Michelle Carbonneau

A shorter duration of pre-transplant abstinence predicts problem drinking after liver transplantation.

OBJECTIVES:Liver transplantation for alcoholic liver disease (ALD) can be complicated by abusive or “problem” drinking (PD) after transplant. There are limited data for evaluating the effect of pre-transplant abstinence on post-transplant PD. Few existing studies have included a substantial number of patients with co-existing causes of hepatic dysfunction, and the effect of PD on survival in recent European studies has been controversial. We hypothesized that a longer duration of pre-transplant abstinence would lead to less PD after transplantation. Accordingly, the objectives of this study are to analyze a North American cohort of patients with ALD with or without a secondary diagnosis of liver disease to estimate (i) the incidence of PD and its predictors, as well as (ii) the effect of PD on patient survival.METHODS:We conducted a retrospective review of all patients transplanted for ALD surviving for more than 3 months after transplant. PD was defined as either any drinking (AD) to the point of intoxication or drinking above the toxic threshold (>20 g/day in women and >40 g/day in men) on at least two separate occasions. We used Coxs proportional hazards regression to estimate risk ratios and Kaplan–Meier curves with log-rank analysis to compare survival.RESULTS:Of 213 eligible transplant patients, 42 were excluded. Of the 171 remaining patients, 78% were male; mean age was 52 years. Overall 53% of patients had co-existing causes of liver dysfunction. The mean follow-up was 64.8 months. The median pre-transplant abstinence was 19 months. In all patients, the risk of AD was 24% and PD 13%. Pre-transplant abstinence duration was the only independent predictor of PD after transplant. For every 1-month increment in pre-transplant abstinence, there was a 5% decrease in the adjusted relapse rate. There was no survival difference noted between problem drinkers and non-drinkers.CONCLUSIONS:The risk of PD decreased with increasing pre-transplant abstinence. Our data support pre-transplant abstinence as an important predictor of post-transplant recidivism; however, the optimal period of abstinence remains unclear. Patients with <18 months of abstinence may benefit from more intensive follow-up and rehabilitation after transplant.

A Rapid Bedside Screen to Predict Unplanned Hospitalization and Death in Outpatients With Cirrhosis: A Prospective Evaluation of the Clinical Frailty Scale

OBJECTIVES:Screening tools to determine which outpatients with cirrhosis are at highest risk for unplanned hospitalization are lacking. Frailty is a novel prognostic factor but conventional screening for frailty is time consuming. We evaluated the ability of a 1 min bedside screen (Clinical Frailty Scale (CFS)) to predict unplanned hospitalization or death in outpatients with cirrhosis and compared the CFS with two conventional frailty measures (Fried Frailty Criteria (FFC) and Short Physical Performance Battery (SPPB)).METHODS:We prospectively enrolled consecutive outpatients from three tertiary care liver clinics. Frailty was defined by CFS >4. The primary outcome was the composite of unplanned hospitalization or death within 6 months of study entry.RESULTS:A total of 300 outpatients were enrolled (mean age 57 years, 35% female, 81% white, 66% hepatitis C or alcohol-related liver disease, mean Model for End-Stage Liver Disease (MELD) score 12, 28% with ascites). Overall, 54 (18%) outpatients were frail and 91 (30%) patients had an unplanned hospitalization or death within 6 months. CFS >4 was independently associated with increased rates of unplanned hospitalization or death (57% frail vs. 24% not frail, adjusted odds ratio 3.6; 95% confidence interval (CI): 1.7–7.5; P=0.0008) and there was a dose response (adjusted odds ratio 1.9 per 1-unit increase in CFS, 95% CI: 1.4–2.6; P<0.0001). Models including MELD, ascites, and CFS >4 had a greater discrimination (c-statistic=0.84) than models using FFC or SPPB.CONCLUSIONS:Frailty is strongly and independently associated with an increased risk of unplanned hospitalization or death in outpatients with cirrhosis. The CFS is a rapid screen that could be easily adopted in liver clinics to identify those at highest risk of adverse events.

Risk of Bacterial Infection in Patients With Cirrhosis and Acute Variceal Hemorrhage, Based on Child–Pugh Class, and Effects of Antibiotics

BACKGROUND & AIMS Antibiotics frequently are overused and are associated with serious adverse events in patients with cirrhosis. However, these drugs are recommended for all patients presenting with acute variceal hemorrhage (AVH). We investigated whether patients should be stratified for antibiotic prophylaxis based on Child-Pugh scores, to estimate risks of bacterial infection, rebleeding, and mortality, and whether antibiotics have equal effects on patients of all Child-Pugh classes. We performed a sensitivity analysis using model for end-stage liver disease (MELD) scores. METHODS In a retrospective study, we analyzed data from 381 adult patients with cirrhosis and AVH (70% men; mean age, 56 y), admitted from 2000 through 2009 to 2 tertiary care hospitals in Edmonton, Alberta, Canada. We excluded patients with bacterial infection on the day of AVH. The association between antibiotic prophylaxis and outcomes was adjusted by liver disease severity and by a propensity score. RESULTS The patients included in the study had mean MELD scores of 16, and 54% received antibiotic prophylaxis. Overall, antibiotic therapy was associated with lower risks of infection (adjusted odds ratio, 0.37; 95% confidence interval, 0.91-0.74) and mortality (adjusted odds ratio, 0.63; 95% confidence interval, 0.31-1.29). Among patients categorized as Child-Pugh class A given antibiotics, only 2% developed infections and the mortality rate was 0.4%. Among patients categorized as Child-Pugh class B given antibiotics, 6% developed infections, compared with 14% of patients who did not receive antibiotics; antibiotics did not affect mortality. Administration of antibiotics to patients categorized as Child-Pugh class C reduced infections and mortality by approximately 50%, compared with patients who did not receive antibiotics. MELD scores were not as useful as Child-Pugh class in identifying patients at risk for infection. CONCLUSIONS Based on a retrospective analysis of patients with cirrhosis and AVH, those categorized as Child-Pugh class A had lower rates of bacterial infection and lower mortality rates in the absence of antibiotic prophylaxis than patients categorized as classes B or C. The recommendation for routine antibiotic prophylaxis for this subgroup requires further evaluation.

Alcohol Use While on the Liver Transplant Waiting List: A Single-Center Experience

Alcoholic liver disease (ALD) is a leading indication for liver transplantation. Our center has randomly checked blood alcohol levels (BALs) in ALD patients on the waiting list since 2004. We aimed to identify the incidence and predictors of inactivation on the transplant list due to alcohol use and to determine the utility of BAL‐screening in this process. We conducted a retrospective review of patients with ALD listed for liver transplantation with at least 3 months of postlisting follow‐up. Alcohol use while on the transplant list was defined as a positive BAL, an admission of alcohol use, or refusal to perform screening within 12 hours of request. Cox proportional hazards regression was used to estimate risk ratios (RRs). Of 134 patients meeting eligibility criteria, 78% were male, and mean age was 52 years. Alcohol use was documented in 23 patients (17%). Of these, 12 refused to have a random screen, 8 had detectable serum ethanol levels, and 3 had self‐reported alcohol use. On multivariable analysis, a higher number of random BAL‐checks [RR = 0.63(0.52, 0.76), P = 0.001] and a longer duration of prelisting abstinence [RR = 0.88(0.83, 0.94), P = 0.001] independently reduced the risk of alcohol use by patients while on the waiting list. None of the patients with >24 months of prelisting abstinence had a positive screen. In conclusion, this study supports random BAL‐screening before transplantation and reinforces the importance of abstinence duration as a predictor of relapse. For patients with <24 months of prelisting abstinence, our center will increase the frequency of random BAL screening and increase the rehabilitation requirements to include an intensive 3‐week rehabilitation program. We hope that these measures will reduce the rate of relapse to alcohol use post‐transplantation. Liver Transpl 16:91–97, 2010.

VSL#3® probiotic therapy does not reduce portal pressures in patients with decompensated cirrhosis

In patients with decompensated cirrhosis, bacterial translocation can contribute to splanchnic vasodilatation, decreased effective circulating volume, and portal hypertension. The primary objective of this randomized, double blind placebo controlled trial was to evaluate the effect of the probiotic VSL#3® on the hepatic venous pressure gradient (HVPG).

The 22/11 risk prediction model: a validated model for predicting 30-day mortality in patients with cirrhosis and spontaneous bacterial peritonitis.

OBJECTIVES:Clinicians do not have a validated tool for estimating the short-term mortality associated with spontaneous bacterial peritonitis (SBP). Accurate prognosis assessment is important for risk stratification and for individualizing therapy. We aimed therefore to develop and validate a model for the prediction of 30-day mortality in SBP patients receiving standard medical treatment (antibiotics and if indicated by guidelines, intravenous albumin therapy).METHODS:We retrospectively identified SBP patients treated at a tertiary care center between 2003 and 2011 (training set). Multivariate regression modeling and receiver operating characteristic (ROC) curves were utilized for statistical analysis. An external data set of 109 SBP patients was utilized for validation.RESULTS:Of the 184 patients in the training set, 66% were men with a median age of 55 years, a median MELD (Model for End-Stage Liver Disease) score of 20, and a 30-day mortality of 27%. Peripheral blood leukocyte count ≥11×109 cells/l (odds ratio (OR) 2.5; 95% confidence interval CI: 1.2–5.2) and MELD score ≥22 (OR 4.6; 95% CI: 2.3–9.6) were independent predictors of 30-day mortality. Patients with neither, one, or both variables had 30-day mortality rates of 8%, 32%, and 52%, respectively. The findings in the validation set mirrored the training set.CONCLUSIONS:In cirrhotic patients with SBP receiving standard therapy, MELD score ≥22 and peripheral blood leukocyte count ≥11×109 cells/l are validated independent predictors of mortality. The mortality in a patient without either poor prognostic variable is ≤10% and with both variables is ≥50%. Trials aiming to reduce mortality should target patients in the moderate-risk to high-risk groups.

Third-Generation Cephalosporin-Resistant Spontaneous Bacterial Peritonitis: A single-Centre Experience and Summary of Existing Studies

BACKGROUND Spontaneous bacterial peritonitis (SBP) is the most prevalent bacterial infection in patients with cirrhosis. Although studies from Europe have reported significant rates of resistance to third-generation cephalosporins, there are limited SBP-specific data from centres in North America. OBJECTIVE To evaluate the prevalence of, predictors for and clinical impact of third-generation cephalosporin-resistant SBP at a Canadian tertiary care centre, and to summarize the data in the context of the existing literature. METHODS SBP patients treated with both antibiotics and albumin therapy at a Canadian tertiary care hospital between 2003 and 2011 were retrospectively identified. Multivariate logistic regression was used to determine independent predictors of third-generation cephalosporin resistance and mortality. RESULTS In 192 patients, 25% of infections were nosocomial. Forty per cent (77 of 192) of infections were culture positive; of these, 19% (15 of 77) were resistant to third-generation cephalosporins. The prevalence of cephalosporin resistance was 8% with community-acquired infections, 17% with health care-associated infections and 41% with nosocomial acquisition. Nosocomial acquisition of infection was the only predictor of resistance to third-generation cephalosporins (OR 4.0 [95% CI 1.04 to 15.2]). Thirty-day mortality censored for liver transplantation was 27% (50 of 184). In the 77 culture-positive patients, resistance to third-generation cephalosporins (OR 5.3 [1.3 to 22]) and the Model for End-stage Live Disease score (OR 1.14 [1.04 to 1.24]) were independent predictors of 30-day mortality. CONCLUSIONS Third-generation cephalosporin-resistant SBP is a common diagnosis and has an effect on clinical outcomes. In an attempt to reduce the mortality associated with resistance to empirical therapy, high-risk subgroups should receive broader empirical antibiotic coverage.

Reply to: Comparing the Variability Between Measurements for Sarcopenia Using Magnetic Resonance Imaging and Computed Tomography Imaging

The meta-analysis by van Vugt and colleagues highlights the independent prognostic value of computed tomography (CT) in evaluating sarcopenia as a predictor of preand posttransplant mortality in cirrhosis (1). These data provide strong evidence for using cross-sectional imaging–based surveillance as an objective diagnostic and prognostic tool in identifying sarcopenia in patients with cirrhosis.

Home Exercise Training Improves Exercise Capacity in Cirrhosis Patients: Role of Exercise Adherence

Cirrhosis patients have reduced peak aerobic power (peak VO2) that is associated with reduced survival. Supervised exercise training increases exercise tolerance. The effect of home-based exercise training (HET) in cirrhosis is unknown. The objective was to evaluate the safety and efficacy of 8 weeks of HET on peak VO2, 6-minute walk distance (6MWD), muscle mass, and quality of life in cirrhosis. Random assignment to 8 weeks of HET (moderate to high intensity cycling exercise, 3 days/week) or usual care. Exercise adherence defined as completing ≥80% training sessions. Paired t-tests and analysis of covariance used for comparisons. Forty patients enrolled: 58% male, mean age 57 y, 70% Child Pugh-A. Between group increases in peak VO2 (1.7, 95% CI: −0.33 to 3.7 ml/kg/min, p = 0.09) and 6MWD (33.7, 95% CI: 5.1 to 62.4 m, p = 0.02) were greater after HET versus usual care. Improvements even more marked in adherent subjects for peak VO2 (2.8, 95% CI: 0.5–5.2 mL/kg/min, p = 0.02) and 6MWD (46.4, 95% CI: 12.4–80.5 m, p = 0.009). No adverse events occurred during testing or HET. Eight weeks of HET is a safe and effective intervention to improve exercise capacity in cirrhosis, with maximal benefits occurring in those who complete ≥80% of the program.

Advance care planning (ACP) for specialists managing cirrhosis: A focus on patient‐centered care

Advance care planning (ACP) and goals of care designation (GCD) are being integrated into modern health care. In cirrhosis, uptake and adoption of these practices have been limited with physicians citing many perceived barriers and limitations. Recognizing the many tangible benefits of ACP and GCD processes in patients with life‐limiting chronic diseases, the onus is on health practitioners to initiate and direct these conversations with their patients and surrogates. Drawing upon the literature and our experiences in palliative care and cirrhosis, we provide an actionable framework that can be readily implemented into a busy clinical setting by a practitioner. Conversation starters, visual aids, educational resources (for patients and practitioners), and videos of mock physician‐patient scenarios are presented and discussed. Importantly, we have customized each of these tools to meet the unique health care needs of patients with cirrhosis. The inherent flexibility of our approach to ACP discussions and GCD can be further modified to accommodate practitioner preferences. Conclusion: In our clinics, this assemblage of “best practice tools” has been well received by patients and surrogates enabling us to increase the number of outpatients with cirrhosis who have actively contributed to their GCD before acute health events and are supported by well‐informed surrogates. (Hepatology 2018;67:2025‐2040).