liver cirrhosis. However, the knowledge regarding how to predict the evolution of PVST in cirrhotic patients is very scant.

Methods: Sixty-nine cirrhotic patients without malignancy, who had undergone repeated contrast-enhanced computed tomography or MRI to evaluate the severity of PVST at the first and last admissions, were included. Logistic regression analysis was performed to identify the risk factors for the evolution of PVST in liver cirrhosis. Odds ratios (ORs) were calculated.

Results: Among 42 patients without PVST at the first admission, 10 (23.8%) developed PVST at the last admission. Serum albumin level (OR = 0.873), prothrombin time (OR = 1.619), activated partial thromboplastin time (OR = 1.169), Child-Pugh score (OR = 1.560) and model for end-stage liver disease (MELD) score (OR = 1.292) at the last admission were significant risk factors associated with the development of PVST. Among 27 patients with PVST at the first admission, 11 (40.7%), 4 (14.8%) and 12 (44.4%) had improvement, stabilization and progression of PVST at the last admission, respectively. ΔMELD score (OR = 0.714) was the only significant risk factor associated with the improvement of PVST; additionally, serum albumin level at the first admission (OR = 1.236) was the only significant risk factor associated with the progression of PVST.

Conclusion: Aggravation and amelioration of liver dysfunction may predict the development and improvement of PVST in liver cirrhosis, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000002123DOI Listing
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14309/ajg.0000000000001158DOI Listing
June 2021

Pancreatitis-related splanchnic vein thrombosis: What role, what warnings for anticoagulation therapy?

J Dig Dis 2021 Mar 14;22(3):122-125. Epub 2021 Mar 14.

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

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1751-2980.12974DOI Listing
March 2021

Post-banding ulcer bleeding in the elective setting: Are there any risk factors?

Dig Liver Dis 2021 May 2;53(5):658-660. Epub 2021 Feb 2.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - UOC Gastroenterologia ed Epatologia, Milano, Italia. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2021.01.016DOI Listing
May 2021

High-dose pre-endoscopic intravenous proton pump inhibitors in upper gastrointestinal bleeding: Utility or futility?

Dig Liver Dis 2021 03 4;53(3):387-388. Epub 2021 Jan 4.

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - UOC Gastroenterologia ed Epatologia, Milano, Italia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2020.12.007DOI Listing
March 2021

Association of portal venous system thrombosis with endoscopic variceal treatment: a systematic review and meta-analysis.

Eur J Gastroenterol Hepatol 2021 02;32(2):125-131

Department of Gastroenterology, General Hospital of Northern Theater Command (formerly called General Hospital of Shenyang Military Area), Shenyang.

The association of endoscopic variceal treatment (EVT) with the development of portal venous system thrombosis (PVST) in liver cirrhosis remains uncertain. A systematic review and meta-analysis aimed to investigate the incidence of PVST after EVT and to explore the association of EVT with the development of PVST in liver cirrhosis. All relevant studies were searched via the PubMed, EMBASE, and Cochrane Library databases. The incidence of PVST in patients treated with and without EVT was pooled. Risk ratios with 95% confidence intervals (CIs) were calculated. Heterogeneity among studies was calculated. Meta-regression, sensitivity, and subgroup analyses were used to analyze the source of heterogeneity. Thirteen studies involving a total of 833 patients were included. The pooled incidence of PVST after EVT was 10.4% (95% CI, 4.9-17.7%). There was a statistically significant heterogeneity (I2 = 83.3%, P < 0.0001). Meta-regression, sensitivity, and subgroup analyses did not find the source of heterogeneity. Four studies compared the incidence of PVST between patients treated with and without EVT. The incidence of PVST was significantly higher in the EVT group than that in the no-EVT group (risk ratio: 2.23; 95% CI, 1.11-4.49; P = 0.02). The heterogeneity was not statistically significant (I2 = 0%, P = 0.43). In conclusion, PVST after EVT may not be scare, and EVT may increase the risk of PVST in liver cirrhosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MEG.0000000000001774DOI Listing
February 2021

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.

View Article and Find Full Text PDF

Download full-text PDF

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

Rebleeding and mortality risk are increased by ACLF but reduced by pre-emptive TIPS.

J Hepatol 2020 11 24;73(5):1082-1091. Epub 2020 Apr 24.

Unit of Gastroenterology and Digestive Endoscopy, Arcispedale Santa Maria Nuova-IRCCS, Reggio Emilia, Italy.

Background & Aims: The relationship between acute-on-chronic liver failure (ACLF) and acute variceal bleeding (AVB) is poorly understood. Specifically, the prevalence and prognosis of ACLF in the context of AVB is unclear, while the role of transjugular intrahepatic portosystemic shunt (TIPS) in the management in patients with ACLF has not been described to date.

Methods: A multicenter, international, observational study was conducted in 2,138 patients from 34 centers between 2011 and 2015. ACLF was defined and graded according to the EASL-CLIF consortium definition. Placement of pre-emptive TIPS (pTIPS) was based on individual center policy. Patients were followed-up for 1 year, until death or liver transplantation. Cox regression and competing risk models (Gray's test) were used to identify independent predictors of rebleeding or mortality.

Results: At admission, 380/2,138 (17.8%) patients had ACLF according to EASL-CLIF criteria (grade 1: 38.7%; grade 2: 39.2%; grade 3: 22.1%). The 42-day rebleeding (19% vs. 10%; p <0.001) and mortality (47% vs. 10%; p <0.001) rates were higher in patients with ACLF and increased with ACLF grades. Of note, the presence of ACLF was independently associated with rebleeding and mortality. pTIPS placement improved survival in patients with ACLF at 42 days and 1 year. This effect was also observed in propensity score matching analysis of 66 patients with ACLF, of whom 44 received pTIPs and 22 did not.

Conclusions: This large multicenter international real-life study identified ACLF at admission as an independent predictor of rebleeding and mortality in patients with AVB. Moreover, pTIPS was associated with improved survival in patients with ACLF and AVB.

Lay Summary: Acute variceal bleeding is a deadly complication of liver cirrhosis that results from severe portal hypertension. This study demonstrates that the presence of acute-on-chronic liver failure (ACLF) is the strongest predictor of mortality in patients with acute variceal bleeding. Importantly, patients with ACLF and acute variceal (re)bleeding benefit from pre-emptive (early) placement of a transjugular intrahepatic portosystemic shunt.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhep.2020.04.024DOI Listing
November 2020

Letter to the Editor: Thromboelastography-Guided Blood Product Transfusion in Cirrhosis With Coagulopathy: Real Saving or Just Less Waste?

Hepatology 2020 09;72(3):1158-1159

Foundation IRCCS Ca' Granda, Ospedale Maggiore Policlinico, "Angelo Bianchi Bonomi" Hemophilia and Thrombosis Center, Milan, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31263DOI Listing
September 2020

Nonselective β-Blockers May Progress the Thrombosis of Portal Venous System in Cirrhotic Patients: A Retrospective Observational Study.

Adv Ther 2020 04 19;37(4):1452-1463. Epub 2020 Feb 19.

Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, China.

Introduction: Occlusive portal venous system thrombosis (PVT) is significantly associated with poor outcomes in cirrhotic patients. Nonselective β-blockers (NSBBs) may be associated with the development of PVT. However, the role of NSBBs in progressing thrombosis remains unclear.

Methods: Forty-three patients on whom contrast-enhanced computed tomography or magnetic resonance imaging was performed twice, and for whom there was detailed information regarding NSBBs, were eligible in this study, including 16 in the NSBBs group and 27 in the no NSBBs group. A composite endpoint of progressing thrombosis included the development of PVT in patients without PVT and aggravation of PVT in patients with PVT. Logistic regression analysis was employed to identify the effect of NSBBs on the progression of PVT.

Results: At the last admission, 13 patients had progressing thrombosis. The incidence of progressing thrombosis was significantly higher in the NSBBs group than in the no NSBBs group [50.0% (8/16) vs. 18.5% (5/27), P = 0.030]. The use of NSBBs (odds ratio 4.400, 95% confidence interval 1.107-17.482, P = 0.035) was significantly associated with progressing thrombosis in univariate logistic regression analyses, but not significant (odds ratio 4.084, 95% confidence interval 0.488-34.158, P = 0.194) in multivariate logistic regression analyses.

Conclusions: NSBBs may play a role in the progression of PVT in liver cirrhosis. The benefits and risks of NSBBs in the management of liver cirrhosis should be fully weighed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12325-020-01250-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140745PMC
April 2020

Incidence and mortality of renal dysfunction in cirrhotic patients with acute gastrointestinal bleeding: a systematic review and meta-analysis.

Expert Rev Gastroenterol Hepatol 2019 Dec 28;13(12):1181-1188. Epub 2019 Nov 28.

Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, P.R. China.

: Gastrointestinal bleeding (GIB) is a common complication in cirrhosis. Renal dysfunction may be crucial for the outcomes of cirrhotic patients with acute GIB. This study aimed to explore the incidence and mortality of renal dysfunction in cirrhotic patients with acute GIB.: The PubMed, EMBASE, and Cochrane Library databases were searched. We pooled the incidence and mortality of renal dysfunction in cirrhotic patients using a random-effect model. Odds ratio (OR) with 95% confidence interval (CI) were calculated.: Seventeen studies were included. The pooled incidence of renal dysfunction was 21% (95%CI = 16%-25%) in cirrhosis with acute GIB. In subgroup analyses, the pooled incidence of renal failure, acute kidney injury (AKI), and renal impairment were 21%, 25%, and 15%, respectively. The pooled mortality was 46% (95%CI = 37%-55%) in cirrhosis with acute GIB and renal dysfunction. In subgroup analyses, the pooled mortality in patients with renal failure, AKI, and renal impairment were 42%, 47%, and 49%, respectively. Renal dysfunction significantly increased the mortality of cirrhosis with acute GIB (OR = 4.92; 95%CI = 3.47-6.96; P < 0.001).: Renal dysfunction is a common indicator for poor outcome of cirrhosis with acute GIB. Prevention of renal dysfunction in such patients should be further explored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17474124.2019.1694904DOI Listing
December 2019

Splanchnic vein thromboses associated with myeloproliferative neoplasms: An international, retrospective study on 518 cases.

Am J Hematol 2020 02 29;95(2):156-166. Epub 2019 Nov 29.

CRIMM, Centro di Ricerca e Innovazione per le Malattie Mieloproliferative, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.

Myeloproliferative Neoplasms (MPN) course can be complicated by thrombosis involving unusual sites as the splanchnic veins (SVT). Their management is challenging, given their composite vascular risk. We performed a retrospective, cohort study in the framework of the International Working Group for MPN Research and Treatment (IWG-MRT), and AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM). A total of 518 MPN-SVT cases were collected and compared with 1628 unselected, control MPN population, matched for disease subtype. Those with MPN-SVT were younger (median 44 years) and enriched in females compared to controls; PV (37.1%) and ET (34.4%) were the most frequent diagnoses. JAK2V617F mutation was highly prevalent (90.2%), and 38.6% of cases had an additional hypercoagulable disorder. SVT recurrence rate was 1.6 per 100 patient-years. Vitamin K-antagonists (VKA) halved the incidence of recurrence (OR 0.48), unlike cytoreduction (OR 0.96), and were not associated with overall or gastrointestinal bleeding in multivariable analysis. Esophageal varices were the only independent predictor for major bleeding (OR 17.4). Among MPN-SVT, risk of subsequent vascular events was skewed towards venous thromboses compared to controls. However, MPN-SVT clinical course was overall benign: SVT were enriched in PMF with lower IPSS, resulting in significantly longer survival than controls; survival was not affected in PV and slightly reduced in ET. MPN-U with SVT (n = 55) showed a particularly indolent phenotype, with no signs of disease evolution. In the to-date largest, contemporary cohort of MPN-SVT, VKA were confirmed effective in preventing recurrence, unlike cytoreduction, and safe; the major risk factor for bleeding was esophageal varices that therefore represent a major therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.25677DOI Listing
February 2020

Etiology of non-cirrhotic portal vein thrombosis in children: Few or many causes?

Dig Liver Dis 2020 01 14;52(1):118-120. Epub 2019 Oct 14.

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.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2019.09.006DOI Listing
January 2020

Plasma miRNA-based signatures in CRC screening programs.

Int J Cancer 2020 02 5;146(4):1164-1173. Epub 2019 Aug 5.

Tumor Genomics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607-0.682), 0.670 (0.626-0.714) and 0.682 (0.580-0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32573DOI Listing
February 2020

Congenital Extrahepatic Portosystemic Shunts (Abernethy Malformation): An International Observational Study.

Hepatology 2020 02 19;71(2):658-669. Epub 2019 Aug 19.

Aparato Digestivo, Hospital Universitario Central de Asturias HUCA, Asturias, España.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30817DOI Listing
February 2020

Porto-sinusoidal vascular disease: proposal and description of a novel entity.

Lancet Gastroenterol Hepatol 2019 05;4(5):399-411

Barcelona Hepatic Hemodynamic Lab, Liver Unit, Hospital Clinic de Barcelona, University of Barcelona, Barcelona, Spain; CIBER Hepatic and Digestive Diseases, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Portal hypertension in the absence of portal vein thrombosis and without cirrhosis, but with mild or moderate alterations of liver histology (eg, obliterative venopathy, nodular regenerative hyperplasia, or incomplete septal cirrhosis) is being increasingly recognised. Owing to the heterogeneity of causes and histological findings, a substantial number of terms have been used to describe such idiopathic non-cirrhotic portal hypertension. Patients with the same clinical and histological features exist, but without portal hypertension at the time of diagnosis. Therefore, improved criteria are needed to define this form of liver disease. Here, we propose the term porto-sinusoidal vascular disease, since all lesions found involve the portal venules or sinusoids. The definition of this entity is based on the characteristic absence of cirrhosis with or without signs of portal hypertension or histological lesions. The presence of known causes of liver disease does not rule out porto-sinusoidal vascular disease, but specific causes of vascular liver disease are excluded from its definition. The diagnosis of porto-sinusoidal vascular disease is based on liver biopsy and might include signs specific for portal hypertension with normal or mildly elevated liver stiffness values and no complete portal vein thrombosis. We provide simple diagnostic criteria, because agreement on a uniform nomenclature is an essential requirement for future collaborative studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2468-1253(19)30047-0DOI Listing
May 2019

Endoscopy in acute variceal bleeding: Not always the sooner, the better?

Dig Liver Dis 2019 07 11;51(7):999-1000. Epub 2019 Feb 11.

Department of Biomedical and Clinical Sciences, University of Milan, Gastroenterology and Endoscopy Unit, ASST Fatebenefratelli Sacco, Milan, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2019.01.025DOI Listing
July 2019

Body mass index reduction improves the baseline procoagulant imbalance of obese subjects.

J Thromb Thrombolysis 2019 Jul;48(1):52-60

IRCCS Cà Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center and Fondazione Luigi villa, Via Pace 9, 20122, Milano, Italy.

Obesity is a risk factor for cardiovascular diseases. The latter being dependent (at least in part) on plasma procoagulant imbalance (i.e., hypercoagulability). Information on hypercoagulability associated with obesity is scanty and mainly based on global traditional coagulation tests or on the measurement of individual components of coagulation (i.e., pro- and anticoagulants). Plasma from 33 obese subjects was investigated soon before endoscopic balloon placement and after removal (6 months later) by thrombin-generation procedures that are thought to represent much better than any other in vitro test the coagulation process occurring in vivo. We found that obese subjects possess a state of hypercoagulability as demonstrated by the modification of the main parameters of thrombin-generation. In particular, the median value (min-max) of the endogenous thrombin potential (ETP) of obese subjects at baseline was higher than that of controls [1968 (1335-2533) vs. 1710 (1010-2119), p < 0.001]. Endoscopic balloon placement achieved a BMI reduction from 38.9 (31.7-62.3) to 31.6 (21.9-53.3), p < 0.001 and a parallel reduction of thrombin-generation as demonstrated by the following findings. The ETP measured soon after balloon removal was significantly smaller than that measured at baseline [1783 (1224-2642) vs. 1968 (1335-2533), p < 0.01]. The other parameters of thrombin-generation, including lag-time, peak-thrombin, time-to-reach the peak and velocity index showed a pattern consistent with the ETP, both at baseline and soon after balloon removal. Endoscopic balloon placement achieves concomitant reduction of BMI and thrombin-generation in subjects with obesity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-019-01818-9DOI Listing
July 2019

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dld.2018.12.025DOI Listing
August 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.

View Article and Find Full Text PDF

Download full-text PDF

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

Preemptive-TIPS Improves Outcome in High-Risk Variceal Bleeding: An Observational Study.

Hepatology 2019 01 10;69(1):282-293. Epub 2018 Dec 10.

Cirrhosis Care Clinic, Division of Gastroenterology (Liver Unit), CEGIIR, University of Alberta, Edmonton, Canada.

Patients admitted with acute variceal bleeding (AVB) and Child-Pugh C score (CP-C) or Child-Pugh B plus active bleeding at endoscopy (CP-B+AB) are at high risk for treatment failure, rebleeding, and mortality. A preemptive transjugular intrahepatic portosystemic shunt (p-TIPS) 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-risk patients. This multicenter, international, observational study included 671 patients from 34 centers admitted for AVB and high risk of treatment failure. Patients were managed according to current guidelines, and use of drugs and endoscopic therapy (D+E) or p-TIPS was based on individual center policy. p-TIPS in the setting of AVB is associated with a lower mortality in CP-C patients compared with D+E (1 year mortality 22% vs. 47% in D+E group; P = 0.002). Mortality rate in CP-B+AB patients was low, and p-TIPS did not improve it. In CP-C and CP-B+AB patients, p-TIPS reduced treatment failure and rebleeding (1-year cumulative incidence function probability of remaining free of the composite endpoint: 92% vs. 74% in the D+E group; P = 0.017) and development of de novo or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion: p-TIPS must be the treatment of choice in CP-C patients with AVB. Because of the strong benefit in preventing further bleeding and ascites, p-TIPS could be a good treatment strategy for CP-B+AB patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30182DOI Listing
January 2019

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cgh.2017.10.016DOI Listing
July 2018
-->