The MELD Score Is Superior to the Maddrey Discriminant Function Score to Predict Short-Term Mortality in Alcohol-Associated Hepatitis: A Global Study.

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.

The clinical significance of intrapulmonary vascular dilations in liver transplant candidates.

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.

Optimising the care of patients with cirrhosis and gastrointestinal haemorrhage: a quality improvement study.

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.

The significance of donor-specific HLA antibodies in rejection and ductopenia development in ABO compatible liver transplantation.

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.

The impact of donor variables on the outcome of orthotopic liver transplantation for hepatitis C.

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.

Review article: current management of alcoholic liver disease.

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.

Drinking behavior and motivation for treatment among alcohol-dependent liver transplant candidates.

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.

Alcoholism treatment after liver transplantation: lessons learned from a clinical trial that failed.

Alcoholic liver disease is the second most common indication for liver transplantation in the United States. The lack of alcoholism treatment studies led us to study motivational enhancement therapy (MET) plus naltrexone after transplant. The authors could not complete this study. Sixty alcoholic patients were to receive MET plus naltrexone or placebo for 6 months. Fifty men and 5 women were screened. Nine died and 15 were not approached. Of 31 approached, 20 were ineligible, 11 refused, and 5 entered but dropped out before completion. Barriers to posttransplant alcoholism included infirmity, intensive medical management, and denial for alcoholism treatment. Because 30%-50% of alcoholic patients drink after transplant, the authors suggest using MET alone pretransplant.

Helicobacter pylori infection is not associated with subclinical hepatic encephalopathy in stable cirrhotic patients.

The importance of ammonia-producing Helicobacter pylori infection as a cause of subclinical encephalopathy in cirrhosis was investigated. In addition, a single psychometric test that can reliably detect subclinical hepatic encephalopathy was sought. Out-patients with cirrhosis and no overt encephalopathy underwent [14C]urea breath testing once and psychometric testing on two separate occasions, with an intervening course of clarithromycin/omeprazole if they had subclinical encephalopathy (two of four psychometric tests abnormal). Subclinical encephalopathy was present in 27 of 69 patients (39%), and Helicobacter pylori infection in 14 of 69 (20%). There was no association between the two conditions (P = 0.769). Subclinical encephalopathy resolved in 75% of treated Helicobacter pylori-positive patients and 37.5% of treated Helicobacter pylori-negative patients (P = 0.285). Number connection test-B had high reproducibility among untreated patients (R = 0.655) and high correlation (P < or = 0.01) with three surrogate gold standards. In stable cirrhotic patients, subclinical hepatic encephalopathy was found to: (1) have a high prevalence, (2) not be associated with Helicobacter pylori infection, and (3) be readily detected with the number connection test-B alone.

Interpreting the significance of drinking by alcohol-dependent liver transplant patients: fostering candor is the key to recovery.

Few studies have examined the value of treating alcohol addiction either before or after liver transplantation. Nevertheless, most liver transplant programs and many insurance companies require 6 months to 1 year of abstinence from alcohol as a condition of eligibility for liver transplantation (the 6-month rule). We believe there are potentially harsh clinical consequences to the implementation of this rule. For example, the natural history of alcohol use disorders often involves brief fallbacks to drinking ("slips"), but when alcoholic liver transplant candidates slip, most are removed from consideration for transplantation or are required to accrue another 6 months of sobriety. Because there is no alternative treatment to liver transplantation for most patients with end-stage liver disease, the 6-month rule could be lethal in some circumstances. In this review, we survey the literature concerning the ability of the 6-month rule to predict drinking by alcoholic patients who undergo liver transplantation and examine its impact on the health consequences of drinking before and after liver transplantation. We believe that fostering candor between the alcoholic patient and the transplant team is the key to recovery from alcoholism. We conclude that it is unethical to force alcoholic liver patients who have resumed alcohol use while waiting for or after transplantation to choose between hiding their drinking to remain suitable candidates for transplantation or risk death by asking for treatment of alcoholism. Consequently, we advocate a flexible approach to clinical decision making for the transplant professional caring for an alcoholic patient who has resumed drinking and provide specific guidelines for patient management.

Endoscopic management of postoperative biliary complications in orthotopic liver transplantation.

BACKGROUND: Surgery, percutaneous cholangiography, and endoscopic retrograde cholangiopancreatography (ERCP) have been used in the management of biliary complications after orthotopic liver transplantation with varied results. We assessed the role of ERCP in the diagnosis, treatment, and outcome of post-orthotopic liver transplantation biliary complications. METHODS: We retrospectively reviewed the records of 260 patients who underwent orthotopic liver transplantation. We examined the number of patients referred for ERCP and the indication, diagnosis, therapeutic intervention, success, and complication rate of ERCP post orthotopic liver transplantation. We compared the survival and retransplantation rates of the patients who underwent ERCP with a control group of post-orthotopic liver transplantation patients not undergoing ERCP. RESULTS: Of the 260 patients undergoing orthotopic liver transplantation, 64 (24.6%) underwent 137 ERCPs. Two categories of indications for ERCP were identified: bile leak (n = 31) and obstruction (n = 39). ERCP identified the site of the bile leak in 27 of 31 cases (87.1%) and the leak was treated by endoscopic means in 26 of 31 (83.9%). Treatment success differed significantly based on location of the leak (T tube, 95.2% vs. anastomosis, 42.9%; p = 0. 009). ERCP identified the site of obstruction in 37 of 39 cases (94. 9%) and obstruction was relieved by endoscopic means in 25 of 35 cases (71.4%). ERCP was significantly less successful in the treatment of biliary casts (25.0%, p = 0.048). There was no difference in survival or retransplantation between patients who did and did not undergo ERCP. CONCLUSION: ERCP should be the primary method for diagnosis and treatment of post-orthotopic liver transplantation biliary complications. Endoscopic therapy is safe and effective for the majority of post-orthotopic liver transplantation complications and temporizes management for those complications that may require surgery.

Payment for immunosuppression after organ transplantation. American Society of Transplantation.

Dramatic improvements in organ transplantation have meant that a growing number of patients must take expensive immunosuppressive medications for the rest of their lives. Currently, Medicare covers most transplantation procedures in the United States, but ends coverage for outpatient immunosuppressive medications after 36 months. Evidence suggests that at least some patients have reduced immunosuppression and their transplants fail because they cannot afford these medication costs. In the years since the advent of effective immunosuppressive therapy, the US Congress has struggled with this issue, and in 1999 temporarily extended medication coverage for eligible patients (based on age and disability) by 8 months. However, a more permanent solution is needed. We advocate that Medicare should cover the cost of all immunosuppressive therapy for all solid organ transplant recipients who cannot afford to pay. A number of potentially cost-effective approaches could be taken, but, in any case, something must be done to ensure that transplants do not fail because recipients cannot pay for immunosuppression.