Faculty Bibliography

BACKGROUND:Clostridium difficile is a bacterial pathogen associated with significant morbidity and mortality in patients with cirrhosis. GOALS:Our primary aim is to identify variables that are predictive of poor outcomes in cirrhosis patients with C. difficile infection (CDI). We also aim to further characterize the risk factors for developing CDI and risk of mortality in this patient population. STUDY:A total of 200 subjects with a diagnosis of cirrhosis and CDI were matched to 200 cirrhosis inpatients without CDI. The groups were compared to evaluate variables associated with decreased survival for cirrhosis inpatients with CDI as well as risk factors for developing CDI. RESULTS:Cirrhosis patients with CDI were more frequently prescribed antibiotics during their hospitalization (P=0.002) and cared for in an intensive care unit (ICU) (P<0.001). Preadmission proton pump inhibitor and spontaneous bacterial peritonitis (SBP) prophylactic antibiotic use were not significantly different between the 2 cohorts. CDI subjects had an increased 30-day mortality (44% vs. 28.5%, P=0.034), however overall mortality was not significantly different (P=0.2). The multivariable logistic regression model demonstrated an increased 30-day and overall mortality in the CDI population was independently associated with albumin <3 g/dL and ICU admission. CONCLUSIONS:C. difficile infections are associated with a significant increase in 30-day mortality, but not overall mortality. Risk factors of ICU admission and antibiotic exposure were associated with the diagnosis of CDI in cirrhosis patients. Hypoalbuminemia and ICU admission were found to be strong predictors of increased mortality in cirrhosis patients with CDI.

INTRODUCTION AND AIM:Thrombosis is a vascular disorder of the liver often associated with significant morbidity and mortality. Cirrhosis is a predisposing factor for portal venous system thrombosis. The aim of this study is to determine differences between cirrhotics and non-cirrhotics that develop thrombosis in portal venous system and to evaluate if cirrhosis severity is related to the development of portal venous system thrombosis. MATERIAL AND METHODS:We studied patients diagnosed with portal venous system thrombosis using contrast-enhanced computed tomography scan and doppler ultrasound at Medica Sur Hospital from 2012 to 2017. They were categorized into two groups; cirrhotics and non-cirrhotics. We assessed the hepatic function by Child-Pugh score and model for end-stage liver disease. RESULTS:67 patients with portal venous system thrombosis (25 with non-cirrhotic liver and 42 with cirrhosis) were included. The mean age (± SD) was 65 ± 9.5 years in cirrhotic group and 57 ± 13.2 years (p = 0.009) in non-cirrhotic group. Comparing non-cirrhotics and cirrhotics, 8 non-cirrhotic patients showed evidence of extra-hepatic inflammatory conditions, while in the cirrhotic group no inflammatory conditions were found (p &lt; 0.001). 27 (64.29%) cirrhotic patients had thrombosis in the portal vein, while only 9 cases (36%) were found in non-cirrhotics (p = 0.02). CONCLUSIONS:In cirrhotic patients, hepatocellular carcinoma and cirrhosis were the strongest risk factors to develop portal venous system thrombosis. In contrast, extrahepatic inflammatory conditions were main risk factors associated in non-cirrhotics. Moreover, the portal vein was the most frequent site of thrombosis in both groups.

OBJECTIVE:Patients with cirrhosis are at increased risk for venous thromboembolism (VTE) and portal vein thrombosis (PVT). Cirrhosis due to non-alcoholic steatohepatitis (NASH) appears to be particularly prothrombotic. We investigated hospitalized patients with NASH cirrhosis to determine if they are at increased risk for VTE. METHODS:Data on adult hospitalized patients with cirrhosis and VTE (deep vein thrombosis and/or pulmonary embolism) between November 1, 2010 and December 31, 2015 were obtained. Cases with VTE were matched by age, gender, and model for end stage liver disease (MELD) score to corresponding controls without VTE. RESULTS:Two hundred and ninety subjects (145 matched pairs) with mean age of 58.4 ± 11.8 years and MELD score of 16.0 ± 7.2 were included. Baseline characteristics were similar between cases and controls. Independent adjusted risk factors for VTE included NASH (OR: 2.46, 95% CI: 1.07-5.65, p = 0.034), prior VTE (OR: 7.12, 95% CI: 1.99-25.5, p = 0.003), and presence of PVT (OR: 2.18, 95% CI: 1.03-4.58, p = 0.041). Thrombocytopenia was associated with decreased risk (OR: 0.49, 95% CI: 0.26-0.95, p = 0.035). CONCLUSIONS:NASH is an independent risk factor for VTE among cirrhosis patients and provides further evidence that NASH is a hypercoagulable state. While all hospitalized patients with cirrhosis at risk for VTE should be considered for medical thromboprophylaxis, those with NASH cirrhosis are at particularly increased risk and therefore a high index of suspicion for VTE should be maintained even in the presence of thromboprophylaxis.

Long thought to be hypocoagulable, new evidence suggests cirrhosis patients have "rebalanced" coagulation in the setting of decreased synthesis of both pro- and anti-coagulant factors. Traditional testing like PT/INR reflects only the decreased synthesis of pro-coagulant factors and thus does not correspond to bleeding or clotting risk in this population. In this review, we discuss the use of viscoelastic testing (VET), an assay of global hemostasis in cirrhosis patients. We describe the technique and interpretation of commercially available VET and assess the application of VET in both transplant and non-transplant cirrhosis populations. VET largely correlates well with traditional testing including platelet count and fibrinogen level, however, is potentially less accurate in patients with low fibrinogen levels. VET may be useful in identifying patients at higher risk of hypercoagulable complications post-transplant and reflects changes in hemostasis in decompensated patients. While VET has been associated with decreased transfusión support in multiple studies, the lack of bleeding in patients who avoided prophylactic transfusion suggests a "rescue" rather than prophylactic approach to transfusion may be ideal and further studies with a "rescue" arm are needed. Additional prospective studies of VET should include clinically relevant endpoints of bleeding and thrombosis.

INTRODUCTION/BACKGROUND:Type-1 hepatorenal syndrome (HRS-1) portends a poor prognosis in patients with cirrhosis. Currently available medical therapies are largely ineffective, save for liver transplantation. We aimed to determine if pentoxifylline (PTX) therapy in addition to the standard of care of volume expansion with albumin and vasoconstriction with midodrine and octreotide (AMO) is safe and efficacious compared to AMO in HRS-1 treatment. MATERIAL AND METHODS/METHODS:Hospitalized subjects with decompensated cirrhosis and HRS-1 were enrolled. PTX or placebo was administered with AMO therapy for up to 14 days. The primary endpoint was HRS-1 resolution (serum creatinine ≤ 1.5 g/dL for &gt; 24 h). Secondary endpoints were change in creatinine and MELD score, partial treatment response, 30-and 180-day overall and transplant free survival. RESULTS:Twelve subjects with mean age 58.9 ± 6.2 years were enrolled and randomized. Mean MELD score was 26.5 ± 7.4 and 58.3% were male. Overall cohort 30- and 180-day survival was 58.3% and 33.3% respectively. Two subjects underwent liver transplantation. HRS-1 resolution (16.7% vs. 16.7%, p = 1.000), partial treatment response (33.3% vs. 16.7%, p = 0.505), change in creatinine (+0.48 g/dL, 95% CI -0.49-1.46 vs. +0.03 g/dL, 95% CI -0.64- 0.70, p = 0.427), 30-day survival (66.6% vs. 50.0%, p = 0.558) and 180-day survival (50.0% vs. 16.7%, p = 0.221) were similar between the two groups. Serious adverse events necessitating treatment discontinuation were rare (n = 1, PTX). DISCUSSION/CONCLUSIONS:The addition of PTX to AMO in the treatment of HRS-1 is safe when compared to the current standard of care. Future large-scale prospective study to validate the efficacy of this treatment seems warranted.

AIM/OBJECTIVE:Geographic disparities persist in the USA despite locoregional organ sharing policies. The impact of national organ sharing policies on waiting-list mortality on a regional basis remains unknown. METHODS:Data on all adult liver transplants between 1 February 2002 and 31 March 2015 were obtained from the United Network for Organ Sharing/Organ and Transplantation Network. Multivariable Cox proportional hazards models were constructed in a time-to-event analysis to estimate waiting-list mortality for the pre- and post-Share35 eras. RESULTS:In the analyzed time period, 134 247 patients were listed for transplantation and 54 510 received organs (42.8%). Listing volume increased following the introduction of the Share35 organ sharing policy (15 976 candidates pre- vs. 18 375 post) without significant regional changes as did the number of transplants (7210 pre- vs. 8224 post). Waiting-list mortality improved from 12.2% to 8.1% (P < 0.001). Adjusted waiting-list mortality ratios remained geographically disparate. Region 10 and region 11 had lower hazard ratios (HR) but still had increased mortality (1.46, 95% confidence interval [CI] 1.34-1.60, P < 0.001; and HR 1.49, 95% CI 1.37-1.62, P < 0.001, respectively). Regions 3 and 6 had increased HR with persistently elevated waiting-list mortality (1.79, 95% CI 1.66-1.93, P < 0.001; and HR 1.29, 95% CI 1.16-1.45, P < 0.001, respectively). Model for End-state Liver Disease (MELD) exception continued to propagate a survival benefit (HR 0.65, 95% CI 0.63-0.68, P < 0.001). CONCLUSIONS:Although overall waiting-list mortality has decreased, geographic disparities persist, but appear reduced despite broader sharing policies enacted by Share35. The advantage afforded by MELD exception, while still present, was diminished by Share35 as organs are being shifted to MELD >35 candidates. The disparities highlighted by our findings imply a need to review current allocation policies to best balance local, regional, and national transplant environments.

BACKGROUND & AIMS:Portal vein thrombosis (PVT) in cirrhosis may lead to hepatic decompensation and increased mortality. We aimed to investigate if decreased portal vein (PV) velocity is associated with future PVT. METHODS:Data on adult patients with cirrhosis and PVT between January 1, 2005 and July 30, 2015 were obtained. Cases with PVT were matched by age, gender and Model for End-stage Liver Disease (MELD) score to corresponding controls without PVT. Cox proportional hazards models, receiver operator curves and Kaplan Meier curves were constructed. RESULTS:One hundred subjects (50 matched pairs) with mean age 53.8±13.1 y and MELD score 14.9±5.5 were included in our analysis. Sixty-four percent were male and 76% were Child-Turcotte-Pugh Class A or B. Baseline characteristics (prior to development of PVT) were similar, except for baseline PV velocity (16.9 cm/s, 95% CI 13.9-20.0 PVT vs 25.0, 95% CI 21.8-28.8 no PVT, P<.001). 30 PVT subjects had PV velocity <15 cm/s compared to five without PVT (P<.001). On adjusted multivariable analysis, PV velocity was the strongest independent risk factor predicting PVT development (HR 0.86, 95% CI 0.80-0.93). The predictive value for PVT development was greatest for flow <15 cm/s (c-statistic 0.77). PV velocity <15 cm/s had a highly significant association with future PVT (HR 6.00, 95% CI 2.20-16.40, P=<.001). CONCLUSIONS:Decreased PV velocity is associated with increased risk of future PVT. Patients with cirrhosis and decreased PV velocity are a high-risk subgroup that warrants further investigation with prospective study.