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INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.

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Intrapulmonary vascular dilations (IPVD) are common in patients with cirrhosis, but the majority do not have hepatopulmonary syndrome (HPS). The clinical significance of IPVD is unknown. Our aim was to determine the clinical impact due to the entire spectrum of IPVD in liver transplant (LT) candidates. A total of 122 evaluees for LT underwent contrast transthoracic echocardiography (cTTE). The degree of shunting was graded 1-3 (severe). HPS was defined as PaO(2) < 70 mmHg in the presence of IPVD and exclusion of other causes of hypoxemia. IPVD were detected in 57/122 (47%), and of these HPS was found in 5. IPVD were associated with higher Alveolar-arterial (A-a) gradients, with the highest occurring in patients with HPS (IPVD vs. no IPVD: p = 0.003; HPS vs. no IPVD: p = 0.004). All patients with HPS had grade 3 shunting, and had significantly widened A-a gradient and lower PaO(2) compared with grade 1 or 2 IPVDs. Presence of IPVD did not affect survival measured from evaluation or after LT. Other clinical outcomes were also similar among patients with and without IPVD. IPVD are common among LT candidates. HPS is unlikely in presence of only mild to moderate shunting. Clinical outcomes are similar among patients with and without IPVD.

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BACKGROUND: Patients with cirrhosis and gastrointestinal haemorrhage are a complex group with high thirty-day mortality rates. AIM: To evaluate the quality of care delivered to patients admitted with gastrointestinal (GI) haemorrhage to a tertiary care centre before and after implementing a quality improvement initiative for better adherence to practice standards. METHODS: This is a prospective cohort study. All patients admitted to a tertiary care centre with a GI haemorrhage and known or suspected chronic liver disease were evaluated before and after the quality improvement initiative was implemented. Interventions to improve quality of care included the delivery of educational sessions for medical practitioners, and creation and implementation of standardised admission order sets. Quality of care measures included delivery of prophylactic antibiotics (PAs) within 24 h of admission, delivery of a somatostatin analogue (SA) and use of a proton pump inhibitor (PPI); optimal care was defined as receiving all three. Secondary outcomes included hospital length of stay (LOS) and 30-day readmission rate. RESULTS: In comparing the preintervention and postintervention groups, we found significant gains in delivering PAs (57% vs. 75%, P=0.05), SAs (54% vs. 76%, P=0.013) and overall optimal care (41% vs. 65%, P=0.008). Use of PPIs did not change and remained in accordance with guidelines (90% vs. 87%, P=0.67). Hospital LOS remained similar between the two groups (6.8 vs. 7.1, P=0.88), whereas the 30-day readmission decreased (41% vs. 13%, P=0.001). CONCLUSION: Implementation of quality improvement initiatives, such as targeted educational efforts and standardised order sets, can improve the quality of care delivered and patient outcomes in patients with cirrhosis and GI haemorrhage.

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The role of humoral alloreactivity in ABO-compatible liver transplantation remains unclear. To understand the significance of donor-specific HLA alloantibodies (DSA) in liver rejection, we applied the currently used strategy for detection of antibody-mediated rejection of other solid allografts. For this purpose we reviewed the data on 43 recipients of ABO identical/compatible donor livers who had indication liver biopsy stained for complement element C4d and contemporaneous circulating DSA determination. Seventeen (40%) patients had significant circulating DSA in association with diffuse portal C4d deposition (DSA+/diffuse C4d+). These DSA+/diffuse C4d+ subjects had higher frequency of acute cellular rejection (ACR) 15/17 versus 13/26 (88% vs. 50%), p = 0.02, and steroid resistant rejection 7/17 versus 5/26 (41% vs. 19%), p = 0.03. Based on detection of the combination DSA+/diffuse C4d+, 53.6% of cases of ACR had evidence of concurrent humoral alloreactivity. Six of the 10 patients with ductopenic rejection had circulating DSA and diffuse portal C4d, three of whom (2 early and 1 late posttransplantation) developed unrelenting cholestasis, necessitating specific antibody-depleting therapy to salvage the allografts. Thus, in ABO-compatible liver transplantation humoral alloreactivity mediated by antibodies against donor HLA molecules appears to be frequently intertwined with cellular mechanisms of rejection, and to play a role in ductopenia development.

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This study performed a systems analysis of the process by which patients under the care of a specialist palliative home care obtained medications, and highlighted factors that delay this process. Systems analysis is the science dealing with analysis of complex, large-scale systems and the interactions within those systems. This study used a mixed-methods approach of questionnaires of general practitioners, pharmacists and patients, and a prospective observational study of delays experienced by patients referred to the home care team over a three-month period. This study found the main factors causing delay to be: medications not being in stock in pharmacies, medications not being available on state reimbursed schemes and inability of patients and carers to courier medications.

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Morphologic characteristics of the graft have been proposed as a major contributor to the long-term outcomes in orthotopic liver transplantation (OLT). Our objective was to determine the impact of donor variables, including donor age, donor-recipient HLA match, and type of donation (DCD vs donation after brain death [DBD]), on the outcome of OLT in 192 patients with hepatitis C virus (HCV). Fourteen patients underwent OLT from donation after cardiac death (DCD) donors and 188 from DBD donors. Mean donor age, warm ischemia time at recovery, and cold ischemia time were similar between the groups. Overall graft survival rate at 1 year (55% DCD vs 85% DBD) and 5 years (46% DCD vs 78% DBD) was significantly lower in the DCD group (P = .0003). Similarly, patient survival rate at 1 year (62% DCD vs 93% DBD) and 5 years (62% DCD vs 82% DBD) was significantly lower in the DCD group (P = .0295). Incidences of hepatic artery thrombosis, portal vein thrombosis, and primary nonfunction were similar between the DCD and DBD groups. The incidence of liver abscess with ischemic-type biliary stricture was higher in recipients from DCD as compared with DBD (42% vs 2%). A trend toward lower graft survival was noted in recipients from donors older than 60 years of age in the HCV population (P = .07), with statistically lower patient survival (P = .02). Donor- recipient HLA matching did not appear to correlate with OLT outcome in patients with HCV. DCD donors and donors older than 60 years of age significantly impact patient and graft survival. Lower graft and patient survival in recipients from DCD donors does not appear to be related to early disease recurrence.

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We report the successful use of vasopressin in the management of hypotension in association with severe right ventricular (RV) failure in two patients with advanced idiopathic pulmonary arterial hypertension. Both patients were pregnant and developed systemic hypotension after delivery by Caesarean section. Placental autotransfusion and possibly oxytocin use were thought to be the major contributing factors in worsening RV function. After the use of vasopressin in both patients, cardiovascular variables improved without untoward effect on RV function, and provided rescue therapy for systemic hypotension in this setting. Vasopressin, a direct vasopressor acting via V1 receptors on the vascular endothelium, has been shown to cause pulmonary vasodilatation experimentally and in animal models of pulmonary hypertension. Its synthetic analogue, terlipressin, has been shown to reduce pulmonary vascular resistance in humans with cirrhosis. Vasopressin may therefore have differential effects on the pulmonary and systemic circulations, allowing systemic pressure to be supported without detrimental effects on the pulmonary circulation.

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Alcoholic liver disease, including acute alcoholic hepatitis and alcoholic cirrhosis, is a major cause of morbidity and mortality in the Western world. Abstinence remains the cornerstone of management of all forms of alcoholic liver disease. Recent research, which has elucidated the mechanisms of alcohol-induced liver injury, offers the prospect of advances in the management of alcoholic liver disease. We review the most recent data on the efficacy of treatment of acute alcoholic injury, including nutritional support, corticosteroids, anti-inflammatory agents and antioxidants, and agents that are directed against the progression to fibrosis, such as colchicines, propylthiouracil and antioxidants. Although these therapies offer a tantalizing glimpse into a future that may include therapies that directly alter the process of injury and repair in the liver, none has been shown consistently to improve the course of alcoholic liver damage. Consequently, liver transplantation remains an ultimate option for selected patients with liver failure due to chronic alcoholic liver damage.

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Following three weeks of extracorporeal lung support for acute respiratory distress syndrome, a 15-year-old male underwent bilateral lung transplantation. This procedure was complicated by massive postoperative haemorrhage. The administration of recombinant activated Factor VII was associated with improved haemostasis. However, development of cardiac tamponade soon after injection required emergency exploration and evacuation of a large mediastinal clot.

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OBJECTIVE: Based on the successful use of neostigmine for the treatment of acute colonic pseudo-obstruction, we hypothesised that neostigmine would increase gastric emptying and improve tolerance to enteral feeding in the critically ill patient. METHODS: Eleven patients intolerant of enteral feeds due to high gastric aspirates, were randomised to receive a 'study infusion' consisting of either neostigmine (0.4 mg/hr) or 0.9% saline. If, after 12 hours the patient was deemed intolerant of the nasogastric feed, the rate of the 'study infusion' was doubled. Those who remained intolerant after 24 hours of the 'study infusion' were 'crossed-over' and continued on the other infusion for a further 24 hours. Gastric emptying was assessed in each group before and after the infusion by measuring the hourly rates of feed "absorption" [(delivery rate + returned aspirates) - total aspirates] and paracetamol absorption using the area under a time-concentration curve at 120 minutes (AUC120). Differences within and between groups were analysed using Students t test and one-way analysis of variance. RESULTS: Six patients received neostigmine first and 5 received the placebo first. Four of the 6 patients receiving the neostigmine first compared with all of those receiving placebo first required to be 'crossed-over' to the other infusion. While the hourly rates of feed "absorption" were greater for patients receiving neostigmine than for placebo, these differences did not achieve statistical significance. The mean paracetamol AUC120 for all patients who received neostigmine was 3996 mg/min/L while that for placebo was 1929 mg/min/L (p = 0.21). CONCLUSIONS: These data suggest that while neostigmine may have a positive effect on gastric emptying and enteral feed absorption in critically ill patients, the results did not reach statistical significance and an adequately powered study will be required to confirm this effect.

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OBJECTIVE: To examine the clinical impact of a management protocol for external ventricular drains (EVD). PATIENTS AND METHODS: All patients with EVDs over a six-month period were reviewed retrospectively. Data concerning the indications for EVD placement, antibiotics and cerebrospinal fluid (CSF) analyses were collected. A restrictive antibiotic protocol (e.g. intravenous cephalothin 1g 6-hourly for 24 hours, unless other antibiotics were prescribed for a documented pre-existing infection) was introduced for all patients requiring placement of an EVD during the following six months and all patients were observed prospectively. Daily CSF samples were collected under sterile conditions and examined for organisms, cells, glucose and protein and sent for microbiological culture. External ventricular drains were removed after five days and replaced if further monitoring or CSF drainage was required. Adherence to the protocol and the incidence of ventriculitis was determined. RESULTS: Twelve patients with EVDs were identified during the 6 month pre-protocol period and 15 patients with EVDs were identified during the 6 month post-protocol period. There was no significant difference between the total (72 vs 88 days) and mean (6 vs 5.9 days) drain placement times between the two groups. There was no significant difference between the mean numbers of CSF samples in the two groups. CSF aspirates were not analysed in 35/72 samples (49%) in the pre-protocol group compared with 45/88 (51%) samples in the post-protocol group. Positive CSF Gram-stains were found in 3/12 (25%) patients in the pre-protocol group and in 0/15(0%) in the post-protocol group. Positive CSF cultures decreased significantly in the post-protocol group (17 vs 5, p = 0.0009). Prophylactic antibiotics were prescribed in 5/12 (42%) patients in the pre-protocol group compared with 12/15 (80%) patients in the post-protocol group. CONCLUSIONS: The protocol was associated with a statistically significant improvement in compliance with antibiotic prescription and reduction in the incidence of positive CSF cultures.

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Alcohol misuse is the second most common indication for liver transplantation in the United States. Our post-transplant alcoholism treatment trial suggested that current interventions might not be transferable to liver transplantees. We sought to identify differences between patients awaiting liver transplantation and alcoholics entering treatment without severe liver disease. Thirty transplant patients were compared to thirty naltrexone study patients on medical status, alcohol and drug use, alcohol craving, motivation for treatment, psychiatric symptoms, and psychosocial problems. Lifetime alcohol consumption was greater for transplant patients compared to naltrexone patients. In contrast to the naltrexone group, transplant patients denied craving for alcohol and showed little motivation for alcoholism treatment. Groups did not differ on other psychosocial measures. Liver transplant patients differ from patients in alcoholism treatment trials on measures of alcohol consumption, alcohol craving and motivation for treatment. Alcoholism interventions should accommodate their medical condition and boost motivation for continued abstinence.

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