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Wu SC, Cheng CC, Yeh HC, Cheng HT, Wang YC, Tzeng CW, Hsu CH, Muo CH. High Volume Plasma Exchange Improves Survival Rates in Surgical Critically Ill Patients With Medical Jaundice and Hepatic Failure: A Comparative Study. World J Surg 2025; 49:364-373. [PMID: 39794861 DOI: 10.1002/wjs.12483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 11/21/2024] [Accepted: 12/29/2024] [Indexed: 01/13/2025]
Abstract
OBJECTIVES Acute liver failure poses a significant challenge in surgical critically ill patients. Treatments typically focus on physiological support and alleviation of hepatic insult. This study aims to evaluate the role of high-volume plasma exchange (HVPE) in surgical critically ill patients with medical jaundice and hepatic failure. METHOD A retrospective review was conducted on surgical critically ill patients with hepatic failure unresponsive to conventional therapy, excluding those with obstructive jaundice. HVPE was considered for patients with persistent hyperbilirubinemia (> 10 mg/dL) and coexisting conditions such as coagulopathy, hyperammonemia, more than Grade II hepato-encephalopathy, or exacerbated sepsis/septic shock status or multiple organ failure. Patients were categorized into standard medical treatment (SMT) and SMT + HVPE groups. Demographics and laboratory data were collected for analysis. RESULT A total of 117 patients were enrolled, with 79 in the SMT group and 38 in the SMT + HVPE group. There were no significant differences in laboratory data and MELD score upon admission. Before treatment, patients in the SMT + HVPE group exhibited higher levels of T-bil., D-bil., and sugar than the SMT group. After treatment, the SMT + HVPE group showed lower serum D-bil. and AST levels but higher levels of albumin and platelets compared to the SMT group. The SMT + HVPE group demonstrated significantly lower delta T-bil., delta D-bil., and higher delta platelet levels. The survival rate was 31.6% (12/38) in the SMT + HVPE group and 1.3% (1/79) in the SMT group. The in-hospital mortality rate in the SMT + HVPE group was lower than that in the SMT group, with a hazard ratio of 0.42 in the crude model and 0.34 (95% CI = 0.20-0.60 and p = 0.0002) in the adjusted model. CONCLUSION Our findings suggest that HVPE improves survival rates in surgical critically ill patients with medical jaundice and hepatic failure. However, due to its retrospective nature, further studies were warranted.
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Affiliation(s)
- Shih-Chi Wu
- School of Medicine, China Medical University, Taichung, Taiwan
- Trauma and Emergency Center, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Chung Cheng
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Hung-Chieh Yeh
- Kidney Institute and Division of Nephrology, China Medical University Hospital, Taichung, Taiwan
| | - Han-Tsung Cheng
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Yu-Chun Wang
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Wei Tzeng
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Hao Hsu
- Department of Surgery, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Hsin Muo
- Management Office for Health Data, China Medical University and Hospital, Taichung, Taiwan
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Ho YL, Nukui Y, Villaça PR, Okazaki E, Tatsui NH, Netto LC, Joelsons D, da Rocha TRF, de Mello Malta F, Pinho JRR, Segurado AAC, Rocha V. Intensive Therapeutic Plasma Exchange-New Approach to Treat and Rescue Patients with Severe Form of Yellow Fever. Trop Med Infect Dis 2025; 10:39. [PMID: 39998043 PMCID: PMC11860207 DOI: 10.3390/tropicalmed10020039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Revised: 01/22/2025] [Accepted: 01/24/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Severe yellow fever (YF) can result in acute liver failure (ALF) and high mortality. The role of therapeutic plasma exchange (TPE) in managing YF-ALF remains unclear. This study evaluated the impact of TPE strategies in severe YF. METHODS This observational case-series study evaluated three groups of patients classified according to treatment: G1 (standard intensive care support [ICS]), G2 (ICS + high-volume-TPE [HV-TPE]), and G3 (ICS + intensive TPE). HV-TPE was performed during 3 consecutive days with extra sessions of one plasma-volume, if necessary, whereas intensive TPE consisted of one plasma volume/session performed twice daily, with additional fresh frozen plasma infusion. Hemostatic agents, including tranexamic acid, platelets, and cryoprecipitate, were administered as needed. TPE was de-escalated based on clinical and laboratory parameters. The primary outcome was mortality. RESULTS Sixty-six patients were included (G1: 41, G2: 11, G3: 14). Groups had similar baseline characteristics. Mortality was significantly lower in G3 (14%) compared to G2 (82%) and G1 (85%) (p < 0.001). Additionally, G3 patients showed a higher frequency of undetectable YF viral load. CONCLUSIONS Intensive TPE is a feasible and effective intervention for severe YF, achieving an 84% reduction in mortality. The limitations of our results are the small sample size, observational and single-center study. Further studies are warranted to elucidate intensive TPE's role in YF management.
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Affiliation(s)
- Yeh-Li Ho
- Departamento de Infectologia e Medicina Tropical, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil (D.J.)
| | - Youko Nukui
- Serviço de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil
| | - Paula Ribeiro Villaça
- Serviço de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil
| | - Erica Okazaki
- Serviço de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil
| | - Nelson Hidekazu Tatsui
- Serviço de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil
| | - Lucas Chaves Netto
- Departamento de Infectologia e Medicina Tropical, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil (D.J.)
| | - Daniel Joelsons
- Departamento de Infectologia e Medicina Tropical, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil (D.J.)
| | - Tania Rubia Flores da Rocha
- Serviço de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil
| | - Fernanda de Mello Malta
- LIM07, Departamento de Gastroenterologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil
| | - João Renato Rebello Pinho
- LIM07, Departamento de Gastroenterologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil
| | - Aluisio Augusto Cotrim Segurado
- Departamento de Infectologia e Medicina Tropical, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil (D.J.)
| | - Vanderson Rocha
- Serviço de Hematologia, Hemoterapia e Terapia Celular, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo 05403-000, Brazil
- Fundacao Pro-Sangue, Sao Paulo 05403-000, Brazil
- Churchill Hospital, Oxford University Hospitals, Oxford OX3 7LE, UK
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Nguyen TT, Ngo PTM, Vo LT. Predicting the risk of mortality in children with dengue-induced hepatitis admitted to the paediatric intensive care unit. World J Crit Care Med 2024; 13:98862. [PMID: 39655306 PMCID: PMC11577541 DOI: 10.5492/wjccm.v13.i4.98862] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 09/26/2024] [Accepted: 10/20/2024] [Indexed: 10/31/2024] Open
Abstract
BACKGROUND Dengue-associated acute liver failure (PALF) accounts for a high mortality rate in children admitted to the pediatric intensive care unit (PICU). To date, there is a lack of data on clinical algorithms for estimating the risk of mortality in pediatric patients with dengue-induced severe hepatitis (DISH). AIM To determine the prevalence of PALF and identify the predictors of mortality among patients with DISH. METHODS This single-institution retrospective study was performed at a tertiary pediatric hospital in Vietnam between 2013 and 2022. The primary outcome was in-hospital mortality in pediatric patients with DISH, which was defined as either aspartate aminotransferase > 350 IU/L or alanine aminotransferase > 400 IU/L. Prognostic models for estimating the risk of death among patients with DISH were developed using a predefined set of clinical covariables and hepatic biomarkers on PICU admission and during the first 72 hours of admission. Area under the curve, multivariable logistic regression, and multiple imputation using the chained equation for missing values were performed. Backward stepwise model selection based on the Akaike information criterion was employed. Bootstrapping, calibration slope, and Brier score were used to assess the final models. RESULTS A total of 459 children with DISH were included in the analysis. The median patient age was 7.7 years (interquartile range: 4.3-10.1 years). The prevalence of dengue-associated PALF in children with DISH was 18.3%. Thirty-nine DISH patients developing PALF (8.5%) died. Hepatic biomarkers, including the international normalized ratio (INR) ≥ 2.11 and total serum bilirubin (≥ 1.7 mg/dL), showed high predictive values for mortality (all P values < 0.001). Multivariable models showed the significant clinical predictors of death from dengue-induced PALF in patients with DISH, including reduced level of consciousness (pain and unresponsive levels on the Alert, Verbal, Pain, Unresponsive scale), high vasoactive-inotropic score (> 30), and elevated levels of blood lactate, INR, and serum bilirubin. The final prognostic model demonstrated high discrimination, Brier score, and an acceptable calibration slope. CONCLUSION The prevalence of PALF in children with DISH is 18.3%. We developed robust prognostic models to estimate the risk of death in hospitalized children with severe dengue-induced hepatitis.
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Affiliation(s)
- Thanh Tat Nguyen
- Department of Tuberculosis, Woolcock Institute of Medical Research, Ho Chi Minh 700000, Viet Nam
- Department of Infectious Diseases, The Children’s Hospital 2, Ho Chi Minh 700000, Viet Nam
| | - Phuong Thi-Mai Ngo
- Department of Infectious Diseases, The Children’s Hospital 2, Ho Chi Minh 700000, Viet Nam
| | - Luan Thanh Vo
- Department of Infectious Diseases, The Children’s Hospital 2, Ho Chi Minh 700000, Viet Nam
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Chowdhry M, Sharma A, Agrawal S, Vohra R, Kumar K, Goyal N, Kumar V A, Jerath N, Malhotra S, Sibal A, Mishra M. Efficacy of therapeutic plasma exchange in pediatric cases of acute liver failure as an extracorporeal liver support system. Transfus Apher Sci 2023; 62:103835. [PMID: 37996345 DOI: 10.1016/j.transci.2023.103835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 10/11/2023] [Accepted: 10/16/2023] [Indexed: 11/25/2023]
Abstract
BACKGROUND Acute liver failure in the pediatric population is often accompanied by deranged metabolism, severe encephalopathy and coagulopathy. A liver transplant is the most viable option for the management of such patients. Therapeutic plasma exchange (TPE) is helpful in improving the liver biochemistry profile, thereby, increasing their likelihood of undergoing a liver transplant METHOD: The study was conducted over a period of 3 years (January 2018 to December 2021). Indications mainly consisted of ALF with hepatic encephalopathy, worsening liver parameters in spite of medical management, and candidacy for undergoing a liver transplant. Plasma exchange was performed daily or alternatively until the patient recovered, succumbed, or was stable enough to undergo a transplant. Biochemical parameters serum bilirubin, ALT, AST serum ammonia serum urea, serum creatinine were recorded before and after TPE sessions. RESULTS The study group comprised 14 patients of which a total of 28 TPE was performed. There were a total of 5 cases of cryptogenic ALF, 4 of Wilson disease, 2 cases each of infection-related ALF and autoimmune hepatitis, and a single case of drug-induced hepatitis. A total of 5 out of 14 patients underwent a liver transplant and amongst the 9 who did not undergo a transplant, 4 patients expired due to septic shock syndrome; the remaining 5 were discharged in a stable condition following TPE sessions. The disease-free survival was 78.9% and the transplant-free survival was 35.71%. CONCLUSION TPE plays a crucial role in improving the biochemistry profile of the liver in children with liver failure.
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Affiliation(s)
- Mohit Chowdhry
- Department of Transfusion Medicin & Transplant Immunology, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India.
| | - Ankita Sharma
- Department of Transfusion Medicine, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
| | - Soma Agrawal
- Department of Transfusion Medicine, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
| | - Rohit Vohra
- Department of Pediatric, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
| | - Karunesh Kumar
- Department of Pediatric Gastroenterology, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
| | - Neerav Goyal
- Department of Liver transplant and hepatic-biliary-pancreatic Surgery, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
| | - Arun Kumar V
- Department of Liver transplant and hepatic-biliary-pancreatic Surgery, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
| | - Nameet Jerath
- Department of Pediatric, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
| | - Smita Malhotra
- Department of Pediatric Gastroenterology, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
| | - Anupam Sibal
- Department of Pediatric Gastroenterology, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
| | - Manoj Mishra
- Department of Transplant Immunology, Indraprastha Apollo Hospitals, Sarita Vihar, Mathura Road, New Delhi 110076, India
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Li L, Huang D, Xu J, Li M, Zhao J, Shi Q, Guo Q. The assessment in patients with acute fatty liver of pregnancy (AFLP) treated with plasma exchange: a cohort study of 298 patients. BMC Pregnancy Childbirth 2023; 23:171. [PMID: 36915067 PMCID: PMC10012504 DOI: 10.1186/s12884-023-05503-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 03/07/2023] [Indexed: 03/16/2023] Open
Abstract
BACKGROUND To assess the prevalence, risk factors, clinical characteristics of Acute fatty liver of pregnancy (AFLP) patients, and outcomes of AFLP patients treated with plasma exchange (PE). METHODS We retrospectively reviewed the AFLP patients admitted to the First Affiliated Hospital of Xi'an Jiaotong University and Xijing Hospital of Air Force Medical University from January 2012 to May 2022. Final prediction model for death among AFLP by means of stepwise backward elimination with p value < 0.05. Patients treated with and without PE were compared by propensity-matched cohort study. RESULTS Two hundred ninety eight patients with the diagnosis of AFLP, and finally 290 patients were enrolled in the cohort study, 50 of whom (17.2%) were dead. Compared with AFLP patients alive, the dead of patients were more likely to be combined encephalopathy (p < 0.01), postpartum hemorrhage (p < 0.01), and found significantly higher frequency of fetal distress (p = 0.04), fetal death (p < 0.01). we developed a predicted probability value and with an area under the receiver operating characteristics (ROC) curve of 0.94 (95%CI 0.87 to 1.00), indicating AFLP patients' death. The patients treated with PE had a significantly lower 60-day mortality rate (OR 0.42, 95% CI 0.29 to 2.64, p = 0.04), and significantly shorter duration of hospital-free days at day 28 (p = 0.01). CONCLUSIONS In conclusion, our study indicated that liver function were risk factors for maternal mortality, and PE was a protective factor for maternal 60-day mortality and hospital-free days at day 28 in AFLP patients.
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Affiliation(s)
- Lingxia Li
- Department of Obstetrics and Gynecology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, China
| | - Dengchao Huang
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, 710061, Shaanxi, China
| | - Jing Xu
- Department of Emergency Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, 710061, Shaanxi, China
| | - Miaojing Li
- Department of Hematopathology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, 710061, Shaanxi, China
| | - Juan Zhao
- Department of Hematopathology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, 710061, Shaanxi, China
| | - Qindong Shi
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, 710061, Shaanxi, China
| | - Qinyue Guo
- Department of Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Street, Xi'an, 710061, Shaanxi, China.
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Cheng CY, Tsai CH, Wang HP, Chiu WT, Hung HC, Chi CY, Tsai IJ. Successful treatment of acute encephalitis and hepatitis in a child with COVID-19 infection. J Formos Med Assoc 2022; 122:182-186. [PMID: 36610889 PMCID: PMC9691442 DOI: 10.1016/j.jfma.2022.11.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/25/2022] [Accepted: 11/20/2022] [Indexed: 11/27/2022]
Abstract
We present the case of a 6-year-old Taiwanese boy with a fulminant course of COVID-19 manifesting as high fever, acute consciousness changes, and status epilepticus. Brain MRI showed restricted diffusion in the bilateral hemisphere. Electroencephalogram showed diffuse slow waves with few spikes. CSF study was clear without evidence of common pathogens. He received treatment with antiviral agents, corticosteroids, intravenous immunoglobulins, and anti-IL-6 monoclonal antibodies. However, progressive fulminant hepatitis, hyperammonaemia, and disseminated intravascular coagulopathy developed. Rescue therapy with hybrid continuous renal replacement therapy and plasma exchange were performed in the first 11 days. The patient improved and was extubated on the 11th day. After physical therapy, his neurological function improved significantly. The patient was discharged under rehabilitation after 1 month of hospitalization. Viral sequencing confirmed infection with the Omicron BA.2.3 variant, one of the dominant strains in Taiwan and Hong Kong. Whole-exome sequencing revealed heterozygous uncertain significance variants in <I>TICAM-1, RNF 31</I>, and mitochondrial <I>MT-RNR1</I>, which provide additional support for the fulminant course. To the best of our knowledge, this is the first reported case of COVID-19 in a child with a fulminant course of acute encephalitis and hepatitis who successfully recovered by hybrid continuous renal replacement therapy and plasma exchange.
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Affiliation(s)
- Chiao-Yu Cheng
- Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan
| | - Cheng-Hsien Tsai
- Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Douliou, Yunlin County, Taiwan,Corresponding author. Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, No. 579, Sec. 2, Yunlin Rd., Douliu City, Yunlin County 640203, Taiwan
| | - Hsin-Pei Wang
- Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Douliou, Yunlin County, Taiwan
| | - Wei-Tse Chiu
- Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Douliou, Yunlin County, Taiwan
| | - Hsi-Chuan Hung
- Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Douliou, Yunlin County, Taiwan
| | - Chun-Yi Chi
- Department of Medical Nephrology, National Taiwan University Hospital Yunlin Branch, Douliou, Yunlin County, Taiwan
| | - I-Jung Tsai
- Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan
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Thanh NT, Dat NT, Thinh TN, Phuong NTM, Thanh MTH, Bao NT, Son PT, Viet DC, Tung TH, Thien V, Luan VT. Therapeutic plasma exchange and continuous renal replacement therapy in pediatric dengue-associated acute liver failure: A case series from Vietnam. Transfus Apher Sci 2022; 62:103617. [PMID: 36522271 DOI: 10.1016/j.transci.2022.103617] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 11/04/2022] [Accepted: 11/23/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND OBJECTIVES Paediatric dengue-associated acute liver failure (PALF) is a rare and fatal complication. To date, clinical data regarding the combination of therapeutic plasma exchange (TPE) and continuous renal replacement therapy (CRRT) for the treatment of dengue-associated PALF are limited. METHODS We conducted a single-center, retrospective study of all children with dengue-associated PALF admitted to the paediatric intensive care unit of Children Hospital No.2, Vietnam, who were treated with TPE+CRRT between January 2021 and March 2022. The main study outcomes were in-hospital survival, normalisation of hepatic function, and hepatic encephalopathy improvement. RESULTS Twelve patients aged from 06 to 12 years underwent TPE+CRRT procedures. Among them, three (25 %) patients died of severe sepsis and septic shock confirmed by Enterobacteriaceae spp. haemocultures (stable on maintenance treatment of COVID-19-associated MIS-C with low dose of oral steroids on hospital admission), acute respiratory distress syndrome (ARDS), and clinically apparent intracranial haemorrhage. Nine patients (75 %) survived. The paediatric mortality risk score improved significantly at discharge compared with PICU admission (P < 0.01). Markedly, all twelve patients were diagnosed with hepatoencephalopathy of grades III and IV on PICU admission. After the combined TPE+CRRT interventions, there were substantial improvements in liver transaminases levels, coagulation profiles, and metabolic biomarkers. Normal neurological functions were observed in nine alive patients at hospital discharge. Only one patient experienced an adverse event of slightly low blood pressure, which rapidly self-resolved. INTERPRETATION AND CONCLUSIONS Combined TPE+CRRT significantly improved survival outcome, neurological status, and rapid normalisation of liver functions in dengue-associated PALF.
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Affiliation(s)
- Nguyen Tat Thanh
- Children Hospital 2, Ho Chi Minh City, Viet Nam; Woolcock Institute of Medical Research, Viet Nam
| | - Nguyen Tat Dat
- University of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam
| | | | - Ngo Thi Mai Phuong
- Children Hospital 2, Ho Chi Minh City, Viet Nam; University of Medicine and Pharmacy, Ho Chi Minh City, Viet Nam.
| | | | | | | | - Do Chau Viet
- Children Hospital 2, Ho Chi Minh City, Viet Nam.
| | | | - Vu Thien
- Shiga University of Medical Science, Otsu City, Shiga, Japan.
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Benić MS, Nežić L, Vujić-Aleksić V, Mititelu-Tartau L. Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review. Front Pharmacol 2022; 12:785790. [PMID: 35185538 PMCID: PMC8847672 DOI: 10.3389/fphar.2021.785790] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 12/30/2021] [Indexed: 12/15/2022] Open
Abstract
Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome.
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Affiliation(s)
- Mirjana Stanić Benić
- Department of Clinical Pharmacology, Clinical Hospital Centre Rijeka, Rijeka, Croatia
| | - Lana Nežić
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
| | - Vesna Vujić-Aleksić
- Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina
- The Republic of Srpska Agency for Certification, Accreditation and Quality Improvement in Health Care, Banja Luka, Bosnia and Herzegovina
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Abstract
Liver failure in the context of acute (ALF) and acute on chronic liver failure (ACLF) is associated with high mortality in the absence of a liver transplant. For decades, therapeutic plasma exchange (TPE) is performed for the management of immune-mediated diseases. TPE has emerged as an attractive extracorporeal blood purification technique in patients with ALF and ACLF. The basic premise of using TPE is to remove the toxic substances which would allow recovery of native liver functions by facilitating liver regeneration. In recent years, encouraging data have emerged, suggesting the benefits of TPE in patients with liver failure. TPE has emerged as an attractive liver support device for the failing liver until liver transplantation or clinical recovery. The data in patients with ALF suggest routine use of high-volume TPE, while the data for such a strategy are less robust for patients with ACLF.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Bilgic Y, Akbulut S, Cengiz A, Sarici A, Cagin Y, Harputluoglu M. Therapeutic Effects of Plasmapheresis on Acute Exacerbations of Chronic Hepatitis B Infection. Cureus 2021; 13:e12779. [PMID: 33628651 PMCID: PMC7890433 DOI: 10.7759/cureus.12779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Objective In this study, we aimed to demonstrate the effectiveness of plasmapheresis therapy in patients with acute exacerbation of chronic Hepatitis B (CHB) infection. Methods We selected 48 patients with acute exacerbation of CHB infection who were treated by plasmapheresis in our intensive care unit between 2009 and 2016. The patients' demographic characteristics and biochemical and hematological parameters, which were recorded before and after plasmapheresis, were assessed, and the effect of plasmapheresis on the course of patients' treatment was examined. The patients were also divided into three groups according to their clinical course (discharged: 24; transplanted: six; exitus: eight). The patients were further divided into four groups and compared based on the underlying causes that led to the exacerbation (spontaneous exacerbation: 25; caused by immunosuppressive drugs: nine; hepatotoxic drugs: six; other agents: eight). Results We observed significant improvements in terms of international normalized ratio (INR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin, direct bilirubin, blood urea nitrogen (BUN), ammonia, and the Model for End-Stage Liver Disease (MELD) score after plasmapheresis therapy. However, there was no significant improvement in hemoglobin (Hb), white blood cell (WBC) count, platelets, albumin, and lactate values. Also, INR, ALP, and ALT values were found to be significantly correlated with transplants and exitus in patients. Conclusion Plasmapheresis therapy is a reliable treatment method that provides clinical recovery and improvement in laboratory parameters in patients with exacerbation of CHB infection.
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Affiliation(s)
- Yilmaz Bilgic
- Gastroenterology and Hepatology, Inonu University, Malatya, TUR
| | - Sami Akbulut
- Surgery/Liver Transplantation, Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, TUR
| | - Ayse Cengiz
- Internal Medicine, Inonu Univeristy, Malatya, TUR
| | | | - Yasir Cagin
- Gastroenterology and Hepatology, Inonu University, Malatya, TUR
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Kim JE, Chun S, Sinn DH, Kim NJ, Kim S, Kang W, Kim JM, Choi GS, Joh JW, Cho D. Initial experience with high-volume plasma exchange in patients with acute liver failure. J Clin Apher 2021; 36:379-389. [PMID: 33400840 DOI: 10.1002/jca.21873] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 12/24/2020] [Accepted: 12/27/2020] [Indexed: 12/21/2022]
Abstract
BACKGROUND/AIMS High-volume plasma exchange (HVPE), defined as an exchange of 8 to 12 L per day per procedure or 15% of the ideal body weight with fresh frozen plasma, has shown promising results in improving the survival of patients with acute liver failure (ALF). However, clinical evidence is limited. The aim of this study was to report our initial experience using HVPE as a bridge treatment in patients with ALF. METHODS We retrospectively reviewed 32 consecutive patients awaiting liver transplantation (LT) due to ALF between 2013 and 2020 at Samsung Medical Center in Korea. HVPE has been used for patients with ALF since May 2016 at our institution. RESULTS During the study period, 16 patients received HVPE. After HVPE, coagulopathies (INR, 4.46 [2.32-6.02] vs 1.48 [1.33-1.76], P < .05), total bilirubin (22.6 [9.1-26.4] vs 8.9 [5.6-11.3], P < .05), alanine aminotransferase (506 [341-1963] vs 120 [88-315], P < .05), and ammonia levels (130.6 [123.7-143.8] vs 98.2 [84.2-116.5], P < .05) were improved. Improvement in the hepatic encephalopathy grade was observed in four patients. Among 16 patients who received HVPE, 12 patients were bridged to LT, and three patients recovered spontaneously. The overall survival was 94% and 69%, respectively at 30 days in patients who received and did not receive HVPE (P = .068). Among 18 patients with high chronic liver failure-sequential organ failure assessment scores (≥13), the overall survival was significantly better for those who received HVPE than for those who did not (91% vs 29%, respectively, at 30 days, P < .05). CONCLUSIONS Our initial clinical experience with HVPE suggests that HVPE can be a viable option in improving the outcomes of patients presenting with ALF.
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Affiliation(s)
- Ji Eun Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Sejong Chun
- Department of Laboratory Medicine, Chonnam National University Medical School & Hospital, Gwangju, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | | | - Semi Kim
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Wonseok Kang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jong Man Kim
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Gyu-Seong Choi
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Duck Cho
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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12
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Ocak İ, Topaloğlu S, Acarli K. Posthepatectomy liver failure. Turk J Med Sci 2020; 50:1491-1503. [PMID: 32718126 PMCID: PMC7605090 DOI: 10.3906/sag-2006-31] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 07/26/2020] [Indexed: 01/02/2023] Open
Abstract
Liver surgery is one of the most complex surgical interventions with high risk and potential for complications. Posthepatectomy liver failure (PHLF) is a serious complication of liver surgery that occurs in about 10% of patients undergoing major liver surgery. It is the main source of morbidity and mortality. Appropriate surgical techniques and intensive care management are important in preventing PHLF. Early start of the liver support systems is very important for the PHLF patient to recover, survive, or be ready for a liver transplant. Nonbiological and biological liver support systems should be used in PHLF to prepare for treatment or organ transplantation. The definition of the state, underlying pathophysiology and treatment strategies will be reviewed here.
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Affiliation(s)
- İlhan Ocak
- Department of Critical Care Unit, İstanbul Memorial Hospital, İstanbul, Turkey
| | - Serdar Topaloğlu
- Department of Surgery, School of Medicine, Karadeniz Technical University, Trabzon, Turkey
| | - Koray Acarli
- Department of Organ Transplantation, Department of Surgery, İstanbul Memorial Hospital, İstanbul, Turkey
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13
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Rodgers SA, Suneja A, Yoshida A, Abouljoud MS, Otrock ZK. Paradoxical embolic strokes in a liver transplant recipient with atrial septal defect undergoing therapeutic plasma exchange. J Clin Apher 2020; 36:206-210. [PMID: 33058311 DOI: 10.1002/jca.21849] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 08/28/2020] [Accepted: 10/02/2020] [Indexed: 11/06/2022]
Abstract
Therapeutic plasma exchange (TPE) is a technique used to separate blood components into layers based on their density difference, thus removing plasma and exchanging it with replacement fluids. A variety of adverse reactions has been described during TPE. Thrombotic events, especially strokes, are extremely rare complications of TPE. Our patient was a 55-year-old female with history of decompensated nonalcoholic steatohepatitis (NASH) liver cirrhosis. She underwent an orthotopic liver transplant (OLT) that was complicated with asystole during reperfusion. Cardiac workup revealed a new atrial septal defect (ASD) with left to right flow. Within the first 5 days after surgery, she developed refractory and persistent hyperbilirubinemia, with total bilirubin levels as high as 42 mg/dL. Our plasmapheresis service was consulted to initiate TPE. Towards the end of the first and only session of TPE, the patient developed hypoxia and left-sided hemiplegia. Stroke response was initiated, and the patient was intubated. MRI done 24 hours after the incident showed multiple acute small embolic infarcts scattered within the bilateral cerebral and cerebellar hemispheres. Bilateral lower and upper extremities venous duplex studies were positive for acute left internal jugular (IJ) vein thrombosis. Patient was treated with anticoagulation and the IJ catheter was removed. Patient also had closure of her ASD. On last follow up, she was doing well with complete reversal of neurologic deficits and stable liver function. Our patient had an uncommon complication of TPE. Her thrombosis manifested with multiple embolic strokes that would not have happened without an ASD with left to right flow.
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Affiliation(s)
- Shannon A Rodgers
- Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, Michigan, USA
| | - Aarushi Suneja
- Department of Neurology, Henry Ford Health System, Detroit, Michigan, USA
| | - Atsushi Yoshida
- Transplant and Hepatobiliary Surgery, Henry Ford Health System, Detroit, Michigan, USA
| | - Marwan S Abouljoud
- Department of Neurology, Henry Ford Health System, Detroit, Michigan, USA
| | - Zaher K Otrock
- Department of Pathology and Laboratory Medicine, Henry Ford Health System, Detroit, Michigan, USA
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14
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Tan EXX, Wang MX, Pang J, Lee GH. Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review. World J Gastroenterol 2020; 26:219-245. [PMID: 31988586 PMCID: PMC6962432 DOI: 10.3748/wjg.v26.i2.219] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Revised: 12/21/2019] [Accepted: 01/01/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute liver failure (ALF) and acute-on-chronic liver (ACLF) carry high short-term mortality rate, and may result from a wide variety of causes. Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant. Other cohort studies demonstrated potential improvement in survival in patients with ACLF.
AIM To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation.
METHODS Databases MEDLINE via PubMed, and EMBASE were searched and relevant publications up to 30 March, 2019 were assessed. Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange, with or without another alternative non-bioartificial liver assist device.
RESULTS Three hundred twenty four records were reviewed, of which 62 studies were found to be duplicates. Of the 262 records screened, 211 studies were excluded. Fifty-one articles were assessed for eligibility, for which 7 were excluded. Twenty-nine studies were included for ALF only, and 9 studies for ACLF only. Six studies included both ALF and ACLF patients. A total of 44 publications were included. Of the included publications, 2 were randomized controlled trials, 14 cohort studies, 12 case series, 16 case reports. All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment (SMT) for ACLF, a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60 (95%CI 0.46-0.77, P < 0.01).
CONCLUSION The level of evidence for use of high volume plasma exchange in selected ALF cases is high. Plasma exchange in ACLF improves survival at 30-and 90-d in non-transplanted patients. Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.
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Affiliation(s)
| | - Min-Xian Wang
- Centre for Infectious Disease Epidemiology and Research, Saw Swee Hock School of Public Health, National University of Singapore, Singapore 119077, Singapore
| | - Junxiong Pang
- Centre for Infectious Disease Epidemiology and Research, Saw Swee Hock School of Public Health, National University of Singapore, Singapore 119077, Singapore
| | - Guan-Huei Lee
- National University Health System, Singapore 119228, Singapore
- National University of Singapore, Singapore 119077, Singapore
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15
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Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, Pham HP, Schneiderman J, Witt V, Wu Y, Zantek ND, Dunbar NM, Schwartz GEJ. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher 2019; 34:171-354. [PMID: 31180581 DOI: 10.1002/jca.21705] [Citation(s) in RCA: 835] [Impact Index Per Article: 139.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating and categorizing indications for the evidence-based use of therapeutic apheresis (TA) in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Eighth Edition of the JCA Special Issue continues to maintain this methodology and rigor in order to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Eighth Edition, like its predecessor, continues to apply the category and grading system definitions in fact sheets. The general layout and concept of a fact sheet that was introduced in the Fourth Edition, has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of TA in a specific disease entity or medical condition. The Eighth Edition comprises 84 fact sheets for relevant diseases and medical conditions, with 157 graded and categorized indications and/or TA modalities. The Eighth Edition of the JCA Special Issue seeks to continue to serve as a key resource that guides the utilization of TA in the treatment of human disease.
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Affiliation(s)
- Anand Padmanabhan
- Medical Sciences Institute & Blood Research Institute, Versiti & Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Laura Connelly-Smith
- Department of Medicine, Seattle Cancer Care Alliance & University of Washington, Seattle, Washington
| | - Nicole Aqui
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rasheed A Balogun
- Department of Medicine, University of Virginia, Charlottesville, Virginia
| | - Reinhard Klingel
- Apheresis Research Institute, Cologne, Germany & First Department of Internal Medicine, University of Mainz, Mainz, Germany
| | - Erin Meyer
- Department of Hematology/Oncology/BMT/Pathology, Nationwide Children's Hospital, Columbus, Ohio
| | - Huy P Pham
- Department of Pathology, Keck School of Medicine of the University of Southern California, Los Angeles, California
| | - Jennifer Schneiderman
- Department of Pediatric Hematology/Oncology/Neuro-oncology/Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois
| | - Volker Witt
- Department for Pediatrics, St. Anna Kinderspital, Medical University of Vienna, Vienna, Austria
| | - Yanyun Wu
- Bloodworks NW & Department of Laboratory Medicine, University of Washington, Seattle, Washington, Yale University School of Medicine, New Haven, Connecticut
| | - Nicole D Zantek
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
| | - Nancy M Dunbar
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
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16
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Heffner GG, Cavanagh A, Nolan B. Successful management of acute bilirubin encephalopathy in a dog with immune‐mediated hemolytic anemia using therapeutic plasma exchange. J Vet Emerg Crit Care (San Antonio) 2019; 29:549-557. [DOI: 10.1111/vec.12876] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Revised: 07/13/2017] [Accepted: 08/11/2017] [Indexed: 12/17/2022]
Affiliation(s)
- Geoff G. Heffner
- Department of Clinical Sciences, Colorado State University Fort Collins CO
- Alpenglow Veterinary Specialty and Emergency Center Boulder CO
| | - Amanda Cavanagh
- Department of Clinical Sciences, Colorado State University Fort Collins CO
- Alpenglow Veterinary Specialty and Emergency Center Boulder CO
| | - Benjamin Nolan
- Department of Clinical Sciences, Colorado State University Fort Collins CO
- Alpenglow Veterinary Specialty and Emergency Center Boulder CO
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17
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Park GE, Peck KR, Kim JM, Kwon CHD, Joh JW, Cho D, Sinn DH. Infectious Complications in Patients Who Received High-Volume Plasma Exchange Prior to Liver Transplant: A Case Report. EXP CLIN TRANSPLANT 2019; 18:392-395. [PMID: 30696393 DOI: 10.6002/ect.2018.0071] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Acute liver failure is a rare but life-threatening medical emergency. Despite advancements in medical management, mortality rates of acute liver failure remain high. Currently, liver transplant is the only definitive therapeutic option available. High-volume plasma exchange has been shown to increase transplant-free survival in patients with acute liver failure before liver transplant. However, the occurrence of infectious complications in patients who receive this treatment has not been well studied. We report 2 cases of severe opportunistic infections occurring within 30 days of transplant in patients who underwent high-volume plasma exchange before liver transplant.
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Affiliation(s)
- Ga Eun Park
- From the Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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18
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Prognostic factors and treatment effect of standard-volume plasma exchange for acute and acute-on-chronic liver failure: A single-center retrospective study. Transfus Apher Sci 2018; 57:537-543. [PMID: 29880246 DOI: 10.1016/j.transci.2018.05.030] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Revised: 05/29/2018] [Accepted: 05/31/2018] [Indexed: 12/15/2022]
Abstract
Patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have a high risk of mortality. Few studies have reported prognostic factors for patients receiving plasma exchange (PE) for liver support. We conducted a retrospective analysis using data of 55 patients with severe ACLF (n = 45) and ALF (n = 10) who received standard-volume PE (1-1.5 plasma volume) in the ICU. Hepatitis B virus infection accounts for the majority of ACLF (87%) and ALF (50%) patients. PE significantly improved the levels of total bilirubin, prothrombin time and liver enzymes (P<0.05). Thirteen ACLF patients (29%) and one ALF patient (10%) underwent liver transplantation. Two ALF patients (20%) recovered spontaneously without transplantation. The overall in-hospital survival rates for ACLF and ALF patients were 24% and 30%, and the transplant-free survival rates were 0% and 20%, respectively. For the 14 transplanted patients, the one-year survival rate was 86%. Multivariate analysis showed that pre-PE hemoglobin (P = 0.008), post-PE hemoglobin (P = 0.039), and post-PE CLIF-C ACLF scores (P = 0.061) were independent predictors of survival in ACLF. The post-PE CLIF-C ACLF scores ≥59 were a discriminator predicting the in-hospital mortality (area under the curve = 0.719, P = 0.030). Cumulative survival rates differed significantly between patients with CLIF-C ACLF scores ≤ 58 and those with CLIF-C ACLF scores ≥ 59 after PE (P< 0.05). The findings suggest that PE is mainly a bridge for liver transplantation and spontaneous recovery is exceptional even in patients treated with PE. A higher improvement in the post-PE CLIF-C ACLF score is associated with a superior in-hospital survival rate.
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19
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Increasing use of therapeutic apheresis as a liver-saving modality. Transfus Apher Sci 2017; 56:385-388. [PMID: 28366590 DOI: 10.1016/j.transci.2017.03.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Revised: 03/02/2017] [Accepted: 03/02/2017] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Therapeutic plasma exchange (TPE) is used for temporary support of liver function in patients presenting with early graft dysfunction after liver transplantation (LT) or liver surgery. We analyzed the effect of therapeutic apheresis on patients with liver disease. METHODS Between January 2011 and August 2016, 93 apheresis procedures were performed for 26 patients at our institution. Anti-ABO isoagglutination immunoglobulin (Ig) M titer was checked using a type A and type B 3% red blood cell (RBC) suspension in saline with two-fold serial dilutions of patient serum. Anti-ABO isoagglutination IgG titer was checked by a type A and B 0.8% RBC suspension using a low-ionic strength/Coombs card. RESULTS ABO-incompatible (ABOi) LT was the most common (n=10, 38.5%) indication for apheresis; early graft dysfunction after LT (n=8, 30.7%) was the second most common. Median initial IgM and IgG anti-ABO titers for ABOi LT recipients were 1:16 (range, 1:8-1:128) and 1:48 (range, 1:8-1:2048). We performed preoperative TPE in 10 recipients (median number of sessions, 1.5; range, 1-11). Among patients with early graft dysfunction, those who underwent living donor LT had better survival (4/4; 100%) than those who underwent nonliving donor LT (0/3; 0%). Patients who underwent living donor LT first and then additional LT also survived after three TPE sessions. CONCLUSION Therapeutic apheresis is associated with a good survival rate and is essential for liver support in patients with early graft dysfunction after LT or posthepatectomy liver failure and during preparation for ABOi LT.
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20
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Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, Dunbar NM, Witt V, Wu Y, Shaz BH. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Seventh Special Issue. J Clin Apher 2017; 31:149-62. [PMID: 27322218 DOI: 10.1002/jca.21470] [Citation(s) in RCA: 276] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Joseph Schwartz
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York
| | - Anand Padmanabhan
- Blood Center of Wisconsin, Department of Pathology, Medical College of Wisconsin, Milwaukee, Wisconsin
| | - Nicole Aqui
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rasheed A Balogun
- Division of Nephrology, University of Virginia, Charlottesville, Virginia
| | - Laura Connelly-Smith
- Department of Medicine, Seattle Cancer Care Alliance and University of Washington, Seattle, Washington
| | - Meghan Delaney
- Bloodworks Northwest, Department of Laboratory Medicine, University of Washington, Seattle, Washington
| | - Nancy M Dunbar
- Department of Pathology and Laboratory Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Volker Witt
- Department for Pediatrics, St. Anna Kinderspital, Medical University of Vienna, Vienna, Austria
| | - Yanyun Wu
- Bloodworks Northwest, Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut
| | - Beth H Shaz
- Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.,New York Blood Center, Department of Pathology.,Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia
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21
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Rammohan A, Sachan D, Logidasan S, Sathyanesan J, Palaniappan R, Rela M. Role of plasmapheresis in early allograft dysfunction following deceased donor liver transplantation. World J Hematol 2017; 6:24-27. [DOI: 10.5315/wjh.v6.i1.24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 09/25/2016] [Accepted: 11/17/2016] [Indexed: 02/05/2023] Open
Abstract
The role of plasmapheresis in liver failure and hepatic encephalopathy is undefined and its use as a strategy to salvage patients with severe allograft dysfunction after liver transplantation remains investigational. We present a case of early allograft dysfunction following deceased donor liver transplantation (DDLT) where plasmapheresis was effective as a bridge to recovery and possibly avoiding a retransplantation. A 16 years old boy, known to have decompensated Wilson’s disease underwent DDLT at our Public Sector Hospital. He received a healthy liver from a brain-dead donor, whose liver was considered too large for the boy. The graft was reduced in situ to a left lobe graft. Surgery was uneventful and the recipient was well for the initial 96 h. On Doppler and further computed tomography scan, a partial portal vein thrombus was noted. He was reexplored and a Fogarty endothombecteomy was performed. Following the second surgery, he developed severe allograft dysfunction with a peak bilirubin of 40 mg/dL. He underwent imaging to rule out technical causes for the dysfunction, followed by a liver biopsy, which revealed acute cellular rejection. Multiple cycles of plasmapheresis were initiated. Over the next two weeks, the graft demonstrated a gradual recovery. He was discharged on the 30th postoperative day, with a serum bilirubin of 5.5 mg/dL. He remains well on follow-up, with the liver function tests improving further. Our report demonstrates the beneficial effect of plasmapheresis, which appears to be an effective treatment option for early allograft dysfunction following liver transplantation and may obviate the need for retransplantation.
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22
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Melgaço JG, Soriani FM, Sucupira PHF, Pinheiro LA, Vieira YR, de Oliveira JM, Lewis-Ximenez LL, Araújo CCV, Pacheco-Moreira LF, Menezes GB, Cruz OG, Vitral CL, Pinto MA. Changes in cellular proliferation and plasma products are associated with liver failure. World J Hepatol 2016; 8:1370-1383. [PMID: 27917263 PMCID: PMC5114473 DOI: 10.4254/wjh.v8.i32.1370] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 08/03/2016] [Accepted: 09/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To study the differences in immune response and cytokine profile between acute liver failure and self-limited acute hepatitis.
METHODS Forty-six patients with self-limited acute hepatitis (AH), sixteen patients with acute liver failure (ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced self-limited AH and ALF. Thus, we worked with five groups: Hepatitis A virus (HAV)-induced self-limited acute hepatitis (HAV-AH), HAV-induced ALF (HAV-ALF), non-viral-induced self-limited acute hepatitis (non-viral AH), non-viral-induced acute liver failure (non-viral ALF), and healthy subjects (HC). Comparisons among HAV and non-viral-induced AH and ALF were performed.
RESULTS The levels of mitochondrial DNA (mtDNA) and the cytokines investigated [interleukin (IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology (P < 0.05). High plasma mtDNA and IL-10 were the best markers associated with ALF [mtDNA: OR = 320.5 (95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8 (95%CI: 1.38-257.94), P = 0.028] and death [mtDNA: OR = 12.1 (95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01 (95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NKbright, NKT and regulatory T cells (TReg) predominated in virus-specific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature.
CONCLUSION mtDNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunological disturbance in HAV-induced ALF.
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Acute Disseminated Encephalomyelitis. J Clin Apher 2016; 31:163-202. [PMID: 27322219 DOI: 10.1002/jca.21474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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Choe W, Kwon SW, Kim SS, Hwang S, Song GW, Lee SG. Effects of therapeutic plasma exchange on early allograft dysfunction after liver transplantation. J Clin Apher 2016; 32:147-153. [PMID: 27306278 DOI: 10.1002/jca.21472] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 03/14/2016] [Accepted: 04/21/2016] [Indexed: 12/26/2022]
Abstract
BACKGROUND Early allograft dysfunction (EAD) is a serious complication of liver transplantation (LT) and is associated with graft failure, which can result in patient mortality. Due to the shortage of organs for retransplantation, only a small proportion of EAD patients undergo retransplantation. Thus, liver support is needed for most patients with EAD. METHODS We evaluated the effects of therapeutic plasma exchange (TPE) in EAD patients. EAD was defined as a sustained hyperbilirubinemia (≥10 mg/dL) within 30 days of LT without concurrent biliary complications. In a 13-year period, 107 EAD patients underwent TPE while 36 EAD patients did not. We investigated the laboratory and clinical outcomes of TPE and non-TPE groups. RESULTS The TPE group showed 1-month and 1-year survival rates of 82.2% and 53.8%, respectively, whereas the non-TPE group showed 58.3% and 22.2%, respectively. In TPE group, statistically significant decreases (P < 0.05) in total bilirubin (15.2 ± 5.2 to 13.1 ± 5.4 mg/dL), and INR (1.72 ± 1.04 to 1.38 ± 1.14), were seen after the final TPE session. TPE responder groups with age <51 years, total bilirubin <11.1 mg/dL, or INR <1.15 after final TPE showed better prognosis. TPE decreased the hazard risk of death in EAD patients whereas older age, male gender, and higher INR on the day of EAD onset increased the risk. CONCLUSIONS TPE effectively removed plasma bilirubin and improved coagulation function in EAD patients, with higher survival in the TPE group than in the non-TPE group. TPE may be an effective liver support for EAD patients. J. Clin. Apheresis 32:147-153, 2017. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Wonho Choe
- Department of Laboratory Medicine, Eulji University School of Medicine, Seoul, Korea.,Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seog-Woon Kwon
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Soo Kim
- Departmnt of Healthcare Management, Cheongju University College of Health Science, Cheongju, Korea
| | - Shin Hwang
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Tian Y, Gong GZ, Yang X, Peng F. Diagnosis and management of fulminant Wilson's disease: a single center's experience. World J Pediatr 2016; 12:209-14. [PMID: 26041495 DOI: 10.1007/s12519-015-0026-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Accepted: 10/23/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND Medical therapy is rarely effective in patients with fulminant Wilson's disease (FWD). Liver transplantation is limited by the lack of donor liver in most patients with FWD at the time of diagnosis. New Wilson's index, model for end-stage liver disease (MELD) and Child-Pugh score are useful tools for decision-making of liver transplantation; however, none of them is an independent decisive tool. It is worthwhile to explore a more effective and practical therapeutic strategy and reevaluate the prediction systems for patients with FWD. METHODS Nine patients with FWD associated with hemolytic crisis and fulminant hepatic failure (FHF) were investigated. The clinical presentation, prognostic score and medical therapies of the patients were analyzed. RESULTS In 7 of the 9 patients with FWD who received the comprehensive therapy of corticosteroid, copper-chelating agent (dimercaptopropansulfonate sodium) and therapeutic plasma exchange (TPE), 6 patients recovered from FHF. The remaining one had been improved through the comprehensive therapy but died of septicemia 51 days later. Two patients with spontaneous bacterial peritonitis (SBP) died from liver failure in three or five hospital days without plasma exchange or chelating therapy. All of the 9 patients with FWD presented with acute hepatic failure, severe jaundice and mild to severe hemolytic anemia. No marked difference in the incidence of severe hemolytic anemia was detected between the survival and deceased groups. However, the incidence and the degree of hepatic encephalopathy (HE) in the non-survival group were higher than those in the survival group. Unlike the deceased group, the survival group had no complications induced by bacterial infection. Compared to new Wilson's index, Child-Pugh score and MELD score, the variation of prothrombin activity (PTA) between the survival and deceased groups was more evident. CONCLUSION For patients with FWD, the episode of severe hepatic encephalopathy or/and spontaneous bacterial peritonitis indicates worse prognosis, and PTA is a recommendable predictor. An emergent liver transplantation should be considered for patients whose PTA is below 20%, or for those with severe HE or/and SBP. The comprehensive therapy of corticosteroid, copper-chelating agent and TPE is effective for patients without SBP and whose PTA is higher than 20%.
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Affiliation(s)
- Yi Tian
- Liver Disease Research Center, Second Xiangya Hospital of Central South University, Changsha, 410011, China.
| | - Guo-Zhong Gong
- Liver Disease Research Center, Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Xu Yang
- Liver Disease Research Center, Second Xiangya Hospital of Central South University, Changsha, 410011, China
| | - Feng Peng
- Liver Disease Research Center, Second Xiangya Hospital of Central South University, Changsha, 410011, China
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Zhou N, Li J, Zhang Y, Lu J, Chen E, Du W, Wang J, Pan X, Zhu D, Yang Y, Chen Y, Cao H, Li L. Efficacy of coupled low-volume plasma exchange with plasma filtration adsorption in treating pigs with acute liver failure: A randomised study. J Hepatol 2015; 63:378-87. [PMID: 25814048 DOI: 10.1016/j.jhep.2015.03.018] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Revised: 03/13/2015] [Accepted: 03/14/2015] [Indexed: 12/26/2022]
Abstract
BACKGROUND & AIMS Extracorporeal blood purification systems for supportive therapy of liver failure are widely used. We developed a novel blood purification system, named Li's artificial liver system (Li-ALS), which couples low-volume plasma exchange (low-volume PE) with plasma filtration adsorption (PFA). This study aims to evaluate the efficacy of our novel system in pigs with acute liver failure (ALF). METHODS Thirty-two pigs were infused with D-galactosamine (1.3g/kg) to induce ALF. All animals were equally and randomly divided into four groups: the ALF control group received intensive care, the PFA group underwent five hour plasma recycling filtration and adsorption purification, the low-volume PE group received one hour low-volume PE, and the Li-ALS group underwent one hour low-volume PE, followed by five hour PFA. Intervention was initiated 36hours after drug administration. The efficacy of each treatment was assessed by survival time and improvement in hematological, biochemical, and immunohistological parameters. RESULTS Pigs in the Li-ALS group survived longer than those in the other groups (p<0.001, ALF control: 60±2h; PFA group: 74±2h; low-volume PE group: 75±2h; and Li-ALS group: 90±3h). Liver enzyme, bilirubin, bile acid and blood ammonia levels were decreased significantly after Li-ALS treatment, and increases in inflammatory cytokines were ameliorated. A higher hepatocyte regeneration index was also observed in the Li-ALS group. CONCLUSION Our novel Li-ALS could expedite liver regeneration and improve survival time; hence, it could be promising for treating ALF.
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Affiliation(s)
- Ning Zhou
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Jianzhou Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Yimin Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Juan Lu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Ermei Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Weibo Du
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Jie Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Xiaoping Pan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Danhua Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Ying Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Yu Chen
- Zhejiang Academy of Traditional Chinese Medicine, Hangzhou, China
| | - Hongcui Cao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Collaborative Innovation Center for Diagnosis and Treatment of Infection Diseases, Zhejiang University, Hangzhou, China.
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Khoury T, Rmeileh AA, Yosha L, Benson AA, Daher S, Mizrahi M. Drug Induced Liver Injury: Review with a Focus on Genetic Factors, Tissue Diagnosis, and Treatment Options. J Clin Transl Hepatol 2015; 3:99-108. [PMID: 26356634 PMCID: PMC4548351 DOI: 10.14218/jcth.2015.00007] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2015] [Revised: 04/25/2015] [Accepted: 04/28/2015] [Indexed: 12/11/2022] Open
Abstract
Drug-induced liver injury (DILI) is a rare but potentially life threatening adverse drug reaction. DILI may mimic any morphologic characteristic of acute or chronic liver disease, and the histopathologic features of DILI may be indistinguishable from those of other causes of liver injury, such as acute viral hepatitis. In this review article, we provide an update on causative agents, clinical features, pathogenesis, diagnosis modalities, and outcomes of DILI. In addition, we review results of recently reported genetic studies and updates on pharmacological and invasive treatments.
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Affiliation(s)
- Tawfik Khoury
- Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- These authors contributed equally to this work
| | - Ayman Abu Rmeileh
- Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
- These authors contributed equally to this work
| | - Liron Yosha
- Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Ariel A. Benson
- Department of Gastroenterology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Saleh Daher
- Department of Gastroenterology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Meir Mizrahi
- Center for Advanced Endoscopy, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Correspondence to: Meir Mizrahi, Center for Advanced Endoscopy, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215, USA. Tel: +1-617-6672135, Fax: +1-617-6671728, E-mail:
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Therapeutic plasma exchange does not reduce vasopressor requirement in severe acute liver failure: a retrospective case series. BMC Anesthesiol 2015; 15:30. [PMID: 25774091 PMCID: PMC4359494 DOI: 10.1186/s12871-015-0017-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 02/24/2015] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND In acute liver failure (ALF) therapeutic plasma exchange (TPE) improves laboratory measures of liver function. In patients with ALF requiring minimal vasoactive support TPE has also been shown to provide haemodynamic benefits including an increase in systemic blood pressure. However the haemodynamic effects of TPE in patients with severe ALF requiring moderate or high dose vasopressor therapy has not been reported. We retrospectively examined the haemodynamic effects of TPE in a cohort of patients with severe ALF requiring vasopressor therapy. METHODS Physiological, laboratory and treatment data were collected on all patients with ALF who received TPE between January 2000 and December 2012. All patients were managed in the intensive care unit of a tertiary referral centre for ALF and liver transplantation. The primary outcome measures were changes in mean arterial pressure (MAP), vasopressor score and the ratio of vasopressor score to MAP (vasopressor dependency index (VDI)) from baseline prior to TPE through to 12 hours after completion of TPE. Secondary outcome measures were changes in other routinely collected physiological variables and laboratory results. Results are presented as median (interquartile range (IQR)). Outcome measures were evaluated using a mixed effect model. RESULTS Thirty nine TPE were performed in 17 patients with ALF (13 paracetamol poisoning). All TPE were performed with a centrifugal apheresis system (duration 130 minutes (IQR 115 - 147.5), plasma volume removed 5.1% body weight (IQR 4.6 - 5.5). Baseline values for primary outcome measures were: MAP 82 mmHg (IQR 72 - 92.5), vasopressor score 8.35 (IQR 3.62 - 24.6) and VDI 0.10 (IQR 0.05 - 0.31). MAP was significantly higher immediately after TPE compared to baseline (p = 0.039), however when corrected for change in vasopressor requirement there was no significant change in VDI with TPE (p = 0.953). Twelve hours after TPE the MAP, vasopressor score and VDI were not significantly different from baseline (p = 0.563, p = 0.317 and p = 0.214 respectively). CONCLUSION In this cohort of patients with severe ALF centrifugal TPE did not significantly affect vasopressor requirements.
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Wang T, Takikawa Y, Watanabe A, Kakisaka K, Oikawa K, Miyamoto Y, Suzuki K. Proliferation of mouse liver stem/progenitor cells induced by plasma from patients with acute liver failure is modulated by P2Y2 receptor-mediated JNK activation. J Gastroenterol 2014; 49:1557-66. [PMID: 24362969 DOI: 10.1007/s00535-013-0927-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2013] [Accepted: 12/09/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND We recently reported that acute liver failure plasma (ALF-P) promotes the proliferation of mouse liver oval cells (OCs) through c-jun N-terminal kinase (JNK) activation. The aim of this study was to investigate the mechanism by which ALF-P induces JNK activation and OC proliferation. METHODS OCs and primary hepatocytes were exposed to ALF-P or normal control plasma (NC-P). Cell proliferation and activation of JNK and other JNK signaling molecules were detected subsequently. Next, we determined the effects of extracellular adenosine triphosphate (ATP) and ATP receptors on ALF-P-stimulated cell growth. Finally, the relationship between the tumor necrosis factor alpha (TNFα) and ATP receptor pathways was investigated. RESULTS Cell proliferation accompanied by JNK activation was only observed in ALF-P-stimulated OCs. ALF-P stimulated the activation of SEK1/MKK4 and ATF2, but not c-Jun. Both PPADS (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid) treatment and P2Y2 (G-protein-coupled) small interfering RNA (siRNA) transfection blocked the effects of ALF-P on cell proliferation and JNK activation. However, ATP levels in ALF-P were significantly lower than that in NC-P, and ATP did not stimulate the proliferation of OCs. On the other hand, TNFα stimulated JNK activation and proliferation of OCs. TNFα receptor antagonist partly inhibited the ALF-P-stimulated proliferation of OCs. Moreover, PPADS significantly inhibited TNFα-stimulated cell proliferation, induced apoptosis, and inhibited the activation of JNK. However, our data showed no significant difference in plasma TNFα levels between the NC-P and ALF-P samples. CONCLUSIONS JNK activation induced by P2Y2 receptor crosstalk with the TNFα signaling pathway is important in mediating the effects of ALF-P on the proliferation and survival of OCs.
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Affiliation(s)
- Ting Wang
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Iwate, Japan,
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Li L, Liu YR, Gao S, Li JF, Li SS, Zhang DD, Liu S, Bai L, Zheng SJ, Duan ZP, Qi M, Chen Y. Inhibition of 5-lipoxygenase pathway attenuates acute liver failure by inhibiting macrophage activation. J Immunol Res 2014; 2014:697560. [PMID: 24987711 PMCID: PMC4058580 DOI: 10.1155/2014/697560] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2014] [Accepted: 05/12/2014] [Indexed: 12/13/2022] Open
Abstract
This study aimed to investigate the role of 5-lipoxygenase (5-LO) in acute liver failure (ALF) and changes in macrophage activation by blocking it. ALF was induced in rats by administration of D-galactosamine (D-GalN)/lipopolysaccharide (LPS). Rats were injected intraperitoneally with AA-861 (a specific 5-LO inhibitor), 24 hr before D-GalN/LPS administration. After D-GalN/LPS injection, the liver tissue was collected for assessment of histology, macrophage microstructure, macrophage counts, 5-LO mRNA formation, protein expression, and concentration of leukotrienes. Serum was collected for detecting alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (Tbil), and tumor necrosis factor- (TNF-) α . Twenty-four hours after injection, compared with controls, ALF rats were characterized by widespread hepatocyte necrosis and elevated ALT, AST, and Tbil, and 5-LO protein expression reached a peak. Liver leukotriene B4 was also significantly elevated. However, 5-LO mRNA reached a peak 8 hr after D-GalN/LPS injection. Simultaneously, the microstructure of macrophages was changed most significantly and macrophages counts were increased significantly. Moreover, serum TNF- α was also elevated. By contrast, AA-861 pretreatment significantly decreased liver necrosis as well as all of the parameters compared with the rats without pretreatment. Macrophages, via the 5-LO pathway, play a critical role in ALF, and 5-LO inhibitor significantly alleviates ALF, possibly related to macrophage inhibition.
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Affiliation(s)
- Lu Li
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Yi-Rong Liu
- Department of Toxic Hepatic Diseases, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Shan Gao
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Jun-Feng Li
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Shan-Shan Li
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Dan-Dan Zhang
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Shuang Liu
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Li Bai
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Su-Jun Zheng
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Zhong-Ping Duan
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Min Qi
- Department of General Medicine, Luoyang Central Hospital, Zhengzhou University, Luoyang 471000, China
| | - Yu Chen
- Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
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Liu CT, Chen TH, Cheng CY. Successful treatment of drug-induced acute liver failure with high-volume plasma exchange. J Clin Apher 2013; 28:430-4. [PMID: 23922237 DOI: 10.1002/jca.21291] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Revised: 07/02/2013] [Accepted: 07/05/2013] [Indexed: 12/13/2022]
Abstract
We report two patients with drug-induced liver injury (DILI)-related acute liver failure (ALF) who were successfully treated with high-volume plasma exchange without liver transplantation. The first patient was a 66-year-old man admitted because of a perforated duodenal ulcer complicated with peritonitis and septic shock. After treatment with multiple antibiotics, the patient developed DILI and ALF. Grade 3 hepatic encephalopathy and profound jaundice were present. Symptoms and signs of ALF improved dramatically after initiation of plasma exchange. The patient was discharged uneventfully. The second patient was a 94-year-old man admitted for treatment of newly diagnosed pulmonary tuberculosis. DILI and ALF developed 5 days after initiation of anti-tuberculosis treatment. Grade 4 hepatic encephalopathy was present. After plasma exchange, the patient's level of consciousness improved dramatically, and he recovered from ALF. These 2 cases show the potential of plasma exchange in the treatment of DILI despite occurrence acute liver failure.
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Affiliation(s)
- Chung-Te Liu
- Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
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Keklik M, Sivgin S, Kaynar L, Pala C, Solmaz M, Cetin M, Eser B, Unal A. Treatment with plasma exchange may serve benefical effect in patients with severe hyperbilirubinemia: a single center experience. Transfus Apher Sci 2013; 48:323-6. [PMID: 23602141 DOI: 10.1016/j.transci.2013.04.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hyperbilirubinemia is a common clinical manifestation, and may be life threatening. Many diseases result in hyperbilirubinemias, some are refractory, and cannot be cured by medication or surgery. Plasma exchange (PE) for hyperbilirubinemia is not a pathogenesis oriented therapy but strives for the opportunity to cure. In the present study, we aimed to present the outcomes of treatment of hyperbilirubinemia with PE in patients with various disorders. Eleven patients who underwent PE due to hyperbilirubinemia between 2006 and 2012 in Apheresis Unit of Erciyes University, were retrospectively reviewed. After PE, we observed a marked decline in total and direct bilirubin levels. The decline in the biochemical values were statically significant (p<0.003). Both total and direct bilirubin levels remained above the normal limits in one of 11 patients. PE should be considered as an effective and safe option in cases with hyperbilirubinemia, and this procedure can improve survival in patients with sufficient residual capacity of liver regeneration.
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Affiliation(s)
- Muzaffer Keklik
- Erciyes University, Department of Hematology, 38039 Kayseri, Turkey.
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Abstract
In this article, the authors review the current recommendations from the American Society for Apheresis regarding the use of plasmapheresis in many of the diseases that intensivists commonly encounter in critically ill patients. Recent experience indicates that therapeutic plasma exchange may be useful in a wide spectrum of illnesses characterized by microvascular thrombosis, the presence of autoantibodies, immune activation with dysregulation of immune response, and some infections.
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Role of plasmapheresis as liver support for early graft dysfunction following adult living donor liver transplantation. Transplant Proc 2012; 44:749-51. [PMID: 22483485 DOI: 10.1016/j.transproceed.2012.01.054] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Severe early graft dysfunction has been occasionally encountered following adult living donor liver transplantation (LDLT). We have assessed the effectiveness of plasmapheresis (PP) as liver support for LDLT recipients with severe early graft dysfunction. METHODS Of the 789 adult LDLTs performed between January 2007 and December 2009, 50 patients (6.3%) underwent PP as a supportive measure during the first month. RESULTS The mean time from LDLT to start of plasmapheresis was 11.2 ± 6.8 days (range 2-28). The 50 patients underwent 517 sessions of PP, or a mean of 10.3 ± 6.8 sessions per patient, over a mean 21.6 ± 9.4 days. Thirty-four patients (68%) required concurrent hemodiafiltration. Mean serum total bilirubin concentration before PP was 16.2 ± 6.7 mg/dL, peaking at 20.3 ± 7.9 mg/dL during PP, and decreasing to 13.4 ± 5.4 mg/dL 1 week after completion of PP (P < .001 compared with before PP). Except for prothrombin time, no other biochemical parameter was significantly altered by PP. There were no serious complications related to PP. Of the 50 patients, 17 (34%) died soon or a few months after PP. The 6-month graft survival rate after completion of PP was 66%; the overall 1-year patient survival rate was 64.0%. CONCLUSION PP appeared to have beneficial effects for LDLT recipients with severe early graft dysfunction, namely total bilirubin concentrations greater than 10 mg/dL.
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Han YJ, Choi JW, Chung WJ, Suh DI, Park JD. A Case of Exertional Heat Stroke with Acute Hepatic Failure Treated with Plasma Exchange - A Case Report -. Korean J Crit Care Med 2012. [DOI: 10.4266/kjccm.2012.27.2.130] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Affiliation(s)
- Young Joo Han
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Wook Choi
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
| | - Woo Jin Chung
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
| | - Dong In Suh
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
| | - June Dong Park
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
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Lin YN, Chou JW, Cheng KS, Peng CY, Jeng LB, Chiang IP. Treatment of Fulminant Autoimmune Hepatitis: Corticosteroid Therapy or Liver Transplantation? A Case Report and Literature Review. Gastroenterology Res 2011; 4:231-235. [PMID: 27957021 PMCID: PMC5139849 DOI: 10.4021/gr323w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/20/2011] [Indexed: 11/22/2022] Open
Abstract
Autoimmune hepatitis initially presenting as fulminant hepatic failure is rare in clinical practice. Although corticosteroid is considered as a good therapeutic agent in treating autoimmune hepatitis in the literature, the effect of corticosteroid in treating fulminant autoimmune hepatitis is still controversial. Because corticosteroid therapy for fulminant autoimmune hepatitis can sometimes overlook any future treatment such as delay the timing of liver transplantation and precipitate postoperative complications. We report a case of a 41-year-old female who was admitted to our hosptal because of acute hepatitis with severe jaundice. Type 1 autoimmune hepatitis complicated by fulminant hepatic failure was diagnosed on the basis of her clinical course and laboratory findings. Although we prescribed aggressive medical treatment, plasma transfusion, and plasma exchange therapy, her liver function deteriorated progressively and she developed hepatic coma later. Finally, her fulminant hepatic fuilure gained dramatic improvement after receiving an orthotopic liver transplant from her younger brother. High MELD score and poor treatment response of corticosteroid therapy are indicators of poor prognosis and need of prompt OLT. Moreover, the preoperative interventions should be applied carefully ensuring that they do not delay OLT or precipitate postoperative complications such as infection, bleeding, or poor wound healing.
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Affiliation(s)
- Yen-Nien Lin
- Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jen-Wei Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan; These authors contribute equally to this article
| | - Ken-Sheng Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan; These authors contribute equally to this article
| | - Cheng-Yuan Peng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan
| | - Long-Bin Jeng
- Organ transplantation center, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan
| | - I-Ping Chiang
- Department of Pathology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, China Medical University, Taichung, Taiwan
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Yilmaz AA, Can OS, Oral M, Unal N, Ayyildiz E, Ilhan O, Tulunay M. Therapeutic plasma exchange in an intensive care unit (ICU): a 10-year, single-center experience. Transfus Apher Sci 2011; 45:161-6. [PMID: 21835700 DOI: 10.1016/j.transci.2011.04.008] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2011] [Indexed: 01/04/2023]
Abstract
Therapeutic plasma exchange (TPE) is a blood purification method that effectively allows for the removal of waste substances by separating out plasma from other components of blood and the removed plasma is replaced with solutions such as albumin and/or plasma, or crystalloid/colloid solutions. Plasma exchange therapies are becoming increasingly essential, being used in daily practice in critical care settings for various indications, either as a first-line therapeutic intervention or as an adjunct to conventional therapies. This retrospective clinical study analyzes 10-year therapeutic plasma exchange activity experience in an 18-bed ICU at a tertiary care university hospital with a large, critically-ill patient population. Medical records of 1188 plasma exchange procedures on 329 patients with different diagnoses admitted from January 2000 to July 2010 were evaluated. The aim of the study was to determine the TPE indications and outcomes of the patients who underwent TPE in the ICU with conventional therapy. The secondary endpoints were to determine the differences between different patient groups (septic vs. non-septic indications) in terms of adverse events and procedural differences.
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Affiliation(s)
- Ali Abbas Yilmaz
- Ankara University, Faculty of Medicine, Anaesthesiology and Intensive Care, Ibn-i Sina Hospital, 06100 Ankara, Turkey.
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Schaefer B, Schaefer F, Engelmann G, Meyburg J, Heckert KH, Zorn M, Schmitt CP. Comparison of Molecular Adsorbents Recirculating System (MARS) dialysis with combined plasma exchange and haemodialysis in children with acute liver failure. Nephrol Dial Transplant 2011; 26:3633-9. [PMID: 21421589 DOI: 10.1093/ndt/gfr115] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Molecular Adsorbents Recirculating System (MARS) is an extracorporeal liver support system eliminating albumin-bound and water-soluble substances. While it is increasingly applied in patients with acute liver failure (ALF), no comparison with standard dialysis methods has yet been performed. METHODS This is an analysis of ten children (0.1-18 years) with ALF, who underwent a total of 22 MARS sessions. Standard adult MARS sets were used in seven (23.5-72 kg) and MARS Mini in three children (2.8-13 kg). In eight children, MARS was alternated with combined plasma exchange (PE) and haemodialysis (HD) treatments. Mean treatment duration was 7.2 (6-10) h for MARS and 5.7 (4.5-6.6) h for PE/HD. RESULTS Standard MARS treatment only slightly decreased serum bilirubin (16.3 ± 6.5-13.8 ± 5.9 mg/dL) and ammonia (113 ± 62-99 ± 68 μmol/L) and international normalized ratio (INR) tended to increase (1.5 ± 0.3 and 2 ± 1.1). Mini-MARS did not reduce serum bilirubin (19.7 ± 3-20.5 ± 3.2 mg/dL), ammonia slightly decreased (70 ± 24-56 ± 9 μmol/L) and INR increased (2.5 ± 0.7-2.9 ± 1.1, all P = n.s.). In contrast, PE/HD reduced serum bilirubin (23 ± 8.4-14.7 ± 7 mg/dL), ammonia (120 ± 60-70 ± 40 μmol/L) and INR (2.4 ± 0.8-1.4 ± 0.1, all P < 0.05). Intraindividual comparison showed a slight increase in bilirubin by 2 ± 22% with MARS and a reduction by 37 ± 11% with PE/HD (P < 0.001 versus MARS) and a decrease in ammonia of 18 ± 27 and 39 ± 23% (P < 0.05). INR increased during MARS by 26 ± 41% and decreased with PE/HD by 37 ± 20% (P < 0.01). All treatment sessions were well tolerated. Five children died, including the three children treated with Mini-MARS. CONCLUSION Our experience suggests superior efficacy of combined PE/HD as compared to intermittent MARS therapy for treating ALF.
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Affiliation(s)
- Betti Schaefer
- Department of General Pediatrics, Center for Pediatric and Adolescent Medicine, University of Heidelberg, Germany
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Kotoh K, Kato M, Kohjima M, Nakamuta M, Enjoji M. A new treatment strategy for acute liver failure. World J Hepatol 2010; 2:395-400. [PMID: 21173907 PMCID: PMC3004032 DOI: 10.4254/wjh.v2.i11.395] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2010] [Revised: 10/18/2010] [Accepted: 10/25/2010] [Indexed: 02/06/2023] Open
Abstract
Acute liver failure (ALF) is a syndrome defined by coagulopathy and encephalopathy and no effective treatments have been established, except for liver transplantation. However, considering the limited supply of donors, we should endeavor to prevent the progression of this syndrome in its early stage to improve the prognosis of patients with ALF. Recently, several authors have reported that over-activation of intrahepatic macrophages plays an important role in the progression of ALF and we have developed a new treatment method, transcatheter arterial steroid injection therapy (TASIT), to suppress macrophage activation. We have now used TASIT for 5 years and have found that TASIT is effective for patients with over-activation of macrophages in the liver but not for those with lesser activation of macrophages. Therefore, to identify the most appropriate patients for TASIT, we tried to categorize patients with ALF or acute liver injury according to markers for the degree of intrahepatic macrophage activation. This approach was helpful to select the appropriate treatment including liver transplantation. We believe that it is essential to analyze disease progression in each patient before selecting the most appropriate treatment.
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Affiliation(s)
- Kazuhiro Kotoh
- Kazuhiro Kotoh, Masaki Kato, Department of Hepatology and Pancreatology, Kyushu University Hospital, Fukuoka 812-8582, Japan
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Szczepiorkowski ZM, Winters JL, Bandarenko N, Kim HC, Linenberger ML, Marques MB, Sarode R, Schwartz J, Weinstein R, Shaz BH. Guidelines on the use of therapeutic apheresis in clinical practice--evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis. J Clin Apher 2010; 25:83-177. [PMID: 20568098 DOI: 10.1002/jca.20240] [Citation(s) in RCA: 354] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The American Society for Apheresis (ASFA) Apheresis Applications Committee is charged with a review and categorization of indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (fourth edition), the subcommittee has incorporated systematic review and evidence-based approach in the grading and categorization of indications. This Fifth ASFA Special Issue has further improved the process of using evidence-based medicine in the recommendations by refining the category definitions and by adding a grade of recommendation based on widely accepted GRADE system. The concept of a fact sheet was introduced in the Fourth edition and is only slightly modified in this current edition. The fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis. The article consists of 59 fact sheets devoted to each disease entity currently categorized by the ASFA as category I through III. Category IV indications are also listed.
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Affiliation(s)
- Zbigniew M Szczepiorkowski
- Transfusion Medicine Service, Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.
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McPhail MJW, Wendon JA, Bernal W. Meta-analysis of performance of Kings's College Hospital Criteria in prediction of outcome in non-paracetamol-induced acute liver failure. J Hepatol 2010; 53:492-9. [PMID: 20580460 DOI: 10.1016/j.jhep.2010.03.023] [Citation(s) in RCA: 97] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2009] [Revised: 03/10/2010] [Accepted: 03/28/2010] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Current techniques for predicting outcome and requirement for emergency liver transplantation (ELT) in acute liver failure (ALF) are imperfect, though The Kings College Criteria (KCC) are the most commonly applied tools for this purpose. Their performance in identification of patients with non-paracetamol-induced ALF (non-POD ALF), who would not survive without ELT, has recently been questioned. Using quantitative techniques, we therefore performed a meta-analysis of outcome data of the KCC for prediction of survival in non-POD ALF. METHODS A systematic database search was performed and retrieved articles graded according to a pre-agreed pro-forma of methodological quality. Collated data was meta-analysed for summary sensitivity, specificity, diagnostic odds ratio (DOR) and ROC curve analysis. Pre-specified sub-group analysis was performed on the basis of methodological quality, the severity of hepatic encephalopathy (HE) of reported patients, timing of KCC application and exclusion of those who underwent ELT. RESULTS Eighteen studies with data on 1105 patients were available for production of 2x2 tables. Summary sensitivity was 68 (95% CI 59-77)%, specificity 82 (75-88)% and DOR 12.6 (6.5-26.1). Heterogeneity was detected in the DOR and related to methodological quality (I(2)=64% for all studies versus 47% for 'good' quality studies) and was lower in studies considering high grade HE or dynamic application of KCC (I(2)=0%). For data where ELT were excluded (13 studies) summary sensitivity was 68 (57-79)%, specificity 81 (72-90)% and DOR 12.2 (4.9-30.1) and a symmetric summary ROC curve was produced. Specificity was highest in studies of patients with high grade HE (93 (80-100)%) and where KCC were applied dynamically through the clinical course (88 (78-97)%). Sensitivity was reduced in studies published post 2005 compared with studies pre 1995 (58 (46-71)% versus 85 (76-82)%). CONCLUSIONS KCC for outcome in non-POD ALF have good specificity and more limited sensitivity. There is significant heterogeneity in the published data partially related to methodological quality. KCC perform best in groups with high grade encephalopathy and in historically earlier studies suggesting modern medical management of ALF may modify performance of KCC.
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Affiliation(s)
- Mark J W McPhail
- Liver Intensive Therapy Unit, Institute of Liver Studies, Kings College Hospital, London SE5 9RS, UK
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42
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Hwang S, Kwon SW, Park GC, Yu YD, Kim KW, Choi NK, Choi YI, Park PJ, Park GB, Jung DH, Song GW, Moon DB, Ahn CS, Kim KH, Ha TY, Min Y, Hong SK, Kyoung KH, Park JI, Lee SG. Effectiveness of Plasmapheresis as a Liver Support for Graft Dysfunction Following Adult Living Donor Liver Transplantation. ACTA ACUST UNITED AC 2009. [DOI: 10.4285/jkstn.2009.23.3.244] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Affiliation(s)
- Shin Hwang
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seog-Woon Kwon
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gil-Chun Park
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Dong Yu
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kwan-Woo Kim
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Nam-Kyu Choi
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Il Choi
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Pyung-Jae Park
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Geum Borae Park
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hwan Jung
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Gi-Won Song
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Deok-Bog Moon
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chul-Soo Ahn
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ki-Hun Kim
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Tae-Yong Ha
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - YuSun Min
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suk-Kyung Hong
- Department of Surgery, Division of General Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyu-Hyouck Kyoung
- Department of Surgery, Division of General Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Ik Park
- Department of Surgery, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Sung-Gyu Lee
- Department of Surgery, Division of Hepatobiliary Surgery and Liver Transplantation, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Chou JW, Yu CJ, Chuang PH, Lai HC, Hsu CH, Cheng KS, Peng CY, Chiang IP. Successful Treatment of Fosinopril-Induced Severe Cholestatic Jaundice with Plasma Exchange. Ann Pharmacother 2008; 42:1887-92. [PMID: 19017832 DOI: 10.1345/aph.1l229] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Objective: To describe a case of fosinopril-induced severe cholestatic jaundice successfully treated with plasma exchange. Case Summary: A 78-year-old Taiwanese male presented with yellowish skin and generalized itching one month after starting fosinopril 10 mg once a day. Other drugs taken by the patient were excluded as the probable cause of jaundice. Diagnostic modalities, including abdominal ultrasound, computed tomography, and endoscopic retrograde cholangiopancreatography, revealed no evidence of biliary tract obstruction or intraabdominal tumor. According to the Council for International Organizations of Medical Science (CIOMS) scale, fosinopril was a highly probable cause of the patient's jaundice. Liver biopsy showed cholestasis without bile duct damage. Based on results of the CIOMS scale assessment and pathological characteristics of the liver, the diagnosis was highly probable that fosinopril had induced cholestatic jaundice in our patient. During hospitalization, the patient developed severe jaundice and liver failure, despite conservative treatment and withdrawal of fosinopril. He underwent a 5-day course of plasma exchange therapy, and the serum bilirubin level declined rapidly after treatment. His liver function returned to normal 2 months after treatment. Discussion: Angiotensin-converting enzyme (ACE) inhibitor–induced hepatotoxicity is rare and only a few cases, with most involving captopril, have been reported in the English-language literature. Hepatotoxicity caused by fosinopril is extremely rare. Most ACE inhibitor–induced hepatotoxicity is mild and transient, but it can be fatal. Although orthotopic liver transplantation (OLT) is the standard method for treating drug-induced liver failure, plasma exchange therapy is an alternative therapeutic method or a bridge to OLT for treating liver failure. Conclusions: Plasma exchange therapy may play a valuable role in the treatment of fosinopril-induced cholestatic jaundice and liver failure. This intervention can be considered for temporary liver support until recovery or OLT.
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Affiliation(s)
- Jen-Wei Chou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Ju Yu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital
| | - Po-Heng Chuang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital
| | - Hsueh-Chou Lai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital
| | | | - Ken-Sheng Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital
| | - Cheng-Yuan Peng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital
| | - I-Ping Chiang
- Department of Pathology, China Medical University Hospital
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Kotoh K, Enjoji M, Kato M, Kohjima M, Nakamuta M, Takayanagi R. A new parameter using serum lactate dehydrogenase and alanine aminotransferase level is useful for predicting the prognosis of patients at an early stage of acute liver injury: a retrospective study. COMPARATIVE HEPATOLOGY 2008; 7:6. [PMID: 18700988 PMCID: PMC2527551 DOI: 10.1186/1476-5926-7-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2007] [Accepted: 08/14/2008] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although most patients with severe acute hepatitis are conservatively cured, some progress to acute liver failure (ALF) with a high rate of mortality. Based on the evidence that over-activation of macrophages, followed by disturbance of the hepatic microcirculation, plays a key role in ALF, we hypothesized that the production of serum lactate dehydrogenase (LDH) might increase in the liver under hypoxic conditions and could be an indicator to discriminate between conservative survivors and fatal patients at an early stage. RESULTS To confirm this hypothesis, we developed a new parameter with serum alanine aminotransferase (ALT) and LDH: the ALT-LDH index = serum ALT/(serum LDH - median of normal LDH range). We analyzed retrospectively 33 patients suffering acute liver injury (serum ALT more than 1000 U/L or prothrombin time expressed as international normalized ratio over 1.5 at admission) and evaluated the prognostic value of the ALT-LDH index, comparing data from the first 5 days of hospitalization with the Model for End-Stage Liver Disease (MELD) score. Patients whose symptoms had appeared more than 10 days before admission were excluded from this study. Among those included, 17 were conservative survivors, 9 underwent liver transplantation (LT) and 7 died waiting for LT. We found a rapid increase in the ALT-LDH index in conservative survivors but not in fatal patients. While the prognostic sensitivity and specificity of the ALT-LDH index was low on admission, at day 3 they were superior to the results of MELD. CONCLUSION ALT-LDH index was useful to predict the prognosis of the patients with acute liver injury and should be helpful to begin preparation for LT soon after admission.
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Affiliation(s)
- Kazuhiro Kotoh
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
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Collection of Large-scale Expanded Lymphocyte Cultures for Adoptive Immunotherapy Using a COBE Spectra Apheresis Machine. J Immunother 2008; 31:563-8. [DOI: 10.1097/cji.0b013e318175f66b] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Adjuvant therapeutic plasma exchange in liver failure: assessments of clinical and laboratory parameters. J Clin Gastroenterol 2008; 42:517-21. [PMID: 18344887 DOI: 10.1097/mcg.0b013e31815878ff] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Therapeutic plasma exchange (TPE) seems to be an effective approach for clearing toxins, immune-mediated antigens, and other particles from the circulation. The aim of this study was to analyze the positive effects of TPE on clinical and biochemical parameters of liver failure. PATIENTS AND METHODS Between January 2001 and March 31, 2005 individuals (men/women, 17/14; median age, 42.7+/-15.8 y) with acute and chronic liver failure who underwent a total of 113 TPEs (median session 3.7) were retrospectively reviewed. TPE was performed using the Fresenius AS-TEC 204 cell separator (Fresenius AG, Germany). The indication for TPE was severe coagulopathy (prothrombin time >20 s), severe hepatic encephalopathy, hyperbilirubinemia, and candidacy for liver transplantation. All patients were examined before and immediately after the last TPE session. RESULTS When compared with baseline, there was significant improvement in hepatic encephalopathy stage (from median score 3.0 to 1.0, P=0.001), serum prothrombin time (from median 26.0 to 20.0 s, P=0.003), aminotransferases (P<0.001), and total bilirubin levels (from median 35.0 to 23.3 mg/dL, P<0.001) after TPE. Thirteen of the thirty-one individuals (41.9%) died in the hospital. The mean follow-up period of 18 survival patients was 35.9+/-5.6 months and 10 of those survived (55.6%, 10/18). No serious adverse effect of TPE was observed in any of the patients during or after completion of TPE. Only 6 patients experienced minor transfusion reactions. CONCLUSIONS TPE seems to be effective in improving hepatic encephalopathy stage and liver tests in individuals with acute and chronic liver failure. The data suggest that TPE is safe and tolerable in such individuals, however, overall survival remains poor despite TPE.
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Abstract
PURPOSE OF REVIEW Liver support devices are used either as a bridge to liver transplantation or liver recovery in patients with acute or acute-on-chronic liver failure. The review analyzes the recent literature and asks if the current enthusiasm for these devices is justified. RECENT FINDINGS Many liver support devices exist and are discussed. Clinical data on artificial devices are rapidly emerging, especially on the molecular adsorbents recirculating system, and fractionated plasma separation and adsorption (Prometheus). While hepatic encephalopathy is improved by the molecular adsorbents recirculating system and probably Prometheus too, neither system has been shown to improve survival. Less clinical data exist for bioartificial support devices. These may use human hepatocytes, such as the extracorporeal liver assist device, although most devices use porcine hepatocytes, such as HepatAssist. SUMMARY Enthusiasm in liver support devices is justified as many nonrandomized studies have suggested some biochemical and clinical benefits. The results of several ongoing multicenter randomized controlled trials are anxiously awaited. Meanwhile, because mortality without liver transplantation remains high despite the use of liver support devices, these devices should only be used in the research setting or by experts proficient in their use and as a bridge to liver transplantation rather than liver recovery.
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Affiliation(s)
- Jason Phua
- Division of Respiratory and Critical Care Medicine, Department of Medicine, National University Hospital, Singapore
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48
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Martin JN, Briery CM, Rose CH, Owens MT, Bofill JA, Files JC. Postpartum plasma exchange as adjunctive therapy for severe acute fatty liver of pregnancy. J Clin Apher 2008; 23:138-43. [DOI: 10.1002/jca.20168] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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49
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Higuchi N, Kato M, Kotoh K, Kohjima M, Aishima S, Nakamuta M, Fukui Y, Takayanagi R, Enjoji M. Methylprednisolone injection via the portal vein suppresses inflammation in acute liver failure induced in rats by lipopolysaccharide and d-galactosamine. Liver Int 2007; 27:1342-8. [PMID: 17900243 DOI: 10.1111/j.1478-3231.2007.01590.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND We have reported that hepatic arterial steroid injection is an effective therapy to rescue patients from fulminant or severe acute hepatic failure. We speculate that a high concentration of steroid suppresses inflammatory processes in the liver directly by restraining activated inflammatory cells, including macrophages. To analyse the detailed mechanism, steroid injection via the portal vein was performed in an experimental model of liver damage. METHODS Rats subjected to lipopolysaccharide and d-galactosamine injection were treated with a methylprednisolone injection via the tail vein or the portal vein. The survival rate, serum levels of inflammatory cytokines and apoptotic cell counts in the liver were analysed. RESULTS The survival rate was significantly improved by steroid injection, especially via the portal vein. Serum values of alanine aminotransferase, tumor necrosis factor-alpha and interferon-gamma were reduced in the treated groups, especially the group given portal venous injections. Apoptotic cell counts in the liver were significantly lower in the group injected with steroid via the portal vein. CONCLUSION In the model rats, high concentrations of steroid in the liver acted on inflammatory cells and suppressed inflammatory cytokines and liver cell death. The mechanism is suggested to be the same for arterial steroid injection therapy in patients with acute hepatic failure.
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Affiliation(s)
- Nobito Higuchi
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyushu University, Higashi-ku, Fukuoka, Japan
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Szczepiorkowski ZM, Bandarenko N, Kim HC, Linenberger ML, Marques MB, Sarode R, Schwartz J, Shaz BH, Weinstein R, Wirk A, Winters JL. Guidelines on the use of therapeutic apheresis in clinical practice—Evidence-based approach from the apheresis applications committee of the American society for apheresis. J Clin Apher 2007; 22:106-75. [PMID: 17394188 DOI: 10.1002/jca.20129] [Citation(s) in RCA: 157] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The American Society for Apheresis (ASFA) Apheresis Applications Committee is charged with a review and categorization of indications for therapeutic apheresis. This elaborate process had been undertaken every 7 years resulting in three prior publications in 1986, 1993, and 2000 of "The ASFA Special Issues." This article is the integral part of the Fourth ASFA Special Issue. The Fourth ASFA Special Issue is significantly modified in comparison to the previous editions. A new concept of a fact sheet has been introduced. The fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis. A detailed description of the fact sheet is provided. The article consists of 53 fact sheets devoted to each disease entity currently categorized by the ASFA. Categories I, II, and III are defined as previously in the Third Special Issue. However, a few new therapeutic apheresis modalities, not yet approved in the United States or are currently in clinical trials, have been assigned category P (pending) by the ASFA Clinical Categories Subcommittee. The diseases assigned to category IV are discussed in a separate article in this issue.
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Affiliation(s)
- Zbigniew M Szczepiorkowski
- Transfusion Medicine Service, Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
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