End-Organ Function and Exercise Performance in Patients With Fontan Circulation: What Characterizes the High Performers?

Background The physiologic hallmarks of the Fontan circulation-chronically elevated central venous pressures and low cardiac output-have significant effects not only on cardiovascular status but also impact other organ systems. Exercise capacity is limited in many and declines with age, accelerating in adolescence, but with wide variability. We explore the relationship between exercise performance and end-organ function in outpatient subjects with a Fontan circulation. Methods and Results This is a cross-sectional analysis of subject end-organ characterization from our outpatient Fontan circulation clinic with peak oxygen consumption (peak Vo2) at cardiopulmonary exercise testing as the primary outcome. We perform linear regression to assess associations between clinical characteristics and peak Vo2 as well as the magnitude of the association of clinical characteristics with peak Vo2. Of 265 subjects age 12.8 (9.5-16.4) years, there is a negative correlation between age and peak Vo2 (-0.49, P<0.001). Of those undergoing ramp cycle exercise testing, 34% perform above 80% predicted peak Vo2. Variables positively associated with peak Vo2 and their effect size include vitamin D sufficiency (+3.00, P=0.020) and absolute lymphocyte count (+0.23, P=0.005). Status as overweight/obese (-3.91, P=0.003) and hemoglobin (-0.77, P=0.003) are negatively associated. Neither ventricular morphology, timing of Fontan palliation, nor Fontan circulation type affect peak Vo2. Conclusions Higher peak Vo2 in those with a Fontan circulation is associated with younger age, vitamin D sufficiency, absence of overweight/obese, lower hemoglobin, and a healthier hepatic profile. Whether exercise training or other initiatives can modify organ characteristics in those with a Fontan circulation is worthy of exploration.

Pediatric NAFLD: an overview and recent developments in diagnostics and treatment.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adults in industrialized countries. Besides liver-related morbidity, NAFLD is also associated with an increased risk of cardiovascular disease, type 2 diabetes and mortality at adult age. However, despite the high prevalence and serious complications, diagnosing and staging of disease remains complicated due to a lack of accurate screening tools and non-invasive methods to detect fibrosis. Areas covered: Recent insights in epidemiology, pathogenesis, diagnostic evaluation and treatment options in pediatric NAFLD are being reviewed, with a particular focus on new developments in diagnostic tools. Expert opinion: Due to their long life span, children with NAFLD are particularly at risk of complications in their lifetime. Therefore, an effective screening strategy for children to identify those with NAFLD at risk of complications is urgently needed. This is further underscored by new pharmacological therapies that are expected to become available in the next 5 years. Momentarily no accurate non-invasive method for diagnosing pediatric NAFLD is available. New promising biomarkers and imaging tools could hopefully provide better screening tools and could contribute to the development of a successful management plan to identify children with NAFLD.

May circulating steroids reveal a predisposition to intrahepatic cholestasis of pregnancy in non-pregnant women?

Intrahepatic cholestasis of pregnancy (ICP) is a frequent liver disorder, mostly occurring in the third trimester. ICP is not harmful to the mothers but threatens the fetus. The authors evaluated steroid alterations in maternal and mixed umbilical blood to elucidate their role in the ICP development. Ten women with ICP were included in the study. Steroids in the maternal blood were measured by Gas Chromatography-Mass Spectrometry (GC-MS) (n=58) and RIA (n=5) at the diagnosis of ICP, labor, day 5 postpartum, week 3 postpartum and week 6 postpartum. The results were evaluated by ANOVA consisting of the subject factor, between subject factors ICP, gestational age at the diagnosis of ICP and gestational age at labor, within-subject factor Stage and ICP × Stage interaction. The 17 controls were firstly examined in the week 36 of gestation. ICP patients showed reduced CYP17A1 activity in the C17,20 lyase step thus shifting the balance between the toxic conjugated pregnanediols and harmless sulfated 5alpha/beta-reduced-17-oxo C19 steroids. Hence, more toxic metabolites originating in maternal liver from the placental pregnanes may penetrate backward to the fetal circulation. As these alterations persist in puerperium, the circulating steroids could be potentially used for predicting the predisposition to ICP even before next pregnancy.

Assessment of the spectrum of hepatic encephalopathy: A multicenter study.

Hepatic encephalopathy (HE) is a major cause of morbidity in cirrhosis. However, its severity assessment is often subjective, which needs to be studied systematically. The aim was to determine how accurately trainee and nontrainee practitioners grade and manage HE patients throughout its severity. We performed a survey study using standardized simulated patient videos at 4 US and 3 Canadian centers. Participants were trainees (gastroenterology/hepatology fellows) and nontrainees (faculty, nurse practitioners, physician assistants). We determined the accuracy of HE severity identification and management options between grades <2 or ≥2 HE and trainees/nontrainees. In total, 108 respondents (62 trainees, 46 nontrainees) were included. For patients with grades <2 versus ≥2 HE, a higher percentage of respondents were better at correctly diagnosing grades ≥2 compared with grades <2 (91% versus 64%; P < 0.001). Specialized cognitive testing was checked significantly more often in grades <2, whereas more aggressive investigation for precipitating factors was ordered in HE grades >2. Serum ammonia levels were ordered in almost a third of grade ≥2 patients. For trainees and nontrainees, HE grades were identified similarly between groups. Trainees were less likely to order serum ammonia and low-protein diets, more likely to order rifaximin, and more likely to perform a more thorough workup for precipitating factors compared with nontrainee respondents. There was excellent concordance in the classification of grade ≥2 HE between nontrainees versus trainees, but lower grades showed discordance. Important differences were seen regarding blood ammonia, specialized testing, and nutritional management between trainees and nontrainees. These results have important implications at the patient level, interpreting multicenter clinical trials, and in the education of practitioners. Liver Transplantation 24 587-594 2018 AASLD.

Underappreciation of non-alcoholic fatty liver disease by primary care clinicians: limited awareness of surrogate markers of fibrosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common cause of incidental liver test abnormalities. General practitioners (GP) have a key role in identifying people with NAFLD at risk of significant liver disease. Recent specialist guidelines emphasise the use of fibrosis algorithms or serum biomarkers rather than routine liver tests, to assess advanced fibrosis. AIM: To evaluate primary care clinicians' current approach to diagnosis, management and referral of NAFLD. METHODS: A cross-sectional survey of primary care clinicians was undertaken through a structured questionnaire about NAFLD. A convenience sample of general practice clinics and general practice conferences in Metropolitan Brisbane and regional south east Queensland was selected. RESULTS: A total of 108 primary care clinicians completed the survey (participation rate 100%). Fifty-one percent of respondents considered the prevalence of NAFLD in the general population to be ≤10%. Twenty-four percent of respondents felt that liver enzymes were sufficiently sensitive to detect underlying NAFLD. Most respondents were unsure whether the Fibrosis 4 score (62.7% unsure) or Enhanced Liver Fibrosis score (63.7% unsure) could help to identify advanced fibrosis or cirrhosis. Although 47% of respondents said they would refer a patient to a Gastroenterologist/Hepatologist if they suspect the patient has NAFLD, 44.1% do not make any referrals. Of concern, 70.6% of clinicians said they were unlikely to refer a patient to Hepatology unless liver function tests are abnormal. CONCLUSION: Our findings demonstrate that many primary care clinicians underestimate the prevalence of NAFLD and under-recognise the clinical spectrum of NAFLD and how this is assessed.

Liver cytolysis in acute heart failure: What does it mean? Clinical profile and outcomes of a prospective hospital cohort.

UNLABELLED: Abnormal liver function tests (LFTs) are a common manifestation of heart failure (HF). Our purpose was to characterize patients hospitalized for acute HF (AHF) with liver cytolysis, analyze cytolysis predictors and explore its prognostic implications. METHODS: In a prospective cohort study, we enrolled patients with AHF consecutively admitted to the Internal Medicine Department of University Hospital between January 2009 and December 2010, and recorded demographic, clinical, laboratory and echocardiogram parameters. A logistic regression was done to identify cytolysis predictors. In survival analysis primary endpoints were all-cause death, readmission due to AHF, and the combined event of all-cause death and readmission for AHF at 90days of follow-up. RESULTS: Fifty-eight patients had cytolysis at admission. AHF attributed to atrial fibrillation (OR 3.235), higher heart rate at admission (OR 1.028), cold/wet profile at admission (OR 7.12) and ejection fraction <30% (OR 2.316) were independent predictors of cytolysis. Death occurred more frequently during follow-up in the cytolysis group (27.6 vs. 15.1%, p=0.014, respectively). On survival analysis, cytolysis remained an independent predictor of death at 90days when adjusted to age (HR 1.066), male gender (HR 1.884), valvular etiology (HR 2.365), neurologic status at admission (sleepy HR 3.854; confusion HR 3.176) and cardiac output (HR 0.762). CONCLUSION: Cytolysis may be a marker of systemic hypoperfusion, so strategies to improve hemodynamic profile should be considered, especially in the presence of cold/wet clinical profile, AHF attributed to AF, tachycardia, and EF<30%. Cytolysis is associated with higher mortality at 90days in patients with AHF.

Imaging-Based Liver Function Tests--Past, Present and Future.

UNLABELLED: Preoperative assessment of liver function and prediction of postoperative functional reserve are important in patients scheduled for liver resection. While determination of absolute liver function currently mostly relies on laboratory tests and clinical scores, postoperative remnant liver function is estimated volumetrically using imaging data obtained with computed tomography (CT) or magnetic resonance imaging (MRI). Accurate estimation of hepatic function is also relevant for intensive care patients, oncologic patients, and patients with diffuse liver disease. The indocyanine green (ICG) test is still the only established test for estimating true global liver function. However, more recent tools such as the LiMAx test also allow global assessment of hepatic function. These tests are limited when liver function is inhomogeneously distributed, which is the case in such conditions as unilateral cholestasis or after portal vein embolization. Imaging-based liver function tests were first developed in nuclear medicine and, compared with laboratory tests, have the advantage of displaying the spatial distribution of liver function. Nuclear medicine scans are obtained using tracers such as 99mTc galactosyl and 99mTc mebrofenin. Liver function is typically assessed using planar scintigraphy. However, three-dimensional volumetry is possible with single-photon emission computed tomography (SPECT-CT). Another technique for image-based liver function estimation is Gd-EOB-enhanced MRI. While metabolization of Gd-EOB in the body is similar to that of ICG and mebrofenin, its distribution in the liver can be displayed by MRI with higher temporal and spatial resolution. Moreover, MRI-based determination of liver function can be integrated into routine preoperative imaging. This makes MRI an ideal candidate for preoperative determination of liver function, though the best pulse sequence and the parameter to be derived from the image information remain to be identified. Another question to be answered is how the results may be affected by renal function and the presence of hyperbilirubinemia. As more results from clinical evaluation including comparison with postoperative liver function data become available, image-based liver function tests, especially with use of Gd-EOB as the contrast medium, have the potential to add another dimension to preoperative imaging. KEY POINTS: Liver function consists of a multitude of subfunctions such as biotransformation, excretion and storage. Global liver function tests are score-based tests such as Child-Pugh or MELD as well as the ICG- and LiMAx-test. Imaging-based liver function tests add spatial information. Current clinical standard is the 99mTc-Mebrofenin-scintigraphy. MRI-based function tests with Gd-EOB-DTPA have the potential to integrate seamlessly into clinical workup, feature a higher temporal and spatial resolution and do not rely on ionizing radiation.

A Laboratory Diagnostic Approach to Hepatobiliary Disease in Small Animals.

Routine biochemical tests generally include serum enzymes, proteins, and other markers useful for identifying hepatobiliary disease in dogs and cats. Obtaining results outside the reference intervals can occur with direct hepatocellular injury, enzyme induction by hepatocytes or biliary epithelium, or decreased hepatic function. However, detection of biochemical abnormalities does not necessarily indicate clinically significant disease. For a comprehensive approach to detection and treatment of hepatobiliary disease, the laboratory results must be correlated with the history and physical examination findings, diagnostic imaging results, and other assays.

Safety and efficacy of reduced fingolimod dosage treatment.

BACKGROUND: Oral fingolimod is a sphingosine-1-phosphate-receptor modulator that prevents the egress of lymphocytes from lymph nodes. Fingolimod reduces relapse rate and delays disability progression in patients with relapsing forms of multiple sclerosis (MS). Elevation of liver function tests (LFTs) and reduction in peripheral-blood lymphocyte counts were among the most common adverse events reported in phase II, phase III, and extension studies. OBJECTIVE: To describe eight patients in whom fingolimod dose was reduced to every other day (n=6) or every third day (n=2) due to increased LFTs more than 3 times the upper limit of normal (ULN) (n=2) or decreased lymphocyte count by ≤0.2×10(9)/L (n=6). RESULTS: Fingolimod dose reduction resulted in reversal of laboratory abnormalities. Clinically, none of the 8 patients developed clinical relapses, but five patients had new lesions on magnetic resonance imaging (MRI), one of whom with disability progression, and one patient converted to secondary progressive MS (SPMS). CONCLUSION: Reducing the frequency of fingolimod administration can reverse laboratory abnormalities but may have a negative impact on drug efficacy.

[Diagnosis and therapies for acute liver failure: scientific developments]. / Diagnostik und Behandlung des akuten Leberversagens: Wissenschaftliche Entwicklungen.

BACKGROUND: In Germany about 200 patients suffer from acute liver failure each year. Due to its rare occurrence and the severity of the disease course only few evidence-based therapeutic strategies are available. OBJECTIVES: This review aims to discuss the most important developments for the diagnosis and therapy of acute liver failure and provides an outlook of their future clinical relevance. RESULTS: The established enzyme parameters combined with synthesis- and detoxification-related markers insufficiently predict the severity and disease course of acute liver failure. In future, levels of released microRNAs or cleaved cytokeratin 18 fragments may improve the diagnostic repertoire. Currently, only few drug-based therapeutic approaches are available, but much effort has been invested in artificial liver support devices. Based on their favorable risk assessment cell-free detoxification systems are applied sporadically during the treatment of patients with advanced liver diseases, even if to date larger studies have failed to prove a significant survival benefit. Extracorporeal liver assist devices and cell transplantation approaches rely on the availability of metabolically active donor hepatocytes and, thus, the generation of liver cells from appropriate stem cells is gaining interest. CONCLUSION: Current research in stem cell biology and tissue engineering suggest in initial animal studies the feasibility of stem cell-based artificial liver support systems for future treatment of acute liver failure.

Longitudinal trends, hemodynamic profiles, and prognostic value of abnormal liver function tests in patients with acute decompensated heart failure: an analysis of the ESCAPE trial.

BACKGROUND: This study analyzed liver function abnormalities in heart failure patients admitted with severe acute decompensated heart failure (ADHF). METHODS AND RESULTS: A post hoc analysis was conducted with the use of data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE). Liver function tests (LFTs) were measured at 7 time points from baseline, at discharge, and up to 6 months follow-up. Survival analyses were used to assess the association between admission Model of End-Stage Liver Disease Excluding International Normalized Ratio (MELD-XI) scores and patient outcome.There was a high prevalence of abnormal baseline (admission) LFTs (albumin 23.8%, aspartate transaminase 23.5%, alanine transaminase 23.8%, and total bilirubin 36.1%). The percentage of patients with abnormal LFTs decreased significantly from baseline to 6-months' follow-up. When mean hemodynamic profiles were compared in patients with abnormal versus normal LFTs, elevated total bilirubin was associated with a significantly lower cardiac index (1.80 vs 2.1; P < .001) and higher central venous pressure (14.2 vs 12.0; P = .03). Multivariable analyses revealed that patients with elevated MELD-XI scores (≥16.8) had a 2-fold (hazard ratio 2.06, 95% confidence interval 1.05-4.03) increased risk of death, rehospitalization, or transplantation after adjusting for baseline LFTs, age, sex, race, body mass index, diabetes, and systolic blood pressure. CONCLUSIONS: Abnormal LFTs are common in the ADHF population and are a dynamic marker of an impaired hemodynamic state. Elevated MELD-XI scores are associated with poor outcomes among patients admitted with ADHF.

Liver function, in-hospital, and post-discharge clinical outcome in patients with acute heart failure-results from the relaxin for the treatment of patients with acute heart failure study.

BACKGROUND: Elevated plasma concentrations of liver function tests are prevalent in patients with chronic heart failure (HF). Little is known about liver function in patients with acute HF. We aimed to assess the prevalence and prognostic value of serial measurements of liver function tests in patients admitted with acute decompensated HF. METHODS: We investigated liver function tests from all 234 patients from the Relaxin for the Treatment of Patients With Acute Heart Failure study at baseline and during hospitalization. The end points were worsening HF through day 5, 60-day mortality or rehospitalization, and 180-day mortality. RESULTS: Mean age was 70 ± 10 years, 56% were male, and most patients were in New York Heart Association functional class III/IV (73%). Abnormal liver function tests were frequently found for alanine transaminase (ALT; 12%), aspartate transaminase (AST; 21%), alkaline phosphatase (12%), and total bilirubin (19%), and serum albumin (25%) and total protein (9%) were decreased. In-hospital changes were very small. On a continuous scale, baseline ALT and AST were associated with 180-day mortality (hazard ratios [HRs; per doubling] 1.52 [P = .030] and 1.97 [P = .013], respectively) and worsening HF through day 5 (HRs [per doubling] 1.72 [P = .005] and 1.95 [P = .008], respectively). Albumin was associated with 180-day mortality (HR 0.86; P = .001) but not with worsening HF (HR 0.95; P = .248). Total protein was associated with only worsening HF (HR 0.91; P = .004). CONCLUSIONS: Abnormal liver function tests are often present in patients with acute HF and are associated with an increased risk for mortality, rehospitalization, and in-hospital worsening HF.

Patterns of preoperative laboratory testing in patients undergoing outpatient plastic surgery procedures.

BACKGROUND: Preoperative laboratory testing is commonplace in the clinical setting and is often utilized at surgeon discretion. We searched the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) data set to determine the impact of preoperative laboratory testing in ambulatory plastic surgery patients. OBJECTIVE: The authors assess the utilization and predictive value of preoperative laboratory testing in outpatient plastic surgery procedures. METHODS: Patients undergoing ambulatory plastic surgery were identified from the 2005 to 2010 NSQIP databases. Laboratory tests were categorized by group: hematologic, chemistry, coagulation, and liver function tests (LFT). We defined complications in 2 groups: major postoperative and wound complications. Multivariate analyses were used to identify patient characteristics associated with testing and to assess the ability of laboratory testing to predict postoperative complications. RESULTS: A total of 5359 (62.0%) patients underwent testing; 881 (16.4%) tests were performed on the day of surgery. In patients with no defined NSQIP comorbidities, 59.4% underwent preoperative testing and had a significantly lower rate of abnormal findings (33.4% vs 25.3%, P < .0001). In multivariate analyses, testing was associated with older age, American Society of Anesthesiologists class >2, Hispanic or African American race, body contouring procedures, epidural or spinal procedures, and with diabetes, hypertension, and cancer. Major complications occurred in 0.34% of patients. Our analysis demonstrated that neither testing nor abnormal results were associated with postoperative complications, either major (P = .178) or wound (P = .150). CONCLUSIONS: We found no association between abnormal laboratory testing and postoperative morbidity. Preoperative testing in low-risk ambulatory plastic surgery patients may be costly and has limited direct clinical benefit.

Evolución de la fibrosis hepática en reclusos coinfectados por VIH y VHC que inician tratamiento con inhibidores de la proteasa potenciados / The progression of liver fibrosis in prison inmates co-infected by HIV and HCV who started on boosted protease inhibitor therapy

Objetivos: Analizar la evolución de la fibrosis hepática medida por elastografía y pruebas bioquímicas en reclusos coinfectados por VIH y VHC que han iniciado tratamiento antirretroviral con lopinavir/ritonavir u otros inhibidores de la proteasa potenciados con ritonavir. Métodos: Estudio prospectivo, observacional y multicéntrico. Se comprobó durante 48 semanas la evolución de la fibrosis hepática medida mediante elastografía de transición (FibroScan) y pruebas bioquímicas en población penitenciaria española coinfectada por VIH y VHC. Resultados: De los 94 pacientes incluidos, 54 (57,4%) fueron seguidos durante 48 semanas. En la semana 48, no hubo cambios significativos en el grado de fibrosis medida mediante FibroScan (8,1 Kpa vs 8,3; p=0.20) o índice de FORNS (5,6 vs 5,1; p=0,50), aunque sí con el índice APRI (0.7 vs 0.6; p=0.05) y el índice FIB-4 (p=0,02). Cuando la medición se realizó en función del grado de fibrosis basal, se observó que el tratamiento redujo el porcentaje de pacientes con fibrosis basal de grado 3/4 (50% vs 15%; p=0,001), pero no hubo cambios en los que ya tenían basalmente grado 4 (20,4% vs 20,4%). Conclusión: Los reclusos coinfectados por VIH y VHC que inician tratamiento antirretroviral con lopinavir/ritonavir muestran una estabilización de la fibrosis hepática medida con FibroScan® tras un año de seguimiento. En conjunto, el tratamiento mejoró la fibrosis cuando la referencia de medición fue el índice APRI y el FIB-4, pero no con el índice FORNS o la elastografía (AU)

Objectives: To analyse the progression of liver fibrosis as measured by elastography and biochemical testing in prison inmates co-infected by HIV and HCVwho started on ritonavir-boosted protease inhibitor (PI) therapy. Methods: A prospective, observational and multi-centre study. The progression of liver fibrosis as measured by transient elastography (FibroScan) and biochemical testing was monitored for 48 weeks in a Spanish prison population co-infected with HIV and HCV. Results: Of the 94 patients included, 54 (57.4%) were followed-up for 48 weeks. At week 48, no significant changes were seen in the grade of fibrosis measured using FibroScan (8.1 kPa vs. 8.3 kPa; p=0.20) or the Forns index (5.6 vs. 5.1; p=0.50), although significant changes were detected using the APRI (0.7 vs. 0.6; p=0.05) and the FIB-4 indexes (p= 0.02).When measurement was done compared to baseline fibrosis, it was seen that therapy reduced the percentage of patients with fibrosis ≥3 but <4 (50% vs. 15%; p=0.001), but no change was seen in those found to have grade 4 fibrosis at baseline (20.4% vs. 20.4%). Conclusion: The inmates co-infected with HIV and HCV who were started on antiretroviral therapy with the boosted protease inhibitor (PI) showed stasterilizationbilisation of the liver fibrosis as measured with FibroScan after one year of follow-up. Overall, the therapy improved fibrosis when measured using the APRI or FIB-4 indexes, but not when using the Forns index or elastography (AU)

Orofacial dyskinesia after moxifloxacin treatment--a case with normal hepatorenal function and review of literature.

BACKGROUND: Orofacial dyskinesia is rarely reported with antibiotics. Among antibiotics, third-generation fluoroquinolones are known to cause movement disorders. We report the first patient who developed orofacial dyskinesia after taking a fourth-generation fluoroquinolone, namely, moxifloxacin. METHODS: The patient is a 58-year-old woman who was treated with moxifloxacin for acute bronchitis. She developed orofacial dyskinesia involving the tongue, lips, and facial muscles after treatment. RESULTS: Discontinuation of moxifloxacin and treatment with clonidine resulted in significant reduction of orofacial dyskinesia over the period of 8 to 12 weeks. A review of literature shows reports of a variety of involuntary movements with third-generation fluoroquinolones, mostly manifesting in patients with impaired renal and kidney function. CONCLUSIONS: The fourth-generation fluoroquinolone moxifloxacin can cause orofacial dyskinesia like third-generation fluoroquinolone antibiotics and in a patient with normal renal and liver function.

Liver function tests in children and adolescents receiving risperidone treatment for a year: a longitudinal, observational study from Turkey.

OBJECTIVE: To determine the changes in liver function tests after long-term risperidone treatment in a child and adolescent population. METHODS: Weight, alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, alkaline phosphatase and serum bilirubin of the patients were assessed in pre-treatment period, and at the sixth and 12th months of treatment. One hundred children and adolescents (aged between 3 and 18 years) were enrolled to the study. RESULTS: Liver enzyme and bilirubin levels are higher than normal in 21.0% of the patients without clinical symptoms. No cases of hepatic failure or jaundice were seen. Only in an 8-year-old boy were there ALT level increases up to three-fold and AST level increases up to two-fold. After discontinuation of the risperidone treatment, enzyme levels were normalized in this patient. Alkaline phosphatase, alanine and aspartate aminotransferases were the most frequently increased enzymes. CONCLUSION: In this study, after long-term risperidone treatment of children and adolescents there was no evidence of clinically significant increases of liver enzymes and bilirubin levels. These results indicate that risperidone treatment may rarely cause serious liver enzyme increases, and may commonly cause clinically insignificant changes in liver function tests.

Acute liver failure: a life-threatening disease.

BACKGROUND: An estimated 200 to 500 patients develop life-threatening acute liver failure (ALF) in Germany each year. Only sparse data are currently available on the epidemiology and causes of this condition and on potential treatments for it. This article summarizes our current knowledge of the causes, clinical course, and treatment of ALF. METHOD: We selectively reviewed the pertinent current literature on ALF from Germany and abroad. RESULTS: A shift is currently taking place in Germany with respect to the predominant causes of ALF: The leading cause was formerly acute viral hepatitis, but now more cases of ALF are induced by toxic substances, while there is also a growing incidence of cryptogenic subacute ALF. Precise epidemiological data are still lacking. Scoring -systems for the assessment of ALF should take account of hepatic function, the regenerative capacity of the liver, the extent of existing extrahepatic complications, and the risk that further ones will develop. The mortality from ALF has been reduced through improved specific treatment for certain etiological types of ALF, the introduction of liver transplantation, and progress in intensive care medicine. The optimal treatment of ALF patients requires close collaboration among specialists in all of the involved clinical disciplines, as well as between peripheral hospitals and transplantation centers. CONCLUSION: Precise epidemiological data on ALF are still lacking in Germany, as are prospective, randomized trials of treatments for it. It is nonetheless clear that progress has been made in its diagnosis and treatment.