A. Sidney Barritt

A Histologic Scoring System for Prognosis of Patients With Alcoholic Hepatitis

BACKGROUND & AIMS There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90-day) mortality. METHODS We analyzed data from 121 patients admitted to the Liver Unit (Hospital Clinic, Barcelona, Spain) from January 2000 to January 2008 with features of AH and developed a histologic scoring system to determine the risk of death using logistic regression. The system was tested and updated in a test set of 96 patients from 5 academic centers in the United States and Europe, and a semiquantitative scoring system called the Alcoholic Hepatitis Histologic Score (AHHS) was developed. The system was validated in an independent set of 109 patients. Interobserver agreement was evaluated by weighted κ statistical analysis. RESULTS The degree of fibrosis, degree of neutrophil infiltration, type of bilirubinostasis, and presence of megamitochondria were independently associated with 90-day mortality. We used these 4 parameters to develop the AHHS to identify patients with a low (0-3 points), moderate (4-5 points), or high (6-9 points) risk of death within 90 days (3%, 19%, and 51%, respectively; P < .0001). The AHHS estimated 90-day mortality in the training and test sets with an area under the receiver operating characteristic value of 0.77 (95% confidence interval, 0.71-0.83). Interrater agreement values were 0.65 for fibrosis, 0.86 for bilirubinostasis, 0.60 for neutrophil infiltration, and 0.46 for megamitochondria. Interestingly, the type of bilirubinostasis predicted the development of bacterial infections. CONCLUSIONS We identified histologic features associated with the severity of AH and developed a patient classification system that might be used in clinical decision making.

Declining liver utilization for transplantation in the United States and the impact of donation after cardiac death

Worsening donor liver quality resulting in decreased organ utilization may be contributing to the recent decline in liver transplants nationally. We sought to examine trends in donor liver utilization and the relationship between donor characteristics and nonuse. We used the United Network for Organ Sharing database to review all deceased adult organ donors in the United States from whom at least 1 solid organ was transplanted into a recipient. Trends in donor characteristics were examined. Multivariate logistic regression was used to evaluate the association between donor characteristics and liver nonuse between 2004 and 2010. Population attributable risk proportions were determined for donor factors associated with nonuse. We analyzed 107,259 organ donors. The number of unused livers decreased steadily from 1958 (66% of donors) in 1988 to 841 (15%) in 2004 but then gradually increased to 1345 (21%) in 2010. The donor age, the body mass index (BMI), and the prevalence of diabetes and donation after cardiac death (DCD) all increased over time, and all 4 factors were independently associated with liver nonuse. DCD had the highest adjusted odds ratio (OR) for nonuse, and the odds increased nearly 4‐fold between 2004 [OR = 5.53, 95% confidence interval (CI) = 4.57‐6.70] and 2010 (OR = 21.31, 95% CI = 18.30‐24.81). The proportion of nonuse attributable to DCD increased from 9% in 2004 to 28% in 2010. In conclusion, the proportion of donor livers not used has increased since 2004. Older donor age, greater BMI, diabetes, and DCD are all independently associated with nonuse and are on the rise nationally. Current trends may lead to significant declines in liver transplant availability. Liver Transpl 19:59–68, 2013.

NAFLD and liver transplantation: Current burden and expected challenges

Because of global epidemics of obesity and type 2 diabetes, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing both in Europe and the United States, becoming one of the most frequent causes of chronic liver disease and predictably, one of the leading causes of liver transplantation both for end-stage liver disease and hepatocellular carcinoma. For most transplant teams around the world this will raise many challenges in terms of pre- and post-transplant management. Here we review the multifaceted impact of NAFLD on liver transplantation and will discuss: (1) NAFLD as a frequent cause of cryptogenic cirrhosis, end-stage chronic liver disease, and hepatocellular carcinoma; (2) prevalence of NAFLD as an indication for liver transplantation both in Europe and the United States; (3) the impact of NAFLD on the donor pool; (4) the access of NAFLD patients to liver transplantation and their management on the waiting list in regard to metabolic, renal and vascular comorbidities; (5) the prevalence and consequences of post-transplant metabolic syndrome, recurrent and de novo NAFLD; (6) the alternative management and therapeutic options to improve the long-term outcomes with particular emphasis on the correction and control of metabolic comorbidities.

Maximizing Opportunities and Avoiding Mistakes in Triple Therapy for Hepatitis C Virus

Recently developed drugs and innovative strategies for the treatment of chronic infection with genotype 1 hepatitis C virus (HCV) have become the standard of care. The protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis) are the first direct-acting antiviral (DAA) agents approved, and many more are being developed. These drugs substantially increased rates of sustained virologic response in treatment-naïve and -experienced patients, in conjunction with peginterferon and ribavirin (triple therapy), in phase 3 trials. The efficacy of triple therapy depends on appropriate selection of patients, although the population of patients that receive triple therapy could be expanded as the risk/benefit ratio improves. Attention to details that reflect the standard of care, such as appropriate dosing, anticipation of adverse effects, and strict adherence to stopping rules, will insure the success of these drugs and lead the way for new combination therapies.

Changing shape of disease: Nonalcoholic fatty liver disease in Crohn's disease—A case series and review of the literature

Background: With improvements in therapy for inflammatory bowel disease (IBD) and changes in the prevalence of obesity, the phenotype of Crohns disease (CD) is changing. These changes may herald an increase in the incidence of nonalcoholic fatty liver disease (NAFLD) in this population. Methods: Over a 10‐month period we identified seven patients with CD who required liver biopsy for elevated liver function tests (LFTs), with an ultimate diagnosis of NAFLD. We performed a retrospective chart review and literature search to identify relevant data on NAFLD and CD. Specifically, we abstracted prior and current IBD‐related medication exposures, disease severity, and the presence of typical comorbidities associated with NAFLD. Results: We describe seven patients with CD and biopsy‐proven NAFLD. The majority of these patients were overweight or obese, had quiescent CD, and were more likely to be receiving a tumor necrosis factor‐alpha inhibitor. Review of the literature produced a total of 29 articles describing NAFLD in IBD patients, primarily restricted to historical autopsy and surgical series. Limited contemporary studies highlight the rising prevalence of NAFLD in treated IBD populations. Conclusions: NAFLD is increasing in incidence and prevalence among the general population. With improvements in therapy, NAFLD is likely increasing among the CD population as well. When evaluating an IBD patient with abnormal LFTs, clinicians need to consider NAFLD. NAFLD may impact IBD management in the future if therapeutic modalities are limited due to elevated LFTs. Further, patients should be monitored for excessive weight gain and counseled regarding healthy dietary and exercise habits. (Inflamm Bowel Dis 2011)

Declining liver graft quality threatens the future of liver transplantation in the United States

National liver transplantation (LT) volume has declined since 2006, in part because of worsening donor organ quality. Trends that degrade organ quality are expected to continue over the next 2 decades. We used the United Network for Organ Sharing (UNOS) database to inform a 20‐year discrete event simulation estimating LT volume from 2010 to 2030. Data to inform the model were obtained from deceased organ donors between 2000 and 2009. If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer LTs. If transplant centers increase their risk tolerance for marginal grafts, utilization would decrease to 48%. The institution of “opt‐out” organ donation policies to increase the donor pool would still result in 1380 to 1866 fewer transplants. Ex vivo perfusion techniques that increase the use of marginal donor livers may stabilize LT volume. Otherwise, the number of LTs in the United States will decrease substantially over the next 15 years. In conclusion, the transplant community will need to accept inferior grafts and potentially worse posttransplant outcomes and/or develop new strategies for increasing organ donation and utilization in order to maintain the number of LTs at the current level. Liver Transpl 21:1040‐1050, 2015.

Paracentesis Is Associated With Reduced Mortality in Patients Hospitalized With Cirrhosis and Ascites

BACKGROUND & AIMS Diagnostic paracentesis is recommended for patients with cirrhosis who are admitted to the hospital for ascites or encephalopathy. However, it is not known whether clinicians in the United States adhere to this recommendation; a relationship between paracentesis and clinical outcome has not been reported. We analyzed a U.S. database to determine the frequency of paracentesis and its association with mortality. METHODS The 2009 Nationwide Inpatient Sample (which contains data from approximately 8 million hospital discharges each year) was used to identify patients with cirrhosis and ascites who were admitted with a primary diagnosis of ascites or encephalopathy. In-hospital mortality, length of stay, and hospital charges were compared for those who did and did not undergo paracentesis. Outcomes were compared for those who received an early paracentesis (within 1 day of admission) and those who received one later. RESULTS Of 17,711 eligible admissions, only 61% underwent paracentesis. In-hospital mortality was reduced by 24% among patients who underwent paracentesis (6.5% vs 8.5%; adjusted odds ratio, 0.55; 95% confidence interval, 0.41-0.74). Most paracenteses (66%) occurred ≤1 day after admission. In-hospital mortality was lower among patients who received early paracentesis than those who received it later (5.7% vs 8.1%, P = .049), although this difference was not significant after adjustment for confounders (odds ratio, 1.26; 95% confidence interval, 0.78-2.02). Among patients who underwent paracentesis, the mean hospital stay was 14% longer and hospital charges were 29% greater than for patients who did not receive the procedure. CONCLUSIONS Paracentesis is underused for patients admitted to the hospital with ascites; the procedure is associated with increased short-term survival. These data support practice guidelines derived from expert opinion. Studies are needed to identify barriers to guideline adherence.

The Influence of Nonalcoholic Fatty Liver Disease and Its Associated Comorbidities on Liver Transplant Outcomes

Goals To define the influence of nonalcoholic fatty liver disease (NAFLD) and its associated comorbidities on liver transplant outcomes. Background NAFLD cirrhosis is an increasing indication for transplant. The transplant outcomes of NAFLD patients with metabolic syndrome comorbidities remain unclear. Study We examined a single center, retrospective cohort between 2004 and 2007 to determine transplant mortality for NAFLD and non-NAFLD patients accounting for the possible independent effects of diabetes, hypertension, obesity, and hyperlipidemia. The primary outcomes were 30-day, 1-year, and 3-year all-cause mortality. Cox proportional hazard ratios were determined controlling for various recipient and donor covariates. Results In our study, of 118 liver transplants, 18% were performed for NAFLD cirrhosis. Adjusted hazard ratios for death for NAFLD compared with non-NAFLD patients at 30 days, 1 year, and 3 years were 8.96 (1.06, 75.8), 1.49 (0.38, 5.81), and 1.05 (0.29, 3.78), respectively. Compared with nondiabetic patients, diabetic patients had hazard ratios at 30 days, 1 year, and 3 years of 2.02 (0.31, 12.9), 2.82 (0.94, 8.47), 3.58 (1.32, 9.71), respectively. Obesity, hypertension, and hyperlipidemia did not have a significant impact on posttransplant mortality. Conclusions We conclude that NAFLD increases 30-day transplant mortality whereas diabetes increases 3-year mortality. Future work should determine the strategies to decrease perioperative mortality among NAFLD patients and ways to improve long-term transplant survival among diabetics.

Intestinal microbiota in liver disease.

The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation.

Time to Rethink Antiviral Treatment for Hepatitis C in Patients with Coexisting Mental Health/Substance Abuse Issues

BackgroundA new era has dawned in the treatment of chronic hepatitis C (HCV) virus with the use of direct-acting antiviral medications augmenting combination therapy. Unfortunately, the significant impact of improvements may not be realized if antiviral treatment is not expanded to include a larger proportion of patients, many of whom have coexisting mental health and/or substance abuse issues and have been historically deferred from treatment.MethodsWe reviewed the extent literature on HCV treatment for individuals with co-occurring mental health and/or substance abuse issues.ResultsA number of empirically-based arguments exist in favor of treating HCV-infected individuals with mental health and/or substance abuse issues within the context of multidisciplinary team approaches. Integrated, collaborative, or hybrid models of care are just a few examples of multidisciplinary approaches that can combine the care of HCV treating providers with mental health and/or addictions providers to safely and effectively treat these patients. Collectively, these arguments and the empirical evidence that supports them, provides a strong rationale for why expanding antiviral therapy to these patients is critical and timely.ConclusionsA decade of evidence suggests that HCV-infected individuals with mental health and/or substance abuse issues can safely and effectively undergo antiviral treatment when delivered through multidisciplinary care settings. Multidisciplinary approaches that combine HCV treating providers with mental health, addictions, and other support systems can facilitate preparation and successful treatment of these patients on antiviral therapy.