Tóm tắt những đóng góp mới của luận án: Đề tài nghiên cứu có ý nghĩa khoa học và thực tiễn. Kết quả nghiên cứu có đóng góp nhất định trong thực tiễn lâm sàng, góp phần tiên lượng và điều trị suy gan cấp. Những kết quả mới đạt được: Nguyên nhân gây suy gan cấp chủ yếu là ngộ độc cấp chiếm 82,22%, trong đó chủ yếu là ngộ độc thuốc đông y. Tỷ lệ tử vongxin về chiếm 46,67%. Độ não gan, SOFA, NH3 và IL6 có mối tương quan thuận, mức độ chặt với nguy cơ tử vong của bệnh nhân suy gan cấp. Một số yếu tố có vai trò tiên lượng tử vong chung ở bệnh nhân suy gan cấp gồm SOFA > 8 điểm, thở máy, NH3 >70 Ul, lactat > 3 mmoll, INR > 2 và IL6 > 38 pgml Có sự cải thiện về lâm sàng và 1 số chỉ số xét nghiệm chức năng gan sau mỗi lần thay huyết tương thể tích cao Không có biến chứng nghiêm trọng do thay huyết tương thể tích cao
MINISTRY OF EDUCATION MINISTRY OF DEFENSE AND TRAINING 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES NGUYEN DANG DUC THIS WORK WAS COMPLETED AT: 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Scientific instructors: Assoc Prof., PhD Be Hong Thu PhD Le Lan Phuong STUDY OF THE EFFECTIVENESS OF TREATMENT SUPPORT FOR ACUTE LIVER FAILURE BY HIGH-VOLUME PLASMA EXCHANGE Reviewer 1: Assoc Prof., PhD Cong Quyet Thang Reviewer 2: Assoc Prof., PhD Tran Ngoc Anh Reviewer 3: Assoc Prof., PhD Nguyen Phuong Dong Specialty: Anesthesiology resuscitation Code: 9720102 The thesis is defended before the Institute-level Thesis Judging Council, which meets at the Institute of Clinical Medical and Pharmaceutical Sciences 108 At……,…… 2023 SUMMARY OF Ph.D THESIS YOU CAN FIND OUT THE THESIS AT: HANOI - 2023 - National Library of Vietnam - Library of 108 Institute of Clinical Medicine and Pharmaceutical LIST OF THE PUBLISHED ARTISCLES RELATED INTRODUCTION RESULTS OF THE Ph.D THESIS Acute liver failure is a sudden and severe loss of liver function due to various agents acting on the liver leading to the onset of hepatic encephalopathysigns and coagulation abnormalities (INR > 1.5), in patients without prior liver disease and the period from jaundice to the onset of hepatic signs is less than 26 weeks According to statistics of the Poison Control Center - Bach Mai Hospital from 2009 - 2011, the rate of drug poisoning tends to increase from 5.0% to 8.7% of the total number of poisoning patients receiving treatment, of which the rate of progression to acute liver failure is very high, death 50-66.7% In the world, there are many studies on acute liver failure in terms of epidemiology, causes, pathogenesis, diagnosis and treatment How ever the mortality rate from acute liver failure is still very high, without liver transplantation, the effectiveness of supportive treatment measures is still controversial The principle in the treatment of acute liver failure is to immediately stop and eliminate agents suspected of causing acute liver failure, use specific antidotes if due to substance poisoning, supportive treatment waiting for the liver to recover naturally or wait for liver transplantation if indicated Currently, liver transplantation is the optimal solution for the treatment of acute liver failure However, in the context of scarcity of organ resources and high costs, this technique is not always possible in Vietnam Plasma exchange is a proven effective mode of liver failure such as elimination of toxins, improvement of cerebral perfusion, immunomodulation, plasma exchange to prolong survival, reduce mortality in patients with acute liver failure Since the early years of the 19th century, there have been many scientists researching plasma exchange in the supportive treatment of some diseases in general and supporting the treatment of acute liver failure in particular Although the efficacy of plasma exchange modalities with different volumes according to studies is still inconsistent, high-volume plasma exchange is currently considered a more effective adjunct treatment of acute Nguyen Dang Duc, Be Hong Thu, Le Lan Phuong, (2022) "Study of clinical, subclinical characteristics and causes of disease in patients with acute hepatic impairment receiving supportive treatment with high-volume plasma exchange", Journal of Clinical Medicine and Pharmacy 108, vol 17, no (2022), 44-50 Nguyen Dang Duc, Be Hong Thu, Le Lan Phuong, Nguyen Hong Tot (2022) "Evaluation of outcomes of supportive treatment of acute liver failure by high-volume plasma exchange", Journal of Clinical Medicine and Pharmacy 108, vol 17, no (2022); 31-36 2 liver failure than normal plasma exchange volume 2B, and highvolume plasma exchange has been included in the American Plasma exchange Association's recommendation with evidence level 1A There are currently no studies in the country to fully and separately investigate the efficacy and undesirable effects of high-volume plasma exchange in patients with acute hepatic impairment Therefore, the project "Research on the effectiveness of supportive treatment of acute liver failure by high-volume plasma exchange method" was carried out with objectives: Comment on clinical and subclinical characteristics before highvolume plasma exchange in patients with acute hepatic impairment and a number of factors related to mortality Evaluate the effectiveness of supporting the treatment of acute liver failure and some undesirable effects of high-volume plasma exchange * New contributions of the thesis: This is the first study in Vietnam to evaluate the effectiveness of treatment of acute liver failure by high-volume plasma exchange Research results make a definite contribution in clinical practice, contributing to the prognosis and treatment of acute liver failure Research has shown that a number of factors are strongly correlated with mortality risk, factors that play a role in the overall prognosis of death in patients with acute liver failure The study also showed improvement in clinical and laboratory indicators of patients with acute hepatic impairment after high-volume plasma exchange * Thesis layout: thesis has 129 pages (excluding appendices and TLTK): Problem Setting 02 pages, Overview 39 pages, Subjects and research methods 25 pages, Results 34 pages, Discussion 25 pages, Conclusion 02 pages, Limitations of the topic 01 page and Recommendations 01 page The thesis has 44 Tables, 04 Charts, 04 Figures, 01 Diagram There are 132 TLTKs (12 Vietnamese, 120 English) CHAPTER OVERVIEW 1.1 Acute liver failure 1.1.1 Definition Acute hepatic failure is a severe and sudden loss of liver function due to various agents acting on the liver leading to the onset of hepatic encephalopathysigns and coagulation abnormalities (INR > 1,5) in patients without prior liver disease and disease course from jaundice until the appearance of lower hepatic encephalopathysigns 26 weeks 1.1.2 Classification There are commonly used classifications: - Classification by time: from the onset of signs of jaundice to the presence of hepatic encephalopathysigns - Classification according to the cause of acute liver failure - Classification according to possible liver transplant status 1.1.3 Epidemiology of acute liver failure There have been no reports of epidemiology of acute liver failure in Viet Nam 1.1.4 Pathogenesis The pathogenesis of acute liver failure includes: the mechanism of direct liver damage, the mechanism of immune-mediated liver damage 1.1.5 Diagnostics Based on clinical and subclinical Grades of acute liver failure by West Haven divided into degrees 1.1.6 Treatment These include: management of hepatic encephalopathystatus, bacterial infections and correction of multi-organ dysfunction, use of artificial liver support systems or emergency liver transplantation 1.1.7 Prognosis The prognosis of liver transplant patients varies and cannot be accurately predicted 4 1.2 Plasma exchange 1.2.1 The concept and history of the formation of the terms of plasma exchange 1.2.2 The principle of plasma exchange Plasma exchange is the process of removing a large volume of plasma and replacing it with purer plasma or albumin, while removing pathological substances such as pathological antibodies, immune complexes, cytokines and toxins 1.2.3 Classification of forms of plasma exchange Based on the amount of plasma of the patient to be replaced, the forms of plasma exchange are classified: low-volume plasma exchange, normal-volume plasma exchange, and high-volume plasma exchange 1.2.4 Indications, contraindications of plasma exchange 1.2.5 Undesirable effects, complications of high-volume plasma exchange 1.3 Overview of domestic and foreign studies on high-volume plasma exchange 1.3.1 In the world Larsen (2016), conducted a randomized, controlled, multicenter clinical trial on 182 patients with acute hepatic impairment The main criteria are survival without liver transplantation during hospitalization, secondary criteria include survival after liver transplantation with or without high-volume plasma changes The overall hospital survival was 58.7% in the high-volume plasma exchange group compared to 47.8% in the control group The incidence of adverse events was similar in the two groups 1.3.2 In Vietnam In Viet Nam, there has not been a single study evaluating the efficacy of high-volume plasma exchange in patients with acute hepatic impairment, particularly due to toxic causes Vuong Xuan Toan (2019), a study of 30 patients with acute liver failure due to different causes who received continuous dialysis and high-volume plasma exchange found that, patients with acute liver failure received high-volume plasma exchange combined with continuous dialysis, liver function improved, reduced incidence of coagulopathy, reduced levels of NH3 and bilirubinemia compared to before treatment CHAPTER OBJECTS AND METHODS 2.1 Subjects of study The study included 45 patients with acute liver failure due to different causes, receiving supportive treatment for high-volume plasma exchange at Bach Mai Hospital's Poison Control Center from June 2017 to April 2021 2.1.1 Patient selection criteria Patients selected for the study included patients with acute hepatic impairment who were adjunctively treated with high-volume plasma exchange with the following criteria: - Have hepatic encephalopathysigns of grade or higher as classified by West Haven - Coagulation abnormalities with an INR > 1.5 - No previous liver disease - The time from jaundice to the onset of hepatic brain signs < 26 weeks - The patient and his family agree to participate in the study 2.1.2 Exclusion criteria - Patients with hepatocardiac disease - Severe acute liver failure on the background of irreversible fibrous liver - Coagulation disorders caused by vitamin K-resistant rat poisoning 2.1.3 Criteria for exclusion from the study - The patient does not agree to participate in the study or participate in the study but does not follow the treatment regimen 2.2 Research methodology 2.2.1 Sample size and sample selection method Sample size is convenient during the study period Sampling method: All patients with acute liver failure are eligible for selection and treatment at Poison Control Center of Bach Mai Hospital during the study period from June 2017 to April 2021 2.2.2 Study design Descriptive studies, prospective treatment interventions, pre- and post-treatment self-control The patient underwent high-volume plasma exchange times consecutively on consecutive days according to the procedure After high-volume plasma changes, the clinical and subclinical course improved well, plasma exchange was stopped If there is no improvement, the patient transfers a liver transplant (if any) or dies in hospital/returns to die 2.2.3 Facilities for research 2.2.4 Research indicators 2.2.5 Background treatments in addition to PEX - Respiratory assurance: Patients receive respiratory support at the following levels (if needed): breathing Frame oxygen, oxygen mask, invasive mechanical ventilation - Ensure circulation: maintain average blood pressure above 65mmHg, vasopressors can be used - Quickly eliminate the causative agent of acute poisoning if identified (through family information extraction, referral paper) by inducing vomiting, gastric lavage, drinking activated charcoal, sorbitol - Toxicology quantification of blood and urine specimens if suspected poisoning can be done at the Poison Control Center - Control of hepatic encephalopathylevels by rapid elimination of NH3, combating cerebral edema by manitol 20% or natricchloride salt 2% - Control blood clotting disorders by compensating blood products corresponding to the same group - Adequate nutrition, water and electrolytes are replenished with normal fluids and nourishing fluids in the most optimal way - Alkaline acid, electrolyte balance - Blood sugar control - Anti-infectious, viruses, parasites, antibiotic supplements, antifungal if necessary 2.2.6 Perform high-volume plasma exchange Plasma exchange according to the Technical Procedure Manual on Resuscitation - Emergency and Antitoxicology, 2014 Alternative fluid: choose alternative fluid: fresh frozen plasma The plasma volume is equal to 15% of the patient's circulating volume according to ideal weight V ( liters) = (15 x P) /100 In which: V: Estimated plasma volume of each plasma exchange P: Ideal body weight is calculated by the formula : P (kg) for men = 50 + 0.91 x [ height (cm) – 152.4] P (kg) for women = 45.5 + 0.91 x [ height (cm) – 152.4] - To ensure plasma quality, plasma after being thawed is divided into 2-3 bags, each bag of 3000ml (equivalent to about hours of machine running) Unused plasma bags will be stored in the refrigerator cooler (temperature 2-8 degrees Celsius) and will be removed 30 minutes before the previous plasma bag runs out - Timing of data collection: + Time of diagnosis of acute liver failure + Before starting the 1st plasma change (within 60 minutes before the 1st plasma exchange) + After the 1st plasma exchange (within 60 minutes after the 1st plasma exchange) 8 + Before the 2nd plasma exchange (within 60 minutes before the 2nd plasma exchange) + Immediately after the 2nd plasma exchange (within 60 minutes after the 2nd plasma exchange) + Before the 3rd plasma exchange (within 60 minutes before the 3rd plasma exchange) + Immediately after the 3rd plasma exchange (within 60 minutes after the 3rd plasma exchange) + At the end of plasma exchanget 2.3 Data analysis and processing The obtained data are managed by Excel software (Microsoft, version 365, USA) and processed by medical statistical algorithms on SPSS 26.0 software (IBM, USA) 2.4 Ethics in research Comply with current regulations of the Ministry of Health Paracetamol (n, %) (20,0) Fungus (n, %) (6,67) Other (n, %) (4,44) Immunity (n,%) 12 (26,67) Metabolism (n,%) (2,22) cause (n, %) 40 (88,89) causes (n, %) (11,11) Comments: 82.22% of patients with acute liver failure are due to poisoning, of which herbal medicine (51.11%) is followed by paracetamol (20%), mushrooms (6.67%) and other causes of poisoning (4.44%) Table 3.5 Clinical features before plasma exchange Result Symptom (n=45) Jaundice, mucous membranes (n,%) 42 (93,33) Edema (n,%) (17,78) Ascites (n,%) (13,33) Hemorrhage (n,%) (4,44) Comment: Jaundice was the most common symptom in 93.33% of CHAPTER RESULT 3.1 Comment on clinical and subclinical characteristics of patients with acute hepatic impairment before high-volume plasma exchange and some factors related to mortality 3.1.1 Clinical and subclinical features of patients with acute hepatic impairment The median age was 47.0 years ± 16.31 years, the youngest was 17 years, the highest was 88 years Males predominate with 53.3% Kinh ethnic group constitutes the majority with 80% Table 3.4 Causes of acute liver failure Result Cause (n=45) General (n, %) 37 (82,22) Herbal medicine (n, 23 (51,11) Poisoning %) patients, followed by edema and ascites Before plasma exchange, the mean hepatic encephalopathy was 2.53±0.59 of which hepatic encephalopathy grade accounted for 51.11%, there were patients with hepatic encephalopathy grade (hepatic coma) Before plasma exchange, patients with acute hepatic impairment had a slight increase in red blood cell index, normal hemoglobin, and leukocytes with 55.56% of patients with leukocytes > 10 G/l and 4.44% of patients with leukopenia < G/l The average platelets were below the normal threshold, of which only 19 patients (42.22%) had 10 11 platelets within the normal range, and 18 patients (40%) had platelets below 100 G/l Prior to plasma exchange, patients with severe coagulopathy were characterized by decreased prothrombin and fibrinogen ratios, prolongation of APTT time, and increased INR, of which 82.2% of patients had prothrombin ratio < 40% and 40% of patients had INR > Before plasma exchange, patients with liver enzyme indices (AST, ALT), bilirubin (total and direct), NH3 very high elevation, slight increase in blood sugar K+ and Ca2+ tend to be below normal thresholds IL6 was elevated above normal with a median of 26.66 pg/ml The average SOFA score is 9.67±2.39, of which 2/3 of patients had SOFA > points, 60% of patients had or more organ failure 3.1.2 Some factors associated with mortality in patients with acute hepatic impairment receiving high-volume plasma exchange There were 46.67% patients with acute hepatic impairment who died despite high-volume plasma exchange There was no difference in age, sex, BMI, causes of poisoning between the living group and the group that died from acute liver failure The death group had a higher average level of hepatic encephalopathy than the live group The prevalence of hepatic encephalopathy of 3.4 was higher in the mortality group, however this difference was absent Statistical significance with P > 0.05 The proportion of patients requiring respiratory intervention in the fatal group was higher than in the statistically significant survival group The hemostatic coagulation indices in the living group were better than in the mortal group The live group had a higher prothrombin rate, the number of patients achieving a prothrobin rate > 40% higher than the death group, the difference was statistically significant The live group had a lower INR and shorter aPTT and a lower proportion of patients with aPTT lasting more than 60 seconds and an >3 INR compared to the mortality group, a statistically significant difference from P < 0.05 The blood sugar of the living group was within normal ranges and lower than that of the death group, the difference had statistical significance Indices of AST, ALT, bilirubin (total and direct), urea, creatinine, IL6 did not differ between the living and mortal groups The SOFA score at hospitalization of the living group was lower than that of the death group, which was statistically significant with p < 0.001 The death group had a higher proportion of patients with or more organ failure than the living group, with differences statistical significance Table 3.26 Correlation of some clinical, subclinical factors with mortality risk Element Correlated Pre-HPEX hepatic encephalopathy 0,215 SOFA before HPEX 0,358 NH3 before HPEX 0,224 IL6 before HPEX 0,073 Hepatic encephalopathy at HPEX stop 0,907 SOFA at HPEX stop 0,598 NH3 at stopping HPEX 0,496 IL6 at HPEX stop 0,539 Comment: - Before starting high-volume plasma exchange: + Hepatic encephalopathylevel, NH3 and IL6 indexes are less correlated with the risk of death in patients with acute liver failure + SOFA score has a positive and moderate correlation with the risk of death in patients with acute liver failure - After stopping plasma exchange (end of 3rd high-volume plasma exchange): 12 13 + Hepatic encephalopathy has a very close correlation with the risk of death in patients with acute liver failure + SOFA, NH3 and IL6 indexes have a positive correlation, tightness level with the risk of death from acute liver failure + NH3 index has a positive correlation, moderate level with the risk of death from acute liver failure Table 3.27 Some risk factors for death in patients with acute liver failure Element Result OR 95%CI p Live Die SOFA before 11 19 11,23 2,12-59,26 < 0,001 HPEX >8 Pre-HPEX 13 2,7 0,81-9,1 > 0,05 hepatic encephalography ≥3 Mechanical 15 7,5 2,0-28,2 < 0,001 ventilation Pre-HPEX NH3 13 15 2,12 0,6 -7,3 < 0,05 >70 U/l Pre-HPEX 16 5,33 1,45-19,57 < 0.01 lactate > mmol/l Pre-HPEX IL6 > 2,24 0,6-8,8 < 0,001 38 pg/ml INR before 16 19 4,75 0,88-25,65 < 0.001 HPEX >2 Comment: SOFA before high-volume plasma exchange above points increased the risk of death in patients with acute hepatic impairment by 11.23 times compared with the acute hepatic failure group with SOFA ≤ points Pre-HPEX hepatic encephalopathy ≥ increased the risk of death in patients with acute hepatic impairment by 2.7 times compared to the acute hepatic impairment group with hepatic encephalopathygrade ≤ 3, however the difference was absent statistical significance Mechanical ventilation increased the risk of death in patients with acute hepatic impairment by 7.5 times compared with the acute hepatic impairment group without mechanical ventilation, statistically significant with p < 0.001 NH3 before HPEX >70 U/l increased the risk of death in patients with acute hepatic impairment by 2.12 times compared with the acute hepatic impairment group with NH3 ≤ 70 U/l, with p < 0.05 Pre-HPEX lactate > mmol/l increased the risk of death in patients with acute hepatic impairment by 5.33-fold compared with the acute hepatic impairment group with lactates ≤ mmol/l, with p< of 0.01 The pre-HPEX > INR increased the risk of death in patients with acute hepatic impairment by 4.75 times compared with the acute hepatic impairment group with a pre-HPEX ≤ INR with p < of 0.001 Pre-HPEX IL6 > 38 pg/ml increased the risk of death in patients with acute hepatic impairment by 2.24-fold compared with the acute hepatic impairment group with IL6 ≤ 38 pg/ml with p < 0.001 3.2 Efficacy and some undesirable effects of high-volume plasma exchange in the supportive treatment of acute liver failure 3.2.1 Effectiveness of high-volume plasma exchange method in the supportive treatment of acute liver failure There were 45 patients selected for the study who received highvolume plasma exchange After the first plasma change, patients died, stable patients no longer indicated for plasma exchange were stopped HPEX After the 2nd plasma exchange, patients died, patients were stable, no longer indicated for high-volume plasma exchange was stopped HPEX After the 3rd plasma exchange, 18 patients with improved acute liver failure were discontinued HPEX The remaining 13 patients did not improve in liver failure These 14 15 patients died in hospital/returned to die within 28 days after the end of the 3rd plasma change Table 3.33 Effective improvement of hepatic encephalopathylevel, SOFA after high-volume plasma changes After HPEX Constant (n,%) (3,2) Increase (n,%) (5,4) (3,2) Decrease (n,%) 45 (100) 37 (94,6) 30 (96,8) Increase (n,%) (5,4) (6,4) Decrease (n,%) 45 (100) 37 (94,6) 29 (93,6) Increase (n,%) 10 (22,2) 10 (27) (22,6) NH3 Decrease (n,%) 34 (75,6) 27 (73) 24 (77,4) Constant (n,%) (2,2) 0 IL6 Increase (n,%) (2,7) (3,2) Decrease (n,%) 45 (100) 36 (97,3) 30(96,8) Comment: Most liver biochemical indices decreased after highvolume plasma exchange compared to before replacement The proportion of patients with increased blood NH3 despite high-volume plasma exchange accounts for more than 20% of patients receiving high-volume plasma exchange IL6 decreased in most patients through all high-volume plasma changes Table 3.41 Efficacy improves hemostatic copper indices after high volume plasma exchange After HPEX 1st time (n=45) Index SOFA Hepatic encephalography Increase (n,%) Decrease (n,%) (4,4) 37 (82,2) Constant (n,%) Increase (n,%) Decrease (n,%) (13,3) 31 (68,9) Constant (n,%) 14 (31,1) 2nd time (n=37) (21,6) 23 (62,2) (16,2) (2,7) 23 (62,2) 13 (35,1) 3rd time (n=31) (25,8) 15 (48,4) (25,8) (9,7) 20 (64,5) (25,8) Observe: - Hepatic encephalopathy level, SOFA score after high-volume plasma exchange general tendency is improvement (decrease compared to before high-volume plasma exchange) of which at the 1st replacement is the greatest improvement Table 3.37 Effective improvement of liver biochemical indices after high-volume plasma changes After HPEX Index AST OLD Increase (n,%) Decrease (n,%) Increase (n,%) Decrease (n,%) 1st time (n=45) (6,7) 42 (93,3) (8,9) 41 (91,1) 2nd time (n=37) (2,7) 36 (97,3) (2,7) 36 (97,3) 3rd time (n=31) (12,9) 27 (87,1) (12,9) 26 (83,9) Total bilirubin Direct bilirubin Index 1st time (n=45) Increase (n,%) Decrease (n,%) Prothrombin Increase (n,%) Decrease (n,%) Fibrinogen Increase (n,%) Decrease (n,%) Platelets (8,9) 41 (91,1) 2nd time (n=37) (18,9) 30 (81,1) (12,9) 27 (87,1) 44 (97,8) (2,2) 35 (94,6) (5,4) 29 (93,5) (6,5) 37 (82,2) (17,8) 30 (81,1) (18,9) 28 (90,3) (9,7) 3rd time (n=31) 16 17 Increase (n,%) (8,1) (6,5) Decrease 45 (100) 34 (91,9) 29 (93,5) (n,%) Comment: In most patients, prothrombin and fibrinogen levels were elevated and INR decreased after high-volume plasma exchange Platelet reduction predominates in the group of patients with highvolume plasma exchange due to acute hepatic failure 3.2.2 Some undesirable effects of high-volume plasma exchange in the supportive treatment of acute liver failure Table 3.42 Complications through plasma changes 1st time 2nd time 3rd time Complication (n=45) (n=37) (n=31) Anaphylaxis (n,%) 13 (28,89) (5,41) (3,23) Bleeding dialysis (2,22) (3,23) catheter site (n,%) Dialysis catheter 0 infection (n,%) Hypocalcemia (n,%) 29 (64,4) 11 (29,7) 15 ((48,4) Observe: Hypocalcemia is the most common complication of highvolume plasma exchange in patients with acute hepatic impairment Anaphylaxis is a complication seen in 16 times, of which patients are common in the 1st time with 28.89%, patients in the 2nd time (5.41%) and patient has anaphylaxis in the 3rd time (3.23%) No cases of venous catheter infections used in plasma Dialysis occlusion is also seen with high-volume plasma exchange All anaphylaxis in plasma exchange is grade Anaphylaxis was more common in the live group than in the death group, the difference was Statistical significance with P < 0.05 Complications of dialysis catheter site bleeding, catheter infection, and hypocalcemia did not differ between the groups CHAPTER DISCUSSION 4.1 Comment on clinical and subclinical characteristics of patients with acute hepatic failure prior to high-volume plasma exchange and some factors related to mortality In the study, the most common cause of acute liver failure was poisoning, accounting for 82.22% Among the causes of acute poisoning, the top was herbal medicine (51.11%), followed by paracetamol and other acute poisonings such as mushroom poisoning (3 patients), anti-tuberculosis drug poisoning (1 patient) Other causes such as immunity and metabolism are less common, accounting for only 26.67% of patients with acute liver failure This result is similar to the report of Le Thai Bao (2011), Le Quang Thuan (2017) Regarding the clinical signs when patients with acute liver failure are admitted to the hospital, the highlight is still jaundice symptoms accounting for 93.3% Other symptoms such as edema and ascites accounted for 17.8% and 13.3%, respectively, and hemorrhage accounted for a very low rate for patients (4.44%) Our results are similar to the study of author Le Quang Thuan (2017), the rate of jaundice accounts for 98.2% Assessing the severity of patients by assessing organ failure in general and acute liver failure in particular, we use the SOFA scale Our results show the average SOFA score of patients at the time of admission was 9.67 ± 2.39, of which 2/3 of patients had SOFA above points, and 60% of patients had or more organ failure; This result is consistent with Wang Xuan Toan's (2019) study with an average SOFA score of 8.2 ± 2.8 and Nguyen Gia Binh average SOFA score of 10.83 ± 5.4 At the end of the treatment course of high-volume plasma exchange in 45 patients with acute hepatic impairment mainly due to poisoning, we found that 46.67% of patients died/returned This result is similar to some reports of authors in the world and Vietnam Pham INR 18 19 Due (2012) studied 64 patients with acute liver failure due to acute poisoning, the final result was that 51.6% of patients were sure of survival, 39.1% of patients died at the hospital and 9.4% of patients asked for unknown final outcome Larsen et al (2016) studied 182 patients with acute hepatic impairment, of which 90 patients received standard regimens (controls) and 92 patients received standard and complementary regimens with high-volume plasma exchange (the research group) found that the hospital survival rate of the group receiving high-volume plasma exchange was 58.7% higher than yes Statistical significance compared to the control group (hospital survival rate was only 47.8%) with a < P of 0.01 Keith (2020) a study of 80 patients divided into groups (1 group of 40 patients who received plasma exchange and group of 40 patients who did not receive plasma exchange) found that the mortality rate at day 28 of the group receiving plasma exchange was 40% less statistically significant than that of the group without plasma exchange, with p < 0.05 When we investigated some of the factors associated with mortality in patients with acute liver failure, we found that there was no difference in age, gender, BMI, the cause of poisoning between the living group and the death group due to acute liver failure This result is consistent with the results of the study Filho (2018) and Cheng (2018), Y-M-Hung (2004) IL6 is a new inflammatory factor included in the evaluation of immune disorders in a variety of conditions including acute liver failure In our study, although IL6 was elevated above normal, there was no statistically significant difference in IL6 levels of survivors and deaths from acute liver failure Lasenz (2019) found a positive association between IL6 and the occurrence of hepatic encephalopathy Wang (2022) also found that IL6 was higher in the group of patients who died from end-stage liver disease (7.13 ± 12.18 pg/mL compared to 9.72 ± 5.56 pg/mL in the live group, with p points increased the risk of death in patients with acute hepatic impairment to 11.23 times that acute liver failure with SOFA ≤ points + Hepatic encephalography >3 increases the risk of death in patients with acute hepatic impairment by 2.7 times that of acute hepatic impairment with hepatic encephalopathy ≤ + Mechanical ventilation increases the risk of death in patients with acute hepatic impairment by 7.5 times compared to the group of acute liver failure without mechanical ventilation +NH3 >70 U/l increases the risk of death in patients with acute hepatic impairment by 2.12 times acute hepatic failure with NH3 ≤ 70 U/l + Lactat > mmol/l increases the risk of death in patients with acute hepatic impairment to 5.33 times with lactate ≤ mmol/l + INR > increases the risk of death in patients with acute liver failure by 4.75 times compared with acute hepatic impairment group with INR ≤ + IL6 > 38 pg/ml increased the risk of death in patients with acute hepatic impairment by 2.24 times compared with the acute hepatic impairment group with IL6 ≤ 38 pg/ml 5.2 Efficacy and some undesirable effects of high-volume plasma exchange in the supportive treatment of acute liver failure - In all plasma exchanges, a statistically significant decrease in hepatic encephalopathy after PEX compared to before PEX - SOFA after PEX decreased in all plasma changes but only 1st, the SOFA reduction was statistically significant 22 23 - At all plasma changes, AST, ALT, total bilirubin, direct bilirubin, INR decreased, fibrinogen and prothrombin all increased statistically significantly, with p < 0.001 - NH3 decreased in all plasma changes but only on the 1st filtration, NH3 decreased statistically significantly - Platelets after plasma exchange tended to decrease more than before PEX but there was no statistically significant difference Anaphylaxis is the most common complication with a total of 16 times in which, it was common in the 1st time with 28.89%, there were patients in the 2nd time (5.41%) and patient with anaphylaxis in the 3rd time (3.23%) - No cases of venous catheter infections used in plasma - Dialysis occlusion is also seen with high-volume plasma exchange - All anaphylaxis in plasma exchange is grade SUGGPESITION Based on the results drawn from this study, we would like to recommend the following: High-volume plasma exchange should be performed for patients with acute hepatic impairment, especially patients with acute hepatic failure due to toxicity, to support treatment, wait for the liver to recover spontaneously or prolong the waiting time for liver transplantation 24 LIMITATIONS OF THE TOPIC This project was conducted during the COVID-19 epidemic, so the number of patients was not large enough There is no control group to clarify the efficacy of high-volume plasma exchange with conventional volumetric plasma exchange, low-volume plasma exchange as well as plasma exchange in combination with continuous dialysis