A Single-Center Assessment of Delayed Graft Function in Recipients of Simultaneous Liver and Kidney Transplant.

BACKGROUND: The effects of delayed graft function on long-term kidney allograft outcomes are poorly defined among simultaneous liver and kidney transplant recipients. METHODS: We analyzed data of all simultaneous liver and kidney recipients transplanted at the University of Wisconsin between 2010 and 2017. Risk factors for the development of delayed graft function, kidney graft failure, and patient mortality were outcomes of interest. RESULTS: There were a total of 60 simultaneous liver and kidney recipients; 28 (47%) had delayed graft function. After adjustment for multiple variables, we found that pretransplant dialysis >6 weeks (hazard ratio [HR] = 5.6, 95% CI: 1.23-25.59, P = .02), pretransplant albumin <3 g/dL (HR = 5.75, 95% CI: 1.76-16.94, P = .003), and presence of pretransplant diabetes (HR = 2.5, 95% CI: 0.97-4.77, P = .05) were significantly associated with delayed graft function. Multivariate analysis showed that pretransplant albumin <3 (HR = 4.86, 95% CI: 1.07-22.02, P = .02) was associated with a higher risk of all-cause kidney allograft failure, whereas the duration of delayed graft function (HR = 1.07 per day, 95% CI: 1.01-1.14, P = .01) was associated with a higher risk of death-censored kidney allograft failure. The presence of delayed graft function was not associated with all-cause or death-censored kidney or liver allograft failure. Similarly, the presence of delayed graft function was not associated with patient mortality. CONCLUSION: The incidence of delayed graft function was high in simultaneous liver and kidney recipients. However, with appropriate management, delayed graft function may not have a negative impact on patient or kidney allograft survival.

Increasing Burden of Hepatic Encephalopathy Among Hospitalized Adults: An Analysis of the 2010-2014 National Inpatient Sample.

BACKGROUND: Hepatic encephalopathy (HE) is associated with substantial morbidity and mortality, contributing significant burden on healthcare systems. AIM: We aim to evaluate trends in clinical and economic burden of HE among hospitalized adults in the USA. METHODS: Using the 2010-2014 National Inpatient Sample, we identified adults hospitalized with HE using ICD-9-CM codes. Annual trends in hospitalizations with HE, in-hospital mortality, and hospital charges were stratified by the presence of acute liver failure (ALF) or cirrhosis. Adjusted multivariable regression models were evaluated for predictors of in-hospital mortality and hospitalization charges. RESULTS: Among 142,860 hospitalizations with HE (mean age 59.3 years, 57.8% male), 67.7% had cirrhosis and 3.9% ALF. From 2010 to 2014, total number of hospitalizations with HE increased by 24.4% (25,059 in 2010 to 31,182 in 2014, p < 0.001). Similar increases were seen when stratified by ALF (29.7% increase) and cirrhosis (29.7% increase). Overall in-hospital mortality decreased from 13.4% (2010) to 12.3% (2014) (p = 0.001), with similar decreases observed in ALF and cirrhosis. Total inpatient charges increased by 46.0% ($8.15 billion, 2010 to $11.9 billion, 2014). On multivariable analyses, ALF was associated with significantly higher odds of in-hospital mortality (OR 5.37; 95% CI 4.97-5.80; p < 0.001) as well as higher mean inpatient charges (122.6% higher; 95% CI + 115.0-130.3%; p < 0.001) compared to cirrhosis. The presence of ascites, hepatocellular carcinoma, and hepatorenal syndrome was associated with increased mortality. CONCLUSIONS: The clinical and economic burden of hospitalizations with HE in the USA continues to rise. In 2014, estimated national economic burden of hospitalizations with HE reached $11.9 billion.

The incidence, etiologies, outcomes, and predictors of mortality of acute liver failure in Thailand: a population-base study.

BACKGROUND: Acute liver failure (ALF) is uncommon but progresses rapidly with high mortality. We investigated the incidence, etiologies, outcomes, and predictive factors for 30-day mortality in patients with ALF. METHODS: We conducted a population-based study of ALF patients hospitalized between 2009 and 2013 from the Thai Nationwide Hospital Admission database, which comprises 76% of all admissions from 858 hospitals across 77 provinces in Thailand. ALF was diagnosed using ICD-10 codes K72.0 and K71.11. Patients with liver cirrhosis were excluded. RESULTS: There were 20,589 patients diagnosed with ALF during the study period with 12,277 (59.6%) males and mean age of 46.6 ± 20.7 years. The incidence of ALF was 62.9 per million population per year. The most frequent causes of ALF were indeterminate (69.4%), non-acetaminophen drug-induced (26.1%), and viral hepatitis (2.5%). Acetaminophen was the presumptive cause in 1.7% of patients. There were 5502 patients (26.7%) who died within 30 days after admission. One patient (0.005%) underwent liver transplantation. The average hospital stay was 8.7 ± 13.9 days, and the total cost of management was 1075.2 ± 2718.9 USD per admission. The most prevalent complications were acute renal failure (ARF)(24.2%), septicemia (18.2%), and pneumonia (12.3%). The most influential predictive factors for 30-day mortality were ARF (HR = 3.64, 95% CI: 3.43-3.87, p < 0.001), malignant infiltration of the liver (HR = 3.37, 95% CI: 2.94-3.85, p < 0.001), and septicemia (HR = 1.96, 95%CI: 1.84-2.08, p < 0.001). CONCLUSIONS: ALF patients have poor outcomes with 30-day mortality of 26.7% and high economic burden. Indeterminate etiology is the most frequent cause. ARF, malignant infiltration of the liver, and septicemia are main predictors of 30-day mortality.

Use of Pediatric Health Information System database to study the trends in the incidence, management, etiology, and outcomes due to pediatric acute liver failure in the United States from 2008 to 2013.

Data were collected of children admitted with ALF to 16 US pediatric liver transplant centers from 2008 to 2013 using the PHIS for a retrospective analysis of PALF trends. Patient data linked to the principal diagnosis code for acute necrosis of the liver (570.00) were analyzed for the following: demographics, regional differences, changes over time, pharmaceutical trends, procedural trends, associated diagnoses, and patient outcomes. In 52.5% of 583 patients who met the selection criteria for PALF, the etiology remained undetermined. Acetaminophen toxicity (18.7%) was the most common identifiable etiology, and hepatic encephalopathy (38.6%) was the most common complication. Mortality was lower than previously reported; 95.4% survived and 73.2% survived without a liver transplant. Acute respiratory failure (OR = 3.4, p = 0.035), acute kidney injury (OR = 3.6, p = 0.003), and cerebral edema (OR = 3.6, p = 0.02) were independently associated with increased risk of mortality. The use of N-acetylcysteine in non-acetaminophen-related ALF, the use of intracranial pressure monitoring, and the proportion of sepsis decreased significantly during the study period. The PHIS database can be a useful tool to study the future trends of PALF patients.

Infectious complications of acute and chronic liver disease.

Acute and chronic liver diseases are frequently complicated by infections, which result in increased morbidity and mortality and place an economic burden on health care systems. This review discusses the epidemiology and the impact on prognosis of infections in liver cirrhosis, nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, acute liver failure, and post-liver transplantation. Possible mechanisms for this increased susceptibility are innate immune dysfunction (Kupffer cells, neutrophils, monocytes), genetic predisposition, and intrinsic cellular defects. The causes for innate immune dysfunction may lie in increased gut permeability, the occurrence of endotoxemia, albumin and lipoprotein dysfunction, or toll-like receptor expression. From a clinical viewpoint this article discusses problems in diagnosing infection. Established (vaccination, antibiotic prophylaxis, antiviral prophylaxis, and nutrition) and experimental (probiotic) prophylactic strategies as well as established (antibiotics) and experimental (liver support, albumin, toll-like receptor antagonists) strategies are also reviewed.

Safety assessment in pediatric studies.

It typically takes many years before an association of a drug with a rare, serious adverse reaction is established. As related to pediatric drug use, evidence is even more erratic, as most drugs are used off labels. To enhance child safety, there is an urgent need to develop robust and rapid methods to identify such associations in as timely a manner as possible. In this chapter, several novel methods, both clinically based pharmacoepidemiological approaches and laboratory-based methods, are described.

Removal of opioid/acetaminophen combination prescription pain medications: assessing the evidence for hepatotoxicity and consequences of removal of these medications.

Opioid/acetaminophen combination products are widely prescribed for the management of moderate to moderately severe pain. Acetaminophen, when improperly used, can lead to liver damage and even acute liver failure. In June 2009, an FDA advisory committee recommended elimination of prescription acetaminophen combination products because of the risk of hepatotoxicity associated with use of these medications. The FDA advisory committee reviewed numerous observational studies and adverse event reporting data. The aims of this article are to: 1) provide a summary and epidemiologic critique of the studies and evidence the FDA advisory committee reviewed; 2) examine the potential consequences, such as poorly managed pain or a shift to treatment with other medications with greater potential toxicity and/or restricted availability, if the FDA follows the advisory committee vote; and 3) outline alternate strategies the FDA should consider for reducing hepatotoxicity associated with opioid/acetaminophen combination products.

Non-paracetamol drug-induced fulminant hepatic failure among adults in Scotland.

BACKGROUND AND METHODS: This study details 30 cases of non-paracetamol drug-induced fulminant hepatic failure (NPDI-FHF) that have presented to the Scottish Liver Transplant Unit since 1992. Using the patients' case notes and a previously constructed database, the demographics of NPDI-FHF in Scotland were studied. The clinical and biochemical features, and the outcome of each individual case were also investigated. RESULTS: Of the 30 patients, 10 died. Our study revealed that antibiotics are the most commonly associated drugs with NPDI-FHF while ecstasy and anti-tuberculous drugs are also commonly implicated. The geographical distribution of referrals mirrors that of the population distribution and NPDI-FHF is not confined to any particular social class. It is, more than twice as common among females than males, however. The incidence is evenly spread across the different age categories, but NPDI-FHF as a consequence of ecstasy ingestion is confined to younger age groups. Ecstasy associated NPDI-FHF was also associated with short latency periods. CONCLUSION: NPDI-FHF is not a common problem in Scotland, but it is a serious problem for those affected and consumes considerable health care resources. Doctors need to be made aware that commonly prescribed drugs may cause fulminant hepatic failure. When a young adult presents with fulminant hepatic failure of sudden onset, ecstasy consumption must be considered.

Pronóstico vital en insuficiencia hepática aguda grave: valor de los índices cuantitativos de evaluación / Life prognosis in severe acute hepatic failure: value of assessment quantitative index

The aim of this study was to assess the predictive value for mortality of admission and daily APACHE II score, mortality due to multiple organ failure and the organ failure score in patients with acute hepatic failure. We retrospectively studied 15 such patients admitted to an intensive care unit. Thirteen patients died (87 percent) and their admission APACHE II score was 22ñ7.5 compared to 21ñ8.5 in survovors. Daily APACHE II score, mortality due to multiple organ failure and multiple organ failure score had a 100 percent sensitivity to predict mortality and a 69.2, 76.9 and 76.9 percent specificity respectively. The predictive accuracies of multiple organ failure and multiple organ failure score were 80 percent and significantly better than the accuracy of admission APACHE II score (53 percent). We conclude that these prognostic scores can be useful in the assessment of patients with acute hepatic failure