BACKGROUND & AIMS According to the National Center for Health Statistics (NCHS), chronic liver disease and cirrhosis is the 12th leading cause of death in the United States. However, this single descriptor might not adequately enumerate all deaths from liver disease. The aim of our study was to update data on liver mortality in the United States. METHODS Mortality data were obtained from the Rochester Epidemiology Project (1999–2008) and the National Death Registry (1979–2008). Liver-specific mortality values were calculated. In contrast to the narrow NCHS definition, updated liver-related causes of death included other specific liver diagnoses (eg, hepatorenal syndrome), viral hepatitis, and hepatobiliary cancers. RESULTS The Rochester Epidemiology Project database contained information on 261 liver-related deaths, with an age- and sex-adjusted death rate of 27.0/100,000 persons (95% confidence interval: 23.7–30.3). Of these, only 71 deaths (27.2%) would have been captured by the NCHS definition. Of cases for which viral hepatitis or hepatobiliary cancer was the cause of death, 96.9% and 94.3% had liver-related immediate causes of death, respectively. In analysis of data from the National Death registry (2008), use of the updated definition increased livermortality by>2-fold (from 11.7 to 25.7 deaths/100,000, respectively). Using NCHS definitions, liver-related deaths decreased from 18.9/100,000 in 1979 to 11.7/100,000 in 2008—a reduction of 38%. However, using the updated estimate, liver-related deaths were essentially unchanged from 1979 (25.8/100,000) to 2008 (25.7/100,000). Mortality burden was systematically under-estimated among non-whites and persons of Hispanic ethnicity. CONCLUSIONS Based on analyses of theRochester Epidemiology Project and National Death databases, liver-related mortality has been under-estimated during the past 2 decades in the United States.
BACKGROUND & AIMS Liver stiffness measurement (LSM), using elastography, can independently predict outcomes of patients with chronic liver diseases (CLDs). However, there is much variation in reporting and consistency of findings. We performed a systematic review and meta-analysis to evaluate the association between LSM and outcomes of patients with CLDs. METHODS We performed a systematic review of the literature, through February 2013, for studies that followed up patients with CLDs prospectively for at least 6 months and reported the association between baseline LSM and subsequent development of decompensated cirrhosis or hepatocellular carcinoma (HCC), as well as mortality. Summary relative risk (RR) estimates per unit of LSM and 95% confidence intervals (CIs) were estimated using the random effects model. RESULTS Our final analysis included 17 studies, reporting on 7058 patients with CLDs. Baseline LSM was associated significantly with risk of hepatic decompensation (6 studies; RR, 1.07; 95% CI, 1.03–1.11), HCC (9 studies; RR, 1.11; 95% CI, 1.05–1.18), death (5 studies; RR, 1.22; 95% CI, 1.05–1.43), or a composite of these outcomes (7 studies; RR, 1.32; 95% CI, 1.16–1.51). We observed considerable heterogeneity among studies—primarily in the magnitude of effect, rather than the direction of effect. This heterogeneity could not be explained by variations in study locations, etiologies and stages of CLD, techniques to measure liver stiffness, adjustment for covariates, or method of imputing relationship in the meta-analysis. CONCLUSIONS Based on a meta-analysis of cohort studies, the degree of liver stiffness is associated with risk of decompensated cirrhosis, HCC, and death in patients with CLDs. LSM therefore might be used in risk stratification.
Health care delivery is increasingly evaluated according to quality measures, yet such measures are underdeveloped for cirrhosis. The Practice Metrics Committee of the American Association for the Study of Liver Diseases was charged with developing explicit process‐based and outcome‐based measures for adults with cirrhosis. We identified candidate measures from comprehensive reviews of the literature and input from expert clinicians and patient focus groups. We conducted an 11‐member expert clinician panel and used a modified Delphi method to systematically identify a set of quality measures in cirrhosis. Among 119 candidate measures, 46 were identified as important measures to define the quality of cirrhosis care, including 26 process measures, 7 clinical outcome measures, and 13 patient‐reported outcome measures. The final process measures captured care processes for ascites (n = 5), varices/bleeding (n = 7), hepatic encephalopathy (n = 4), hepatocellular cancer (HCC) screening (n = 1), liver transplantation evaluation (n = 2), and other care (n = 7). Clinical outcome measures included survival, variceal bleeding and rebleeding, early‐stage HCC, liver‐related hospitalization, and rehospitalization within 7 and 30 days. Patient‐reported outcome measures covered physical symptoms, physical function, mental health, general function, cognition, social life, and satisfaction with care. The final list of patient‐reported outcomes was validated in 79 patients with cirrhosis from nine institutions in the United States. Conclusion: We developed an explicit set of evidence‐based quality measures for adult patients with cirrhosis. These measures are a tool for providers and institutions to evaluate their care quality, drive quality improvement, and deliver high‐value cirrhosis care. The quality measures are intended to be applicable in any clinical care setting in which care for patients with cirrhosis is provided.
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Acute and chronic kidney disease after liver transplantation is common and results in significant morbidity and mortality. The introduction of MELD has directly correlated with an increased prevalence of perioperative renal dysfunction and the number of simultaneous liver-kidney transplants performed. Thus, kidney dysfunction in this population is typically multifactorial and related to pre-existing conditions, pre-transplant renal injury, peri-operative events, and post-transplant nephrotoxic immunosuppressive therapies. The management of kidney disease following liver transplantation is challenging, as by the time the serum creatinine is significantly elevated, few interventions impact the course of progression. Also, immunological factors such as antibody-mediated rejection have become of greater interest given the rising liver-kidney transplant population. Therefore this review, assembled by experts in the field and endorsed by the American Society of Transplantation Liver and Intestinal Community of Practice, provides a critical assessment of measures of renal function and interventions aimed at preserving renal function early and late after liver and simultaneous liver-kidney transplantation. Key points and practice-based recommendations for the prevention and management of kidney injury in this population are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.
Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma‐derived C3A cells express anti‐inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End‐Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3‐5 days of continuous ELAD treatment plus SOC. After a minimum follow‐up of 91 days, overall survival (OS) was assessed by using a Kaplan‐Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent‐to‐treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380–393 2018 AASLD.
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