Coma Grade Research Articles

Autoimmune hepatitis presenting as acute liver failure: A 20-year retrospective review of North America.

Autoimmune hepatitis is a common cause of acute liver failure. Treatment includes steroids for acute liver injury and liver transplantation in those who fail to respond or develop acute liver failure. The aim of this study is to further characterize acute liver failure secondary to autoimmune hepatitis and identify variables that predict 21-day transplant-free survival. This study included adults hospitalized with acute liver failure enrolled in the Acute Liver Failure Study Group Registry between 1998 and 2019 from 32 centers within the US. The etiology of all cases was reviewed by the Adjudication Committee, and all cases identified as autoimmune hepatitis were included. Acute liver injury was defined as an INR ≥2.0 without encephalopathy and acute liver failure as INR ≥ 1.5 with encephalopathy. Laboratory and clinical data were reviewed. Variables significantly associated with 21-day transplant-free survival were used to develop a multivariable logistic regression model. A total of 193 cases of acute liver failure secondary to autoimmune hepatitis were identified and reviewed. There were 161 patients (83.4%) diagnosed with acute liver failure on enrollment, and 32 (16.6%) developed acute liver failure during hospitalization. At 21 days, 115 (59.6%) underwent liver transplantation, 28 (14.5%) had transplant-free survival, and 46 (23.8%) died before liver transplantation. Higher admission values of bilirubin, INR, and coma grade were associated with worse outcomes. A prognostic index incorporating bilirubin, INR, coma grade, and platelet count had a concordance statistic of 0.84. Acute liver failure secondary to autoimmune hepatitis is associated with a high short-term mortality. We developed a model specifically for autoimmune hepatitis that may be helpful in predicting 21-day transplant-free survival and early identification of patients in need of expedited liver transplant evaluation.

Genesis of Antibiotic Resistance (AR) LXXVIII: Turbulence Modeling of Hemodynamics in Simplified Severe Sepsis Protocol‐2 (SSSP‐2)‐NCT01663701(ERP‐EGDT): Correlation of time (& fluid bolus) dependent pressure drop in boundary layer separation with adverse pressure gradient (APG) in tandem with exacerbated in‐hospital mortality(ihm)

The objective is to identify the underlying hemodynamic alteration in usual care group registered with 5 patients @ 100% ihm; vs the sepsis protocol cohort registered with 11 patients @ 90.05% ihmwith a median hospital stay of 5 days; GCS 3‐8(SAPS3≥56, (Ref: Fig 3) NCT01663701(PMID: 28973227). Cause for Concern: The pivotal clinical indices such as, i. antibiogram, ii.drug resistance index(DRI), iii.resistance map(RM), iv.antibiotic resistance footprint (ARF), v.AR stewardship data, and vi. Global Antimicrobial Resistance and Use Surveillance System (GLASS) data, for the entire patients’ cohorts before and after admitting to ED as a part of baseline characteristics, not presented. Rationale: Based on the aforesaid factor, it is inferred that patients in any given ERP‐EGDT, are: i. pre‐disposed to unknown level of infectious diseases burden with AR clinical persister(s)(ARClPrs); ii. activation of leucocytes, platelets, and erythrocytes forming LPE aggregates; iii. unknown extent of laceration in the precapillary arterioles, and post‐capillary venules, and iv. deposition of LPE aggregates on the pre‐capillary/post‐capillary vessels, w/o intravascular (loss of glycocalyx), in the cerebral/coronary/pulmonary/hepatic pre‐capillary arterioles, Fig 3.1 to 3.3; Fig 3.4, Derived rheological factors based on the data from Table 2: elements of sepsis resuscitation p1238; Fig 3: Risk of In‐hospital Mortality, p1239; predicted to be PI <1.05%, SpO2≦95%, PaO2 of 55 mmHg, SaO2<90%, SvO2<90%, StO2 below normal, DO2I below normal range, FiO2 <0.21(21%), PaCO2< 38 – 42 mmHg and PaO2/FiO2 <200mmHg. Derivation inclusive of CC, MCC (major complication or comorbidity), DDx:Pulmonary Edema, hypoxemia, tachypnea, and respiratory failure. GCS 3‐8: Coma Grade IV‐ unconscious, deep sleep, vestibular ocular reflex(VOR) negative, craniocaudally loss of brainstem reflexes, no reaction to pain, flabby tone, pupil dilated & fixed). Geometry: Blood flow network and mother‐daughters branching several generation of arterioles (or venules) with specific mean blood flow velocity (Vn), arbitrary generation (g) where rn = vessel radius of generation(n), r1 and v1 = radius, Fig 3.4 (p90 ISBN13‐978‐0128024089). Hypothesis & Governing Equation: eq: 3.2; eq 3.3; eq 3.4; Poiseuille eq (to determine and analyze the cause & effect relationship of flow pressure drop in a long cylindrical pipe/pre‐capillary vessels): DP=8mLQ /p R4 where DP = pressure difference between the two ends, m = dynamic viscosity, L=length of pipe, Q = volumetric flow rate, p = the dynamic viscosity, R = pipe radius (http://hyperphysics.phy‐astr.gsu.edu/hbase/ppois.html). Prospect: Simulation efforts are in progress to determine the sequence of fluid flow within the time scale of <0hrÛEDÜ120hrs>, pseudo‐plastic fluidÜdilatantÜBingham plasticÜ Hershel‐BuckleyÜ ThixotropicÜ Rheopectic)and its role in physiological (capillary) shunt augmented ihm.

Effects of Oxidative Stress in Acute Poisoning in Central India

Background: Tissue inflammation, low food intake of micronutrients due to sleepiness, free radical burst from activated macrophages, and excessive medication cause oxidative stress in acute poisoning. If not neutralised by antioxidants, these free radicals may contribute to tissue inflammation. The word oxidative stress refers to a scenario in which free radical generation and antioxidant defence are out of balance. In humans, oxidative stress is caused by a reduction in bodily antioxidants when free radical generation exceeds endogenous antioxidant levels, resulting in significant cell damage/death.
 Free radicals may destroy all major macromolecules, including lipids, proteins, and nucleic acids, but lipids are the most vulnerable.
 Aim: To evaluate antioxidant status in acute amitriptyline poisoning (AP) cases undergoing routine standard treatment (RST) after supplementation with Vitamin C and alpha lipoic acid either alone or in combination, and compare it with that of normal healthy volunteers.
 Material and Method: A total of 150 people were enrolled in the study, and they were split into five groups. They came from the IMCU and the Toxicology Ward. The consent of the patients' attendants was sought. The patients were chosen at random. To classify the level or grade of coma in poisoned individuals, the Edinburgh scale was utilized. At the time of admission and discharge, the levels of plasma cholinesterase, SOD, catalase, Glut-peroxidase, Glutathione transferase, MDA, Total-Antioxidant, LDH, and CK were measured.
 Results: This study offers quantifiable recommendations for vitamin C and alpha lipoic acid intake to aid in rapid recovery and glutathione antioxidant status. On supplementation with vitamin C and alpha lipoic acid, we detected a significant decrease in catalase activity in all groups of acute Amitriptyline poisoning cases. For Gr. V (acute Amitriptyline poisoning cases), we found reduced glutathione activity on admission and higher values on discharge. In light of the preceding discussion, it is worth noting that the higher LDH and CPK in groups that may be attributable to pulmonary infarction rather than cardiac or skeletal muscle involvement could be due to pulmonary infarction.
 Conclusion: Supplementation with vitamin C and alpha lipoic acid improved antioxidant levels during therapy. We propose that the antioxidant level of acute amitriptyline poisoning cases be examined for more successful recovery, and that diets poor in antioxidants may cause recovery to be sluggish. Oral supplementation, in our opinion, will be more successful for chronic Amitriptyline poisoning patients for a longer period of time, while IV form of vitamin C and alpha lipoic acid will be more effective for acute Amitriptyline poisoning instances.
 Keywords: Amitriptyline, MDA, Total-Antioxidant, LDH, CK, SOD, AP, RST.

Evaluation of Acute Cannabis Intoxication in Pre- School Children Admitted to Poison Control Center –Ain Shams University Hospitals

Background: In Egypt, cannabis is on the top list of the substances abused according to statistics of Fund for Drug Control and Treatment of Addiction. Its widespread use translates to greater access for children. Cannabis intoxication in young children can cause encephalopathy and coma. Aim: to evaluate the prevalence of acute cannabis intoxication in pre-school children (less than 6yrs) in Egypt; analysis of different factors related to the problem, clinical picture, management, assessment of severity and outcome of the problem by poison severity score (PSS). Method: prospective observational cross sectional study carried on all pre-school children (less than 6yrs) of both sex who admitted to PCC-ASUH, during the period from first of March 2019 to the end of December 2019, with history of acute cannabis intoxication and confirmed by cannabis positive screen. Results: The prevalence of acute cannabis intoxicated pre-school children (less than 6yrs) was 89.9%.The mean age was (17.38 month ±8.75). Fifty four percentages were males. As regard PSS, the majority of patients (55.1%) were of group II, while (31.4%) were of group I & (13.5%) were of group III. Regarding clinical manifestations; tachycardia observed in (5.8%), hypertension in (13.5%), tachypnea (18%), drowsiness (31.4%), muscle rigidity (21.5%), extra-pyramidal manifestations presented in (21.5%), coma grade I in (67.7%), coma grade II in (0.9%), respiratory distress in (1.8%), vomiting in (17.9%), mydriasis in (13%), miosis in (18.8%), flushed skin (12.1%) and respiratory acidosis (26.5%) of patients .ICU admission occurred in (68,7%) of patients and the majority were admitted ≥24 hours (65.9%). Conclusions: The prevalence of acute cannabis toxicity in pre-school children (less than 6yrs) has dramatically increased. Severity of acute cannabis intoxication in pre-school children(less than 6yrs) can be evaluated simply by using PSS. Recommendation: Public education is very necessary to decrease the problem. Early arterial blood gas analysis with careful neurological examination could help in identifying patients at risk.

Four Biomarkers Linked to Activation of Cluster of Differentiation 8-Positive Lymphocytes Predict Clinical Outcomes in Pediatric Acute Liver Failure.

Immune dysregulation contributes to the pathogenesis of pediatric acute liver failure (PALF). Our aim was to identify immune activation markers (IAMs) in PALF that are associated with a distinct clinical phenotype and outcome. Among 47 PALF study participants, 12 IAMs collected ≤6days after enrollment were measured by flow cytometry and IMMULITE assay on blood natural killer and cluster of differentiation 8-positive (CD8+ ) lymphocytes and subjected to unsupervised hierarchical analyses. A derivation cohort using 4 of 12 IAMs which were available in all participants (percent perforin-positive and percent granzyme-positive CD8 cells, absolute number of CD8 cells, soluble interleukin-2 receptor level) were sufficient to define high (n=10), medium (n=15), and low IAM (n=22) cohorts. High IAM was more frequent among those with indeterminate etiology than those with defined diagnoses (80% versus 20%, P<0.001). High IAM was associated with higher peak serum total bilirubin levels than low IAM (median peak 21.7 versus 4.8mg/dL, P<0.001) and peak coma grades. The 21-day outcomes differed between groups, with liver transplantation more frequent in high IAM participants (62.5%) than those with medium (28.2%) or low IAM (4.8%) (P=0.002); no deaths were reported. In an independent validation cohort (n=71) enrolled in a prior study, segregation of IAM groups by etiology, initial biochemistries, and short-term outcomes was similar, although not statistically significant. High serum aminotransferases, total bilirubin levels, and leukopenia at study entry predicted a high immune activation profile. Four circulating T-lymphocyte activation markers identify a subgroup of PALF participants with evidence of immune activation associated with a distinct clinical phenotype and liver transplantation; these biomarkers may identify PALF participants eligible for future clinical trials of early targeted immunosuppression.

Outcome of patients with acute liver failure awaiting liver transplantation in Japan.

To clarify the outcome and predictive factors in patients with acute liver failure (ALF) awaiting deceased donor liver transplantation (DDLT) in Japan. Of the DDLT candidates in Japan between 2007 and 2016, 264 adult patients with ALF were retrospectively enrolled in this study. Factors associated with DDLT and waiting-list mortality were assessed using the Cox proportional hazard model. The DDLT and transplant-free survival probabilities were evaluated using Kaplan-Meier analysis and the log-rank test. The waiting-list registration year after the Transplant Law revision in 2010 was a significant factor associated with DDLT. The adjusted hazard ratio indicated that DDLT probability after 2010 was four times higher than that before, and the 28-day cumulative DDLT probability was more than 35%. The median survival time of the entire cohort was 40days. Multivariate analysis identified the following three factors associated with waiting-list mortality: age, coma grade, and international normalized ratio. The transplant-free survival probabilities were significantly stratified by the number of risks, and patients with all three risks showed extremely poor short-term prognosis (median survival time = 23days). The DDLT probability of ALF patients increased after the law revision in 2010; however, patients at high risk of short-term waiting-list mortality might need emergent living donor transplantation.

Clinical profile and outcome of patients with indeterminate acute liver failure

Background: Acute liver failure (ALF) is a rare medical emergency and devastating clinical syndrome associated with high mortality. Indeterminate ALF still forms a significant number of cases in India as well in the world. We aimed to determine the clinical profile and outcome of patients with indeterminate ALF.Methods: A total of 30 patients with a diagnosis of Indeterminate ALF were included in the study. The variables evaluated were demographic, signs and symptoms, biochemical parameters, severity of liver injury, outcome, complications and duration of hospital stay.Results: Overall mortality was 18 (60%). Majority of the patients were females (56.7%). Majority of patients (60%) had grade III and IV encephalopathy at the time of admission. The mean age in Survived group was 30.6±11.6 years and in Died group was 42.6±10.2 years (p=0.005). INR, bilirubin AST, ALT and creatinine were significantly higher in Died group than Survived group. Mean grade of coma was significantly higher in Died group than Survived group (p=0.010). MELD Score was significantly higher in Died group 35.8±6.7 than Survived group 27.5±5.8 (P = 0.001). Sepsis and renal failure occurred more frequently in Died group. Duration of hospital stay was also significantly more in Died group versus Survived group (p=0.003).Conclusions: Indeterminate ALF disproportionately affected young females. Mortality was as high as 60%. The marked difference in spontaneous survival can be explained by the severity of hepatic dysfunction on admission and more frequent complications.

N-acetylcysteine treatment in viral-induced acute liver failure

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; Acute liver failure (ALF) is characterized by acute derangement of liver function and carries high mortality. Viral hepatitis is still one of the main causes of ALF in the India as well in world. A prospective case control study was carried with the aim to determine the effect of N-acetylcysteine (NAC) on survival of viral-ALF patients.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; 37 patients with a diagnosis of viral-ALF were included in the study. 18 patients received NAC infusion for 72 hrs whereas 19 patients in control group received placebo. The variables evaluated were demographic, biochemical, outcome and length of hospital stay.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; Out of 37 viral-ALF patients, acute HEV-induced ALF (48.6%) was most common followed by HBV (24.3%) and HAV (21.6%). The two groups were comparable for the various baseline characteristics (age, INR, bilirubin, ALT, creatinine, albumin, grade of encephalopathy, mean grade of coma etc.). Use of NAC was associated with a shorter length of hospital stay of survived patients (p=0.024). A total of 20 of 37 (54.1%) patients died with ALF complications; 7 (38.9%) patients belonged to NAC group and 13 (68.4%) patients to control group (p=0.079). HEV induced ALF showed significant improved in survival than Non HEV induced ALF with NAC administration (p=0.022).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;HEV was the most frequently cause of viral-ALF. Overall survival was not improved by NAC. HEV induced ALF showed significant improved in survival than Non HEV induced ALF with NAC administration. NAC reduced duration of hospital stay.&lt;/p&gt;

Predicting daily outcomes in acetaminophen-induced acute liver failure patients with machine learning techniques

Background/objectiveAssessing prognosis for acetaminophen-induced acute liver failure (APAP-ALF) patients during the first week of hospitalization often presents significant challenges. Current models such as the King's College Criteria (KCC) and the Acute Liver Failure Study Group (ALFSG) Prognostic Index are developed to predict outcome using only a single time point on hospital admission. Models using longitudinal data are not currently available for APAP-ALF patients. We aim to develop and compare performance of prediction models for outcomes during the first week of hospitalization for APAP-ALF patients. MethodsModels are developed for the ALFSG registry data to predict longitudinal outcomes for 1042 APAP-ALF patients enrolled 01/1998–02/2016. The primary outcome is defined as daily low versus high coma grade. Accuracy in prediction of outcome (AC), sensitivity (SN), specificity (SP) and area under the receiver operating curve (AUC) are compared between the following models: classification and regression tree, random forest, frequentist generalized linear mixed model (GLMM), Bayesian GLMM, BiMM tree, and BiMM forest using original and imputed datasets. ResultsBiMM tree offers predictive (test set) 63% AC, 72% SP and 53% SN for the original dataset, whereas BiMM forest offers predictive (test set) 69% AC, 63% SP and 74% SN for the imputed dataset. BiMM tree has the highest AUC for the original testing dataset (0.697), whereas BiMM forest and standard random forest have the highest AUC for the imputed testing dataset (0.749). The three most important predictors of daily outcome for the BiMM tree are pressor use, bilirubin and creatinine. The BiMM forest model identifies lactate, ammonia and ALT as the three most important predictors of outcome. ConclusionsBiMM tree offers a prognostic tool for APAP-ALF patients, which has good accuracy and simple interpretation of predictors which are consistent with clinical observations. BiMM tree and forest models are developed using the first week of in-patient data and are appropriate for predicting outcome over time. While the BiMM forest has slightly higher predictive AC, the BiMM tree model is simpler to use at the bedside.

Clinical features, laboratory characteristics and outcome of patients with drug-induced acute liver failure

Background: Acute liver failure (ALF) is a rare medical emergency. Its rapid progression and high mortality demand early diagnosis and expert management. Drug-induced ALF (DI-ALF) remains the uncommon cause of ALF in India. Clinical and etiological profile varies with geographical area and time. A prospective study of DI-ALF was carried with the aim to determine the clinical features, laboratory characteristics, outcome and hospital course.Methods: A total of 15 patients with a diagnosis of DI-ALF were included in the study. The variables evaluated were demographic, signs and symptoms, biochemical parameters [bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), internal normalization ratio (INR) etc.], outcome and course during hospitalization.Results: Out of 15 DI-ALF patients, 12 had Anti-tuberculosis therapy (ATT) induced ALF and 3 patients had ayurvedic induced ALF. Majority of the patients were females (73.3%) and middle-aged (42.60±14.30 years). Coma grade at the time of admission showed that majority of patients (66.8%) had grade I and II encephalopathy. Depending on the pattern of liver injury, hepatocellular pattern was most common (53.3%) followed by mixed and cholestatic pattern. 40% of patients died with DI-ALF complications of which ATT induced ALF contributed 41.7%. Mean AST was more increased as compared to ALT. Development of ascites (P = 0.030) and mannitol use (P = 0.025) was significantly more common in non survived group than survived group. Length of hospital stay was significantly more in non survived group than survived group (P = 0.009).Conclusions: ATT was the class of drugs most frequently associated with DI-ALF. DI-ALF disproportionately affected middle-aged women. Most DILI ALF patients had hepatocellular injury pattern. 40% of patients died with DI-ALF complications. Development of ascites, mannitol use and length of hospital stay was significantly more in non survived group than survived group.

Therapeutic Strategies and Current Management for Hepatic Encephalopathy in Liver Cirrhosis

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome showing a wide spectrum and one of the serious complications seen in patients with acute and chronic liver disease or spontaneous portal-systemic shunting. Recently, HE has been classified into two categories: covert HE, which involves minimal HE and is identified solely through psychometric or neurological tests, and overt HE (coma grade II-IV). Although recent therapies based on evidence-based results have improved the therapeutic outcomes of HE patients, repeat recurrent or resistant HE is often seen, and the prognosis in patients with severe liver dysfunction is still poor. In this issue, we discuss the therapeutic strategies and current management, except liver transplantation and interventional procedures for portal-systemic shunting, in cirrhotic patients with HE.

Liver Transplant Listing in Pediatric Acute Liver Failure: Practices and Participant Characteristics.

Liver transplant (LT) decisions in pediatric acute liver failure (PALF) are complex. Three phases of the PALF registry, containing data on 1,144 participants over 15 years, were interrogated to characterize clinical features associated with listing status. A decrease in the cumulative incidence of listing (P < 0.005) and receiving (P < 0.05) LT occurred without an increase in the cumulative incidence of death (P = 0.67). Time to listing was constant and early (1 day; quartiles 1-3 = 0-2; P = 0.88). The most frequent reasons for not listing were "not sick enough" and "medically unsuitable." Participants listed for LT were more likely male, with coma grade scores >0; had higher international normalized ratio, bilirubin, lactate, and venous ammonia; and had lower peripheral lymphocytes and transaminase levels compared to those deemed "not sick enough." Participants listed versus those deemed "medically unsuitable" were older; had higher serum aminotransferase levels, bilirubin, platelets, and albumin; and had lower lactate, venous ammonia, and lymphocyte count. An indeterminate diagnosis was more prevalent in listed participants. Ventilator (23.8%) and vasopressor (9.2%) support occurred in a significant portion of listed participants but less frequently than in those who were not "medically suitable." Removal from the LT list was a rare event. Conclusion: The cumulative incidence of listing for and receiving LT decreased throughout the PALF study without an increase in the cumulative incidence of death. While all participants fulfilled entry criteria for PALF, significant differences were noted between participants listed for LT and those deemed "not sick enough" as well as those who were "medically unsuitable." Having an indeterminate diagnosis and a requirement for cardiopulmonary support appeared to influence decisions toward listing; optimizing listing decisions in PALF may reduce the frequency of LT without increasing the frequency of death.

L-Carnitine for the Treatment of Overt Hepatic Encephalopathy in Patients with Advanced Liver Cirrhosis.

Hepatic encephalopathy is a major complication in patients with advanced cirrhosis and is associated with poor prognosis. To evaluate the effectiveness of L-carnitine supplementation in patients with overt hepatic encephalopathy (OHE), outcomes were retrospectively analyzed in patients with OHE who were treated with intravenous branched-chain amino acids (BCAA), with or without intravenous L-carnitine. Twenty-six patients were treated with intravenous BCAA in addition to conventional agents such as lactulose and non-absorbable antibiotics (Group A), and 19 patients were treated with these agents plus intravenous L-carnitine (Group L). Changes in blood ammonia concentrations, hepatic coma grade and the Glasgow Coma Scale (GCS) were compared in the two groups. Recurrence-free survival (RFS) was evaluated in the two groups and in patients who were and were not administered oral L-carnitine supplementation. At baseline, GCS scores were significantly lower and deterioration in liver function greater in Group L. After 3 d of intravenous L-carnitine, however, GCS showed a significantly greater improvement in Group L than in Group A. Blood ammonia levels improved stably over time in Group L. Overall survival and RFS were similar in Group L and Group A, but median RFS was significantly longer in patients who did than did not receive oral L-carnitine supplementation (735 versus 497 d, p=0.03). Although these findings are preliminary, L-carnitine supplementation may be a therapeutic option for patients with OHE and disturbed consciousness.

Cross-over study in hyperammonemia patients for efficacy, safety, and acceptability of a new lactulose preparation (SK-1202) compared to approved drug.

A novel jelly lactulose preparation (SK-1202) has been developed to improve compliance and reduce the elevation of blood glucose levels in diabetic patients. To compare the equivalence in the efficacy and safety of SK-1202 and an approved commercially available syrup preparation, we undertook a randomized multicenter cross-over study in hyperammonemia patients with liver cirrhosis who were taking lactulose. Forty-four patients were enrolled and took each preparation for 2weeks. Efficacy was evaluated using the Number Connection Test, blood ammonia concentration, coma grade, and the flapping tremor grade. Safety was evaluated by the number of adverse events observed, vital signs, and laboratory tests. We also examined the acceptability of each preparation using questionnaires evaluating sweetness, aftertaste, ease of use, and preference of the preparations. There were no differences in efficacy or safety between SK-1202 and the approved syrup preparation. With regard to the acceptability evaluation, given over 80% of the participants chose the SK-1202 preparation, it appears to be preferred by patients. It is expected that SK-1202 could represent a useful agent for patients with hepatic encephalopathy.

Clinical features of pediatric autoimmune hepatitis in Japan: A nationwide survey.

The purpose of this study was to determine the characteristics of children with autoimmune hepatitis (AIH) in Japan. Questionnaires that asked about patients newly diagnosed with AIH from 2009 to 2013 were sent to hospitals certified as training facilities for pediatrics in January 2015. A total of 35 patients were enrolled. The median age at diagnosis was 10years (range, 3months-15years), and the male-to-female ratio was 2:3. Female patients were more prevalent among those older than 10years and male patients were more prevalent in those younger than 10years. Fifteen patients had jaundice as a subjective symptom, and 5 had hepatic coma grade II. Liver histology classified 20 as chronic hepatitis, 8 as acute hepatitis, and 4 as cirrhosis. Liver histology was not described in 4 patients. Among the 35 patients, 32 were treated with corticosteroids and 29 were initially treated with methylprednisolone pulse therapy. Corticosteroid therapy was effective in 27 patients and ineffective in 1 patient. Plasma exchange with continuous i.v. infusion of cyclosporine A was given to 7 patients with acute hepatitis. Of these, 4 patients presented with fulminant hepatitis and received high-flow, continuous hemodiafiltration. This survey clarified that the clinical profile of pediatric AIH in Japan is not only different from that of adult AIH in Japan but is also different from that of pediatric AIH in other countries.

Evaluation of the efficacy of steroid therapy on acute liver failure.

The effects of corticosteroids in the treatment of patients with acute or subacute liver failure (ALF or SALF) are controversial. The aims of the present study were to evaluate the efficacy of corticosteroids in improving spontaneous survival (SS) rate in patients with ALF and SALF, and to determine the groups with the highest rates of response to, and the most effective timing of, corticosteroid administration. A retrospective analysis was performed of all patients with ALF and SALF who were hospitalized in the Department of Infectious Diseases, Southwest Hospital, Chongqing, China from 2000-2012. The most common result of this was SS. A total of 238 patients were studied, including 73 patients with ALF (n=34 steroids, n=39 no steroids) and 165 patients with SALF (n=21 steroids, n=144 no steroids). Corticosteroids improved rates of SS in patients with liver failure (steroids vs. no steroids, 38.2 vs. 20.2%; P=0.011), including patients with ALF (steroids vs. no steroids, 29.4 vs. 5.1%; P=0.013) and with SALF (steroids vs. no steroids, 52.4 vs. 24.3%; P=0.013), patients with viruses (steroids vs. no steroids, 32.4 vs. 14.1%; P=0.042) and patients without viruses (steroids vs. no steroids, 50.0 vs. 24.1%; P=0.043). SS rates were extremely low for patients with coma grade 4 or Model for End-stage Liver Disease (MELD) scores ≥35 (2.2 vs. 11.8%; P=0.180). A significantly improved rate of SS associated with steroid use was observed among patients who had alanine aminotransferase (ALT) levels ≥30 × the upper limit of normal and coma grade <4 and MELD scores <35 (65.0 vs. 17.4%; P=0.002). SS associated with steroid use was significantly higher in patients with an illness duration ≤2 weeks compared with patients with an illness duration >2 weeks (51.4 vs. 15.0%; P=0.010). Corticosteroids improved the prognosis of patients with ALF and SALF. The highest rates of response were observed in patients with a lower MELD score and coma grade but who had extremely high ALT levels. The most effective treatment time was within 2 weeks of the onset of symptoms.

N-Acetylcysteine Use in Non-Acetaminophen-Induced Acute Liver Failure.

This article will review the available evidence related to the management of non-acetaminophen induced acute liver failure with N-acetylcysteine. Randomized controlled trials and a meta-analysis were included in this review. The efficacy of N-acetylcysteine in the treatment of acute liver failure from causes other than acetaminophen toxicity was evaluated. The efficacy of N-acetylcysteine in non-acetaminophen-induced acute liver failure is limited to specific patient populations. Patients classified as Coma Grade I or II are more likely to benefit from the use of this agent. The use of N-acetylcysteine is associated with improved transplant-free survival, not overall survival, in adults. N-Acetylcysteine does not improve the overall survival of patients with non-acetaminophen-induced acute liver failure but may be beneficial in those patients with Coma Grades I-II. Liver transplantation remains the only definitive therapy in advanced disease.

Determinants of outcome among patients with acute liver failure listed for liver transplantation in the United States.

Analyses of outcomes after acute liver failure (ALF) have typically included all ALF patients regardless of whether they were listed for liver transplantation (LT). We hypothesized that limiting analysis to listed patients might provide novel insights into factors associated with outcome, focusing attention on disease evolution after listing. Listed adult ALF patients enrolled in the US Acute Liver Failure Study Group registry between 2000 and 2013 were analyzed to determine baseline factors associated with 21-day outcomes after listing. We classified 617 patients (36% of overall ALF group) by 3-week outcome after study admission: 117 were spontaneous survivors (SSs; survival without LT), 108 died without LT, and 392 underwent LT. Only 22% of N-acetyl-p-aminophenol (APAP) ALF patients were listed; however, this group of 173 patients demonstrated greater illness severity: higher coma grades and more patients requiring ventilator, vasopressor, or renal replacement therapy support. Only 62/173 (36%) of APAP patients received a graft versus 66% for drug-induced liver injury patients, 86% for autoimmune-related ALF, and 71% for hepatitis B-related ALF. APAP patients were more likely to die than non-APAP patients (24% versus 17%), and the median time to death was sooner (2 versus 4.5 days). Despite greater severity of illness, the listed APAP group still had a SS rate of 40% versus 11% for non-APAP causes (P < 0.001). APAP outcomes evolve rapidly, mainly to SS or death. Patients with APAP ALF listed for LT had the highest death rate of any etiology, whereas more slowly evolving etiologies yielded higher LT rates and, consequently, fewer deaths. Decisions to list and transplant must be made early in all ALF patients, particularly in those with APAP ALF.

Acetaminophen dose does not predict outcome in acetaminophen-induced acute liver failure.

Acetaminophen is a dose-dependent toxin. Prognosis in severe acute liver injury is related presumably in part to the dose ingested. We sought to assess the value of acetaminophen dosing information in patients with acute liver failure (ALF) due to acetaminophen toxicity to determine the role of dose as a prognostic indicator. Prospective data from 113 patients with ALF having single-time-point ingestions of acetaminophen were analyzed. Multivariate and chi tests were used to determine the relationship of dose to clinical outcome. We also used the Mann-Whitney U test to compare prognosis and survival in ALF with acetaminophen dose ingested. Multivariate and chi analyses failed to show any relationship between acetaminophen dose and spontaneous survival. A separate analysis showed no correlation between acetaminophen dose and clinical prognostic indicators. Dose of acetaminophen ingested did not seem to play a role in prognosis. The most important prognostic factor was coma grade on admission to study. Acetaminophen dosing information is not always obtainable. When it is, it adds little to the clinical assessment. Severity of encephalopathy is a more reliable indicator of prognosis in these critically ill patients.

Clinical, Radiologic, and Legal Significance of "Extensor Response" in Posttraumatic Coma.

The timely detection of neurologic deterioration can be critical for the survival of a neurosurgical patient following head injury. Because little reliable evidence is available on the prognostic value of the clinical sign "extensor response" in comatose posttraumatic patients, we investigated the correlation of this clinical sign with outcome and with early radiologic findings from magnetic resonance imaging (MRI). This retrospective analysis of prospectively obtained data included 157 patients who had remained in a coma for a minimum of 24 hours after traumatic brain injury. All patients received a 1.5-T MRI within 10 days (median: 2 days) of the injury. The correlations between clinical findings 12 and 24 hours after the injury-in particular, extensor response and pupillary function, MRI findings, and outcome after 1 year-were investigated. Statistical analysis included contingency tables, Fisher exact test, odds ratios (ORs) with confidence intervals (CIs), and weighted κ values. There were 48 patients with extensor response within the first 24 hours after the injury. Patients with extensor response (World Federation of Neurosurgical Societies coma grade III) statistically were significantly more likely to harbor MRI lesions in the brainstem when compared with patients in a coma who had no further deficiencies (coma grade I; p = 0.0004 by Fisher exact test, OR 10.8 with 95% CI, 2.7-42.5) and patients with unilateral loss of pupil function (coma grade II; p = 0.0187, OR 2.8 with 95% CI, 1.2-6.5). The correlation of brainstem lesions as found by MRI and outcome according to the Glasgow Outcome Scale after 1 year was also highly significant (p ≤ 0.016). The correlation of extensor response and loss of pupil function with an unfavorable outcome and with brainstem lesions revealed by MRI is highly significant. Their sudden onset may be associated with the sudden onset of brainstem dysfunction and should therefore be regarded as one of the most fundamental warning signs in the clinical monitoring of comatose patients.