Prognosis In Fulminant Hepatic Failure Research Articles

The Prognosis of Fulminant Hepatic Failure in Pregnant Women due to Hepatitis E

Objectives: Jaundice in pregnancy carries with it a high mortality rate. In this study, we examined the characteristics of women on survival of women with hepatitis E due to the stress of labor in terms of multiorgan failure after delivery. Design: A retrospective study of hospital records was done on women of hepatitis E from December 2010 to August 2011 at Civil Hospital, Ahmedabad, India. The women were divided into two groups: expired and survived. Results: Fatality rate during the epidemic months (March/ during nonepidemic months (June to February). The overall mortality rate of fulminant hepatic failure was 94%. The mean duration of jaundice, levels of bilirubin, serum glutamic pyruvic transaminase (SGPT), and prothrombin time (PT) were ! altered creatinine and PT [International Normalized Ratio (INR) >1.5] had a high mortality rate of 88 and 76%, respectively. All those who were conscious at the time of delivery (no hepatic encephalopathy) survived while those who were unconscious expired after delivery. All those who were intubated died. Conclusion: Hepatitis E is endemic in India and is an important indirect cause of maternal mortality. Study of the expired group helps understand the critical levels of liver function tests. This can help in appropriate counselling of patients and their relatives regarding the prognosis. Although delivery does not have any effect on survival, blood loss, infection and raised intracranial tension can cause liver hypoxia and worsen the disease state.

The different etiology of fulminant hepatic failure (FHF) in Korea and prognostic factors in patients undergoing liver transplantation for FHF

The prognosis of fulminant hepatic failure (FHF) depends on the etiology and reversibility. In this study, we identified the etiological difference of FHF in Korea and analyzed the prognostic factors after liver transplantation (LT) for FHF. We retrospectively reviewed 42 patients with FHF who underwent LT from April 1999 to April 2011 at Samsung Medical Center, Seoul, Korea. The patients were categorized into two groups according to the short-term result of LT, and perioperative profiles were compared to identify the short-term poor prognostic factors. Unlike Western countries, there was no paracetamol-related FHF but herbal/folk medicines were the most frequent causes of FHF (26.2%). HAV-related FHF increased significantly and comprised the main portion of FHF with Herbal/folk medicines after 2005. Encephalopathy grade, onset time, pre-transplantation need of renal replacement, and ventilator treatment were significantly different between groups in univariate analysis. In multivariate analysis, pre-transplantation renal replacement treatment and hepatic encephalopathy grade IV were the independent prognostic factors after LT. The etiologies of FHF in Korea were different compared with Western reports. The requirement of renal replacement treatment and hepatic encephalopathy grade IV were identified as independent poor prognostic factors after LT for FHF in this study.

Analysis of the clinical features of and responsive factors on the prognosis in patients with fulminant hepatic failure

To judge the prognosis in the patients with fulminant hepatic failure and to provide the evidences of correct therapy. The clinical features and the indexes which may affect the prognosis of the patients with fulminant hepatic failure were analyzed. Indexes including prothrombin time (PT), the routine biochemical analysis of liver and kidney functions, the plasma levels of glucose and ammonia, cortisol, lipases, amylase, age, gender and complications were analyzed using the software Statistical Product and Service Solutions (SPSS)15.0. The differences between the died and living patients were compared. The mortality of the patients was 65% and the highest was 80% for those with HBV and HEV coinfection. The age and gender had no influence on mortality (P value was 0.423 and 0.728 respectively). HBV infection was the main factor which caused fulminant hepatic failure (52%), The next was hepatitis E virus infection (39%). Among the indexes analyzed, the plasma levels of total bilirubin, usea nitrogen, creatinine, glucose, cholesterol and prothrombin time had positive correlations with the prognosis of the patients (P value was 0.005, 0.001, 0.001, 0.005, 0.010 and 0.049 respectively). The incidence rate of hepatic coma, hepatorenal syndrome, and adrenal insufficiency were higher in the died group than that in the living group (P value was 0.005, 0.012 and 0.025 respectively). But prothrombin time was the only factor which had correlation with the prognosis (P=0.035) analyzed by multivariate logistic regression analysis. The scores of MELD were higher in the died group than that in living group (t=18.236, P<0.01) and especially in the patients with hepatic coma and hepatorenal syndrome. The scores of MELD also had positive correlation with the plasma level of TNFa (r=0.585, P<0.01). The HBV infection was the main cause of fulminant hepatic failure and HBV and HEV coinfection had the highest mortality. The plasma levels of total bilirubin, cholesterol, glucose , prothrombin time and some complications including hepatic coma, hepatorenal syndrome, and adrenal insufficiency maybe had positive correlations with the prognosis of fulminant hepatic failure. The scores of MELD may predict the prognosis of these patients.

A novel scoring system for prognostic prediction in d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure BALB/c mice

BackgroundIt is frequently important to identify the prognosis of fulminant hepatic failure (FHF) patients as this will influence patient management and candidacy for liver transplantation. Therefore, a novel scoring system based on metabonomics combining with multivariate logistic regression was developed to predict the prognosis of FHF mouse model.MethodsBALB/c mice were used to construct FHF model. Parts of plasma were collected at 4, 5, and 6-h time points after treatment, respectively, and detected using gas chromatography/time-of-flight mass spectrometry (GC/TOFMS). The acquired data were processed using partial least square discriminant analysis (PLS-DA). The metabolic markers identified were used to construct a scoring system by multivariate regression analysis.Results28 mice of survival group and 28 of dead group were randomly selected and analyzed. PLS regression analysis showed that both the PLS models of 5 h and 6 h after d-galactosamine/lipopolysaccharide treatment demonstrated good performances. Loadings plot suggested that phosphate, beta-hydroxybutyrate (HB), urea, glucose and lactate concentrations in plasma had the highest weightings on the clustering differences at the three time points. By the multivariate logistic regression analysis, the death/survival index (DSI) was constructed based on relative concentrations of HB, urea and phosphate. It provided general accurate rate of prediction of 93.3% in the independent samples.ConclusionsThe novel scoring system based on metabonomics combining with multivariate logistic regression is accurate in predicting the prognosis of FHF mouse model and may be referred in clinical practice as a more useful prognostic tool with other available information.

In Order to Improve the Prognosis of Fulminant Hepatic Failure(FHF), the Author has Established the Following 3 Therapeutic Strategies

In Order to Improve the Prognosis of Fulminant Hepatic Failure(FHF), the Author has Established the Following 3 Therapeutic Strategies

Dynamic metabonomic analysis of BALB/C mice with different outcomes after D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure

Fulminant hepatic failure (FHF) is one of the most challenging gastrointestinal emergencies encountered in clinical practice. Early identification of patients with FHF who need liver transplantation is very important. To construct a prediction model for the early diagnosis and prognosis of FHF, we studied the dynamics of metabolic intermediates and metabolic profiles with a D-galactosamine (GalN)/lipopolysaccharide (LPS)-treated BALB/c mouse model of FHF. Levels of plasma metabolites were quantified with gas chromatography/time-of-flight mass spectrometry, and data were processed with partial least squares discriminant analysis (PLS-DA). Distinct clustering differences were observed 5 and 6 hours after GalN/LPS treatment between mice that survived and those that died, but there were no differences between these groups 4 hours after treatment. Five hours after treatment, plasma levels of some metabolites differed significantly between the survival, dead, and control groups. Ketogenesis and the tricarboxylic acid cycle were inhibited in both the survival and dead groups, but in the dead group, the urea cycle was also inhibited, and glycolysis was elevated. PLS-DA indicated that principal component weighting was greatest for plasma levels of phosphate, beta-hydroxybutyrate, urea, glucose, and lactate. The Y-predicted scatter plot in the partial least squares (PLS) model assigned samples to the survival or dead groups with an a priori cutoff of 0.10 with 100% sensitivity and specificity. Similar results were observed in 11 FHF patients with different outcomes. In conclusion, the PLS model based on metabonomic analysis can be used to predict outcomes well, and plasma levels of phosphate, beta-hydroxybutyrate, urea, glucose, and lactate may constitute a set of markers for the early diagnosis and prognosis of FHF.

Cerebral diffusion tensor imaging and in vivo proton magnetic resonance spectroscopy in patients with fulminant hepatic failure

Cerebral edema is a major complication in patients with fulminant hepatic failure (FHF). The aim of this study was to evaluate the metabolite alterations and cerebral edema in patients with FHF using in vivo proton magnetic resonance spectroscopy (MRS) and diffusion tensor imaging, and to look for its reversibility in survivors. Ten FHF patients along with 10 controls were studied. Five of the 10 patients who recovered had a repeat imaging after three weeks. N-acetylaspartate, choline (Cho), glutamine (Gln), glutamine/glutamate (Glx), and myoinositol ratios were calculated with respect to creatine (Cr). Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in different brain regions. Patients exhibited significantly increased Gln/Cr and Glx/Cr, and reduced Cho/Cr ratios, compared to controls. In the follow-up study, all metabolite ratios were normalized except Glx/Cr. Significantly decreased Cho/Cr were observed in deceased patients compared to controls. In patients, significantly decreased MD and FA values were observed in most topographical locations of the brain compared to controls. MD and FA values showed insignificant increase in the follow-up study compared to their first study. We conclude that the Cho/Cr ratio appears to be an in vivo marker of prognosis in FHF. Decreased MD values suggest predominant cytotoxic edema may be present. Persistence of imaging and MRS abnormalities at three weeks' clinical recovery suggests that metabolic recovery may take longer than clinical recovery in FHF patients.

MELD Is Superior to King's College and Clichy's Criteria to Assess Prognosis in Fulminant Hepatic Failure

MELD Is Superior to King's College and Clichy's Criteria to Assess Prognosis in Fulminant Hepatic Failure

Early Indicators of Prognosis in Fulminant Hepatic Failure: An Assessment of the Model for End-Stage Liver Disease (MELD) and King's College Hospital Criteria

Early Indicators of Prognosis in Fulminant Hepatic Failure: An Assessment of the Model for End-Stage Liver Disease (MELD) and King's College Hospital Criteria

MELD is superior to King's college and Clichy's criteria to assess prognosis in fulminant hepatic failure

Assessment of prognosis in fulminant hepatic failure (FHF) is essential for the need and appropriate timing of orthotopic liver transplantation (OLT). In this study we investigated the prognostic efficacy of King's College criteria, Clichy's criteria, Model for End-Stage Liver Disease (MELD), and Pediatric End-Stage Liver Disease (PELD) in 120 consecutive patients with FHF. Survival with medical therapy (18%), death without OLT (15%), and receipt of a liver transplant were similar in adults (n = 64) and children (n = 56). MELD scores were significantly higher in patients who died compared to those who survived without OLT, both in adults (38 +/- 7 vs. 26 +/- 7, P = 0.0003) and children (39 +/- 7 vs. 23 +/- 6, P = 0.0004). Using logistic regression analysis in this cohort of patients, concordance statistics were significantly higher for MELD (0.95) and PELD (0.99) when compared to King's College (0.74) and Clichy's criteria (0.68). When data was analyzed in a Cox model including patients receiving transplants and censoring the time from admission, the concordance statistic for MELD (0.77) and PELD (0.79) remained significantly higher than that of King's College criteria but not higher than that of Clichy's criteria. In conclusion, this study is the first to show that MELD and PELD are superior to King's College and Clichy's criteria to assess prognosis in FHF. However, because data was generated from a single center and included a rather low number of patients who survived or died without OLT, further confirmation of our findings is required.

Early indicators of prognosis in fulminant hepatic failure: An assessment of the Model for End-Stage Liver Disease (MELD) and King's College Hospital Criteria

While King's Hospital Criteria (KCH) criteria are used worldwide, the Model for End-Stage Liver Disease (MELD) is a more recently developed scoring system that has been validated as an independent predictor of patient survival in conditions for liver transplantation (LT). The aim of the present study was to compare MELD and KCH criteria with other early clinical prognostic indicators (CPI) in a cohort of patients with fulminant hepatic failure (FHF). A total of 144 patients (mean age 31.7 +/- 14.7 yr; range 12-82 yr; 62 males) with FHF due to acute viral hepatitis were included into the study. Variables found significant on univariate analysis were entered into a multivariate logistic regression analysis. A total of 52 (36.1%) patients survived, the remaining 92 (63.9%) died. Univariate analysis showed that age, duration of jaundice, jaundice-encephalopathy interval (JEI), grade of encephalopathy, presence of cerebral edema, bilirubin, prothrombin time, creatinine, and MELD score were significantly different between survivors and nonsurvivors. Multivariate logistic regression identified 6 independent CPI of adverse outcome on admission: age >or=50 yr, JEI >7 days, grade 3 or 4 encephalopathy, presence of cerebral edema, prothrombin time >or=35 seconds, and creatinine >or=1.5 mg/dL. Presence of any 3 of 6 CPI was optimum in identifying survivors and nonsurvivors. A MELD score of >or=33 was found to be best discriminant between survivors and nonsurvivors by the construction of receiver operating characteristic (ROC) curves. Any 3 CPI were superior to MELD and KCH criteria in predicting the outcome (c-statistic [95% confidence interval]: CPI 0.802 [0.726-0.878], MELD 0.717 [0.636-0.789], and KCH criteria 0.676 (0.588-0.764); P values: CPI vs. MELD 0.045, CPI vs. KCH criteria 0.019, and MELD vs. KCH criteria 0.472). In conclusion, MELD and KCH criteria are not as useful as a combination of other early CPI in predicting adverse outcome in patients with FHF due to acute viral hepatitis.

Reply: To MELD or not to MELD: Early assessment of prognosis in fulminant hepatic failure

Reply: To MELD or not to MELD: Early assessment of prognosis in fulminant hepatic failure

Value of computed tomography‐derived estimated liver volume/standard liver volume ratio for predicting the prognosis of adult fulminant hepatic failure in Japan

The prognosis of fulminant hepatic failure (FHF) has been improved but is still unsatisfactory, and liver atrophy has been reported as a poor prognostic factor for this disease. The aim of this study was to assess the clinical value of the estimated liver volume (ELV) compared to the standard liver volume (SLV) in patients with FHF. Estimated liver volume of 24 adult patients with FHF receiving artificial liver support (ALS) was measured by using computed tomography. Actual liver weight (ALW) was measured if possible, and the calculated ELV/SLV ratio was compared to the ALW/SLV ratio and the ALW/BW (bodyweight) ratio. Sequential ELV/SLV ratios during the clinical course were analyzed in relation to the prognosis. The ELV/SLV ratio was significantly correlated with both the ALW/SLV and ALW/BW ratios. The mean ALW/SLV ratio of patients who underwent living donor liver transplantation (LDLT) was 0.59 +/- 0.17. The mean ELV/SLV ratio at the time of starting ALS (day 0) in the patients who survived (group 1) was 1.081 +/- 0.183, but that of cases who underwent LDLT or died without LDLT (group 2) was 0.764 +/- 0.255. The mean ELV/SLV ratios were 1.084 +/- 0.222 and 0.650 +/- 0.195 in groups 1 and 2, respectively, 5 days after starting ALS (day 5). Among the group 2 patients, those who had no liver atrophy on day 0 had a significantly decreased ELV/SLV ratio on day 5. These results suggest that the ELV/SLV ratio is a very useful objective marker to estimate liver atrophy and this marker reflects the prognosis of FHF patients very well.

Mannose-binding lectin and the prognosis of fulminant hepatic failure caused by HBV infection.

The mannose-binding lectin (MBL) gene was reported to play an important role in determining the clinical outcome of persistent hepatitis B virus (HBV) infection. We investigated serum MBL concentrations and MBL gene mutations to determine whether they were related to the prognosis of patients with fulminant hepatic failure (FHF) caused by HBV infection. We investigated serum MBL concentrations and MBL gene mutations in 43 HBV-infected Japanese patients with FHF and 260 HBsAg-negative healthy controls. Serum MBL concentrations were measured by an enzyme-linked immunosorbent assay, and mutations in the MBL gene were analysed by nested PCR and direct DNA sequencing. Only a mutation in codon 54 of the MBL gene was found. The frequency of this mutation in nonsurvivors (40%, 8/20) was higher than in survivors (13%, 3/23), and the difference was slightly significant (p = 0.043). The H allele frequency in survivors (70.5%, 31/44) was higher than in nonsurvivors (39.5%, 15/38) (p = 0.0048). Because of these factors the mean serum MBL concentration in survivors, 1.61 ,micro/ml (range 0.3-3.86), was significantly higher than in nonsurvivors, 0.79 microg/ml (range 0.04-1.51) (p < 0.0001). The likelihood ratio for nonsurvival was 0 for over 2.0 microg/ml, 0.67 for 1.0-2.0 microg/ml, and 2.24 for 0-1.0 microg/ml. The mutation in codon 54 of the MBL gene tended to be higher in nonsurvivors than in survivors. The H allele frequency (high producing allele in H/Y) in survivors was higher than that in nonsurvivors. High levels of serum MBL correlated with the survival of patients with FHF due to HBV infection. Serum MBL may be useful as a predictive factor for the survival of patients with FHF caused by HBV.

Indications and criteria for liver transplantation for fulminant hepatic failure.

Liver transplantation is the only effective treatment for potentially fatal cases of fulminant hepatic failure. However, it is very difficult to predict which cases will be fatal. The mortality may depend on alternative medical therapies. According to a nationwide survey of patients with fulminant hepatic failure presenting with encephalopathy of a coma grade greater than II within 8 weeks from the first symptoms of illness with a prothrombin time less than 40% of normal value, there were 93 patients in 311 hospitals between January and December 1998 in Japan. During this period, there were 11 patients with late-onset hepatic failure. The etiology was HAV infection in 4%, HBV infection in 44%, and nonA-nonB in 41%. Specific therapies were intensively used in all patients. The mean survival rate was 41%, with differences depending on the etiology. Six patients underwent liver transplantation, and 5 survived. In animal experiments, sinusoidal fibrin deposition caused massive liver necrosis. Activation of Kupffer cells and hepatic macrophages was a major contributing factor of this development. There were different mechanisms of such fibrin deposition. Tumor necrosis factor-alpha and superoxide anions released from hepatic macrophages after endotoxin administration destroyed endothelial cells, and then coagulopathy occurred in the sinusoids in rats given Propionibacteriom acnes, while a tissue factor from Kupffer cells played that role in rats undergoing partial hepatectomy. The prognosis of fulminant hepatic failure may depend on the etiology. The indication for liver transplantation for this disease must be carefully decided by analyzing the etiology, pathological conditions, and response to therapies in each case.

Value of color doppler ultrasonography for assessing fulminant hepatitis

Color Doppler US is a valuable diagnostic tool in evaluating or predicting prognosis of fulminant hepatic failure as it is simple and provides more accurate information about portal circulation than the other existing modalities.

Early indicators of prognosis in fulminant hepatic failure

The successful use of orthotopic liver transplantation in fulminant hepatic failure has created a need for early prognostic indicators to select the patients most likely to benefit at a time when liver transplantation is still feasible. Univariate and multivariate analysis was performed on 588 patients with acute liver failure managed medically during 1973–1985, to identify the factors most likely to indicate a poor prognosis. In acetaminophen-induced fulminant hepatic failure, survival correlated with arterial blood pH, peak prothrombin time, and serum creatinine—a pH < 7.30, prothrombin time >100 s, and creatinine >300 μmol/L indicating a poor prognosis. In patients with viral hepatitis and drug reactions three static variables [etiology (non A, non B hepatitis or drug reactions), age <11 and >40 yr, duration of jaundice before the onset of encephalopathy >7 days] and two dynamic variables (serum bilirubin >300 μmol/L and prothrombin time >50 s) indicated a poor prognosis. The value of these indicators in determining outcome was tested retrospectively in a further 175 patients admitted during 1986–1987, leading to the construction of models for the selection of patients for liver transplantation.

Intracranial pressure rises and its association with clinical signs and prognosis in fulminant hepatic failure

Intracranial pressure rises and its association with clinical signs and prognosis in fulminant hepatic failure

Assessment of prognosis in fulminant hepatic failure.

Assessment of prognosis in fulminant hepatic failure.

Mannitol treatment of cerebral edema in rats with galactosamine-induced severe hepatitis.

Severe hepatitis is induced with D-galactosamine hydrochloride in rats. Animals develop brain edema which was treated with mannitol. 1 h after the last mannitol infusion brain water content decreased, but it was not decreased 6 h after treatment. The therapy reduced lethality (p<0.025). The rigorous brain edema therapy impoved the prognosis of fulminant hepatic failure in the rat.