- Email: [email protected]
Validation of Early Dynamic Model (EDM) in Predicting the Outcome of Acute Liver Failure (ALF): A Prospective Study
ACUTE LIVER FAILURE AND ACUTE ON CHRONIC LIVER FAILURE
sensorium improved, and thyroid symptoms gradually resolved. There was improvement in liver function parameters with total bilirubin trending down up to 8 mg/dl and INR to 1.32. However, she died suddenly 3 months later probably due to cardiac arrhythmias/arrest. This case demonstrates a rare cause of acute liver failure. Conclusion: Acute liver failure is a very rare manifestation of thyroid storm which needs prompt identification and management. Corresponding author: Vishnu Vardhan Kalluru. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2015.07.250
ALF and ACLF
PREVALENCE OF ACUTE KIDNEY INJURY NETWORK (AKIN) IN PEDIATRIC NONACETAMINOPHEN ACUTE LIVER FAILURE (PNA-ALF) AND ADDITION OF AKIN STAGING TO KING’S COLLEGE CRITERIA (KCC) IN PNA-ALF IMPROVES PROGNOSTIC VALUE Veena Raghunathan, Maninder Dhaliwal, Sakshi Karkra, Neelam Mohan Medanta The Medicity Hospital, Gurgaon, India
Introduction: Recent studies have shown lower and variable diagnostic accuracy of KCC with ALF for liver transplantation (LT). Data on prevalence of AKI (Acute Kidney Injury Network Staging, 2007) in pediatric non-acetaminophen ALF (pNA-ALF) are scarce. AKI as an adjunct to existing prognostic models in pNA-ALF has not been evaluated. Aim: To determine prevalence of AKI in pNA-ALF, and assess its utility as an adjuvant to KCC for prognosis of ALF and need for LT. Methods: Over three years, 86 children with ALF in PICU were evaluated. Serum Creatinine (Cr), worst AKIN staging in first 48 hours and KCC were recorded. Patients were classified as having no AKI (Stage 0) or AKI (Stages 1, 2 and 3). Categorical data analysis and Chi-square testing were used. Eventual LT patients were excluded (10); remaining: 76 of which 41 survived and 35 died. Sex: M:F 60:16; Age: 3 months to 18 years. Etiology: Infections—48%, drugs—5%, metabolic— 15%, autoimmune—7%, cryptogenic—21%, mixed— 4%. Forty-one of 76 patients survived. Only 21% of patients had Cr of >1 mg/dl but by AKIN staging 73% patients developed AKI (Stages 1–21%, –25% and 3– 27%). Cr did not correlate with mortality (P = 0.72). S8
KCC revealed a positive predictive value (PPV) and negative predictive value (NPV) of 75.2% and 75%. Advanced stages of AKI (2 and 3) had PPV of 94.1% and NPV of 92.8%. When AKI Stage 2 and 3 in adjunct to KCC; PPV for mortality improved from 75.2% to 80.9%; NPV for survival from 75% to 97% (P < 0.01). Conclusions: Prevalence of AKI in pNA-ALF is 3fold higher than detected by Cr. Cr does not correlate with mortality whereas AKI Stage 2 and 3 have high PPV for mortality. When AKIN staging is used adjuvant to KCC, it increases NPV and predicts survival better. Our data support the addition of AKIN to KCC to improve prognostic accuracy in pNA-ALF in selecting patients for urgent LT; larger studies are suggested. Corresponding author: Neelam Mohan. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2015.07.251
VALIDATION OF EARLY DYNAMIC MODEL (EDM) IN PREDICTING THE OUTCOME OF ACUTE LIVER FAILURE (ALF): A PROSPECTIVE STUDY Gul Javid, Ramees Mohiudin Mir, Syed Mudassar, Altaf Shah, Mushtaq Khan, Ghulam Mohmad Gulzar, Jaswinder Sodhi, Showkat Zargar Sheir-i-Kashmir Institute of Medical Sciences, Srinagar, India
Background and Aims: Acute liver failure (ALF) has a very high mortality rate and proper risk stratification plays a very important role in its management. Our aim was to validate early dynamic model in ALF patients, to stratify ALF into low, moderate and high risk, and to compare EDM with preexisting models like MELD and KCH. Materials and Methods: 40 patients of ALF were enrolled (19 males, 21 females), who fulfilled the eligibility criteria. Besides baseline investigations and etiological workup of ALF, arterial ammonia levels were taken. The EDM which takes into consideration 4 dynamic variables (Hepatic encephalopathy, INR, Arterial ammonia levels, and serum bilirubin) was applied to ALF patients on day 1 and day 3 and accordingly classified into low risk, moderate risk, and high risk. Results: The mean age of ALF patients was 28.30 16.1 yrs. ALF had a mortality of 65% in our cohort. The most common cause of ALF was undetermined (30%), followed by DILI (22%), Hep. A (15%), Hep.B (12%), Hep.E (10%), AFLP (7.5%) and Wilson’s disease (12.5%). © 2015, INASL
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
Undetermined group had the maximum mortality. ALFED Score classified 8 patients as low risk with 0% mortality, 8 patients as moderate risk with 25% mortality and 24 patients into high risk with 100% mortality. The ALFED Model showed an excellent area under ROC of 0.992 with std. error of 0.009 at cutoff score of 4 with P value 0.0001 which is highly significant, and hence accurately predicts the outcome in ALF. Conclusion: Acute liver failure Early Dynamic model is a simple, dynamic, reliable model in predicting the outcome of ALF. It assists of clinicians to select appropriate candidates for liver transplantation. ALFED Model is superior to both KCH and MELD scores even when their 3 days scores are taken into consideration
were significantly higher in healthy controls compared to cases. These metabolites are suggested to be involved in various metabolic activities. Conclusion: These results may indicate that metabonomic analysis of the serum samples can provide integrative information to assess the severity of the liver failure, which is beneficial for predicting the pathogenetic condition and the course of liver disease.
Corresponding author: Gul Javid. E-mail: [email protected]
PROFILE AND PREDICTORS OF OUTCOME IN PEDIATRIC ACUTE-ON-CHRONIC LIVER FAILURE
http://dx.doi.org/10.1016/j.jceh.2015.07.252
Corresponding author: P. Kar. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2015.07.253
Bikrant Lal, Seema Alam, Rajeev Khanna, Vikrant Sood
A METABONOMIC SCREENING OF ACUTE LIVER FAILURE PATIENTS IN HEPATITIS E VIRUS INFECTION V.K. Karra, B. Varghese, S.K. Polipalli, R. Ruttala, S. Kapoor, P. Kar Maulana Azad Medical College, University of Delhi, New Delhi, India
Background: Hepatitis E is mainly an acute and selflimiting disease, which is endemic to resource poor regions of the world. Some patients have an increased susceptibility to develop fulminant hepatitis, which is a rare disorder with high mortality and resource cost. In this study a metabonomic approach was used to investigate the biochemical perturbation of the serum samples from acute liver failure patients induced by hepatitis E virus. Methods: Serum samples from HEV-related acute liver failure patients (n = 20) and healthy controls (n = 20) were studied. Gas chromatography– mass spectrometry (GC–MS) technique integrated with a commercial mass spectral library for the peak identification was used to detect the serum metabonome. Results: Out of the 24 metabolites detected, the serum levels of benzenepropanoic acid, lactic acid, hexadecanoic acid, L-proline, serine and butanoic acid were significantly higher in the acute liver failure patients than those in the healthy control. Whereas Octadecanoic acid, N-formylglycine and isoleucine
Introduction: ACLF as an entity has not been studied well in children. The nature of acute precipitating event, the underlying chronic liver diseases and the outcome has not been studied in children. Objective: (i) To study the prevalence and outcome of acute-on-chronic liver failure (ACLF) in children. (ii) To identify the factors affecting outcome in these children. Methods: All children between the ages of 3 months to 18 years presenting with chronic liver disease from Dec’2010 to Feb’2015 were included. ACLF was defined as per APASL definition. Good outcome was defined as survival with native liver at 12 weeks. Results: Out of the total 439 cases of childhood CLD, 41 (9.2%) were diagnosed as ACLF with the median age of 10 years (1.5–17 years). Median bilirubin and INR were 17.5 mg/dl and 3.3 respectively. Commonest underlying etiologied of CLD were Wilson’s disease 19(52%), autoimmune hepatitis (AIH) 11(29.7%), and cryptogenic 5(11.1%). None of the cases with metabolic liver disease (n = 92) had ACLF. The common acute events were viral insult 14(22.2%) and drugs 4(14.8%). Flare of the underlying condition was seen in 11 Wilson’s disease and 7 AIH patients. Out of 41 children with ACLF, 25(61%) survived with native liver at 12 weeks. 14 (34%) died and 2 (5%) received liver transplantation. The predictors of mortality were presence of > 2 organ dysfunction, higher CLIF-SOFA, APACHE II and INR. The organ failures strongly associated with mortality were
Journal of Clinical and Experimental Hepatology | June/July 2015 | Vol. 5 | No. S2 | S5–S12
S9
ALF and ACLF
Institute of Liver and Biliary Sciences, New Delhi, India
sensorium improved, and thyroid symptoms gradually resolved. There was improvement in liver function parameters with total bilirubin trending down up to 8 mg/dl and INR to 1.32. However, she died suddenly 3 months later probably due to cardiac arrhythmias/arrest. This case demonstrates a rare cause of acute liver failure. Conclusion: Acute liver failure is a very rare manifestation of thyroid storm which needs prompt identification and management. Corresponding author: Vishnu Vardhan Kalluru. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2015.07.250
ALF and ACLF
PREVALENCE OF ACUTE KIDNEY INJURY NETWORK (AKIN) IN PEDIATRIC NONACETAMINOPHEN ACUTE LIVER FAILURE (PNA-ALF) AND ADDITION OF AKIN STAGING TO KING’S COLLEGE CRITERIA (KCC) IN PNA-ALF IMPROVES PROGNOSTIC VALUE Veena Raghunathan, Maninder Dhaliwal, Sakshi Karkra, Neelam Mohan Medanta The Medicity Hospital, Gurgaon, India
Introduction: Recent studies have shown lower and variable diagnostic accuracy of KCC with ALF for liver transplantation (LT). Data on prevalence of AKI (Acute Kidney Injury Network Staging, 2007) in pediatric non-acetaminophen ALF (pNA-ALF) are scarce. AKI as an adjunct to existing prognostic models in pNA-ALF has not been evaluated. Aim: To determine prevalence of AKI in pNA-ALF, and assess its utility as an adjuvant to KCC for prognosis of ALF and need for LT. Methods: Over three years, 86 children with ALF in PICU were evaluated. Serum Creatinine (Cr), worst AKIN staging in first 48 hours and KCC were recorded. Patients were classified as having no AKI (Stage 0) or AKI (Stages 1, 2 and 3). Categorical data analysis and Chi-square testing were used. Eventual LT patients were excluded (10); remaining: 76 of which 41 survived and 35 died. Sex: M:F 60:16; Age: 3 months to 18 years. Etiology: Infections—48%, drugs—5%, metabolic— 15%, autoimmune—7%, cryptogenic—21%, mixed— 4%. Forty-one of 76 patients survived. Only 21% of patients had Cr of >1 mg/dl but by AKIN staging 73% patients developed AKI (Stages 1–21%, –25% and 3– 27%). Cr did not correlate with mortality (P = 0.72). S8
KCC revealed a positive predictive value (PPV) and negative predictive value (NPV) of 75.2% and 75%. Advanced stages of AKI (2 and 3) had PPV of 94.1% and NPV of 92.8%. When AKI Stage 2 and 3 in adjunct to KCC; PPV for mortality improved from 75.2% to 80.9%; NPV for survival from 75% to 97% (P < 0.01). Conclusions: Prevalence of AKI in pNA-ALF is 3fold higher than detected by Cr. Cr does not correlate with mortality whereas AKI Stage 2 and 3 have high PPV for mortality. When AKIN staging is used adjuvant to KCC, it increases NPV and predicts survival better. Our data support the addition of AKIN to KCC to improve prognostic accuracy in pNA-ALF in selecting patients for urgent LT; larger studies are suggested. Corresponding author: Neelam Mohan. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2015.07.251
VALIDATION OF EARLY DYNAMIC MODEL (EDM) IN PREDICTING THE OUTCOME OF ACUTE LIVER FAILURE (ALF): A PROSPECTIVE STUDY Gul Javid, Ramees Mohiudin Mir, Syed Mudassar, Altaf Shah, Mushtaq Khan, Ghulam Mohmad Gulzar, Jaswinder Sodhi, Showkat Zargar Sheir-i-Kashmir Institute of Medical Sciences, Srinagar, India
Background and Aims: Acute liver failure (ALF) has a very high mortality rate and proper risk stratification plays a very important role in its management. Our aim was to validate early dynamic model in ALF patients, to stratify ALF into low, moderate and high risk, and to compare EDM with preexisting models like MELD and KCH. Materials and Methods: 40 patients of ALF were enrolled (19 males, 21 females), who fulfilled the eligibility criteria. Besides baseline investigations and etiological workup of ALF, arterial ammonia levels were taken. The EDM which takes into consideration 4 dynamic variables (Hepatic encephalopathy, INR, Arterial ammonia levels, and serum bilirubin) was applied to ALF patients on day 1 and day 3 and accordingly classified into low risk, moderate risk, and high risk. Results: The mean age of ALF patients was 28.30 16.1 yrs. ALF had a mortality of 65% in our cohort. The most common cause of ALF was undetermined (30%), followed by DILI (22%), Hep. A (15%), Hep.B (12%), Hep.E (10%), AFLP (7.5%) and Wilson’s disease (12.5%). © 2015, INASL
JOURNAL OF CLINICAL AND EXPERIMENTAL HEPATOLOGY
Undetermined group had the maximum mortality. ALFED Score classified 8 patients as low risk with 0% mortality, 8 patients as moderate risk with 25% mortality and 24 patients into high risk with 100% mortality. The ALFED Model showed an excellent area under ROC of 0.992 with std. error of 0.009 at cutoff score of 4 with P value 0.0001 which is highly significant, and hence accurately predicts the outcome in ALF. Conclusion: Acute liver failure Early Dynamic model is a simple, dynamic, reliable model in predicting the outcome of ALF. It assists of clinicians to select appropriate candidates for liver transplantation. ALFED Model is superior to both KCH and MELD scores even when their 3 days scores are taken into consideration
were significantly higher in healthy controls compared to cases. These metabolites are suggested to be involved in various metabolic activities. Conclusion: These results may indicate that metabonomic analysis of the serum samples can provide integrative information to assess the severity of the liver failure, which is beneficial for predicting the pathogenetic condition and the course of liver disease.
Corresponding author: Gul Javid. E-mail: [email protected]
PROFILE AND PREDICTORS OF OUTCOME IN PEDIATRIC ACUTE-ON-CHRONIC LIVER FAILURE
http://dx.doi.org/10.1016/j.jceh.2015.07.252
Corresponding author: P. Kar. E-mail: [email protected] http://dx.doi.org/10.1016/j.jceh.2015.07.253
Bikrant Lal, Seema Alam, Rajeev Khanna, Vikrant Sood
A METABONOMIC SCREENING OF ACUTE LIVER FAILURE PATIENTS IN HEPATITIS E VIRUS INFECTION V.K. Karra, B. Varghese, S.K. Polipalli, R. Ruttala, S. Kapoor, P. Kar Maulana Azad Medical College, University of Delhi, New Delhi, India
Background: Hepatitis E is mainly an acute and selflimiting disease, which is endemic to resource poor regions of the world. Some patients have an increased susceptibility to develop fulminant hepatitis, which is a rare disorder with high mortality and resource cost. In this study a metabonomic approach was used to investigate the biochemical perturbation of the serum samples from acute liver failure patients induced by hepatitis E virus. Methods: Serum samples from HEV-related acute liver failure patients (n = 20) and healthy controls (n = 20) were studied. Gas chromatography– mass spectrometry (GC–MS) technique integrated with a commercial mass spectral library for the peak identification was used to detect the serum metabonome. Results: Out of the 24 metabolites detected, the serum levels of benzenepropanoic acid, lactic acid, hexadecanoic acid, L-proline, serine and butanoic acid were significantly higher in the acute liver failure patients than those in the healthy control. Whereas Octadecanoic acid, N-formylglycine and isoleucine
Introduction: ACLF as an entity has not been studied well in children. The nature of acute precipitating event, the underlying chronic liver diseases and the outcome has not been studied in children. Objective: (i) To study the prevalence and outcome of acute-on-chronic liver failure (ACLF) in children. (ii) To identify the factors affecting outcome in these children. Methods: All children between the ages of 3 months to 18 years presenting with chronic liver disease from Dec’2010 to Feb’2015 were included. ACLF was defined as per APASL definition. Good outcome was defined as survival with native liver at 12 weeks. Results: Out of the total 439 cases of childhood CLD, 41 (9.2%) were diagnosed as ACLF with the median age of 10 years (1.5–17 years). Median bilirubin and INR were 17.5 mg/dl and 3.3 respectively. Commonest underlying etiologied of CLD were Wilson’s disease 19(52%), autoimmune hepatitis (AIH) 11(29.7%), and cryptogenic 5(11.1%). None of the cases with metabolic liver disease (n = 92) had ACLF. The common acute events were viral insult 14(22.2%) and drugs 4(14.8%). Flare of the underlying condition was seen in 11 Wilson’s disease and 7 AIH patients. Out of 41 children with ACLF, 25(61%) survived with native liver at 12 weeks. 14 (34%) died and 2 (5%) received liver transplantation. The predictors of mortality were presence of > 2 organ dysfunction, higher CLIF-SOFA, APACHE II and INR. The organ failures strongly associated with mortality were
Journal of Clinical and Experimental Hepatology | June/July 2015 | Vol. 5 | No. S2 | S5–S12
S9
ALF and ACLF
Institute of Liver and Biliary Sciences, New Delhi, India