Nipun Verma1, Radha Krishan Dhiman2, Ashok Choudhury3, Sunil Taneja1, Ajay Duseja1, Virender Singh1, Mamun Al Mahtab4, Harshad Devarbhavi5, Akash Shukla6, Q Ning7, Saeed Sadiq Hamid8, Amna Shubhan Butt8, Wasim Jafri8, Soek Siam Tan9, Jinhua Hu10, Duan Zhongping11, Sombat Treeprasertsuk12, Guan H Lee13, Hasmik Ghazinyan14, Laurentius A Lesmana15, Ajit Sood16, Vandana Midha16, Omesh Goyal16, Dong Joon Kim17, C E Eapen18, Ashish Goel18, Han Tao19, Xin Shaojie20, Nan Yuemin21, A Kadir Dokmeci22, Manoj Sahu23, Ayaskanta Singh23, Anil Arora24, Ashish Kumar24, Ramesh Kumar25, V G Mohan Prasad26, Ananta Shresta27, Jose Sollano28, Diana Alcantara Payawal29, Samir Shah30, P N Rao31, Anand Kulkarni31, George K Lau32, Shiv Kumar Sarin3. 1. Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. 2. Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. rkpsdhiman@hotmail.com. 3. Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India. 4. Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. 5. Department of Hepatology, St John Medical College, Bangalore, India. 6. Department of Gastroenterology, Lokmanya Tilak Municipal General Hospital, and Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India. 7. Institute and Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 8. Department of Medicine, Aga Khan University Hospital, Karachi, Pakistan. 9. Department of Medicine, Hospital Selayang, Bata Caves, Selangor, Malaysia. 10. Department of Medicine, 302 Military Hospital, Beijing, China. 11. Translational Hepatology Institute Capital Medical University, Beijing You'an Hospital, Beijing, China. 12. Department of Medicine, Chulalongkorn University, Bangkok, Thailand. 13. Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore, Singapore. 14. Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia. 15. Digestive Disease and GI Oncology Centre, Medistra Hospital, Jakarta, Indonesia. 16. Department of Gastroenterology, DMC, Ludhiana, India. 17. Department of Internal Medicine, Hallym University College of Medicine, Seoul, South Korea. 18. Department of Hepatology, CMC, Vellore, India. 19. Department of Hepatology and Gastroenterology, The Third Central Clinical College of Tianjin Medical University, No. 83, Jintang Road, Hedong District, Tianjin, 300170, China. 20. Liver Failure Treatment and Research Center, The Fifth Medical Center of Chinese, PLA General Hospital, Beijing, China. 21. Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China. 22. Department of Medicine, Ankara University School of Medicine, Ankara, Turkey. 23. Department of Gastroenterology and Hepatology Sciences, IMS and SUM Hospital, Bhubaneswar, Odisha, India. 24. Institute of Liver Gastroenterology and Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India. 25. Department of Gastroenterology, All India Institute of Medical Sciences, Patna, Bihar, India. 26. Department of Gastroenterology, VGM Hospital, Coimbatore, India. 27. Department of Hepatology, Foundation Nepal Sitapaila Height, Kathmandu, Nepal, India. 28. Department of Medicine, Cardinal Santos Medical Center, Manila, Philippines. 29. Fatima University Medical Center Manila, Manila, Philippines. 30. Global Hospitals, Mumbai, India. 31. Asian Institute of Gastroenterology, Hyderabad, India. 32. Department of Medicine, Humanity, and Health Medical Group, Hong Kong, People's Republic of China.
Abstract
BACKGROUND: We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence. METHODS: ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted. RESULTS: Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I-II in 981 (74.6%) and grades III-IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p < 0.05; each). The progressive course of HE was noted in 10.0% of patients without HE and 8.2% of patients with HE at baseline, respectively. Independent predictors of progressive course of HE were AARC score (≥ 9) and ammonia levels (≥ 85 μmol/L) (p < 0.05; each) at baseline. A final grade of HE was achieved within 7 days in 70% of patients and those with final grades III-IV had the worst survival (8.9%). Ammonia levels were a significant predictor of HE occurrence, higher HE grades and 30-day mortality (p < 0.05; each). The dynamic increase in the ammonia levels over 7 days could predict nonsurvivors and progression of HE (p < 0.05; each). Ammonia, HE grade, SIRS, bilirubin, INR, creatinine, lactate and age were the independent predictors of 30-day mortality in ACLF patients. CONCLUSIONS: HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients.
BACKGROUND: We evaluated the dynamics of hepatic encephalopathy (HE) and ammonia estimation in acute-on-chronic liver failure (ACLF) patients due to a paucity of evidence. METHODS: ACLF patients recruited from the APASL-ACLF Research Consortium (AARC) were followed up till 30 days, death or transplantation, whichever earlier. Clinical details, including dynamic grades of HE and laboratory data, including ammonia levels, were serially noted. RESULTS: Of the 3009 ACLF patients, 1315 (43.7%) had HE at presentation; grades I-II in 981 (74.6%) and grades III-IV in 334 (25.4%) patients. The independent predictors of HE at baseline were higher age, systemic inflammatory response, elevated ammonia levels, serum protein, sepsis and MELD score (p < 0.05; each). The progressive course of HE was noted in 10.0% of patients without HE and 8.2% of patients with HE at baseline, respectively. Independent predictors of progressive course of HE were AARC score (≥ 9) and ammonia levels (≥ 85 μmol/L) (p < 0.05; each) at baseline. A final grade of HE was achieved within 7 days in 70% of patients and those with final grades III-IV had the worst survival (8.9%). Ammonia levels were a significant predictor of HE occurrence, higher HE grades and 30-day mortality (p < 0.05; each). The dynamic increase in the ammonia levels over 7 days could predict nonsurvivors and progression of HE (p < 0.05; each). Ammonia, HE grade, SIRS, bilirubin, INR, creatinine, lactate and age were the independent predictors of 30-day mortality in ACLF patients. CONCLUSIONS: HE in ACLF is common and is associated with systemic inflammation, poor liver functions and high disease severity. Ammonia levels are associated with the presence, severity, progression of HE and mortality in ACLF patients.
Authors: Ee Teng Goh; Caroline S Stokes; Sandeep S Sidhu; Hendrik Vilstrup; Lise Lotte Gluud; Marsha Y Morgan Journal: Cochrane Database Syst Rev Date: 2018-05-15