Faculty Bibliography

Non-tumoral portal vein thrombosis (PVT) remains a highly relevant topic in the field of hepatology and liver transplantation with much surrounding controversy. Although multiple studies have shown that PVT is associated with adverse outcomes with increased morbidity and mortality rates, others have not reported the same clinical impact of PVT, arguing rather that incident PVT reflects worsening portal hypertension and the natural history of the disease. Despite this uncertainly, PVT is a dilemma facing the clinician on a daily basis often requiring a multidisciplinary team-based approach between hepatologists, transplant surgeons, interventional radiologists and hematologists. In this review, the authors provide a summary of the evidence supporting best clinical practices in the management of non-tumoral PVT in patients with cirrhosis.

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 < 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.

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.

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/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.