ObjectiveTo describe liver disease related mortality in the United States during 1999-2016 by age group, sex, race, cause of liver disease, and geographic region.DesignObservational cohort study.SettingDeath certificate data from the Vital Statistics Cooperative, and population data from the US Census Bureau compiled by the Center for Disease Control and Prevention’s Wide-ranging Online Data for Epidemiologic Research (1999-2016).ParticipantsUS residents.Main outcome measureDeaths from cirrhosis and hepatocellular carcinoma, with trends evaluated using joinpoint regression.ResultsFrom 1999 to 2016 in the US annual deaths from cirrhosis increased by 65%, to 34 174, while annual deaths from hepatocellular carcinoma doubled to 11 073. Only one subgroup—Asians and Pacific Islanders—experienced an improvement in mortality from hepatocellular carcinoma: the death rate decreased by 2.7% (95% confidence interval 2.2% to 3.3%, P<0.001) per year. Annual increases in cirrhosis related mortality were most pronounced for Native Americans (designated as “American Indians” in the census database) (4.0%, 2.2% to 5.7%, P=0.002). The age adjusted death rate due to hepatocellular carcinoma increased annually by 2.1% (1.9% to 2.3%, P<0.001); deaths due to cirrhosis began increasing in 2009 through 2016 by 3.4% (3.1% to 3.8%, P<0.001). During 2009-16 people aged 25-34 years experienced the highest average annual increase in cirrhosis related mortality (10.5%, 8.9% to 12.2%, P<0.001), driven entirely by alcohol related liver disease. During this period, mortality due to peritonitis and sepsis in the setting of cirrhosis increased substantially, with respective annual increases of 6.1% (3.9% to 8.2%) and 7.1% (6.1% to 8.4%). Only one state, Maryland, showed improvements in mortality (−1.2%, −1.7% to −0.7% per year), while many, concentrated in the south and west, observed disproportionate annual increases: Kentucky 6.8% (5.1% to 8.5%), New Mexico 6.0% (4.1% to 7.9%), Arkansas 5.7% (3.9% to 7.6%), Indiana 5.0% (3.8% to 6.1%), and Alabama 5.0% (3.2% to 6.8%). No state showed improvements in hepatocellular carcinoma related mortality, while Arizona (5.1%, 3.7% to 6.5%) and Kansas (4.3%, 2.8% to 5.8%) experienced the most severe annual increases.ConclusionsMortality due to cirrhosis has been increasing in the US since 2009. Driven by deaths due to alcoholic cirrhosis, people aged 25-34 have experienced the greatest relative increase in mortality. White Americans, Native Americans, and Hispanic Americans experienced the greatest increase in deaths from cirrhosis. Mortality due to cirrhosis is improving in Maryland but worst in Kentucky, New Mexico, and Arkansas. The rapid increase in death rates among young people due to alcohol highlight new challenges for optimal care of patients with preventable liver disease.

BACKGROUND & AIMS:Accurate estimates for the contemporary burden of chronic liver disease (CLD) are vital for setting clinical, research, and policy priorities. We aimed to review the incidence, prevalence, and mortality of CLD and its resulting complications, including cirrhosis and hepatocellular carcinoma (HCC). METHODS:We reviewed the published literature on the incidence, prevalence, trends of various etiologies of CLD and its resulting complications. In addition, we provided updated data from the Centers for Disease Control and Global Burden of Disease Study on the morbidity and mortality of CLD, cirrhosis, and hepatocellular carcinoma (HCC). Lastly, we assessed the strengths and weaknesses of available sources of data in hopes of providing important context to these national estimates of cirrhosis burden. RESULTS:An estimated 1.5 billion persons have CLD worldwide and the age-standardized incidence of CLD and cirrhosis is 20.7/100,000, a 13% increase since 2000. Similarly, cirrhosis prevalence and mortality has increased in recent years in the United States. The epidemiology of CLD is shifting, reflecting implementation of large-scale hepatitis B vaccination and hepatitis C treatment programs, the increasing prevalence of the metabolic syndrome, and increasing alcohol misuse. CONCLUSIONS:The global burden of CLD and cirrhosis is substantial. Although vaccination, screening, and antiviral treatment campaigns for hepatitis B and C have reduced the CLD burden in some parts of the world, concomitant increases in injection drug use, alcohol misuse, and metabolic syndrome threaten these trends. Ongoing efforts to address CLD-related morbidity and mortality require accurate contemporary estimates of epidemiology and outcomes.

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...

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Abbreviation: ADLs, activities of daily living.

Loss of muscle mass and function, or sarcopenia, is a common feature of cirrhosis and contributes significantly to morbidity and mortality in this population. Sarcopenia is a main indicator of adverse outcomes in this population, including poor quality of life, hepatic decompensation, mortality in patients with cirrhosis evaluated for liver transplantation (LT), longer hospital and intensive care unit stay, higher incidence of infection following LT, and higher overall health care cost. Although it is clear that muscle mass is an important predictor of LT outcomes, many questions remain, including the best modality for assessing muscle mass, the optimal cut-off values for sarcopenia, the ideal timing and frequency of muscle mass assessment, and how to best incorporate the concept of sarcopenia into clinical decision making. For these reasons, we assembled a group of experts to form the North American Working Group on Sarcopenia in Liver Transplantation to use evidence from the medical literature to address these outstanding questions regarding sarcopenia in LT. We believe sarcopenia assessment should be considered in all patients with cirrhosis evaluated for liver transplantation. Skeletal muscle index (SMI) assessed by computed tomography constitutes the best-studied technique for assessing sarcopenia in patients with cirrhosis. Cut-off values for sarcopenia, defined as SMI < 50 cm 2 /m 2 in male and < 39 cm 2 /m 2 in female patients, constitute the validated definition for sarcopenia in patients with cirrhosis. Conclusion: The management of sarcopenia requires a multipronged approach including nutrition, exercise, and additional pharmacological therapy as deemed necessary. Future studies should evaluate whether recovery of sarcopenia with nutritional management in combination with an exercise program is sustainable as well as how improvement in muscle mass might be associated with improvement in clinical outcomes.

A high proportion of patients with cirrhosis are readmitted to the hospital (often to a different hospital) within 30 or 90 days; encephalopathy is most strongly associated with readmission. Reasons for readmission differ based on the cause of liver disease, and there are opportunities for quality improvement.