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Hajijama S, Marashi M, Ho SB. Acute Liver Failure due to Wilson's Disease and Rescue Therapy with Plasma Exchange: A Case Report and Literature Review. Case Rep Gastroenterol 2025; 19:340-351. [PMID: 40365554 PMCID: PMC12074618 DOI: 10.1159/000544927] [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] [Received: 11/06/2024] [Accepted: 02/18/2025] [Indexed: 05/15/2025] Open
Abstract
Introduction Wilson's disease (WD) is a rare genetic condition characterized by impaired copper metabolism and can rarely present as acute liver failure with an associated high mortality rate. Treatment often requires liver transplantation, and few rescue treatments have been shown to be effective by randomized trials. This is a case report and scoping literature review on plasmapheresis in acute liver failure due to WD. Case Presentation We report a case of a previously undiagnosed 32-year-old female who presented with acute liver failure due to WD. Initial severity indices (MELD = 31 and RWPI - Revised Wilson Prognostic Index = 14) warranted liver transplant referral; however, no facilities were available. The patient was managed by two sessions of plasmapheresis with plasma exchange with persistent improvement in MELD score over 1 week. Subsequent ongoing chelation therapy resulted in a total reversal of clinical liver disease over 2 years. Literature review resulted in 74 patients reported to have been treated with plasmapheresis for WD and acute liver failure. Of these, 40% survived without transplant. Out of the total patients reported, 54 patients had an available NWI score, with 46 patients having a high-risk score of ≥11 (85%) and 8 patients had a score <11 (15%). Of the 46 patients with a score ≥11, 21 (46%) recovered without liver transplantation, 16 (35%) underwent liver transplantation, 8 (17%) died of liver failure, and 1 (∼2%) died of sepsis. Of the 8 patients with a score of <11, 4 (50%) recovered without a liver transplantation, and 4 (50%) underwent transplantation. Conclusion The outcomes observed in the literature and the favorable outcome of our patient suggest an emphasis on the use of urgent plasmapheresis with plasma exchange as an initial intervention for acute liver failure in WD, although further randomized controlled trials are needed for determining the optimal dose and duration of treatment.
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Affiliation(s)
- Sameera Hajijama
- Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, United Arab Emirates
| | - Mahmoud Marashi
- Department of Medicine, Mediclinic City Hospital, Dubai Healthcare City, Dubai, United Arab Emirates
| | - Samuel B. Ho
- Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, United Arab Emirates
- Department of Medicine, Mediclinic City Hospital, Dubai Healthcare City, Dubai, United Arab Emirates
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Ferrarese A, Cazzagon N, Burra P. Liver transplantation for Wilson disease: Current knowledge and future perspectives. Liver Transpl 2024; 30:1289-1303. [PMID: 38899966 DOI: 10.1097/lvt.0000000000000422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Accepted: 06/06/2024] [Indexed: 06/21/2024]
Abstract
Liver transplantation currently represents a therapeutic option for patients with Wilson disease presenting with end-stage liver disease or acute liver failure. Indeed, it has been associated with excellent postoperative survival curves in view of young age at transplant and absence of recurrence. Attention has shifted over the past decades to a wise expansion of indications for liver transplantation. Evidence has emerged supporting the transplantation of carefully selected patients with primarily neuropsychiatric symptoms and compensated cirrhosis. The rationale behind this approach is the potential for surgery to improve copper homeostasis and consequently ameliorate neuropsychiatric symptoms. However, several questions remain unanswered, such as how to establish thresholds for assessing pretransplant neuropsychiatric impairment, how to standardize preoperative neurological assessments, and how to define postoperative outcomes for patients meeting these specific criteria. Furthermore, a disease-specific approach will be proposed both for the liver transplant evaluation of candidates with Wilson disease and for patient care during the transplant waiting period, highlighting the peculiarities of this systemic disease.
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Affiliation(s)
- Alberto Ferrarese
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Nora Cazzagon
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
| | - Patrizia Burra
- Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
- Gastroenterology, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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Wang XH, Peng BB, Zhang L, Zhao J, Zhang L, Ren H, Hu P, Li H, Zhong S. Mixed mode of artificial liver support in patients with acute-on-chronic liver failure: a retrospective cohort study. Hepatol Int 2023; 17:1241-1250. [PMID: 37550499 DOI: 10.1007/s12072-023-10573-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 07/17/2023] [Indexed: 08/09/2023]
Abstract
BACKGROUND AND AIMS Different modes of artificial liver support (ALS) therapy can improve the survival of patients with acute-on-chronic liver failure (ACLF). This study aimed to compare the effects of mixed using different modes of ALS (MALS) and single using one mode of ALS (SALS) on 28- and 90-day survival rates of ACLF. METHODS Clinical data and survival times of patients with ACLF treated for ALS between January 1, 2018 and December 30, 2021 were retrospectively collected. Cox regression analysis was performed to identify risk factors of 28- and 90-day mortalities. RESULTS Of the 462 eligible ACLF patients, 388 belonged to the SALS group (76.3% male, 74.2% cirrhosis) and 74 to the MALS group (86.5% male, 71.6% cirrhosis). Comparison of 28-day and 90-day crude mortality between the SALS and MALS groups showed no significant differences (28-day: 20.4% vs. 14.9%, p = 0.27; 90-day: 44.6% vs. 52.7%, p = 0.20). After adjusting for confounders, the 28-day mortality (adjusted hazard ratio [aHR]: 0.32, 95% confidence interval [CI] 0.16-0.65) and 90-day mortality (aHR: 0.65, 95% CI 0.44-0.95) in the MALS group were significantly lower than those in the SALS group. These associations were consistently observed across pre-specified subgroups according to age, sex, etiology, and Child-Pugh grade. However, positive interactions between MALS and 90-day mortality were found between MALS and 90-day mortality in those with MELD score ≥ 22 and international normalized ratio ≥ 1.9 (p for interaction < 0.05). CONCLUSION MALS therapy significantly decreased 28- and 90-day mortalities of ACLF than SALS did, especially in advanced stages.
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Affiliation(s)
- Xiao-Hao Wang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, No. 288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Bin-Bin Peng
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, No. 288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Lu Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, No. 288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Jing Zhao
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, No. 288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Li Zhang
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, No. 288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Hong Ren
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, No. 288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Peng Hu
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, No. 288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China
| | - Hu Li
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, No. 288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China.
| | - Shan Zhong
- Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, No. 288, Tianwen Avenue, Chayuan, Nan'an District, Chongqing, 401336, China.
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Papamichalis P, Oikonomou KG, Valsamaki A, Xanthoudaki M, Katsiafylloudis P, Papapostolou E, Skoura AL, Papamichalis M, Karvouniaris M, Koutras A, Vaitsi E, Sarchosi S, Papadogoulas A, Papadopoulos D. Liver replacement therapy with extracorporeal blood purification techniques current knowledge and future directions. World J Clin Cases 2023; 11:3932-3948. [PMID: 37388799 PMCID: PMC10303607 DOI: 10.12998/wjcc.v11.i17.3932] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 05/04/2023] [Accepted: 05/11/2023] [Indexed: 06/12/2023] Open
Abstract
Clinically, it is highly challenging to promote recovery in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). Despite recent advances in understanding the underlying mechanisms of ALF and ACLF, standard medical therapy remains the primary therapeutic approach. Liver transplantation (LT) is considered the last option, and in several cases, it is the only intervention that can be lifesaving. Unfortunately, this intervention is limited by organ donation shortage or exclusion criteria such that not all patients in need can receive a transplant. Another option is to restore impaired liver function with artificial extracorporeal blood purification systems. The first such systems were developed at the end of the 20th century, providing solutions as bridging therapy, either for liver recovery or LT. They enhance the elimination of metabolites and substances that accumulate due to compromised liver function. In addition, they aid in clearance of molecules released during acute liver decompensation, which can initiate an excessive inflammatory response in these patients causing hepatic encephalopathy, multiple-organ failure, and other complications of liver failure. As compared to renal replacement therapies, we have been unsuccessful in using artificial extracorporeal blood purification systems to completely replace liver function despite the outstanding technological evolution of these systems. Extracting middle to high-molecular-weight and hydrophobic/protein-bound molecules remains extremely challenging. The majority of the currently available systems include a combination of methods that cleanse different ranges and types of molecules and toxins. Furthermore, conventional methods such as plasma exchange are being re-evaluated, and novel adsorption filters are increasingly being used for liver indications. These strategies are very promising for the treatment of liver failure. Nevertheless, the best method, system, or device has not been developed yet, and its probability of getting developed in the near future is also low. Furthermore, little is known about the effects of liver support systems on the overall and transplant-free survival of these patients, and further investigation using randomized controlled trials and meta-analyses is needed. This review presents the most popular extracorporeal blood purification techniques for liver replacement therapy. It focuses on general principles of their function, and on evidence regarding their effectiveness in detoxification and in supporting patients with ALF and ACLF. In addition, we have outlined the basic advantages and disadvantages of each system.
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Affiliation(s)
| | - Katerina G Oikonomou
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
| | - Asimina Valsamaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
| | - Maria Xanthoudaki
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
| | | | | | - Apostolia-Lemonia Skoura
- Department of Transfusion Medicine, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
| | - Michail Papamichalis
- Department of Cardiology, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
| | | | - Antonios Koutras
- 1st Department of Obstetrics and Gynecology, General Hospital of Athens “ALEXANDRA”, National and Kapodistrian University of Athens, Athens 11528, Greece
| | - Eleni Vaitsi
- Intensive Care Unit, General Hospital of Larissa, Larissa 41221, Thessaly, Greece
| | - Smaragdi Sarchosi
- Department of Anesthesiology, University Hospital of Larissa, Larissa 41110, Thessaly, Greece
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Jagadisan B, Dhawan A. Emergencies in paediatric hepatology. J Hepatol 2022; 76:1199-1214. [PMID: 34990749 DOI: 10.1016/j.jhep.2021.12.027] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022]
Abstract
The aetiology of several liver diseases in children is age specific and many of these conditions have significant and potentially long-term clinical repercussions if not diagnosed early and managed in a timely fashion. We address 5 clinical scenarios that cover most of the diagnostic and therapeutic emergencies in children: infants with liver disease; acute liver failure; management of bleeding varices; liver-based metabolic disorders; and liver tumours and trauma. A wide spectrum of conditions that cause liver disease in infants may present as conjugated jaundice, which could be the only symptom of time-sensitive disorders - such as biliary atresia, metabolic disorders, infections, and haematological/alloimmune disorders - wherein algorithmic multistage testing is required for accurate diagnosis. In infantile cholestasis, algorithmic multistage tests are necessary for an accurate early diagnosis, while vitamin K, specific milk formulae and disease-specific medications are essential to avoid mortality and long-term morbidity. Management of paediatric acute liver failure requires co-ordination with a liver transplant centre, safe transport and detailed age-specific aetiological work-up - clinical stabilisation with appropriate supportive care is central to survival if transplantation is indicated. Gastrointestinal bleeding may present as the initial manifestation or during follow-up in patients with portal vein thrombosis or chronic liver disease and can be managed pharmacologically, or with endoscopic/radiological interventions. Liver-based inborn errors of metabolism may present as encephalopathy that needs to be recognised and treated early to avoid further neurological sequelae and death. Liver tumours and liver trauma are both rare occurrences in children and are best managed by a multidisciplinary team in a specialist centre.
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Affiliation(s)
- Barath Jagadisan
- Pediatric Liver GI and Nutrition Centre and MowatLabs, King's College Hospital, London, UK
| | - Anil Dhawan
- Pediatric Liver GI and Nutrition Centre and MowatLabs, King's College Hospital, London, UK.
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Feng CX, Chen XQ, He XL, Lan LC, Tang Q, Huang L, Shan QW. Screening for Wilson's disease in acute liver failure: A new scoring system in children. Front Pediatr 2022; 10:1003887. [PMID: 36210929 PMCID: PMC9534029 DOI: 10.3389/fped.2022.1003887] [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] [Received: 07/26/2022] [Accepted: 09/02/2022] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Wilson's disease (WD) is a rare cause of acute liver failure (ALF) and has a high fatality rate. Rapid and accurate diagnosis is important for ALF because of WD (ALF-WD). Our objective was to establish a simple, rapid, and accurate diagnostic test to distinguish ALF-WD from non-WD ALF (NWDALF) in children. MATERIALS AND METHODS The data from all cases with pediatric ALF were retrospectively collected and analyzed. We performed receiver operator characteristics curve (ROC) analysis and confirmed the optimum cut-off points. RESULTS Fifty-eight patients with pediatric ALF (12 with WD, 46 with other etiologies) were included. Older age was observed in ALF-WD compared to NWDALF (11.16 ± 2.51 years vs. 3.34 ± 3.81 years, p < 0.001). An analysis based on routine biochemical testings revealed that total bilirubin (TBil), direct bilirubin, indirect bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST:ALT ratio, alkaline phosphatase (ALP), ALP:TBil ratio, serum albumin, gamma-glutamyl transferase, cholinesterase, hemoglobin, and platelet were statistically significant between the ALF-WD and NWDALF groups. The optimum cut-off points were obtained through ROC analysis. A scoring system was formed by assigning a score of 1 or 0 to patients who met the 13 cut-off points. Using ROC analysis, we determined a cut-off point of ≥ 6.5 for ALF-WD with 91.7% sensitivity and 97.8% specificity (p < 0.0001). In addition, a best cut-off point of ≥ 1.5 based on only five variables (ALT, AST, AST:ALT ratio, ALP, and ALP:TBil ratio), had 100% sensitivity and 91.3% specificity for ALF-WD (p < 0.0001). Based on this, when age was calculated as the sixth indicator, the best cut-off value of ≥ 2.5 had 100% sensitivity and 97.8% specificity (p < 00.0001). CONCLUSION Our study developed a new scoring system that consists of simple laboratory tests with good sensitivity and specificity and can be used by clinicians to quickly distinguish ALF-WD from NWDALF in children.
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Affiliation(s)
- Cai-Xia Feng
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiu-Qi Chen
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Xiao-Li He
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Lian-Cheng Lan
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Qing Tang
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Li Huang
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Qing-Wen Shan
- Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Mirza N, Bharadwaj R, Malhotra S, Sibal A. Wilson Disease-Induced Acute Liver Failure (NWI = 13) Salvaged without Liver Transplant by Plasmapheresis. JOURNAL OF CHILD SCIENCE 2021. [DOI: 10.1055/s-0041-1731079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
AbstractWilson disease (WD) is a disorder of copper metabolism resulting in accumulation of copper in vital organs of the human body, predominantly in the liver and the brain. Acute liver failure in WD has a bad prognosis, especially with a score ≥11 in the revised WD prognostic index; emergency liver transplantation is considered the only life-saving option in this scenario. Here, we reported a girl patient with WD-induced liver failure and poor prognostic score who was rescued by plasmapheresis. She also manifested severe Coombs negative hemolytic anemia and acute kidney injury. This case report highlights the utility of an adjunctive modality besides liver transplantation for the management of fulminant liver failure caused by WD.
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Affiliation(s)
- Nida Mirza
- Department of Paediatrics, Sri Aurobindo Institute of Medical Science, Indore, Madhya Pradesh, India
| | - Ravi Bharadwaj
- Department of Paediatric Gastroenterology, Indraprastha Apollo Hospital, New Delhi, India
| | - Smita Malhotra
- Department of Paediatric Gastroenterology, Indraprastha Apollo Hospital, New Delhi, India
| | - Anupam Sibal
- Department of Paediatric Gastroenterology, Indraprastha Apollo Hospital, New Delhi, India
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Fulminant Wilson Disease in Children: Recovery After Plasma Exchange Without Transplantation. J Pediatr Gastroenterol Nutr 2020; 71:720-725. [PMID: 32804913 DOI: 10.1097/mpg.0000000000002894] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
OBJECTIVES Since 2005, a New Wilson Index (NWI) ≥11 is used as a predictor of death without transplantation in fulminant Wilson disease (WD). Plasma exchange is advocated as a new treatment modality. METHODS We present a patient with fulminant WD treated with plasma exchange. All published cases applying plasma exchange for fulminant WD were reviewed systematically. RESULTS A 14-year-old girl presented with hemolysis and fulminant liver failure. She had no encephalopathy; NWI was 14. As a bridge to transplantation plasma exchange was started immediately. Complete remission was achieved with plasma exchange and later chelation therapy with D-penicillamine. She is now at 3-year transplant-free survival. Literature review identified 37 patients presenting with fulminant WD and NWI ≥11 who were treated with plasma exchange. Seventeen of these patients (ie, 46%) recovered without transplantation. CONCLUSIONS Multiple case reports and case series demonstrate transplant free survival after plasma exchange and subsequent chelation therapy, despite a NWI ≥11. Plasma exchange affects the clinical course and is a therapeutic option in children and young adults presenting with fulminant WD.
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Gembillo G, Siligato R, Cernaro V, Santoro D. Complement Inhibition Therapy and Dialytic Strategies in Paroxysmal Nocturnal Hemoglobinuria: The Nephrologist's Opinion. J Clin Med 2020; 9:1261. [PMID: 32357555 PMCID: PMC7287718 DOI: 10.3390/jcm9051261] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 04/18/2020] [Accepted: 04/21/2020] [Indexed: 12/24/2022] Open
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disease that presents an estimated incidence of 1.3 cases per million per year, with a prevalence of 15.9 cases per million. It is characterized by hemolysis, bone marrow dysfunction with peripheral blood cytopenia, hypercoagulability, thrombosis, renal impairment and arterial and pulmonary hypertension. Hemolysis and subsequent hemosiderin accumulation in tubular epithelium cells induce tubular atrophy and interstitial fibrosis. The origin of PNH is the somatic mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene located on Xp22: this condition leads to the production of clonal blood cells with a deficiency in those surface proteins that protect against the lytic action of the activated complement system. Despite the increased knowledge of this syndrome, therapies for PNH were still only experimental and symptomatic, until the introduction of the C5 complement blockade agent Eculizumab. A second generation of anti-complement agents is currently under investigation, representing future promising therapeutic strategies for patients affected by PNH. In the case of chronic hemolysis and renal iron deposition, a multidisciplinary approach should be considered to avoid or treat acute tubular injury or acute kidney injury (AKI). New promising perspectives derive from complement inhibitors and iron chelators, as well as more invasive treatments such as immunoadsorption or the use of dedicated hemodialysis filters in the presence of AKI.
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Affiliation(s)
- Guido Gembillo
- Unit of Nephrology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy; (R.S.); (V.C.); (D.S.)
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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: 66] [Impact Index Per Article: 13.2] [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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