This is the first American Association for the Study of Liver Diseases (AASLD) Practice Guidance on the management of malnutrition, frailty, and sarcopenia in patients with cirrhosis. This guidance represents the consensus of a panel of experts after a thorough review and vigorous debate of the literature published to date, incorporating clinical experience and common sense to fill in the gaps when appropriate. Our goal was to offer clinicians pragmatic recommendations that could be implemented immediately in clinical practice to target malnutrition, frailty, and sarcopenia in this population. This AASLD Guidance document differs from AASLD Guidelines, which are supported by systematic reviews of the literature, formal rating of the quality of the evidence and strength of the recommendations, and, if appropriate, meta-analysis of results using the Grading of Recommendations Assessment Development and Evaluation system. In contrast, this Guidance was developed by consensus of an expert panel and provides guidance statements based on formal review and analysis of the literature on the topics, with oversight Accepted ArticleThis article is protected by copyright. All rights reserved provided by the AASLD Practice Guidelines Committee at all stages of Guidance development. The AASLD Practice Guidelines Committee chose to perform a Guidance on this topic because a sufficient number of randomized controlled trials (RCTs) were not available to support the development of a Guideline. Definitions of Malnutrition, Frailty, and Sarcopenia and Their Relationship in Patients With CirrhosisCirrhosis is a major predisposing condition for the development of malnutrition, frailty, and sarcopenia.Multiple, yet complementary, definitions of these conditions exist in the published domain outside of the field of hepatology, but consensus definitions have not yet been established by the AASLD for patients with cirrhosis. Furthermore, there has been ambiguity related to operationalization of these constructs in clinical practice. To address this, we offer definitions of the theoretical constructs of malnutrition, frailty, and sarcopenia as commonly represented in all populations, partnered with operational definitions, developed by consensus, to facilitate pragmatic implementation of these constructs in clinical practice as applied to patients with cirrhosis (Table 1). Malnutrition is a clinical syndrome that results from "an imbalance (deficiency or excess) of nutrients that causes measurable adverse effects on tissue/body form (body shape, size, composition) or function, and/or clinical outcome." 1 Key to this definition is the recognition that malnutrition represents a spectrum of nutritional disorders across the entire range of body mass index (BMI)from underweight to obese. By this definition, malnutrition leads to adverse physical effects, which, in patients with cirrhosis, are commonly manifested phenotypically as frailty or sarcopenia. Frailty has most commonly been defined as a clinical state of decreased physiologic reserve...

Cholestatic jaundice in infancy affects approximately 1 in every 2500 term infants and is infrequently recognized by primary providers in the setting of physiologic jaundice. Cholestatic jaundice is always pathologic and indicates hepatobiliary dysfunction. Early detection by the primary care physician and timely referrals to the pediatric gastroenterologist/hepatologist are important contributors to optimal treatment and prognosis. The most common causes of cholestatic jaundice in the first months of life are biliary atresia (25%-40%) followed by an expanding list of monogenic disorders (25%), along with many unknown or multifactorial (eg, parenteral nutrition-related) causes, each of which may have time-sensitive and distinct treatment plans. Thus, these guidelines can have an essential role for the evaluation of neonatal cholestasis to optimize care. The recommendations from this clinical practice guideline are based upon review and analysis of published literature and the combined experience of the authors. The committee recommends that any infant noted to be jaundiced after 2 weeks of age be evaluated for cholestasis with measurement of total and direct serum bilirubin, and that an elevated serum direct bilirubin level (direct bilirubin levels >1.0 mg/dL or >17 μmol/L) warrants timely consideration for evaluation and referral to a pediatric gastroenterologist or hepatologist. Of note, current differential diagnostic plans now incorporate consideration of modern broad-based next-generation DNA sequencing technologies in the proper clinical context. These recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the care of all infants with cholestasis. Broad implementation of these recommendations is expected to reduce the time to the diagnosis of pediatric liver diseases, including biliary atresia, leading to improved outcomes.

In this pilot study, 60% of pediatric recipients of parental living donor liver transplants remained off immunosuppression therapy for at least 1 year with normal graft function and stable allograft histology.

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The factors that influence the long‐term histological outcome of transplanted liver allografts in children are not yet fully understood, and the role of surveillance biopsies in patients with normal graft function remains controversial. The aims of this study were to describe the long‐term graft histology of pediatric liver transplant recipients surviving at least 3 years and to analyze factors correlating with long‐term histological outcome. Histological slides of 63 long‐term liver transplant recipients were assessed for inflammation and fibrosis. The histological findings were correlated with clinical, biochemical, serological, and radiological findings. A significant proportion of biopsies from these patients showed some type of histological abnormalities, with fibrosis being observed in 61 (97%) patients. Duration of transplantation of >6 years and ≥grade 2 inflammation were significantly associated with advanced fibrosis. We could not identify any correlation between ≥stage 3 fibrosis and donor age, cold and warm ischemia time, history of de novo autoimmune hepatitis, hepatic artery thrombosis, chronic rejection, or alanine aminotransferase, aspartate aminotransferase, and gamma‐glutamyl transferase values. In conclusion, liver fibrosis appears to be a common finding in long‐term pediatric liver transplant survivors. The cause of this fibrosis is uncertain, and normal alanine aminotransferase, aspartate aminotransferase, and gamma‐glutamyl transferase levels do not exclude the presence of significant fibrosis. Liver Transpl 14:1582–1587, 2008. © 2008 AASLD.