Utilización no apropiada del término de insuficiencia hepática aguda en un hospital de tercer nivel / Inappropriate use of the term of acute liver failure in a tertiary hospital

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Utilización no apropiada del término de insuficiencia hepática aguda en un hospital de tercer nivel / Inappropriate use of the term of acute liver failure in a tertiary hospital

No disponible

Classification and Epidemiologic Aspects of Acute Liver Failure.

Acute liver failure is a rare condition with high short-term morbidity and mortality. The most widely accepted definition is an abnormality in coagulation with any degree of encephalopathy in a patient without cirrhosis and an illness duration of less than 26 weeks. Multiple classifications systems are currently in use to help categorize the condition. This article reviews the most commonly used systems. The epidemiologic aspects of the disease are also reviewed, including incidence, prevalence, demographics, geographic distribution, and racial and cultural factors and are discussed for the various subtypes of acute liver failure.

The Pathology of Acute Liver Failure.

Varied injuries may manifest clinically as acute liver failure. The pathologic features include variable amounts of necrosis and regeneration. This article reviews pathologic classification of patterns of necrosis and associated inflammatory and regenerative responses in specimens from patients with acute liver failure. Detailed pathologic examination of these specimens with clinical pathologic correlation can give the multidisciplinary team vital information regarding etiology and timing as well as extent of injury, and regenerative response. Pathologists are a vital component of the health care team for patients with acute liver failure.

From Child-Pugh to Model for End-Stage Liver Disease: Deciding Who Needs a Liver Transplant.

This article reviews the historical evolution of the liver transplant organ allocation policy and the indications/contraindications for liver transplant, and provides an overview of the liver transplant evaluation process. The article is intended to help internists determine whether and when referral to a liver transplant center is indicated, and to help internists to counsel patients whose initial evaluation at a transplant center is pending.

Pediatric acute liver failure: variations in referral timing are associated with disease subtypes.

UNLABELLED: In pediatric acute liver failure (PALF), rapid referral to a transplant center (TC) is advocated. Clinical variability of PALF may influence referral timing. We aimed to analyze early or late timing of referral in relation to clinical characteristics and outcome in PALF. We conducted a retrospective, single-center, comparative analysis of clinical and liver function parameters in two PALF cohorts (n = 23 per cohort): cohort 1 (early referral, duration of in-patient care before referral (DCR) <7 days) vs. cohort 2 (late referral, DCR ≥ 7 days). Compared to late referrals, patients referred early were more frequently non-icteric and encephalopathic at initial presentation (n = 14 vs. 5 and n = 13 vs. 4, each p < 0.05). Early referred PALF patients had lower hepatic encephalopathy (HE) grades and bilirubin (grade 1 vs. 2, p < 0.02; 215 vs. 439 µmol/l, p < 0.001, respectively) but higher alanine aminotransferase (ALAT) levels (4,340 vs. 963 U/l, p < 0.001). Cumulative poor prognostic indicators were lower in early referrals (2 vs. 4, p < 0.001). In multivariate analysis, subacute liver failure (SLF >7 days between disease onset and development of encephalopathy) was independently associated with late referral (relative risk 9.48; 95 % CI 1.37-64.85, p < 0.02). Differences in survival to discharge were not significant. CONCLUSION: In PALF, referral timing variability is associated with distinct clinical and liver function patterns. Early recognition of prognostic indicators and of SLF may help to improve referral timing and thus PALF management.

Acute kidney injury and acute-on-chronic liver failure classifications in prognosis assessment of patients with acute decompensation of cirrhosis.

OBJECTIVE: Prognostic stratification of patients with cirrhosis is common clinical practice. This study compares the prognostic accuracy (28-day and 90-day transplant-free mortality) of the acute-on-chronic liver failure (ACLF) classification (no ACLF, ACLF grades 1, 2 and 3) with that of acute kidney injury (AKI) classification (no AKI, AKI stages 1, 2 and 3). DESIGN: The study was performed in 510 patients with an acute decompensation of cirrhosis previously included in the European Association for the Study of the Liver-Chronic Liver Failure consortium CANONIC study. ACLF was evaluated at enrollment and 48 h after enrollment, and AKI was evaluated at 48 h according to Acute Kidney Injury Network criteria. RESULTS: 240 patients (47.1%) met the criteria of ACLF at enrollment, while 98 patients (19.2%) developed AKI. The presence of ACLF and AKI was strongly associated with mortality. 28-day transplant-free mortality and 90-day transplant-free mortality of patients with ACLF (32% and 49.8%, respectively) were significantly higher with respect to those of patients without ACLF (6.2% and 16.4%, respectively; both p<0.001). Corresponding values in patients with and without AKI were 46% and 59%, and 12% and 25.6%, respectively (p<0.0001 for both). ACLF classification was more accurate than AKI classification in predicting 90-day mortality (area under the receiving operating characteristic curve=0.72 vs 0.62; p<0.0001) in the whole series of patients. Moreover, assessment of ACLF classification at 48 h had significantly better prognostic accuracy compared with that of both AKI classification and ACLF classification at enrollment. CONCLUSIONS: ACLF stratification is more accurate than AKI stratification in the prediction of short-term mortality in patients with acute decompensation of cirrhosis.

Random forest classification of etiologies for an orphan disease.

Classification of objects into pre-defined groups based on known information is a fundamental problem in the field of statistics. Although approaches for solving this problem exist, finding an accurate classification method can be challenging in an orphan disease setting, where data are minimal and often not normally distributed. The purpose of this paper is to illustrate the application of the random forest (RF) classification procedure in a real clinical setting and discuss typical questions that arise in the general classification framework as well as offer interpretations of RF results. This paper includes methods for assessing predictive performance, importance of predictor variables, and observation-specific information.

Fixed point observation of etiology of acute liver failure according to the novel Japanese diagnostic criteria.

BACKGROUND: There has existed important differences in the definition of acute liver failure (ALF) between Japanese criteria and those of other countries. The novel diagnostic criteria for ALF in Japanese patients were established by the Intractable Hepato-Biliary Diseases Study Group of Japan, in order to correspond to those for ALF in Europe and the USA. We prospectively diagnosed our ALF patients based on this novel criteria, and discussed the etiology by a fixed point observation. METHODS: We investigated the etiology of 54 adult inpatients and outpatients with ALF between 2010 and 2012. RESULTS: Of 54 patients, 36 were ALF without coma, 17 ALF with coma and one late onset hepatic failure. The etiology was due to viral infections in 38.9%, autoimmune hepatitis in 11.1%, drug-induced liver injury in 13.0%, etiologies without hepatitis in 29.6% (circulatory disturbance in 18.5%, infiltration of the liver by malignant cells in 7.4%, and metabolic diseases in 3.7%) and indeterminate causes in 7.4%. CONCLUSIONS: Circulatory disturbance was the most frequent etiology according to the novel criteria. Indeterminate etiology was less observed in our study than the nation-wide survey with significance (P = 0.0014).

Nationwide longitudinal analysis of acute liver failure in taiwan.

Acute liver failure (ALF) is uncommon but fatal. Current management is based mostly on clinical experience. We aimed to investigate the incidence, etiology, outcomes, and prognostic factors of ALF in Taiwan. Patients with the admission diagnosis of ALF between January 2005 and September 2007 were identified from the Longitudinal Health Insurance Database of Taiwan. ALF was further confirmed by disease severity based on laboratory orders, prescriptions, and duration of hospital stay, and acute onset without prior liver disease. Prognostic factors were identified using Cox regression analysis. During the study period, 218 eligible cases were identified from 28,078 potential eligible ALF patients. The incidence was 80.2 per million person-years in average and increased with age. The mean age was 57.9 ±â€Š17.1 years and median survival was 171 days. The most common etiologies were viral (45.4%, mainly hepatitis B virus) and followed by alcohol/toxin (33.0%). Independent prognostic factors included alcohol consumption (hazard ratio, HR, 1.67 [1.01-2.77]), malignancy (HR 2.90 [1.92-4.37]), frequency of checkups per week for total bilirubin (HR 1.57 [1.40-1.76]), sepsis (HR 1.85 [1.20-2.85]), and the use of hemodialysis/hemofiltration (HR 2.12 [1.15-3.9]) and proton pump inhibitor (HR 0.94 [0.90-0.98]). Among the 130 patients who survived ≥90 days, 66 (50.8%) were complicated by liver cirrhosis. Eight (3.7%) were referred for liver transplantation evaluation, but only 1 received transplantation and survived. ALF in Taiwan is mainly due to viral infection. Patients with malignancy and alcohol exposure have worst prognosis. The use of proton pump inhibitor is associated with improved survival. Half of the ALF survivors have liver cirrhosis.

A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality.

BACKGROUND: An early and proper diagnosis of acute on chronic liver failure (ACLF), together with the identification of indicators associated with disease severity is critical for outcome prediction and therapy. OBJECTIVE: To systematically identify and summarize prognostic indicators for patients with ACLF and to evaluate the predictive value of these indicators. METHODS: Embase and Ovid-Medline were searched for English-language articles. The search criteria focused on identifying clinical trials and observational studies reporting on indicators used for prediction of mortality in patients with ACLF. RESULTS: Of 2382 studies identified, 19 were included for detailed analysis. Thirteen different definitions of ACLF were found. The main differences were related to acute deterioration in liver function, coagulopathy and hyperbilirubinaemia/jaundice. Seventy three prognostic indicators and their association with mortality were extracted and categorized into seven categories: general markers (n = 13), viral markers (n = 6), bio-markers (n = 22), hemodynamics (n = 1), morphology/histology (n = 17), scoring systems (n = 10) and treatments (n = 4). CONCLUSIONS: The ambiguity and variability in the definition of ACLF and in its predictive indicators hampers comparability among studies. There is a need for a single uniform definition of ACLF. Also absence of a gold standard is an obstacle to render one indicator superior to another. The age, hepatic encephalopathy, model for end-stage liver disease score, total bilirubin and International normalized ratio (prothrombin time) appeared to be promising candidates for evaluation in future studies. The result of this review may be useful as a starting point in developing a standard list of indicators for clinical outcome that concur with the clinicians' subjective views on prognosis in ACLF.

Falência hepática aguda / Acute liver failure

Falência hepática aguda é uma síndrome clínica devastadora, com alta taxa de mortalidade, apesar dos recentes avanços da terapia intensiva. Determinar a causa tem importantes implicações prognósticas, e o transplante de fígado é um tratamento que salva vidas em casos selecionados. O conhecimento das últimas diretrizes e protocolos pode levar a melhores resultados.

Acute liver failure is a devasting clinical syndrome, with high mortality rate, despite critical care advances. Determining the cause has important prognostic implications, and the orthotopic liver transplantation is a life-saving treatment in select cases. Knowledge of the latest guidelines and treatment protocols can lead to improved patient case.

Acute liver failure in Japan: definition, classification, and prediction of the outcome.

Acute liver failure is a clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to severe impairment of liver function caused by massive or submassive liver necrosis. Viral hepatitis is the most important and frequent cause of acute liver failure in Japan. The diagnostic criteria for fulminant hepatitis, including that caused by viral infections, autoimmune hepatitis, and drug allergy induced-liver damage, were first established in 1981. Considering the discrepancies between the definition of fulminant hepatitis in Japan and the definitions of acute liver failure in the United States and Europe, the Intractable Hepato-Biliary Disease Study Group established the diagnostic criteria for "acute liver failure" for Japan in 2011, and performed a nationwide survey of patients seen in 2010 to clarify the demographic and clinical features and outcomes of these patients. According to the survey, the survival rates of patients receiving medical treatment alone were low, especially in those with hepatic encephalopathy, despite artificial liver support, consisting of plasma exchange and hemodiafiltration, being provided to almost all patients in Japan. Thus, liver transplantation is inevitable to rescue most patients with hepatic encephalopathy. The indications for liver transplantation had, until recently, been determined according to the guideline published by the Acute Liver Failure Study Group in 1996. Recently, however, the Intractable Hepato-Biliary Disease Study Group established a scoring system to predict the outcomes of acute liver failure patients. Algorithms for outcome prediction have also been developed based on data-mining analyses. These novel guidelines need further evaluation to determine their usefulness.

Systematic review: acute liver failure - one disease, more than 40 definitions.

BACKGROUND: Acute liver failure (ALF) is a clinical syndrome with very high mortality estimates ranging between 60% and 80%. AIM: To investigate the explicitness and extent of variability in the used ALF definitions in the ALF prognostic literature. METHODS: All studies that pertain to the prognosis of patients with ALF were electronically searched in MEDLINE (1950-2012) and EMBASE (1950-2012). Identified titles and abstracts were independently screened by three reviewers to determine eligibility for additional review. We included English articles that reported original data from clinical trials or observational studies on ALF patients. RESULTS: A total of 103 studies were included. Of these studies 87 used 41 different ALF definitions and the remaining 16 studies did not report any explicit ALF definition. Four components underlying ALF definitions accounted for the differences: presence and/or grading of hepatic encephalopathy (HE); the interval between onset of disease and occurrence of HE; presence of coagulopathy and pre-existing liver disease. CONCLUSIONS: The diversity in acute liver failure definitions hinders comparability and quantitative analysis among studies. There is room for improvement in the reporting of acute liver failure definitions in prognostic studies. The result of this review may be useful as a starting point to create a uniform acute liver failure definition.

Two distinct subtypes of hepatitis B virus-related acute liver failure are separable by quantitative serum immunoglobulin M anti-hepatitis B core antibody and hepatitis B virus DNA levels.

UNLABELLED: Hepatitis B virus (HBV)-related acute liver failure (HBV-ALF) may occur after acute HBV infection (AHBV-ALF) or during an exacerbation of chronic HBV infection (CHBV-ALF). Clinical differentiation of the two is often difficult if a previous history of HBV is not available. Quantitative measurements of immunoglobulin M (IgM) anti-hepatitis B core antibody (anti-HBc) titers and of HBV viral loads (VLs) might allow the separation of AHBV-ALF from CHBV-ALF. Of 1,602 patients with ALF, 60 met clinical criteria for AHBV-ALF and 27 for CHBV-ALF. Sera were available on 47 and 23 patients, respectively. A quantitative immunoassay was used to determine IgM anti-HBc levels, and real-time polymerase chain reaction (rtPCR) was used to determine HBV VLs. AHBV-ALFs had much higher IgM anti-HBc titers than CHBV-ALFs (signal-to-noise [S/N] ratio median: 88.5; range, 0-1,120 versus 1.3, 0-750; P < 0.001); a cut point for a S/N ratio of 5.0 correctly identified 44 of 46 (96%) AHBV-ALFs and 16 of 23 (70%) CHBV-ALFs; the area under the receiver operator characteristic curve was 0.86 (P < 0.001). AHBV-ALF median admission VL was 3.9 (0-8.1) log10 IU/mL versus 5.2 (2.0-8.7) log10 IU/mL for CHBV-ALF (P < 0.025). Twenty percent (12 of 60) of the AHBV-ALF group had no hepatitis B surface antigen (HBsAg) detectable on admission to study, wheras no CHBV-ALF patients experienced HBsAg clearance. Rates of transplant-free survival were 33% (20 of 60) for AHBV-ALF versus 11% (3 of 27) for CHBV-ALF (P = 0.030). CONCLUSIONS: AHBV-ALF and CHBV-ALF differ markedly in IgM anti-HBc titers, in HBV VLs, and in prognosis, suggesting that the two forms are, indeed, different entities that might each have a unique pathogenesis.

Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions.

In recent years, acute-on-chronic liver failure has been recognized as a specific clinical form of liver failure associated with cirrhosis. The syndrome refers to an acute deterioration of liver function and subsequently of other end organs over a period of weeks following a precipitating event in a patient with previously well- or reasonably well-compensated cirrhosis. These precipitating events include either an indirect (e.g., variceal hemorrhage, sepsis) or a direct (e.g., drug-induced) hepatotoxic factor. The short-term mortality for this condition is more than 50%. At present, considerable efforts are ongoing to better characterize the syndrome, to gain further insight into its pathophysiology and to optimize therapy. This article aims to highlight the current concepts of these various aspects.

Novel classification of acute liver failure through clustering using a self-organizing map: usefulness for prediction of the outcome.

BACKGROUND: Patients with acute liver failure are classified according to the interval between the onset of hepatitis symptoms and the development of hepatic encephalopathy. We examined the validity of such classifications. METHODS: The subjects were 1,022 patients enrolled in a nationwide survey in Japan. The intervals between the onset of the hepatitis symptoms and the development of encephalopathy were 10 days or less in 472 patients (group-A), between 11 and 56 days in 468 patients (group-B), and longer than 56 days in 82 patients (group-C). Data on a total of 104 items collected from the patients were subjected to clustering using a self-organizing map. RESULTS: The patients were classified into three clusters. The first cluster consisted of 411 patients (group-A: 57%, group-B: 39%, group-C: 4%). Their incidence of complications was low; 34% underwent liver transplantation (LT), and their survival rate was 90%, while 94% of those treated without transplant were rescued. The second cluster consisted of 320 patients (21, 65, and 14% groups A, B, and C, respectively), who showed a high incidence of complications; the survival rate was 7% in the patients treated conservatively without LT. Sixteen percent underwent LT and survival rate of these patients was 52%. There was a third cluster, of 291 patients (59, 34, and 7% groups A, B, and C, respectively). Without LT, 81% of the patients died. Seven percent were treated by LT and their survival rate was 60%. CONCLUSIONS: Clustering revealed that patients with acute liver failure could be classified into three clusters independent of the interval between the onset of disease symptoms and the development of encephalopathy. This technique may be useful, since the outcomes of the patients differed markedly among the clusters.