Outcome Of Acute Liver Failure Research Articles

Incidence and Clinical Outcome of Acute Liver Failure Caused by Dengue in a Hospital for Tropical Diseases, Thailand.

Acute liver failure is an atypical manifestation of dengue with a high mortality. We performed a retrospective cohort study at the Hospital for Tropical Diseases, Bangkok, Thailand. In total, 1,926 patients with serologically confirmed dengue were enrolled in the study from 2011 to 2015. Of these, six patients presented with acute liver failure, four died, and two survived. The incidence of dengue-associated acute liver failure was 0.31%. Dengue-associated acute liver failure was most common among young adults (median age, 29 years). The median duration from onset of fever to development of acute liver failure was 7.5 days. Patients with the severe stage of dengue had a higher risk of developing acute liver failure (P < 0.001). The baseline risk factors associated with the development of acute liver failure were an age of ≤ 40 years (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.1-2.0, P < 0.05), a > 10% ratio of atypical lymphocytes (OR = 2.3, 95% CI = 1.8-3.0, P < 0.001), and a platelet count of < 50,000 mm3 (OR = 2.8, 95% CI = 2.2-3.6, P < 0.001). The incidence of acute liver failure in patients with dengue was quite low, but its impact on morbidity, mortality, and poor clinical outcomes was significant. In summary, this study indicates that various baseline risk factors are associated with acute liver failure in patients with dengue.

Incidence, Management, and Outcomes of Acute Liver Failure Secondary to Thyroid Storm in the United States

Introduction: Thyroid storm (TS) accounts for approximately 1-2% of admissions for thyrotoxicosis. In these patients liver dysfunction can result from hepatic congestion, hypoperfusion, or direct effect from the hyperthyroidism. While the pathophysiology for this has been described in small case series, the epidemiology and outcomes of acute liver failure (ALF) is described only in small case series and large nationally representative data is lacking. Methods: We queried the National Inpatient Sample database for patients with the discharge diagnosis of thyroid storm from 2003 to 2011. Results: We identified a total of 42,765 patients with a discharge diagnosis of TS. The overall incidence of ALF was 1.3% with a rise in incidence from 0.3% in 2003 to 3.7% in 2011. This increase was independent of sex, race and a dichotomized age of 65 years. Patients with ALF were more likely to be younger (p=0.001), men (p < 0.001), alcoholic (p=0.002) and have pre-existing iron deficiency anemia, congestive heart failure, coagulopathy, chronic liver disease, electrolyte disturbances, psychoses and renal failure (p < 0.001 for all). 8.1% of patients with ALF developed hepatic encephalopathy and mortality was high at 34.5%. However, mortality has decreased from 46.9% in 2003 to 27.4% in 2011 (p=0.005). 8.1% of patients received liver transplantation during their hospital stay and mean duration of hospitalization was 17.4 ±18.7 days Conclusion: While incidence of ALF is increasing, mortality from this condition has reduced significantly from 2003 to 2011.Figure 1

Improvements in Acute Liver Failure Outcomes in the U.S.

To determine recent trends in causes, treatments, and outcomes of acute liver failure (ALF) in the U.S., researchers conducted an observational cohort

The changing face of liver transplantation for acute liver failure: Assessment of current status and implications for future practice.

The etiology and outcomes of acute liver failure (ALF) have changed since the definition of this disease entity in the 1970s. In particular, the role of emergency liver transplantation has evolved over time, with the development of prognostic scoring systems to facilitate listing of appropriate patients, and a better understanding of transplant benefit in patients with ALF. This review examines the changing etiology of ALF, transplant benefit, outcomes following transplantation, and future alternatives to emergency liver transplantation in this devastating condition.

THU-410 - Higher Ferritin Concentrations are Associated with Worse Outcome in Acute Liver Failure

THU-410 - Higher Ferritin Concentrations are Associated with Worse Outcome in Acute Liver Failure

Changing outcomes in acute liver failure: Can we transplant only the ones who really need it?

Samuel, Didier*,1,2,3,4; Saliba, Faouzi1,2,3,4; Ichai, Philippe1,2,3,4 Author Information

The concept of "the inflamed brain" in acute liver failure: mechanisms and new therapeutic opportunities.

The presence and severity of a systemic inflammatory response is a major predictor of brain edema and encephalopathy in acute liver failure (ALF) and polymorphisms of the gene coding for the proinflammatory cytokine TNF-alpha are known to influence the clinical outcome in ALF. Recent reports provide robust evidence for a role of neuroinflammation(inflammation of the brain per se) in ALF with the cardinal features of neuroinflammation including activation of microglial cells and increased production in situ of pro-inflammatory cytokines such as TNF-alpha and interleukins IL-1beta and IL-6. Multiple liver-brain signalling pathways have been proposed to explain the phenomenon of neuroinflammation in liver failure and these include direct effects of systemically-derived cytokines, recruitment of monocytes relating to microglial activation as well as effects of liver failure-derived toxins and altered permeability of the blood-brain barrier. Synergistic mechanisms involving ammonia and cytokines have been proposed. Currently-available strategies aimed at lowering of blood ammonia such as lactulose, probiotics and rifaximin have the potential to dampen systemic inflammation as does the anti-oxidant N-acetyl cysteine, mild hypothermia and albumin dialysis. Experimental studies demonstrate that deletion of genes coding for TNF-alpha or IL-1 leads to attenuation of the CNS consequences of ALF and administration of the TNF-alpha receptor antagonist etanercept has comparable beneficial effects in experimental ALF. Together, these findings confirm a major role for central neuroinflammatory mechanisms in general and mechanisms involving TNF-alpha in particular in the pathogenesis of the cerebral consequences of ALF and open the door to novel therapeutic interventions in this often fatal disorder.

Hepatobiliary Quiz (Answers)—15 (2015)

Hepatobiliary Quiz (Answers)—15 (2015)

Prevalence of genetic variants of keratins 8 and 18 in patients with drug-induced liver injury.

BackgroundKeratin 8 and 18 (K8/K18) cytoskeletal proteins protect hepatocytes from undergoing apoptosis and their mutations predispose to adverse outcomes in acute liver failure (ALF). All known K8/K18 variants occur at relatively non-conserved residues and do not cause keratin cytoskeleton reorganization, whereas epidermal keratin-conserved residue mutations disrupt the keratin cytoskeleton and cause severe skin disease. The aim of our study was to identify keratin variants in idiosyncratic drug-induced liver injury (DILI).MethodsGenomic DNA was isolated from 800 patients enrolled in an ongoing US multicenter study, with DILI attributed to a wide range of drugs. Specific K8/K18 exonic regions were PCR-amplified and screened by denaturing HPLC followed by DNA sequencing. The functional impact of keratin variants was assessed using cell transfection and immune staining.ResultsHeterozygous and compound amino acid-altering K8/K18 variants were identified in 86 DILI patients and non-coding variants in 15 subjects. Five novel amino acid-altering (K8 Lys393Arg, K8 Ala351Val, K8 Ala358Val, K8 Ile346Val, K18 Asp89His) and two non-coding variants were observed. Several variants segregated with specific ethnic backgrounds but were found at similar frequencies in DILI subjects and ethnically matched population controls. Notably, variants in highly conserved residues of K8 Lys393Arg (ezetimibe/simvastatin-related) and K18 Asp89His (isoniazid-related) were found in patients with fatal DILI. These novel variants also led to keratin network disruption in transfected cells.ConclusionsNovel K8/K18 cytoskeleton-disrupting variants were identified in two patients and segregated with fatal DILI. Other non-cytoskeleton-disrupting keratin variants did not preferentially associate with DILI.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0418-0) contains supplementary material, which is available to authorized users.

Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

IntroductionChanges in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF.Methods84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined.ResultsMore than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression.ConclusionsIn patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.

Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called “second pathway of liver regeneration.” The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

Validation of Early Dynamic Model (EDM) in Predicting the Outcome of Acute Liver Failure (ALF): A Prospective Study

Validation of Early Dynamic Model (EDM) in Predicting the Outcome of Acute Liver Failure (ALF): A Prospective Study

Severe and fulminant hepatitis of indeterminate etiology in a Japanese center.

The outcome of acute liver failure (ALF) is influenced by its etiology, making etiological consideration of ALF important. However, specific etiology could not be identified in 30-40% of adult patients in a Japanese nationwide survey. We examined our patients with severe (SH) and fulminant hepatitis (FH) of indeterminate etiology for the better understanding of ALF. We investigated 106 adult patients with SH or FH including 24 of indeterminate etiology between 2000 and 2013, retrospectively. Of 24 patients, 12 were men. Seventeen were SH and seven FH (three FH acute type and four FH subacute type). Eighty-three percent of patients were positive for antinuclear antibody. Seventeen recovered without liver transplantation (LT), two received LT and five died without LT. Histology of 15 patients showed a pattern of acute hepatitis (massive necrosis in four, submassive necrosis in one, severe acute hepatitis in two and acute hepatitis in eight). The involvement of immune-mediated liver injury was histologically suggested in some patients. There was no large cluster of etiology in our patients with indeterminate cause. The causes of ALF of indeterminate etiology were the mixture of various minor or rare ones, if precise diagnosis of acute AIH was done. Outcome of our patients with indeterminate cause was not poor if they were treated as early as possible after the diagnosis of severe disease. Careful examination of unknown viral infection, drugs, toxins, undefined metabolic disorders and histology may help detect some of these etiologies.

Higher thyroid hormone levels are associated with better outcome in acute liver failure

Background: Changes in thyroid stimulating hormone (TSH) and thyroid hormone levels, mostly in the form of non-thyroidal illness syndrome (NTIS), have been described in many disease entities including myocardial infarction and sepsis. However, the relationship of acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The purpose of our present study was to evaluate potential correlations of select thyroid functional parameters with ALF. Methods: 84 consecutively recruited ALF patients were divided in groups according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), total thyroxine (TT4), and total triiodothyronine (TT3). NTIS was defined as low or normal TSH, low fT3 or low fT4 without known pre-existing thyroid illness. Results: More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had a greater risk for an adverse outcome than euthyroid patients. Patients in the SR group had significantly higher TSH, TT4, and TT3 (but not fT4) concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR.

Liver transplantation in acute-on-chronic liver failure: lessons learnt from acute liver failure setting.

Acute-on-chronic liver failure is a clinical entity with high risk of mortality. These patients can have severe liver dysfunction complicated with multiple organ failure. Liver transplantation is the definitive treatment for these patients. Literature regarding management of acute liver failure with special emphasis on liver transplantation was reviewed. Lessons learnt from the management of patients with acute liver failure which could be extrapolated to the management of patients with acute-on-chronic liver failure are discussed. Significant improvement in outcomes of acute liver failure has been reported across the world. Several aspects in transplantation for acute liver failure were found to be relevant to the management of acute-on-chronic liver failure. These include defining criteria to identify patients needing early liver transplantation, prioritizing patients with acute liver failure on the waiting list, defining when to abandon transplantation in acute liver failure, emphasis on graft quality and the need for a multi-disciplinary approach to manage multiple organ dysfunction. Useful lessons can be learnt from the progress made in the management of acute liver failure and these can be extrapolated to the management of patients with acute-on-chronic liver failure.

Acute liver failure in pregnancy: Challenges and management.

Acute liver failure (ALF) in pregnancy negatively affects both maternal and foetal outcome. The spectrum of liver disease in pregnancy may range from mild asymptomatic transaminitis to fatal and irreversible deterioration in liver functions leading to significant morbidity and even mortality. In this comprehensive review, we searched articles published as review articles, clinical trials, and case series in the Medline from 1970 to 2012. The overall outcome of ALF in pregnancy depends on the aetiology, timely diagnosis, prompt management, and early referral to a centre equipped in managing medical or obstetric complication. The foetal outcome is affected by the stage of pregnancy in which the mother has a deterioration of the liver function, with a worst prognosis associated with first or second-trimester liver failure. When ALF complicates pregnancy, liver transplantation is the one of the viable options. Management protocols need to be individualised for each case keeping in mind the risk versus benefit to both the mother and the foetus.

Frontal electroencephalogram variables are associated with the outcome and stage of hepatic encephalopathy in acute liver failure.

Acute liver failure (ALF) and hepatic encephalopathy (HE) can lead to an elevated intracranial pressure (ICP) and death within days. The impaired liver function increases the risks of invasive ICP monitoring, whereas noninvasive methods remain inadequate. The purpose of our study was to explore reliable noninvasive methods of neuromonitoring for patients with ALF in the intensive care unit (ICU) setting; more specifically, we wanted to track changes in HE and predict the outcomes of ALF patients treated with albumin dialysis. The study included 20 patients with severe ALF at admission who had been referred to the ICU of the liver transplantation (LT) center for albumin dialysis treatment and evaluation for transplantation. Data were collected from all study patients in the form of continuous frontal electroencephalography (EEG) recordings and transcranial Doppler (TCD) measurements of cerebral blood flow. Among the studied EEG variables, the 50% spectral edge frequency decreased and the delta power increased as the HE stage increased. Both variables were predictive of the stage of HE [prediction probability (PK) of 50% spectral edge frequency = 0.23, standard error (SE) = 0.03; PK of delta power = 0.76, SE = 0.03]. The total wavelet subband entropy, a novel variable that we used for tracking abnormal EEG activity, predicted the outcome of ALF patients treated with albumin dialysis (PK = 0.88, SE = 0.09). With a threshold value of 1.6, the TCD pulsatility index had an odds ratio of 1.1 (95% confidence interval = 0.1-9.3) for a poor outcome (LT or death). In conclusion, EEG variables are useful for the monitoring of HE and can be used to predict outcomes of ALF. TCD measurements do not predict patient outcomes.

MicroRNAs play a role in spontaneous recovery from acute liver failure.

Acute liver failure (ALF) represents a life-threatening situation characterized by sudden and massive liver cell death in the absence of preexisting liver disease. Although most patients require liver transplantation to prevent mortality, some recover spontaneously and show complete liver regeneration. Because of the rarity of this disease, the molecular mechanisms regulating liver regeneration in ALF patients remain largely unknown. In this study, we investigated the role of microRNAs (miRs) that have been implicated in liver injury and regeneration in sera from ALF patients (n = 63). Patients with spontaneous recovery from ALF showed significantly higher serum levels of miR-122, miR-21, and miR-221, compared to nonrecovered patients. In liver biopsies, miR-21 and miR-221 displayed a reciprocal expression pattern and were found at lower levels in the spontaneous survivors, whereas miR-122 was elevated in both serum and liver tissue of those patients. As compared to nonrecovered patients, liver tissue of spontaneous survivors revealed not only increased hepatocyte proliferation, but also a strong down-regulation of miRNA target genes that impair liver regeneration, including heme oxygenase-1, programmed cell death 4, and the cyclin-dependent kinase inhibitors p21, p27, and p57. Our data suggest that miR-122, miR-21, and miR-221 are involved in liver regeneration and might contribute to spontaneous recovery from ALF. Prospective studies will show whether serological detection of those miRNAs might be of prognostic value to predict ALF outcome.

Low levels of blood lipids are associated with etiology and lethal outcome in acute liver failure.

Background/AimsEmerging data links different aspects of lipid metabolism to liver regeneration. In patients with acute liver failure (ALF), low levels of lipids may correlate with disease severity. Thus, we determined whether there is an etiology-specific link between lipid levels in patients suffering from ALF and aimed to investigate an effect of lipid levels on the prognosis of ALF.MethodsIn this retrospective single center study, we reviewed 89 consecutive ALF patients, who met the criteria of the “Acute Liver Failure Study Group”. Patient characteristics, clinical data and laboratory parameters were individually analyzed at admission and correlated with the patients' outcome after a four week follow up. Possible endpoints were either discharge, or death or liver transplantation.ResultsHigh-density lipoprotein (HDL), cholesterol and triglyceride levels were significantly lower in patients who died or required a liver transplant. HDL levels were significantly higher in patients with ALF caused by acetaminophen intoxication, compared to fulminant HBV infection or drug induced liver injury. HDL levels correlated with hepatic injury by ALT levels, and Albumin, and inversely correlated with the MELD score, INR, and bilirubin.ConclusionIn our cohort of patients with ALF, we could show that HDL and cholesterol are suppressed. In addition novel etiology specific patterns between acteminophen and non-acteminophen induced liver failure were detected for serum lipid components. Further studies are needed to address the role of cholesterol and lipid metabolism and the according pathways in different etiologies of ALF.

Correction: Causes and Outcomes of Acute Liver Failure in China

Correction: Causes and Outcomes of Acute Liver Failure in China