Filippo Schepis, MD Università degli Studi di Modena e Reggio Emilia

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Filippo Schepis, MD Università degli Studi di Modena e Reggio Emilia Il sottoscritto dichiara di non aver avuto/di aver avuto negli ultimi 12 mesi conflitto d interesse in relazione a questa presentazione e che la presentazione non contiene/contiene discussione di farmaci in studio o ad uso off-label

Ascites: old and new non-pharmacological treatments Filippo Schepis, MD Hepatic Hemodynamic Laboratory Gastroenterology Unit University Hospital of Modena - Italy

NATURAL HISTORY OF CIRRHOSIS Baveno VI, 2015 D Amico et al, AP&T 2014

NATURAL HISTORY OF ASCITES FIRST ONSET ASCITES RESPONSIVE TO DIURETICS REFRACTORY ASCITES Hyponatremia Hepatorenal syndrome type I/II Salerno et al, Am J Gastroenterol 1993 Modified from Bernardi & Caraceni

ASCITES PATHOPHYSIOLOGY THE CLASSICAL PARADIGMA PORTAL HYPERTENSION SPLANCHNIC VASODILATION EFFECTIVE HYPOVOLEMIA RAAs SNS ADH REDUCED RENAL PERFUSION Ascites RETENTION OF Na + RETENTION OF H 2 O Modified from Bernardi & Caraceni

ASCITES PATHOPHYSIOLOGY THE CLASSICAL PARADIGMA PORTAL HYPERTENSION SPLANCHNIC VASODILATION EFFECTIVE HYPOVOLEMIA RAAs SNS ADH REDUCED RENAL PERFUSION AlfaPump TIPS LV paracentesis Peritoneovenous shunt Ascites RETENTION OF Na + RETENTION OF H 2 O Modified from Bernardi & Caraceni

HISTORY OF ASCITES TREATMENT A SCOPUS Overview Keywords: Ascites AND Cirrhosis Type: Article OR Review Resuls: 12,018 items

HISTORY OF ASCITES TREATMENT A SCOPUS Overview Keywords: Ascites AND Cirrhosis AND Diuretic Type: Article OR Review Resuls: 1,687 items

HISTORY OF ASCITES TREATMENT A SCOPUS Overview Keywords: Peritoneovenous shunts AND Ascites AND Cirrhosis Type: Article OR Review Resuls: 367 items

HISTORY OF ASCITES TREATMENT A SCOPUS Overview Keywords: Paracentesis AND Cirrhosis Type: Article OR Review Resuls: 1,356 items

HISTORY OF ASCITES TREATMENT A SCOPUS Overview Keywords: Transjugular shunt AND Ascites Type: Article OR Review Resuls: 1,377 items

HISTORY OF ASCITES TREATMENT A SCOPUS Overview Keywords: Alfapump AND Ascites Type: Article OR Review Resuls: 11 items

RECCOMANDATIONS FOR THE MANAGEMENT OF ASCITES Modified from Pericleous et al, EJGH 2016

RECCOMANDATIONS FOR THE MANAGEMENT OF ASCITES

PERITONEOVENOUS SHUNTING

PERITONEOVENOUS SHUNTING Renal impairment Readmission for Ascites

PERITONEOVENOUS SHUNTING

REPEATED PARACENTESIS + ALBUMIN INFUSION Survival Survival Gines et al Gastroenterology 1988

POST-PARACENTESIS CIRCULATORY DYSFUNCTION (PPCD) * * 8 g/l * * Gines et al, Gastroenterology 1988 Gines et al, Gastroenterology 1996

TOTAL PARACENTESIS + ALBUMIN INFUSION Large-volume paracentesis (LVP) is the first-line therapy in patients with large ascites (grade 3 ascites) (A1). LVP should be completed in a single session (A1). LVP should be performed together with the administration of albumin (8 g/l of ascitic fluid removed) to prevent circulatory dysfunction after LVP (A1). Readmission Survival EASL guidelines 2010 Titò et al Gastroenterology 1990

PARACENTESIS TECNIQUE

TIPS Courtesy of A. Rampoldi

TIPS

REFRACTORY ASCITES TIPS vs PARACENTESIS Salerno et al. Gastroenterology 2007

REFRACTORY ASCITES TIPS vs PARACENTESIS INCIDENCE OF HEPATIC ENCEPHALOPATHY 57% 36% Saab, Cochrane 2006

1,0 0,8 0,6 0,4 0,2 TIPS PTFE-covered vs Bare stents Free of TIPS Dysfunction P = 0.001 PTFE (n=39) Bare stents (n=41) 0 200 400 600 Days Clinical Recurrence PTFE Bare n VB / Ascites (n) 3 12 2/1 4/8 p <0.05 Bureau et al. Gastroenterology 2004

TIPS With Covered Stents Increase Transplant-free Survival of Patients With Cirrhosis and Recurrent Ascites eptfe-tips vs LVP (LVP every 3 w, not > 6 in 2 months) Post-TIPS PSPG < 12mmHg Bureau et al, Gastroenterology 2016

Post-TIPS PSPG Influences Survival Independently of MELD in Patients With Cirrhosis and Refractory Ascites (N=168) Log rank test: p 0,729 Log rank test: p 0,043 Schepis et al submitted

UNDER-DILATED TIPS ASSOCIATE WITH EFFICACY AND REDUCED ENCEPHALOPATHY IN CIRRHOTIC PATIENTS Schepis et al CGH, 2018

AlfaPump Back to the origin?

AlfaPump Refractory ascites 96% vs. 81% primary or secondary antibiotic prophylaxis for spontaneous bacterial peritonitis Bureau et al J Hep 2017

Fig. 2 AlfaPump Bureau et al J Hep 2017

AlfaPump Bureau et al J Hep 2017

Fig. 3 AlfaPump Bureau et al J Hep 2017

AlfaPump Bureau et al J Hep 2017

AlfaPump Solà et al, Liver Transplant 2017

AlfaPump Bureau et al J Hep 2017

AlfaPump Bureau et al J Hep 2017

Take Home Messages After more than 2000 years, paracentesis remains the fastest non pharmacological way to remove ascites Large volume paracentesis must be performed in association to albumin infusion The only available non pharmacological treatment which improves survival is TIPS A better definition of candidate patients to TIPS together with a better control of post TIPS hemodynamic events will decrease mortality and morbidity related to TIPS Future palliative treatment of refractory or difficult to treat ascites should take into account its physiopathology

GRAZIE PER L ATTENZIONE