Fabio Tuzzolino

Short- and long-term effects of the transjugular intrahepatic portosystemic shunt on portal vein thrombosis in patients with cirrhosis

Background and aims Portal vein thrombosis (PVT) negatively impacts the prognosis in patients with cirrhosis. The aim of our study was to evaluate the effects of transjugular intrahepatic portosystemic shunt (TIPS) placement in patients with cirrhosis complicated by PVT. Methods Seventy consecutive cirrhotic patients with non-tumoural PVT treated with TIPS for portal hypertension complications from January 2003 to February 2010 in a tertiary-care centre were followed until last clinical evaluation, liver transplantation, or death. Results TIPS was successfully placed without major procedure-related complications. After TIPS, the portal venous system was completely recanalised in 57% of patients, a marked decrease in thrombosis was observed in 30%, and no improvement was seen in 13%. 95% of patients with complete recanalisation after TIPS maintained a patent portal vein. Predictors of complete recanalisation were a less severe and extensive PVT, de novo diagnosis of PVT, and absence of gastro-oesophageal varices. At follow-up, 1 patient had recurrence of bleeding, and 2 had spontaneous bacterial peritonitis. The rate of TIPS dysfunction at 12 and 24 months was 38% and 85% for bare stent and 21% and 29% for covered stent (p=0.001), respectively. Occurrence of encephalopathy at 12 and 24 months was 27% and 32%, respectively. Fifteen patients underwent liver transplantation. Survival at 1, 12 and 24 months was 99%, 89% and 81%, respectively. Conclusion Long-term outcome of non-tumoural PVT in patients with cirrhosis treated with TIPS placement is excellent. Prospective randomised studies should investigate whether TIPS placement is the best therapeutic option in patients with cirrhosis who develops non-tumoural PVT.

Early Liver Failure after Transjugular Intrahepatic Portosystemic Shunt in Patients with Cirrhosis with Model for End-Stage Liver Disease Score of 12 or Less: Incidence, Outcome, and Prognostic Factors

Purpose To evaluate the incidence, outcomes, and prognostic factors of early liver failure (ELF) after transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with cirrhosis with Model for End-Stage Liver Disease (MELD) score of 12 or less. Materials and Methods Institutional review board approved this retrospective study, with waiver of written informed consent. Two-hundred sixteen consecutive patients with cirrhosis (140 men, 76 women; mean age, 55.9 years; virus-related cirrhosis, 67.6% [146 of 216 patients]) with baseline MELD score of 12 or less who underwent TIPS placement between September 1999 and July 2012 were followed until last clinical evaluation, liver transplantation, or death. The Kaplan-Meier method, log-rank test, area under the receiver operating characteristic curve, and univariate and multivariate analyses were used, as appropriate. Results Twenty of 216 patients (9.2%) developed ELF within 3 months of TIPS (10 patients died, one required liver transplantation, and nine increased the MELD score to >18). ELF was associated with lower survival, 37% versus 95% at 6 months, and 24% versus 86% at 12 months (P < .001) compared with patients without ELF. ELF occurred in 16 of 95 (16.8%) patients with refractory ascites and in four of 121 (3.3%) patients with other indications for TIPS. Multivariate analysis confirmed MELD scores of 11 or 12 (odds ratio, 3.96 [95% confidence interval: 1.07, 14.67]; P = .040), decreased hemoglobin level (odds ratio, 0.68 [95% confidence interval: 0.49, 0.95]; P = .022), and decreased platelet count (odds ratio, 0.99 [95% confidence interval: 0.99, 0.99]; P = .024) as predictors for ELF in patients with refractory ascites. Conclusion ELF is not uncommon in cirrhotic patients with a MELD score of 12 or less who undergo TIPS placement for refractory ascites (especially in patients with MELD of 11 or 12) and decreased hemoglobin level and platelet count. (©) RSNA, 2016.

Lamivudine monoprophylaxis for de novo HBV infection in HBsAg-negative recipients with HBcAb-positive liver grafts.

Vizzini G, Gruttadauria S, Volpes R, D’Antoni A, Pietrosi G, Filì D, Petridis I, Pagano D, Tuzzolino F, Maria Santonocito M, Gridelli B. Lamivudine monoprophylaxis for de novo HBV infection in HBsAg‐negative recipients with HBcAb‐positive liver grafts.
Clin Transplant 2011: 25: E77–E81.

Phases I-II Matched Case-Control Study of Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Disease:

Fetal hepatocytes have a high regenerative capacity. The aim of the study was to assess treatment safety and clinical efficacy of human fetal liver cell transplantation through splenic artery infusion. Patients with endstage chronic liver disease on the waiting list for liver transplantation were enrolled. A retrospectively selected contemporary matched-pair group served as control. Nonsorted raw fetal liver cell preparations were isolated from therapeutically aborted fetuses. The end points of the study were safety and improvement of the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores. Nine patients received a total of 13 intrasplenic infusions and were compared with 16 patients on standard therapy. There were no side effects related to the infusion procedure. At the end of follow-up, the MELD score (mean ± SD) in the treatment group remained stable from baseline (16.0 ± 2.9) to the last observation (15.7 ± 3.8), while it increased in the control group from 15.3 ± 2.5 to 19 ± 5.7 (p = 0.0437). The Child-Pugh score (mean ± SD) dropped from 10.1 ± 1.5 to 9.1 ± 1.4 in the treatment group and increased from 10.0 ± 1.2 to 11.1 ± 1.6 in the control group (p = 0.0076). All treated patients with history of recurrent portosystemic encephalopathy (PSE) had no further episodes during 1-year follow-up. No improvement was observed in the control group patients with PSE at study inclusion. Treatment was considered a failure in six of the nine patients (three deaths not liver related, one liver transplant, two MELD score increases) compared with 14 of the 16 patients in the control group (six deaths, five of which were caused by liver failure, four liver transplants, and four MELD score increases). Intrasplenic fetal liver cell infusion is a safe and well-tolerated procedure in patients with end-stage chronic liver disease. A positive effect on clinical scores and on encephalopathy emerged from this preliminary study.

Quantification of hepatic steatosis: A comparison of computed tomography and magnetic resonance indices in candidates for living liver donation

RATIONALE AND OBJECTIVES To evaluate, in a group of candidates for liver donation, the role of unenhanced computed tomography (CT) and magnetic resonance (MR) as noninvasive means to measure hepatic steatosis (HS). MATERIALS AND METHODS Sixty-one consecutive candidates underwent CT and MR evaluation for liver donation within 3 weeks of liver biopsy. On CT, three methods of HS quantification were evaluated: the measurement of hepatic attenuation (CT L), the ratio of hepatic attenuation to splenic attenuation (CT L/S), and the difference between the hepatic and splenic attenuation (CT L-S). On MR, HS was reported in terms of fat signal fraction (FSF) using in-phase/opposed-phase and fat/non-fat- saturated images, with and without normalization with the spleen (T1W IP/OP FSF, T1W IP/OP FSF spleen and T2W ± FS FSF, TW2 ± FS FSF spleen). The accuracy of each imaging index in the diagnosis of HS, according to various thresholds, was assessed using receiver operating characteristic analysis. RESULTS On biopsy, 35 donors showed no significant HS (<5%); the remaining 26 showed HS ranging from 5% to 40%. With all CT and MR indices, there was a trend toward increasing diagnostic accuracy as the threshold levels of HS increased. When comparing all the indices, TW2 ± FS FSF(spl) showed higher accuracy at threshold levels of 5% and 10% of steatosis but without reaching statistical significance. CONCLUSIONS In candidates for living donation, MR and CT indices are similar in estimating liver-fat content; however, MR with T2W ± FS FSF(spl) sequences shows higher accuracy when low threshold levels of steatosis (≤5% and ≤10% HS) are selected.

Early regeneration of the remnant liver volume after right hepatectomy for living donation: A multiple regression analysis

Early liver regeneration was studied in a series of 70 patients who underwent right hepatectomy for living donation between November 2004 and January 2010. Liver regeneration was evaluated with multidetector computed tomography (MDCT) at a mean of 61.07 days after surgery. Presurgical variables [eg, age, weight, height, body mass index (BMI), liver function tests, creatinine levels, platelet counts, international normalized ratio, and glucose levels] and variables detected with preoperative MDCT imaging [eg, main portal vein diameter, steatosis, original liver volume, and spleen volume (SV)] were investigated as potential predictors of liver regeneration. The future remnant liver volume (FRLV) was preoperatively calculated with a virtual surgical cut. Liver function tests and creatinine levels were recorded on the 30th postoperative day. In addition, the onset of postoperative complications occurring within 90 days of surgery was analyzed, and the complications were codified according to the 5 tiers of the Clavien‐Dindo classification. In 26 of the 70 patients (37.14%), 100% or greater hepatic regeneration had occurred at 2 months. There was no association between the clinical outcome and the liver regeneration rate. A stepwise multiple regression analysis showed that a higher BMI (coefficient = 0.035, P < 0.0001) and preoperative parameters such as a smaller FRLV (coefficient = −0.002, P < 0.0001) and a greater SV/FRLV ratio (coefficient = 1.196, P < 0.0001) were predictors of greater liver regeneration. Liver Transpl, 2012.

Sildenafil in severe pulmonary hypertension associated with chronic obstructive pulmonary disease: A randomized controlled multicenter clinical trial

BACKGROUND Pulmonary hypertension (PH) is a well-known independent prognostic factor in chronic obstructive pulmonary disease (COPD) and a sufficient criterion for lung transplant candidacy. Limited data are currently available on the hemodynamic and clinical effect of phosphodiesterase 5 inhibitors in patients with severe PH associated with COPD. This study assessed the effect of sildenafil on pulmonary hemodynamics and gas exchange in severe PH associated with COPD. METHODS After screening, this multicenter, randomized, placebo-controlled double-blind trial randomized patients to receive 20 mg sildenafil or placebo 3 times a day (ratio 2:1) for 16 weeks. The primary end point was the reduction in pulmonary vascular resistance. Secondary end points included BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, 6-minute walk test, and quality of life questionnaire. Changes in the partial pressure of arterial oxygen were evaluated as a safety parameter. RESULTS The final population included 28 patients, 18 in the sildenafil group and 10 in the placebo group. At 16 week, patients treated with sildenafil had a decrease in pulmonary vascular resistance (mean difference with placebo -1.4 WU; 95% confidence interval, ≤ -0.05; p = 0.04). Sildenafil also improved the BODE index, diffusion capacity of the lung for carbon monoxide percentage, and quality of life. Change from baseline in the partial pressure of arterial oxygen was not significantly different between the sildenafil and placebo groups. CONCLUSIONS This pilot study found that treatment with sildenafil reduced pulmonary vascular resistance and improved the BODE index and quality of life, without a significant effect on gas exchange.

Definitive outcomes of self-expandable metal stents in patients with refractory post-transplant biliary anastomotic stenosis.

BACKGROUND Endoscopic retrograde cholangio-pancreatography is the gold standard of treatment in patients with biliary complications after liver transplantation. The benefits of fully covered self-expandable metal stents (FCSEMS) lie in their relative simplicity and the need for only two procedures, one for insertion, and the other for removal. Several case series have been published on such stents with generally good outcomes. Objective is to analyze definitive long-term outcomes of this treatment. METHODS Prospective, observational study in a single, tertiary-care referral centre. All consecutive patients with post-transplant biliary stenosis/leak were treated with FCSEMS after failure of conventional treatment. Recurrence was evaluated after four years. RESULTS From February 2008 to April 2012, 70 patients were included. In all patients, the metal stent was successfully placed. After a mean of 86.7 ± 38.4 days, the stent was removed. Forty-six patients (65.7%) showed resolution. After a mean of 4 ± 1.2 years, 61% of patients maintained the results, but 39% showed recurrence. On the tested variables the diagnosis of stenosis, the number of previous procedures and plastic stents placed correlate with better long-term results. CONCLUSIONS This series suggests a lack of long-term advantages of FCSEMS over plastic stents in the management of biliary stenosis after liver transplantation.

Transjugular Intrahepatic Portosystemic Shunts in Patients with Cirrhosis with Refractory Ascites: Comparison of Clinical Outcomes by Using 8- and 10-mm PTFE-covered Stents

Purpose To compare the efficacy and complications of transjugular intrahepatic portosystemic shunt (TIPS) creation performed by using a 10-mm or an 8-mm-diameter polytetrafluoroethylene (PTFE)-covered stent in a consecutive series of patients with cirrhosis with refractory ascites (RA). Materials and Methods The institutional review board approved this retrospective study and informed consent was waived. One hundred seventy-one patients with RA (mean age, 58.7 years ± 10.3; 95% confidence interval [CI]: 57.2 years, 60.3 years) had undergone TIPS placement by using 10-mm (60 patients) or 8-mm (111 patients) covered stent between January 2004 and December 2012. Median follow-up time was 16.8 months (range, 3.4-84.8 months). Hemodynamic changes, incidence of hepatic encephalopathy, and long-term (>3 months) need for paracentesis after TIPS placement were evaluated and calculated by using the Kaplan-Meier method and were compared by using the log-rank test. Results Pre-TIPS demographics and clinical characteristics of the two groups were comparable. The portosystemic gradient before TIPS was 17.0 mm Hg ± 4.2 (95% CI: 15.9 mm Hg, 18.1 mm Hg) in the 10-mm group versus 16.1 mm Hg ± 3.7 (95% CI: 15.4 mm Hg, 16.8 mm Hg) in the 8-mm group (P = .164). After TIPS, the portosystemic gradient was 6.5 mm Hg ± 3.4 (95% CI: 5.7 mm Hg, 7.4 mm Hg) in the 10-mm group versus 7.5 mm Hg ± 2.6 (95% CI: 6.9 mm Hg, 7.9 mm Hg) in the 8-mm group (P = .039). The long-term need for paracentesis was greater in the 8-mm group (64 of 111 patients [58%] vs 18 of 60 patients [31%], P = .003). Overall, hepatic encephalopathy was similar in both groups (45 of 111 patients [41%] vs 26 of 60 patients [44%], P = .728). Conclusion A10-mm PTFE-covered stent leads to better control of RA secondary to portal hypertension in patients with cirrhosis, compared with an 8-mm stent, without increasing the incidence of hepatic encephalopathy.

Prognostic relevance of pulmonary arterial compliance after therapy initiation or escalation in patients with pulmonary arterial hypertension

BACKGROUND Conventional hemodynamic parameters are considered to be the gold standard indices of outcome in pulmonary arterial hypertension (PAH); on the contrary, few data support the hypothesis that the pulsatile component of right ventricular afterload provides important prognostic information. The aim of the study was to investigate the prognostic significance of pulmonary arterial compliance (PCa) after therapy initiation or escalation in PAH patients. METHODS A cohort of 419 consecutive PAH patients (308 naive and 111 prevalent) underwent right heart catheterisation (RHC) prior to initiating or escalating PAH-targeted therapy. RHC was repeated in 255 patients (61%) after 4 to 12months of therapy as 62 patients (15%) died and 102 (24%) did not undergo a follow-up RHC within the first year. RESULTS After the follow-up RHC, 63 patients died over a median follow-up period of 39months. At multivariate analysis, age>50years old, male gender, etiology associated with systemic sclerosis, persistence of WHO class III/IV, and reduced PCa at follow-up RHC were the independent parameters significantly associated with poor prognosis. At ROC analysis, the optimal cut-off point of PCa to predict survival was 1.4mL/mmHg (AUC 0.73, sensitivity 81.8%, specificity 58.8%). CONCLUSIONS In PAH patients hospitalized to initiate or to escalate PAH-specific therapy, failure to improve PCa after therapy is a strong hemodynamic predictor of poor prognosis.