A. Nicolini

TIPS for Budd-Chiari syndrome: long-term results and prognostics factors in 124 patients.

BACKGROUND & AIMS Budd-Chiari syndrome (BCS) is a rare and life-threatening disorder secondary to hepatic venous outflow obstruction. Small series of BCS patients indicate that transjugular intrahepatic portosystemic shunt (TIPS) may be useful. However, the influence of TIPS on patient survival and factors that predict the outcome of TIPS in BCS patients remain unknown. METHODS One hundred twenty-four consecutive BCS patients treated with TIPS in 6 European centers between July 1993 and March 2006 were followed until death, orthotopic liver transplantation (OLT), or last clinical evaluation. RESULTS Prior to treatment with TIPS, BCS patients had a high Model of End Stage Liver Disease and high Rotterdam BCS prognostic index (98% of patients at intermediate or high risk) indicating severity of liver dysfunction. However, 1- and 5-year OLT-free survival were 88% and 78%, respectively. In the high-risk patients, 5-year OLT-free survival was much better than that estimated by the Rotterdam BCS index (71% vs 42%, respectively). In the whole population, bilirubin, age, and international normalized ratio for prothrombin time independently predicted 1-year OLT-free survival. A prognostic score with a good discriminative capacity (area under the curve, 0.86) was developed from these variables. Seven out of 8 patients with a score >7 died or underwent transplantation vs 5 out of 114 patients with a score <7. CONCLUSIONS Long-term outcome for patients with severe BCS treated with TIPS is excellent even in high-risk patients, suggesting that TIPS may improve survival. Furthermore, we identified a small subgroup of BCS patients with poor prognosis despite TIPS who might benefit from early OLT.

Diastolic dysfunction is associated with poor survival in patients with cirrhosis with transjugular intrahepatic portosystemic shunt

Background: Transjugular intrahepatic portosystemic shunt (TIPS) is a treatment for portal hypertension-related complications. Accurate prediction of the outcome of patients treated with TIPS is important, because some patients have very short survival. Diastolic dysfunction is frequently observed in patients with cirrhosis. Aim: To investigate whether or not diastolic dysfunction can predict the outcome after TIPS. Methods: Echocardiography with Doppler exploration was performed before and 28 days after TIPS insertion in 32 patients with cirrhosis. Several echocardiographic measures, including the early maximal ventricular filling velocity/late filling velocity (E/A) ratio as indicative of diastolic function, as well as laboratory, clinical and demographic variables were evaluated as predictors of survival. Results: Univariate analysis revealed that the presence of diastolic dysfunction observed 28 days after TIPS (E/A ratio ⩽1) and baseline model of end-stage liver disease score were related to survival. Multivariate analysis identified diastolic dysfunction as an independent predictor of death (RR 8.9, 95% CI 1.9 to 41.5, p = 0.005). During the first year of follow–up, six out of 10 patients with an E/A ratio ⩽1 died, whereas all 22 patients with E/A ratio >1 survived. Conclusions: Diastolic dysfunction estimated using E/A ratio is a promising predictor of death in patients with cirrhosis who are treated with TIPS.

Cirrhosis and portal hypertension: The importance of risk stratification, the role of hepatic venous pressure gradient measurement

Portal hypertension is the main prognostic factor in cirrhosis. The recent emergence of potent antiviral drugs and new algorithm of treatment for the management of complications due to portal hypertension have sensibly changed our perception of cirrhosis that can be now considered as a multistage liver disease whose mortality risk can be reduced by a tailored approach for any stage of risk. Experts recommend to move toward a pathophysiological classification of cirrhosis that considers both structural and functional changes. The hepatic venous pressure gradient HVPG, is the reference gold standard to estimate the severity of portal hypertension in cirrhosis. It correlates with both structural and functional changes that occur in cirrhosis and carries valuable prognostic information to stratify the mortality risk. This article provides a general overview of the pathophysiology and natural course of cirrhosis and portal hypertension. We propose a simplified classification of cirrhosis based on low, intermediate and high mortality stage. The prognostic information provided by HVPG is presented according to each stage. A comparison with prognostic models based on clinical and endoscopic variables is discussed in order to evidence the additional contribute given by HVPG on top of other clinical and instrumental variables widely used in clinical practice.

TACE with drug-eluting beads is effective for the maintenance of the milan-in status in patients with a small hepatocellular carcinoma

Transarterial chemoembolization (TACE) is the standard of care for the treatment of patients with an intermediate (Barcelona Clinic Liver Cancer [BCLC] B) hepatocellular carcinoma and to bridge patients with an early cancer to liver transplantation (LT). We explored the efficacy of TACE with drug‐eluting beads (DEB) in BCLC A patients. Included are all BCLC A patients unsuitable for resection or locoregional ablation who underwent a DEB TACE between 2006 and 2012. Treatment was carried out “a la demande” until complete tumor devascularization or progression beyond Milan criteria. In patients with a complete response (CR), a contrast computed tomography (CT) scan was repeated at 3‐month intervals during the first 2 years and then every 6 months alternating with abdominal ultrasound in the subsequent 3 years. Fifty‐five patients had 79 tumor nodules ranging 7 to 50 mm; 32 (58%) achieved a CR that was maintained up to 4 and 7 months in 21 (38%) and 17 (31%) patients, respectively. The 24‐ and 36‐month tumor‐free survivals were 21% and 9%, respectively. The overall cumulative progression beyond Milan criteria at 3, 6, 12, and 24 months was 2%, 5%, 30%, and 54%. LT eligibility was maintained for a median of 19 months (range, 2‐63 months). CR to first TACE was the strongest independent predictor of Milan‐in maintenance. In conclusion, DEB TACE may effectively bridge patients with an early cancer to LT, and a CR to the first procedure may guide patient prioritization during the waiting list. Liver Transpl 21:1259‐1269, 2015.

Transarterial chemoembolization with drug‐eluting beads is effective for the maintenance of the Milan‐in status in patients with a small hepatocellular carcinoma

Transarterial chemoembolization (TACE) is the standard of care for the treatment of patients with an intermediate (Barcelona Clinic Liver Cancer [BCLC] B) hepatocellular carcinoma and to bridge patients with an early cancer to liver transplantation (LT). We explored the efficacy of TACE with drug‐eluting beads (DEB) in BCLC A patients. Included are all BCLC A patients unsuitable for resection or locoregional ablation who underwent a DEB TACE between 2006 and 2012. Treatment was carried out “a la demande” until complete tumor devascularization or progression beyond Milan criteria. In patients with a complete response (CR), a contrast computed tomography (CT) scan was repeated at 3‐month intervals during the first 2 years and then every 6 months alternating with abdominal ultrasound in the subsequent 3 years. Fifty‐five patients had 79 tumor nodules ranging 7 to 50 mm; 32 (58%) achieved a CR that was maintained up to 4 and 7 months in 21 (38%) and 17 (31%) patients, respectively. The 24‐ and 36‐month tumor‐free survivals were 21% and 9%, respectively. The overall cumulative progression beyond Milan criteria at 3, 6, 12, and 24 months was 2%, 5%, 30%, and 54%. LT eligibility was maintained for a median of 19 months (range, 2‐63 months). CR to first TACE was the strongest independent predictor of Milan‐in maintenance. In conclusion, DEB TACE may effectively bridge patients with an early cancer to LT, and a CR to the first procedure may guide patient prioritization during the waiting list. Liver Transpl 21:1259‐1269, 2015.

Role of transjugular liver biopsy in the diagnostic and therapeutic management of patients with severe liver disease

Purpose. This study sought to assess the diagnostic yield, the impact on treatment and the safety of transjugular liver biopsyMaterials and methods. We reviewed the medical records of 72 patients with severely impaired liver function who underwent transjugular biopsy at our department. Contraindications to percutaneous liver biopsy included thrombocytopenia, severe coagulopathy, marked ascites or a combination of the above. Patients were divided into four groups based on the clinically suspected cause of liver disease. Group 1 included 44 patients (58%) with acute abnormalities of liver function, whereas groups 2, 3 and 4 included patients with chronic abnormalities suspected to be due to infectious cirrhosis (12 patients, 16%), alcoholic cirrhosis (seven patients, 9%) and cirrhosis of unknown origin (13 patients, 17%), respectively. A Quick-Core (Cook, ProAct Ltd., State College, Pennsylvania, USA) needle allowing automated tissue sampling was used for all biopsiesResults. Biopsy specimens were diagnostic in 69 out of 72 patients (91%). Biopsy findings influenced treatment in 34 out of 69 patients (49%). The most significant results were obtained in group 1, where the histological diagnosis differed from clinical suspicion in 25/39 patients. There was only one major complication and four minor complications. The major complication was an arteriovenous and arteriobiliary fistula with haemorrhage and anaemia, which was successfully embolised by the same team of interventional radiologistsConclusions. Transjugular liver biopsy proved to be a safe procedure that provided important information for the clinical and therapeutic management of patients in whom treatment would have been either empirical or unfeasibleRiassuntoObiettivo. Valutare l’efficacia diagnostica, l’impatto sul trattamento terapeutico e la sicurezza della biopsia epatica transgiugulareMateriali e metodi. Abbiamo revisionato le cartelle cliniche di 72 pazienti con severa alterazione della funzionalità epatica che sono stati sottoposti a biopsia transgiugulare presso il nostro Dipartimento. I pazienti sono stati suddivisi in 4 gruppi, in base al sospetto clinico dell’origine della malattia epatica. Il gruppo 1 includeva 44 pazienti (58%) con un’alterazione acuta della funzionalità epatica, mentre i gruppi 2, 3, 4 includevano pazienti in cui l’alterazione era cronica e in cui il sospetto clinico era rispettivamente di cirrosi di tipo infettivo (12 pazienti, 16%), alcolico (7 pazienti, 9%) e di origine sconosciuta (13 pazienti, 17%). Per la biopsia è stato utilizzato un ago Quick Core (Cook, ProAct Ltd., State College, Pennsylvania, USA), che permette il prelievo in modo automaticoRisultati. Materiale bioptico diagnostico è stato ottenuto in 69 pazienti su 72 (91%). I dati forniti dalla biopsia hanno permesso un cambiamento terapeutico in 34 su 69 soggetti (49%). I risultati più significativi sono stati ottenuti nel gruppo 1 dove in 25 casi su 39 pazienti si è ottenuta una diagnosi diversa da quella sospettata. Abbiamo avuto una sola complicanza maggiore, risolta dallo stesso gruppo di radiologi interventisti e 4 complicanza minoriConclusioni. La biopsia epatica per via transgiugulare permette di ottenere importanti dati relativi al trattamento clinico e terapeutico di pazienti nei quali la terapia sarebbe altrimenti empirica o non proponibile, con una bassa incidenza di complicanze

Usefulness and limits of distal echo-Doppler velocimetric indices for assessing renal hemodynamics in stenotic and non-stenotic kidneys.

Background Distal echo-Doppler velocimetric indices are widely used for revealing the presence of a renal artery stenosis but there is scarce information as to whether they reflect the renal hemodynamics in stenotic and non-stenotic kidneys. Objectives and methods We evaluated the pulsatility and resistive indices (PI and RI), acceleration (A) and acceleration time (A t) and correlated their values with those of effective renal plasma flow (ERPF), glomerular filtration rate (GFR), renal vascular resistance (RVR) and filtration fraction (FF) estimated by single kidney scintigraphy in 24 kidneys with 70–95% renal artery stenosis (atherosclerotic n = 17, fibromuscular n = 7) and in 27 non-stenotic kidneys (11 contralateral to renal artery stenosis and 16 of patients with essential hypertension). In patients with stenotic kidneys, these measurements were repeated within 7 days after a successful percutaneous transluminal renal angioplasty (PTRA) (in 11 arteries performed in combination with stent implantation). Results Prior to dilation we found that the stenotic kidneys had significantly lower values of ERPF, GFR and higher RVR than the non-stenotic kidneys and that these hemodynamic alterations were associated with those, also statistically significant, of the four velocimetric indices. In non-stenotic kidneys, there were highly significant relationships between PI and ERPF, and RVR (r = − 0.68 and 0.81 respectively P < 0.01); similar relationships were found for RI (r = − 0.67 and 0.78 P < 0.01) whereas no such correlations were found between these two velocimetric indices and GFR and FF; also no correlations were found between A and A t and ERPF, GFR, RVR and FF. In stenotic kidneys no significant correlations were found between any of the velocimetric and the hemodynamic indices. Renal artery dilation induced clear cut increments in ERPF, GFR and reduction in RVR in post-stenotic kidneys, which were associated with normalization of all four velocimetric indices. No relationships were observed between the renal hemodynamic and the velocimetric changes induced by dilation; however in post-stenotic kidneys the relationships between PI and RI, ERPF and RVR were restored as in non-stenotic kidneys. Conclusions These data indicate that PI and RI can be used to assess ERPF and RVR both in non-stenotic and post-stenotic kidneys; however, none of the velocimetric indices examined in this study can provide valid informations on the renal hemodynamics of stenotic kidneys and on their changes induced by PTRA.

Transarterial embolization with microspheres in the treatment of monofocal HCC

BACKGROUND Transarterial embolization using one permanent embolic agent alone enhances tumour ischaemia and spares patients with hepatocellular carcinoma form toxic chemotherapeutic drugs. PURPOSE We assessed feasibility, tolerability and efficacy of transarterial embolization with microspheres in patients with a single node hepatocellular carcinoma. MATERIALS AND METHODS Eighteen consecutive patients with compensated cirrhosis, hypervascularized single hepatocellular carcinoma, in whom liver transplantation was indicated (no.=3), or excluded from radical therapies (no.=15), received selective transarterial embolization with microspheres. Treatment was repeated every other month until complete devascularitazion was demonstrated by computed tomography, for a maximum of 3 cycles. RESULTS Fifty transarterial embolization courses (mean: 2.8 courses, range 1-6) were administered, corresponding to a 100% applicability rates. Initial complete response was achieved in 16 (89%) patients and confirmed by histology in 2 transplanted patients. During 21-month follow-up (range 8-36), hepatocellular carcinoma recurred in 10 (62%) patients who achieved initial complete response, and de novo tumour nodes developed in 10 (56%). No patient required analgesics and none had liver function deteriorated following transarterial embolization. CONCLUSIONS Transarterial embolization is a well-tolerated treatment for patients with early or intermediate hepatocellular carcinoma who are not suitable for radical treatment or await liver transplantation, but it allows to achieve a sustained complete response in a minority of patients.

Is there still a role for the hepatic locoregional treatment of metastatic neuroendocrine tumors in the era of systemic targeted therapies

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) frequently present with distant metastases at the time of diagnosis and the liver is the most frequent site of spreading. The early identification of metastatic disease represents a major prognostic factor for GEP-NENs patients. Radical surgical resection, which is feasible for a minority of patients, is considered the only curative option, while the best management for patients with unresectable liver metastases is still being debated. In the last few years, a number of locoregional and systemic treatments has become available for GEP-NEN patients metastatic to the liver. However, to date only a few prospective studies have compared those therapies and the optimal management option is based on clinical judgement. Additionally, locoregional treatments appear feasible and safe for disease control for patients with limited liver involvement and effective in symptoms control for patients with diffuse liver metastases. Considering the lack of randomized controlled trials comparing the locoregional treatments of liver metastatic NEN patients, clinical judgment remains key to set the most appropriate therapeutic pathway. Prospective data may ultimately lead to more personalized and optimized treatments. The present review analyzes all the locoregional therapy modalities (i.e., surgery, ablative treatments and transarterial approach) and aims to provide clinicians with a useful algorithm to best treat GEP-NEN patients metastatic to the liver.

P0206 : Prevention of bleeding following invasive procedures in cirrhotic patients: A single center experience

Background: Risk of bleeding in cirrhosis has predominantly been associated with coagulopathy and thrombocytopenia due to impaired liver function and splenomegaly. The evaluation of the actual bleeding risk in cirrhotic patientsundergoing invasiveprocedures is a critical point to optimizemanagement in termsof platelet (Plt) or plasma prophylactic transfusions. Methods: During 2013, 480 cirrhotic patients underwent diagnostic or therapeutic invasive procedures at our Liver Unit (Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, Milan, Italy). Plt transfusion was performed when Plt count less than 50,000/mmc while fresh frozen plasma was infused when international normalized ratio (INR) >1.5, except those undergoing paracentesis. Low-molecular-weight-heparin was discontinued 24h before any procedure while antiaggregant therapy was interrupted five days before any procedure except oesophageal varices band ligation and paracentesis. Major hemorrhagic events were those requiring hospitalisation or blood transfusion; minor events was a haemoglobin decline >1.5 g/dl post procedure without clinical relevance. Results: 174 Transarterial Chemo-Embolization (TACE), 16 Radio-Frequency Termal Alblation (RFTA), 214 paracentesis, 59 oesophageal varices banding, 6 trans-jugular liver biopsy (LB) and 11 Percutaneous Ethanol Injection (PEI) were performed. Overall, 61 procedures met the criteria for plasma or Plt infusion and major bleeding complications occurred in 3 patients (0,6%). In 2 patients, anemia-related paracentesis was treated by blood transfusions whereas one patient following variceal band ligation had to be hospitalized for severe anemia. Major complications rate was 1.6% in Plt/plasma infusion exposed patients versus 0.47% in unexposed (p=0.28).Minor eventswith a>1.5 g/dl haemoglobindecline occurred in 17 patients (15 paracentesis and 2 band ligations), rate was 3.2% in Plt/plasma infusion exposed patients versus 3.5% in unexposed (p=0.9). Conclusion: Pre-treatment platelet transfusion in cirrhotic patients with Plt count 1.5, was associated with a negligible risk of bleeding and appeared as a safe, cost/effective strategy.