Hepatic Coma Grade Research Articles

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.

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.

Right-Lobe Living-Donor Liver Transplantation in Adult Patients With Acute Liver Failure

BackgroundRight-lobe living-donor liver transplantation (RLDLT) is an excellent option to reduce donor shortages for adult patients with acute liver failure (ALF). The aim of this study was to evaluate the etiologies and outcomes of 30 consecutive adult patients who underwent emergency RLDLT for ALF. MethodsBetween January 2007 and September 2011, we examined data from medical records of patients with ALF who underwent RLDLT. ResultsTheir mean age was 32.2 ± 13.05 years. The etiologies of ALF were acute hepatitis B (n = 11; 36.6%), hepatitis A (n = 4; 13.3%), drug intoxication (n = 4; 13.3%), pregnancy (n = 2; 6.7%), hepatitis B with pregnancy (n = 1; 3.3%), mushroom intoxication (n = 1; 3.3%), and unknown (n = 7; 23.3%). The mean hepatic coma grade (Model for End-Stage Liver Disease score) was 34.13 ± 8.72. The 43 (48.7%) postoperative complications were minor (grades I–II) and 44 (51.3%) were major (grades III–V). Reoperation was required in 14 of 30 (47%) recipients (grades IIIb–IVa). Deaths occurred owing to pulmonary (n = 2), cardiac (n = 1), septic (n = 2), or encephalopathic (n = 4) complications. The mean durations of intensive care unit stay and postoperative hospitalization were 3.2 ± 2.3 and 29.5 ± 23 days, respectively. The survival rate was 70%. The mean follow-up duration was 305 days (range, 1–1582). ConclusionLiver transplantation is potentially the only curative modality, markedly improving the prognosis of patients with ALF. The interval between ALF onset and death is short and crucial because of the rapid, progressive multiorgan failure. Thus, RLDLT should be considered to be a life-saving procedure for adult patients with ALF, requiring quicker access to a deceased-donor liver graft and a short ischemia time.

Right Lobe Living Donor Liver Transplantation for Adult Patients with Acute Liver Failure: A Single-Center Experience in Turkey

Introduction: Acute liver failure (ALF), a life-threatening clinical syndrome of sudden and severe liver dysfunction, is associated with a coagulation abnormality and hepatic encephalopathy in patients without previous clinically liver disease. Therefore, ALF is very complicated status and the chance of spontaneous healing is poor. Liver transplantation (LT) is the only definitive treatment modality with well demonstrated efficacy for ALF patients. Right lobe living donor liver transplantation (RLDLT) is an excellent option for adult patients with ALF in cadeveric donor shortage. We analyzed the etiologies and our experiences in adult patients who underwent emergency RLDLT for ALF. Methods: We evaluated the charts of adult patients with ALF underwent RLDLT at Turgut Ozal Medical Center (Malatya, Turkey) between January, 2007 and September, 2011. All of the ALF patients were identified by retrospective review of a prospectively acquired liver database that contained recipient and donor demographics, perioperative findings, and postoperative outcomes. Continuous variables are reported as means ± standard deviations, and categorical variables as numbers and percentages. Results: We performed 643 liver transplants including cadaveric and live donors, and of thirty adult patients 30 (4.7%) with ALF underwent RLDLT during this study period. The median age was 32,2±13.05 years. The etiologies of ALF in the RLDLT patients were acute hepatitis B in 11 (36.6%) patients, hepatitis A in 4 (13.3%), drug intoxication in 4 (13.3%), pregnancy in 2 (6.7%), hepatitis B with pregnancy in 1 and mushroom intoxication in one (3.3%), and 7 (23.3%) unknown etiologies. The mean of hepatic coma grade (Model for End-Stage Liver Disease scores) was 34.13± 8.72. Mean graft-to-recipient weight percentage was 1.3 ± 0.3%. Mean interval between indication for transplant and LT procedure was 19.7 ± 23.6 h. Mean cold ischemia time was 154.35 ± 59.6 min. Mean recipient operation time was 605 ± 120 min. The RLDLT patients had a higher biliary and vascular complication rate (40%, 20% respectively). Survival rate of RLDLT patients was 70%, nine deaths occurred due to pulmonary (n=2), cardiac (n=1), sepsis (n=2), encephalopathy (n=4) complications. The mean intensive care unit stay was 3.2 ± 2.3 days and the mean postoperative hospital stay was 29.5 ± 23 days for RLDLT patients. The mean follow-up times were 305 days (1-1582). All of the donors remained alive and well with normal liver function at the time of the final follow-up examination. Conclusions: Liver transplantation is potentially the only curative modality and has markedly improved the prognosis of ALF patients. The interval between onset of ALF and death is short and crucial because of progressive multi-organ failure at a rapid rate in addition to the liver. Therefore, RLDLT should be considered a life-saving procedure, characterized by quicker access to liver grafts and very short ischemia time, for adult patients with ALF in shortage of deceased donor. Declaration of Interest: The authors report no conflict of interest and no funding from any company.

SIRS Score Reflects Clinical Features of Non-Acetaminophen-Related Acute Liver Failure with Hepatic Coma

In acetaminophen-induced acute liver failure (ALF), the hepatic coma grade worsens and mortality rates increase, as the number of systemic inflammatory response syndrome components fulfilled (SIRS score) increases. This study aimed to investigate the impact of SIRS score on clinical features of non-acetaminophen-related ALF. Ninety-nine patients with non-acetaminophen-related ALF with hepatic coma who did not undergo liver transplantation were investigated. Each patient was given a SIRS score of 0, 1, 2, 3 or 4 at the time of diagnosis. At the diagnosis of ALF with hepatic coma, with the increase of SIRS score, hepatic coma grade and prothrombin activity were deteriorated. After the diagnosis of ALF with hepatic coma, 25 patients (25%) developed acute respiratory distress syndrome (ARDS), 31 patients (31%) developed disseminated intravascular coagulation (DIC), and 21 patients (22%) developed acute renal failure (ARF). Thirty-eight patients (38%) developed MOF. With the increase of SIRS score, frequencies of the development of ARDS, DIC and MOF increased. ARF was more frequently developed in patients with a SIRS score of 2 or higher. Overall, 36 patients (36%) survived. Overall survival rate was 66% in 29 patients with a score of 0, 43% in 21 patients with a score of 1, 17% in 29 patients with a score of 2 and 15% in 20 patients with a score of 3 or 4. SIRS score will be useful for predicting not only the overall survival but also the development of complications such as ARDS, DIC and MOF in non-acetaminophen-related ALF with hepatic coma.

Use of Nucleoside (Tide) Analogues in Patients with Hepatitis B-Related Acute Liver Failure

The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF. The US Acute Liver Failure Study Group, a 23-site registry, prospectively enrolled 1,413 patients with ALF with different etiologies between 1998 and 2008. Of those, 105 patients were identified as HBV-ALF patients, of whom we excluded those without data on NA use or with co-infection with hepatitis C, leaving 85 patients, 43 of whom had received NA treatment. HBV-DNA on admission was quantified by real time polymerase chain reaction. The treated and untreated groups were similar in most respects but differed significantly in regard to higher aminotransferase and bilirubin levels and hepatic coma grades, all being observed in the untreated group. Median duration of NA treatment was 6 days (range, 1-21 days). Overall survival in the NA treated and untreated groups were 61 and 64%, respectively (P=0.72). Rates of transplant-free survival were 21 and 36% in the treated and untreated groups, respectively (P=0.42). Multivariate analysis revealed that not using a NA [odds ratio (OR) 4.4, 95% CI 1.1-18.1, P=0.041], hepatic coma grade I or II [OR 14.4, 95% CI 3.3-62.8, P<0.001] and prothrombin time (PT) [OR 0.59, 95% CI 0.39-0.89, P=0.012] were predictors of improved transplant-free survival. Patients who are admitted with established HBV-ALF do not appear to benefit from viral suppression using nucleoside(tide) analogues presumably because of rapid disease evolution and short treatment duration. Despite the lack of benefit, NAs should still be given to transplantation candidates since viral suppression prevents recurrence after grafting.

Fulminant hepatitis: Who survives without liver transplantation?

In order to rescue more patients with fulminant hepatitis (FH) in a setting of the shortage of liver grafts, it is important not only to determine the suitable timing for liver transplantation (LT) but also to reduce avoidable operations for patients surviving without LT. This study aimed to identify prognostic parameters for survival without LT in FH patients. In 96 FH patients who did not receive LT, we examined prognostic parameters at the time of the diagnosis of FH, which were associated with patient's survival. Fifty-three patients (55%) were female. The median age was 48 years. At the time of the diagnosis of FH, hepatic coma grade was II in 63 patients (66%), III in 22 (23%) and IV in 11 (11%). Forty-six patients (48%) were in a state of systemic inflammatory response syndrome (SIRS). Four parameters of age (<45 years), SIRS (no), direct bilirubin/total bilirubin ratio (>0.65), and total bilirubin (<12.0 mg/dL) were associated with patient's survival. Overall survival rate of eight patients ulfilling all four parameters were 88%. In 17 patients fulfilling any three parameters, 2-week, 4-week and overall survival rates were 82%, 77% and 71%, respectively. On the other hand, overall survival rate of 38 patients fulfilling any one parameter or none was less than 10%. Patients fulfilling all four parameters will be successfully treated without LT. In patients fulfilling any three parameters, intensive care including artificial liver support in expectation of hepatic regeneration during a few weeks may be possible.

Prognostic factors for fatal outcomes prior to receiving liver transplantation in patients with non‐acetaminophen‐related fulminant hepatic failure

Many patients continue to die due to the rapid development of cerebral edema and/or multiple organ failure prior to receiving a liver transplantation. We investigated the prognostic factors associated with 1-week fatal outcomes after the diagnosis of fulminant hepatic failure, which were associated with fatal outcomes prior to receiving liver transplantation, in 104 patients with non-acetaminophen-related fulminant hepatic failure. With a multivariate logistic regression analysis, age (>40 years), systemic inflammatory response syndrome (SIRS) and plasma prothrombin activities (<or=10%) were significantly associated with fatal outcomes at 1 week after diagnosis in 104 patients. At the time of diagnosis, 50 patients (48%) were in a state of SIRS. Significant differences were observed between patients with and without SIRS regarding the period from the initial symptoms to the diagnosis of fulminant hepatic failure, hepatic coma grade, serum alanine aminotransferase level, serum creatinine level and plasma prothrombin activity. With a multivariate logistic regression analysis, age (>40 years), cause of fulminant hepatic failure (viral hepatitis), plasma prothrombin activity (<or=10%) and no administration of protease inhibitor were significantly associated with the 1-week fatal outcomes of 50 patients with SIRS. Patients with SIRS exhibited hepatic failure of increased severity and SIRS may reduce the probability of receiving a liver transplantation. In order to estimate the efficacy of protease inhibitor for patients with SIRS, a prospective randomized trial is required.

New Prognostic Scoring Model for Liver Transplantation in Patients with Non-Acetaminophen-Related Fulminant Hepatic Failure

Many patients with fulminant hepatic failure die before receiving liver transplantation because of the difficulty of pinpointing the suitable timing for liver transplantation. The revised King's College criteria are useful for patients with acetaminophen-related fulminant hepatic failure; however, in those with non-acetaminophen-related fulminant hepatic failure, a new prognostic system that can accurately identify the suitable timing for liver transplantation is required. Using the first sample consisted of eighty patients with fulminant hepatic failure, we examined 2-week poor prognostic parameters at the time of diagnosis of fulminant hepatic failure (day 1) and on days 4, 8, and 15, respectively, and a 2-week prognostic scoring model was constructed. To confirm the accuracy of this model, validation was performed in the second sample consisting of 26 patients. Cause of fulminant hepatic failure (hepatitis B virus or indeterminate), hepatic coma grade (III or IV), systemic inflammatory response syndrome (yes) and ratio of total to direct bilirubin (> 2.0) were associated with 2-week outcomes during days 1-15. Each of these four parameters was valued at +1. The 2-week survival rate in patients scoring <3 was > or = 80% in contrast to less than 30% in patients scoring > or = 3. When this scoring model was applied to the second sample, the sensitivity, specificity, and positive and negative predictive values were 87.5%, 90.0%, 93.3%, and 81.8%, respectively. This scoring model may be useful for predicting 2-week outcomes and determining the suitable timing for liver transplantation in patients with non-acetaminophen-related fulminant hepatic failure.

Etiology and outcome for 295 patients with acute liver failure in the United States.

Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.

Prediction of Hepatic Encephalopathy in Paracetamol Overdose: A Prospective and Validated Study

Background: Paracetamol overdose may cause hepatic encephalopathy (HE). This condition demands specialized care and, in some instances, liver transplantation evaluation. No model is available for predicting HE. We aimed to set up and validate a model for predicting the occurrence of HE in paracetamol overdose. Methods: Prospectively, 161 patients with single-dose paracetamol overdose and no HE (defined as hepatic coma grade II or more) on admission were studied during a 26-month period. Patients admitted during the first 13-month period constituted a learning set to construct a model to predict the occurrence of HE. Patients admitted in the second 13-month period constituted the validation set. Serial biochemical variables (measured twice daily), the time line after the overdose, and demographic data were used for univariate testing, and significant factors were assessed in various multiple logistic regression analyses. Results: Thirty-two patients (20%), 15 in the first period and 17 in the second, developed HE grade II. The best model (the highest chi-square) for HE included: log10 (hours from overdose to antidote treatment), log10 (plasma coagulation factors on admission), and platelet count · hours from overdose (chi-square = 41.2, P < 0.00001). In the validation set 88% (confidence interval (CI), 64%-99%) of the patients who developed HE were correctly predicted by the constructed model, whereas 90% (CI, 79%-96%) of the patients in the non-HE group were correctly predicted. Conclusions: The constructed model for predicting HE in paracetamol overdose proved sensitive and accurate in the validation set and should be valuable for transferring high-risk patients to a liver intensive care unit/transplantation facility.

Fractional Excretion of Beta-2-Microglobulin in the Urine of Patients with Normal or Reduced Renal Function and Hepatic Coma

The purpose of this prospective study was to evaluate beta-2-microglobulin (beta 2m) as a differential diagnostic indicator between hepatic nephropathy (HN) and acute tubulointerstitial nephropathy (ATIN) in patients with reduced renal function and hepatic coma, and to determine whether beta 2m excretion could be used as a marker of renal impairment before increased serum creatinine (S-Cr) concentration or decreased creatinine clearance (Cr-Cl). Finally, the use of beta 2m as a prognostic indicator was investigated. Eighteen patients in hepatic coma grade III-IV were entered in the study and were divided into two groups in accordance with their renal function (serum creatinine above/below 180 mumol/l). The fractional excretion of beta 2m (FE-beta 2m) was used to monitor beta 2m elimination. The study failed to show any distinction in FE-beta 2m between HN and ATIN patients, presumably owing to the small number of patients. FE-beta 2m could not predict the development of renal failure earlier than the increase in S-Cr or decrease in Cr-Cl. However, a few patients who survived paracetamol intoxication had increased FE-beta 2M in the beginning of the coma and normal S-Cr and Cr-Cl. Patients who died as a result of paracetamol intoxication had both abnormal FE-beta 2m and abnormal S-Cr and Cr-Cl, suggesting that if therapy had been initiated earlier, when only FE-beta 2m was affected, these patients might have survived. All patients who survived, except three paracetamol- and one aminoglycoside-intoxicated patient, had normal FE-beta 2m in the beginning of the coma.(ABSTRACT TRUNCATED AT 250 WORDS)