|
1
|
Heyerick L, Dhondt A, Van Vlierberghe H, Verhelst X, Raevens S, Geerts A. Early plasmapheresis in type 2 benign recurrent intrahepatic cholestasis: A case report and review of literature. World J Hepatol 2025; 17:102375. [PMID: 40027565 PMCID: PMC11866144 DOI: 10.4254/wjh.v17.i2.102375] [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: 10/15/2024] [Revised: 12/06/2024] [Accepted: 01/07/2025] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND Benign recurrent intrahepatic cholestasis (BRIC) is a rare autosomal recessive liver disease, causing episodic cholestasis with intense pruritus. This case report highlights the effectiveness of early plasmapheresis as a therapeutic option for BRIC type 2, offering rapid symptom relief and early termination of cholestatic episodes. It contributes to the limited evidence supporting plasmapheresis as a treatment for BRIC flares resistant to conventional therapies. CASE SUMMARY A 43-year-old male with BRIC type 2 presented with fatigue, jaundice, and severe pruritus, triggered by a recent mild severe acute respiratory syndrome coronavirus 2 infection. Laboratory results confirmed cholestasis with elevated bilirubin and alkaline phosphatase. First-line pharmacological treatments, including cholestyramine and rifampicin, failed. Endoscopic nasobiliary drainage was ineffective, prompting initiation of plasmapheresis. This intervention rapidly relieved pruritus, with complete biochemical normalisation after 11 sessions. Two years later, a similar episode occurred, and early reinitiation of plasmapheresis led to symptom resolution within two sessions and biochemical recovery within two weeks. The patient tolerated the procedure well, with no adverse effects observed. Follow-up showed no signs of cholestasis recurrence. CONCLUSION Plasmapheresis is a safe and effective option for therapy-refractory BRIC type 2, particularly when initiated early in cholestasis.
Collapse
Affiliation(s)
- Lander Heyerick
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent 9000, Belgium.
| | - Annemieke Dhondt
- Department of Nephrology, Ghent University Hospital, Ghent 9000, Belgium
| | - Hans Van Vlierberghe
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent 9000, Belgium
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent 9000, Belgium
| | - Sarah Raevens
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent 9000, Belgium
| | - Anja Geerts
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent 9000, Belgium
| |
Collapse
|
|
2
|
Gabrielli F, Crepaldi E, Cavicchioli A, Rivi M, Costanzo AC, Cursaro C, Andreone P. Itching for Answers: A Comprehensive Review of Cholestatic Pruritus Treatments. Biomolecules 2024; 14:1227. [PMID: 39456160 PMCID: PMC11505983 DOI: 10.3390/biom14101227] [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: 07/23/2024] [Revised: 08/21/2024] [Accepted: 08/28/2024] [Indexed: 10/28/2024] Open
Abstract
Cholestasis is a clinical and laboratory syndrome indicating impaired bile production or excretion. One of the hallmark symptoms of cholestasis is pruritus. Itch can be severe and debilitating for patients, impacting their quality of life similarly to pain, and, in some cases, it can be refractory. Current therapies like anion exchange resins and rifampicin, offer partial relief but with side effects. Effective, well-tolerated treatments are urgently needed. This literature review examines existing options (bile acid sequestrants, antihistamines, opioid antagonists, sertraline, and rifampicin) and explores novel therapies (monoclonal antibodies, PPAR agonists, and bile-acid-based therapies). We analyze mechanisms, limitations, and adverse effects to aid clinicians and researchers. Novel approaches include monoclonal antibodies to inhibit bile recirculation and PPAR agonists targeting pruritus signaling. Despite the limited current options, ongoing research promises better treatments for cholestatic pruritus, addressing its distressing impact. In summary, cholestasis-associated pruritus poses a significant challenge with limited treatments. Advancements in understanding its pathophysiology offer hope for more effective therapies in the future.
Collapse
Affiliation(s)
- Filippo Gabrielli
- Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Internal and Metabolic Medicine, AOU of Modena-Baggiovara, 41126 Modena, Italy
| | - Eleonora Crepaldi
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Alessia Cavicchioli
- Internal and Metabolic Medicine, AOU of Modena-Baggiovara, 41126 Modena, Italy
| | - Marco Rivi
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Arianna Carmen Costanzo
- Department of Hepato-bilio-pancreatic Surgery and Liver Transplantation, Hautepierre Hospital, Avenue Molière, 67200 Strasbourg, France
| | - Carmela Cursaro
- Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41126 Modena, Italy
| | - Pietro Andreone
- Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, 41126 Modena, Italy
- Internal and Metabolic Medicine, AOU of Modena-Baggiovara, 41126 Modena, Italy
- Postgraduate School of Allergology and Clinical Immunology, University of Modena and Reggio Emilia, 41126 Modena, Italy
| |
Collapse
|
|
3
|
Ebhohon E, Chung RT. Systematic review: efficacy of therapies for cholestatic pruritus. Therap Adv Gastroenterol 2023; 16:17562848231172829. [PMID: 37255856 PMCID: PMC10226044 DOI: 10.1177/17562848231172829] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 04/13/2023] [Indexed: 06/01/2023] Open
Abstract
Background Pruritus is a symptom of several cholestatic liver diseases (CLDs) that can impair health-related quality of life (HRQoL). Despite evidence-based guideline therapy, managing cholestatic pruritus (CP) remains challenging, thus making the need for newer, more effective therapeutic agents more evident. Objective Our study evaluated the efficacy of existing CP therapies. Design Systematic review. Data sources From inception until March 2023, we conducted a comprehensive search of MEDLINE, Cochrane, EMBASE, Scopus, ClinicalTrial.gov, and other sources, including pharmaceutical webpages and conference proceedings published in English that reported on CP interventions. Methods Two reviewers independently conducted screening and full-text review of articles with extraction conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The methodological quality of studies included in our qualitative synthesis was assessed by using the Cochrane ROBINS-I and ROBINS-II tools for interventional studies and the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The primary outcome assessed in our systematic review was the severity of CP after therapy. Results Of 3293 screened articles, 92 studies were eligible for inclusion in the qualitative synthesis. Some patients' HRQoL improved with evidence-based standard therapy. Others, particularly those with severe and refractory CP, often required conversion to or addition of experimental noninvasive (e.g., ondansetron) or extracorporeal liver support to alleviate CP. In addition, studies investigating a newer class drug, the ileal bile acid transporter inhibitor (IBATi), demonstrate its effectiveness in reducing serum bile acid and alleviating CP with sustained improvement noted in patients with the inherited childhood cholestatic disorders - progressive familial intrahepatic cholestasis and Alagille syndrome. Conclusion Our findings consolidate data on the efficacy of guideline-based approaches and newer therapies for CP. While the initial findings are promising, additional clinical trials will be needed to determine the full extent of IBATi's efficacy and potential use in treating other common CLDs. These results provide a foundation for future research and highlight the need for continued investigation into the management and treatment of CLDs.
Collapse
Affiliation(s)
| | - Raymond T. Chung
- Gastrointestinal Division, Liver Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
4
|
Lynch EN, Campani C, Innocenti T, Dragoni G, Biagini MR, Forte P, Galli A. Understanding fatigue in primary biliary cholangitis: From pathophysiology to treatment perspectives. World J Hepatol 2022; 14:1111-1119. [PMID: 35978669 PMCID: PMC9258253 DOI: 10.4254/wjh.v14.i6.1111] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 04/18/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis (PBC), affecting over 50% of PBC patients. One in five patients with PBC suffer from severe fatigue, which significantly impairs quality of life. Fatigue is made up of a central and a peripheral component, whose pathophysiology is still greatly unresolved. Central fatigue is characterised by a lack of self-motivation and can manifest both in physical and mental activities (lack of intention). Peripheral fatigue includes neuromuscular dysfunction and muscle weakness (lack of ability). Peripheral fatigue could be explained by an excessive deviation from aerobic to anaerobic metabolism leading to excessive lactic acid accumulation and therefore accelerated decline in muscle function and prolonged recovery time. As opposed to itching, and with the exception of end-stage liver disease, fatigue is not related to disease progression. The objective of this review is to outline current understanding regarding the pathophysiology of fatigue, the role of comorbidities and contributing factors, the main tools for fatigue assessment, the failed therapeutic options, and future treatment perspectives for this disabling symptom. Since fatigue is an extremely common and debilitating symptom and there is still no licensed therapy for fatigue in PBC patients, further research is warranted to understand its causative mechanisms and to find an effective treatment.
Collapse
Affiliation(s)
- Erica Nicola Lynch
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Claudia Campani
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence 50134, Italy
| | - Tommaso Innocenti
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Gabriele Dragoni
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
- Department of Medical Biotechnologies, University of Siena, Siena 53100, Italy
| | - Maria Rosa Biagini
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| | - Paolo Forte
- Division of Gastroenterology, University Hospital “Careggi”, Florence 50134, Italy
| | - Andrea Galli
- Gastroenterology Research Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence 50134, Italy
| |
Collapse
|
|
5
|
When LDL Cholesterol Is Not LDL Cholesterol: LpX, A Clinical Lesson. JACC Case Rep 2022; 4:690-693. [PMID: 35677796 PMCID: PMC9168776 DOI: 10.1016/j.jaccas.2022.03.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 02/15/2022] [Accepted: 03/07/2022] [Indexed: 11/20/2022]
Abstract
LpX is a lipoprotein formed in cholestatic conditions and often erroneously reported as LDL-C. A low ApoB level can support the diagnosis of LpX. Treatment should not automatically focus on lowering serum lipid levels, but primarily on resolving the cause of cholestasis. (Level of Difficulty: Advanced.)
Collapse
|
|
6
|
Dervout C, Boulais N, Barnetche T, Nousbaum JB, Brenaut E, Misery L. Efficacy of Treatments for Cholestatic Pruritus: A Systemic Review and Meta-analysis. Acta Derm Venereol 2022; 102:adv00653. [PMID: 35088869 PMCID: PMC9609979 DOI: 10.2340/actadv.v102.310] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Cholestatic itch is a disabling symptom that may be secondary to liver or biliary diseases. Management of cholestatic pruritus is complex. A systematic review and meta-analysis on the efficacy of treatments for cholestatic pruritus were performed. PubMed and Cochrane Library were searched using the algorithm “(hepatitis OR cholestatic OR liver) AND (pruritus OR itch) AND (management OR treatment OR treatments)” for 1975–2019. Of the 2,264 articles identified, 93 were included in a systematic review and 15 in a meta-analysis (studies evaluating pruritus with a visual analogue scale). Some treatments act by reducing levels of pruritogens in the enterohepatic cycle, others modify the metabolism or secretion of these pruritogens, or act on pruritus pathways. A further possible treatment is albumin dialysis. However, due to many heterogeneities in the reviewed studies it is difficult to identify and recommend an optimum treatment. Only 15 studies were included in the meta-analysis, due to the small number of randomized studies using a visual analogue scale.
Collapse
Affiliation(s)
| | | | | | | | - Emilie Brenaut
- Department of Dermatology, University Hospital, FR-29609 Brest, France.
| | | |
Collapse
|
|
7
|
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.
Collapse
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
| |
Collapse
|
|
8
|
Kattah L, Gómez A, Gutiérrez S, Puerto K, Moreno-Pallares ED, Jaramillo A, Mendivil CO. Hypercholesterolemia Due to Lipoprotein X: Case Report and Thematic Review. Clin Med Insights Endocrinol Diabetes 2019; 12:1179551419878687. [PMID: 31632171 PMCID: PMC6769215 DOI: 10.1177/1179551419878687] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2019] [Accepted: 08/28/2019] [Indexed: 12/15/2022] Open
Abstract
The liver is a key organ in lipid and lipoprotein metabolism, hence hepatic diseases often manifest as lipid disturbances. Cholestatic liver diseases are frequently associated with an important increase in total cholesterol at the expense of lipoprotein X (LpX), an abnormal lipoprotein isolated and characterized in the 1960s to 1970s in patients with obstructive jaundice. Lipoprotein X is rich in phospholipids, albumin, and free cholesterol, has a density similar to low-density lipoprotein (LDL), and a size similar to very low-density lipoprotein (VLDL), which has hampered its detection through routine laboratory tests. Unlike LDL, LpX has no apoB-100, so it is not removed from circulation via the LDL receptor, and it is not clear whether or not it can be atherogenic. Although LpX was initially described in patients with cholestasis, it has also been found in patients with genetic deficiency of lecithin-cholesterol acyltransferase (LCAT), in patients who receive lipid-rich parenteral nutrition and most recently in patients with graft versus host disease of the liver. In the presence of LpX, plasma total cholesterol can rise up to 1000 mg/dL, which may lead to the development of skin xanthomas and hyperviscosity syndrome. Treatment of LpX-dependent hypercholesterolemia with conventional hypolipidemic drugs is frequently ineffective, and definitive treatment relies on correction of the underlying cause of cholestasis. Here, we present the case of a patient with LpX-dependent hypercholesterolemia in the context of primary biliary cholangitis.
Collapse
Affiliation(s)
- Laura Kattah
- Endocrinology Section, Fundación Santa Fe de Bogotá, Bogotá, Colombia
| | - Andrés Gómez
- Division of Gastroenterology, Fundación Santa Fe de Bogotá, Bogotá, Colombia
| | | | | | | | - Andrés Jaramillo
- Endocrinology Section, Fundación Santa Fe de Bogotá, Bogotá, Colombia
| | - Carlos O Mendivil
- Endocrinology Section, Fundación Santa Fe de Bogotá, Bogotá, Colombia
- School of Medicine, Universidad de los Andes, Bogotá, Colombia
| |
Collapse
|
|
9
|
Chkheidze R, Joseph R, Burner J, Matevosyan K. Plasma exchange for the management of refractory pruritus of cholestasis: A report of three cases and review of literature. J Clin Apher 2018; 33:412-418. [PMID: 28792089 DOI: 10.1002/jca.21573] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2017] [Revised: 07/17/2017] [Accepted: 07/21/2017] [Indexed: 01/06/2025]
Abstract
BACKGROUND Intractable pruritus of cholestasis leads to significant morbidity. Therapeutic plasma exchange (TPE) has been shown to be an effective alternative in the setting of refractory pruritus associated with cholestatic liver disease based on several individual reports. Due to rarity of this approach to intractable pruritus, the literature is sparse and therefore TPE, as a treatment for refractory pruritus is currently not in the apheresis guidelines. We present three additional patients with severe intractable pruritus of cholestasis successfully treated with plasma exchange to add to the mounting literature showing this as an effective and safe adjunctive therapy. METHODS Three patients underwent serial plasma exchange procedures to control pruritus. Frequency of plasma exchange was three times a week, with slow taper upon improvement of pruritus. Total bile acid levels were assessed before procedures. RESULTS All three patients had an intractable pruritus with different underlying etiologies of cholestasis. All three patients showed significant improvement in pruritus, with none or minimal pruritus in one patient with primary biliary cirrhosis. Pre procedure bile acids levels were decreased initially, but showed rebound increase upon tapering of plasma exchange, without increased pruritus. No serious side effects or complications were observed. CONCLUSION Our results in conjunction with the published literature show that severe and intractable pruritus associated with cholestasis could be successfully treated with TPE, irrespective of the underlying disease, and can be done safely.
Collapse
Affiliation(s)
- Rati Chkheidze
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390
| | - Ranjit Joseph
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390
| | - James Burner
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390
| | - Karen Matevosyan
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, 75390
| |
Collapse
|
|
10
|
Geiger H, Klepper J, Lux P, Heidland A. Biochemical Assessment and Clinical Evaluation of a Bilirubin Adsorbent Column (Br-350) in Critically ILL Patients with Intractable Jaundice. Int J Artif Organs 2018. [DOI: 10.1177/039139889201500107] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
We investigated the efficacy of an anion-exchange adsorbent column (ASAHI BR-350, DIAMED) for removal of bilirubin and bile acids in five patients with intractable jaundice of various origin. Four litres of plasma were separated by membrane plasma separation (Plasmaflow OP-05) at a rate of 22.5 ml/min. The plasma was then perfused through an anion exchange adsorbent and returned to the venous blood line of the plasma separator. In some of the patients this procedure was combined with regular hemodialysis treatment. The concentration of total bilirubin was cut by 31 to 60%; total bile acids were reduced by 20 to 74%. Three patients recovered and had a favourable outcome. Two patients died despite the bilirubin adsorption treatment. The effects of the adsorbent column on specific blood parameters, including the coagulation system, were measured. Our data suggest that bilirubin adsorption should be examined further as a treatment for critically ill patients with intractable jaundice.
Collapse
Affiliation(s)
- H. Geiger
- IV Medical Clinic, University of Erlangen-Nürnberg, Erlangen
| | - J. Klepper
- Department of Nephrology, University of Würzburg, Würzburg - Germany
| | - P. Lux
- Department of Nephrology, University of Würzburg, Würzburg - Germany
| | - A. Heidland
- Department of Nephrology, University of Würzburg, Würzburg - Germany
| |
Collapse
|
|
11
|
Pazzi P, Scagliarini R, Puviani A, Lodi G, Morsiani E, Gullini S. Biochemical Assessment and Clinical Evaluation of a Non-Ionic Adsorbent Resin in Patients with Intractable Jaundice. Int J Artif Organs 2018. [DOI: 10.1177/039139880002300505] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
We investigated in vitro and in vivo the ability of a non-ionic adsorbing resin (styrenedivinylbenzene copolymer) to remove bilirubin and bile acids from human plasma. In preliminary experiments, human plasma from healthy donors, enriched in conjugated bile acids and bilirubin, and pooled plasma from jaundiced patients were recirculated through the resin column. The removal of bilirubin and bile acids was evaluated at two different flow rates (200 ml/min and 40 ml/min), and compared to an activated charcoal column. Four patients with severe jaundice were subsequently treated by 4-hour plasmaperfusion through the resin. The in vitro studies showed that after 1 hour the removal of bile acids was almost complete and bilirubin level decreased significantly, reaching a plateau after 4 hours. In the in vivo study, all treatments were well tolerated. After plasmaperfusion, serum bile acid levels decreased by 64.9–94.6% and total bilirubin by 35.3–57.7%. No clinical or biochemical side effects were observed. Our data suggest that plasmaperfusion through this resin is safe and efficient for removal of bilirubin and bile acids in jaundiced patients. Thus, it may serve as a method of artificial liver support in the treatment of cholestatic syndromes.
Collapse
Affiliation(s)
- P. Pazzi
- Department of Gastroenterology Ferrara - Italy
| | | | | | - G. Lodi
- Department of Transfusional Service Ferrara - Italy
| | - E. Morsiani
- Department of Surgery, S. Anna Hospital and University of Ferrara, Ferrara - Italy
| | - S. Gullini
- Department of Gastroenterology Ferrara - Italy
| |
Collapse
|
|
12
|
Trivedi HD, Lizaola B, Tapper EB, Bonder A. Management of Pruritus in Primary Biliary Cholangitis: A Narrative Review. Am J Med 2017; 130:744.e1-744.e7. [PMID: 28238692 DOI: 10.1016/j.amjmed.2017.01.037] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 01/27/2017] [Accepted: 01/30/2017] [Indexed: 12/16/2022]
Abstract
Primary biliary cholangitis is an autoimmune condition characterized by destruction of intrahepatic bile ducts. It causes debilitating symptoms that dramatically affect the patient's quality of life. Pruritus affects 60% to 70% of individuals with primary biliary cholangitis and leads to sleep disturbances, fatigue, depression, and suicidal ideation. A complete search was performed with studies from PubMed, EMBASE, Web of Science, Cochrane database, Countway Library, and CINAHL with specific search terms. This narrative review was prepared after a comprehensive literature review. Treating patients with cholestatic pruritus is challenging and may have a profound impact on quality of life. The standard of therapy for primary biliary cholangitis, ursodeoxycholic acid, does not have a beneficial effect in cholestatic pruritus. Patients often do not respond to conventional therapies such as cholestyramine, rifampicin, opioid antagonists, and sertraline. These therapies lack long-term efficacy and have side effects. Patients who have not responded to these initial treatments can be considered for experimental therapies or clinical trials. This review outlines the current and emerging treatment modalities for patients with primary biliary cholangitis who have pruritus.
Collapse
Affiliation(s)
- Hirsh D Trivedi
- Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass
| | - Blanca Lizaola
- Department of Medicine, St Elizabeth's Medical Center, Brighton, Mass
| | | | - Alan Bonder
- Liver Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass.
| |
Collapse
|
|
13
|
Krawczyk M, Liebe R, Wasilewicz M, Wunsch E, Raszeja-Wyszomirska J, Milkiewicz P. Plasmapheresis exerts a long-lasting antipruritic effect in severe cholestatic itch. Liver Int 2017; 37:743-747. [PMID: 27778443 DOI: 10.1111/liv.13281] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Accepted: 10/18/2016] [Indexed: 02/13/2023]
Abstract
BACKGROUND & AIMS The amelioration of refractory cholestatic pruritus after plasmapheresis has been reported in single patients. Here, we analyse the efficacy of plasmapheresis in a cohort of patients with primary biliary cholangitis (PBC). METHODS Seventeen consecutive patients with PBC (age range 39-85 years, 16 females, 9 with cirrhosis) and refractory pruritus underwent 129 plasmapheresis procedures during 40 admissions. Pruritus was quantified by the 10-point numeric rating scale (NRS) before and after plasmapheresis, as well as ~30 and ~90 days later. RESULTS The mean pruritus before plasmapheresis did not differ between patients with and without cirrhosis (P>.05). Cirrhotics presented, however, with significantly higher serum alanine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and bilirubin before plasmapheresis. Plasmapheresis decreased itching to NRS≤5 in all but five admissions: Mean pruritus decreased from 8.3±1.4 to 3.1±2.2 (P<.0001) in the entire cohort. It also led to a significant decrease in serum ALT, ALP, AST, GGT (all P<.001) and bilirubin (P=.002). Antipruritic effect persisted throughout the 90-days follow-up (P<.0001). The amelioration of pruritus was not affected by the presence of cirrhosis. CONCLUSIONS Plasmapheresis is a promising method for reducing intractable itch in a significant proportion of PBC patients regardless of liver fibrosis. Long-lasting improvement of symptoms requires repeated procedures.
Collapse
Affiliation(s)
- Marcin Krawczyk
- Laboratory of Metabolic Liver Diseases, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.,Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Roman Liebe
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Michał Wasilewicz
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Ewa Wunsch
- Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Joanna Raszeja-Wyszomirska
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Piotr Milkiewicz
- Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.,Department of Clinical and Molecular Biochemistry, Pomeranian Medical University in Szczecin, Szczecin, Poland
| |
Collapse
|
|
14
|
Kittanamongkolchai W, El-Zoghby ZM, Eileen Hay J, Wiesner RH, Kamath PS, LaRusso NF, Watt KD, Cramer CH, Leung N. Charcoal hemoperfusion in the treatment of medically refractory pruritus in cholestatic liver disease. Hepatol Int 2016; 11:384-389. [DOI: 10.1007/s12072-016-9775-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Accepted: 11/09/2016] [Indexed: 01/01/2023]
|
|
15
|
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.
Collapse
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
| |
Collapse
|
|
16
|
Gibson B, Williams LA, Marques MB, Pham HP. Therapeutic plasma exchange for intractable pruritus secondary to primary sclerosing cholangitis. J Clin Apher 2015; 31:495-6. [DOI: 10.1002/jca.21436] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 10/08/2015] [Indexed: 11/09/2022]
Affiliation(s)
- Briana Gibson
- Department of Pathology; University of Alabama at Birmingham; Birmingham Alabama
| | - Lance A. Williams
- Department of Pathology; University of Alabama at Birmingham; Birmingham Alabama
| | - Marisa B. Marques
- Department of Pathology; University of Alabama at Birmingham; Birmingham Alabama
| | - Huy P. Pham
- Department of Pathology; University of Alabama at Birmingham; Birmingham Alabama
| |
Collapse
|
|
17
|
Axelsson CG, Hallbäck DA. Twenty-six years of plasma exchange for symptomatic treatment of pruritus in primary biliary cirrhosis. Transfus Apher Sci 2013; 49:652-4. [DOI: 10.1016/j.transci.2013.07.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Accepted: 07/05/2013] [Indexed: 11/29/2022]
|
|
18
|
|
|
19
|
Abstract
Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that mainly targets the cholangiocytes of the interlobular bile ducts in the liver. It is a rare disease with prevalence of less than one in 2000. Its prevalence in developing countries is increasing presumably because of growth in recognition and knowledge of the disease. PBC is thought to result from a combination of multiple genetic factors and superimposed environmental triggers. The contribution of the genetic predisposition is evidenced by familial clustering. Several risk factors, including exposure to infectious agents and chemical xenobiotics, have been suggested. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The prognosis of PBC has improved because of early diagnosis and use of ursodeoxycholic acid, the only established medical treatment for this disorder. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. However, some patients do not respond adequately to ursodeoxycholic acid and might need alternative therapeutic approaches.
Collapse
Affiliation(s)
- Nadya Al-Harthy
- Gastroenterology and Hepatology, Royal Hospital, Muscat, Oman
| | - Teru Kumagi
- Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| |
Collapse
|
|
20
|
Wong ML, Raghavan RP, Hedger NA, Ellis RD, Meeking DR, Albon L. The use of plasmapheresis in managing primary biliary cirrhosis presenting with profound hypercholesterolaemia. ACTA ACUST UNITED AC 2012. [DOI: 10.1177/1474651412442410] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Mo Lee Wong
- Diabetes and Endocrinology, Royal Bournemouth Hospital, Bournemouth, UK
| | - Rajeev P Raghavan
- Diabetes & Endocrinology, Royal Wolverhampton NHS Trust, Wolverhampton, UK
| | | | - Richard D Ellis
- Gastroenterology, Queen Alexandra Hospital, Portsmouth Hospitals NHS Trust, Portsmouth, UK
| | - Darryl R Meeking
- Academic Department of Diabetes and Endocrinology, Portsmouth Hospitals NHS Trust, Portsmouth, UK
| | - Lorraine Albon
- Academic Department of Diabetes and Endocrinology, Portsmouth Hospitals NHS Trust, Portsmouth, UK
| |
Collapse
|
|
21
|
Abstract
Cholestasis develops either from a defect in bile synthesis, impairment in bile secretion, or obstruction to bile flow, and is characterized by an elevated serum alkaline phosphatase and gamma-glutamyltransferase disproportionate to elevation of aminotransferase enzymes. Key elements to the diagnostic workup include visualization of the biliary tree by cholangiography and evaluation of liver histology. The hope is that recent advances in understanding the genetic factors and immune mechanisms involved in the pathogenesis of cholestasis will lead to newer therapeutic interventions in the treatment of these diseases.
Collapse
Affiliation(s)
- Asma Siddique
- Department of Gastroenterology, Center for Liver Disease, Digestive Disease Institute, Seattle, WA 98111, USA
| | | |
Collapse
|
|
22
|
Abstract
Pruritus is a troublesome complication in patients with cholestatic liver disease. Several links to its pathogenesis have been proposed, including the role of bile acids, endogenous opioid and serotonins, and lysophosphatidic acid. The management of pruritus in cholestasis is challenging. Medical treatment of the underlying cholestatic condition may provide benefit. Extracorporeal albumin dialysis can be pursued for those who have a poor quality of life and failed the various therapeutic interventions, while awaiting liver transplantation. Experimental interventions, and the management of pruritus in certain conditions such as intrahepatic cholestasis of pregnancy and benign recurrent intrahepatic cholestasis, are also briefly reviewed.
Collapse
Affiliation(s)
- Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, USA
| | | |
Collapse
|
|
23
|
Fuhrmann V, Drolz A, Trauner M. Extracorporeal artificial liver support systems in the management of intractable cholestatic pruritus. Liver Int 2011; 31 Suppl 3:31-3. [PMID: 21824282 DOI: 10.1111/j.1478-3231.2011.02584.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Pruritus can occur as a severe complication of cholestasis. Several hypotheses suggest an important role for the accumulation of bile acids, endogenous opioids and - mire recently - lysophosphatidic acid. Bile acid sequestrants are the first-line therapeutic agents. In refractory cases, a stepwise approach using rifampicin, oral opiate antagonists and the selective serotonin reuptake inhibitor sertraline should be tested. Recent case series reported effective relief of pruritus using extracorporal liver support systems and plasmapheresis.
Collapse
Affiliation(s)
- Valentin Fuhrmann
- Department of Internal Medicine 3, Division of Gastroenterology and Hepatology, Medical University Vienna, Vienna, Austria.
| | | | | |
Collapse
|
|
24
|
Kremer AE, Oude Elferink RPJ, Beuers U. Pathophysiology and current management of pruritus in liver disease. Clin Res Hepatol Gastroenterol 2011; 35:89-97. [PMID: 21809485 DOI: 10.1016/j.clinre.2010.10.007] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Pruritus is frequently reported by patients with cholestatic hepatobiliary diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy and hereditary cholestatic syndromes, but may accompany almost any other liver disease. Increased concentrations of bile salts, histamine, progesterone metabolites or endogenous opioids have been controversially discussed as potential pruritogens in cholestasis in the past. Most recently, novel insights unravelled lysophosphatidic acid (LPA), a potent neuronal activator, as a potential pruritogen in pruritus of cholestasis. Nevertheless, the pathogenesis of pruritus in cholestasis is still not clearly defined and current antipruritic treatment strategies provide relief only in a part of the affected patients. Based on recent experimental and clinical findings, this review outlines the actual insight in pathogenesis of pruritus in cholestasis and summarizes evidence-based and experimental therapeutic interventions for cholestatic patients suffering from itch.
Collapse
Affiliation(s)
- Andreas E Kremer
- Tytgat Institute for liver and intestinal research, Department of gastroenterology and hepatology, Academic Medical Center, S1-164, University of Amsterdam, Meibergdreef 69-71, NL-1105 BK Amsterdam, The Netherlands.
| | | | | |
Collapse
|
|
25
|
Treatment of resistant pruritus from cholestasis with albumin dialysis: combined analysis of patients from three centers. J Hepatol 2010; 53:307-12. [PMID: 20580987 DOI: 10.1016/j.jhep.2010.02.031] [Citation(s) in RCA: 88] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2009] [Revised: 01/18/2010] [Accepted: 02/08/2010] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Albumin dialysis using molecular adsorbent recirculating system (MARS) is a new procedure for treating resistant pruritus from cholestasis, but it is usually published as a case report or a short series. Therefore, we analyzed patients with resistant pruritus treated with MARS from three centers, to assess the changes on pruritus and the indices of cholestasis. METHODS Twenty patients (12 female, mean age: 51+/-3.4 years) with chronic cholestatic liver disease or chronic liver-graft rejection were evaluated. The severity of pruritus was assessed using a visual analogue scale (VAS) before and after treatment, and 30 days thereafter. Liver tests, including total bilirubin, alkaline phosphatase, gamma-glutamyl-transferase, cholesterol, triglycerides, and total bile acid were also determined, as well as the number of sessions and the coupled procedure (dialysis or perfusion). RESULTS Albumin dialysis resulted in a decrease of pruritus (VAS: from 70.2+/-4.8 to 20.1+/-4.2, p<0.001), which partially resumed after 30 days (38.7+/-6.6). VAS decreased by 72% immediately after treatment and by 51% after 1 month. Pruritus decreased in all but one patient. MARS resulted in a significant bile acid decrease of 41% after treatment and by 37% after 1 month. The effect of MARS on pruritus and markers of cholestasis was similar in patients with different diseases and was independent of the coupled procedure. The improvement of pruritus in individuals was positive in 75% of patients. No major adverse effects were observed. CONCLUSIONS Albumin dialysis using MARS is an effective procedure for managing resistant pruritus in most patients with chronic cholestasis and graft rejection.
Collapse
|
|
26
|
Abstract
The management of autoimmune and cholestatic liver disorders is a challenging area of hepatology. Autoimmune and cholestatic liver diseases represent a comparatively small proportion of hepatobiliary disorders, yet their appropriate management is of critical importance for patient survival. In this article, management strategies are discussed, including the indications and expectations of pharmacologic therapy, endoscopic approaches, and the role of liver transplantation.
Collapse
Affiliation(s)
- Karen L Krok
- Division of Gastroenterology and Hepatology, University of Pennsylvania School of Medicine, 3400 Spruce Street, 3 Ravdin, Philadelphia, PA 19104, USA
| | | |
Collapse
|
|
27
|
Kremer AE, Beuers U, Oude-Elferink RPJ, Pusl T. Pathogenesis and treatment of pruritus in cholestasis. Drugs 2009; 68:2163-82. [PMID: 18840005 DOI: 10.2165/00003495-200868150-00006] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Pruritus is an enigmatic, seriously disabling symptom accompanying cholestatic liver diseases and a broad range of other disorders. Most recently, novel itch-specific neuronal pathways, itch mediators and their relevant receptors have been identified. In addition, new antipruritic therapeutic strategies have been developed and/or are under evaluation. This review highlights recent experimental and clinical findings focusing on the pathogenesis and actual treatment of pruritus in cholestatic liver disease. Evidence-based therapeutic recommendations, including the use of anion exchange resins cholestyramine, colestipol and colesevelam, the microsomal enzyme inducer rifampicin, the opioid receptor antagonists naltrexone and naloxone, and the serotonin reuptake inhibitor sertraline, are provided.
Collapse
Affiliation(s)
- Andreas E Kremer
- Liver Center, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
| | | | | | | |
Collapse
|
|
28
|
Lemoine M, Revaux A, Francoz C, Ducarme G, Brechignac S, Jacquemin E, Uzan M, Ganne-Carrié N. Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus. World J Gastroenterol 2008; 14:6572-4. [PMID: 19030215 PMCID: PMC2773349 DOI: 10.3748/wjg.14.6572] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.
Collapse
|
|
29
|
Role of plasmapheresis in the treatment of severe pruritus in pregnant patients with primary biliary cirrhosis: case reports. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2008; 22:505-7. [PMID: 18478137 DOI: 10.1155/2008/969826] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Primary biliary cirrhosis (PBC) may be associated with pruritus and, when present, may be accentuated during pregnancy. Several therapeutic modalities have been used to control itching caused by cholestasis, with variable responses. Drug therapies are ill-advised, particularly in early pregnancy. Plasmapheresis has been successful in controlling pruritus in patients with cholestasis. The use of plasmapheresis to alleviate severe life-threatening pruritus during pregnancy is reported in two patients with PBC. CASE PRESENTATIONS Two patients with PBC presented during their second trimester of pregnancy with severe pruritus that did not respond to the anion exchange resin cholestyramine. Their symptoms were disabling to the point that one patient had suicidal ideation. Given the severity of their symptoms, multiple sessions of plasmapheresis were instituted with good control of pruritus. Both patients tolerated the procedure well and delivered healthy babies. CONCLUSION Plasmapheresis is a relatively safe and rapidly effective treatment for severe pruritus during pregnancy in patients with PBC.
Collapse
|
|
30
|
Kumagi T, Heathcote EJ. Successfully treated intractable pruritus with rifampin in a case of benign recurrent intrahepatic cholestasis. Clin J Gastroenterol 2008; 1:160-163. [DOI: 10.1007/s12328-008-0027-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2008] [Accepted: 07/25/2008] [Indexed: 11/28/2022]
|
|
31
|
Abstract
Most care of liver disease is in the ambulatory setting, and therefore the clinical needs of patients represent those of any other chronic illness. Emphasis must be given to preventative strategies such that liver lifetime (including pre-emptive strategies related to potential allograft survival) is maximised through timely intervention and avoidance of side effects. This review addresses the pertinent practical clinical concerns faced by clinicians as they manage adult patients with chronic liver disease, with an emphasis on preventing and managing symptoms and complications directly and indirectly related to the underlying disease.
Collapse
Affiliation(s)
- Gideon M Hirschfield
- Toronto Western Hospital, University Health Network, University of Toronto, ON, Canada.
| | | | | |
Collapse
|
|
32
|
Kumagi T, Heathcote EJ. Primary biliary cirrhosis. Orphanet J Rare Dis 2008; 3:1. [PMID: 18215315 PMCID: PMC2266722 DOI: 10.1186/1750-1172-3-1] [Citation(s) in RCA: 81] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2007] [Accepted: 01/23/2008] [Indexed: 12/15/2022] Open
Abstract
Primary biliary cirrhosis (PBC) is a chronic and slowly progressive cholestatic liver disease of autoimmune etiology characterized by injury of the intrahepatic bile ducts that may eventually lead to liver failure. Affected individuals are usually in their fifth to seventh decades of life at time of diagnosis, and 90% are women. Annual incidence is estimated between 0.7 and 49 cases per million-population and prevalence between 6.7 and 940 cases per million-population (depending on age and sex). The majority of patients are asymptomatic at diagnosis, however, some patients present with symptoms of fatigue and/or pruritus. Patients may even present with ascites, hepatic encephalopathy and/or esophageal variceal hemorrhage. PBC is associated with other autoimmune diseases such as Sjogren's syndrome, scleroderma, Raynaud's phenomenon and CREST syndrome and is regarded as an organ specific autoimmune disease. Genetic susceptibility as a predisposing factor for PBC has been suggested. Environmental factors may have potential causative role (infection, chemicals, smoking). Diagnosis is based on a combination of clinical features, abnormal liver biochemical pattern in a cholestatic picture persisting for more than six months and presence of detectable antimitochondrial antibodies (AMA) in serum. All AMA negative patients with cholestatic liver disease should be carefully evaluated with cholangiography and liver biopsy. Ursodeoxycholic acid (UDCA) is the only currently known medication that can slow the disease progression. Patients, particularly those who start UDCA treatment at early-stage disease and who respond in terms of improvement of the liver biochemistry, have a good prognosis. Liver transplantation is usually an option for patients with liver failure and the outcome is 70% survival at 7 years. Recently, animal models have been discovered that may provide a new insight into the pathogenesis of this disease and facilitate appreciation for novel treatment in PBC.
Collapse
Affiliation(s)
- Teru Kumagi
- Department of Medicine, Toronto Western Hospital (University Health Network/University of Toronto), Toronto, Ontario, Canada.
| | | |
Collapse
|
|
33
|
|
|
34
|
Abstract
Cholestasis secondary to infiltration of the liver by malignant tumors or by obstruction of the biliary tree can be complicated by pruritus. The clinician and ancillary personal must recognize how debilitating pruritus is and identify the treatment of this symptom as a priority. Because robust clinical trials have not been conducted in patients who have pruritus with cholestasis, a network connecting the services that provide care for these patients (eg, hospices) may be useful for disseminating information.
Collapse
Affiliation(s)
- Nora V Bergasa
- Department of Medicine, State University of New York at Downstate, 451 Clarkson Avenue, Brooklyn, NY 11203, USA.
| |
Collapse
|
|
35
|
Mansour-Ghanaei F, Taheri A, Froutan H, Ghofrani H, Nasiri-Toosi M, Bagherzadeh AH, Farahvash MJ, Mirmomen S, Ebrahimi-Dariani N, Farhangi E, Pourrasouli Z. Effect of oral naltrexone on pruritus in cholestatic patients. World J Gastroenterol 2006; 12:1125-1128. [PMID: 16534857 PMCID: PMC4087908 DOI: 10.3748/wjg.v12.i7.1125] [Citation(s) in RCA: 57] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2005] [Revised: 07/29/2005] [Accepted: 12/26/2005] [Indexed: 02/06/2023] Open
Abstract
AIM To determine the efficacy and potential complications of oral naltrexone used in the treatment of pruritus in cholestatic patients and to compare them with other studies. METHODS Thirty-four enrolled cholestatic patients complaining of pruritus were studied. In the initial phase, pruritus scores during day and night were evaluated. Subsequently, patients were given a placebo for one week followed by naltrexone for one week. In each therapeutic course (placebo or naltrexone) day and night pruritus scores were distinguished by a visual analogue scale (VAS) system and recorded in patients' questionnaires. RESULTS Both naltrexone and placebo decreased VAS scores significantly. Naltrexone was more effective than placebo in decreasing VAS scores. Both day and night scores of pruritus decreased by half of the value prior to therapy in thirteen patients (38%). Daytime pruritus improved completely in two patients (5.9%), but no improvement in the nighttime values was observed in any patient. Sixteen patients (47%) suffered from naltrexone complications, eleven (32%) of them were related to its withdrawal. Complications were often mild. In the case of withdrawal, the complication was transient (within the first 24-28 h of therapy) and self-limited. We had to cease the drug in two cases (5.9%) because of severe withdrawal symptoms. CONCLUSION Naltrexone can be used in the treatment of pruritus in cholestatic patients and is a safe drug showing few, mild and self-limited complications.
Collapse
Affiliation(s)
- Fariborz Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Sardar-Jangle Ave, Razi Hospital, Rasht 41448 - 95655, Iran.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Affiliation(s)
- Nora V Bergasa
- Division of Hepatology, State University of New York at Downstate, Box 50, Brooklyn, NY 11203, USA.
| |
Collapse
|
|
37
|
Affiliation(s)
- Marshall M Kaplan
- Division of Gastroenterology, Tufts-New England Medical Center, Boston, MA 02111, USA.
| | | |
Collapse
|
|
38
|
Warren JE, Blaylock RC, Silver RM. Plasmapheresis for the treatment of intrahepatic cholestasis of pregnancy refractory to medical treatment. Am J Obstet Gynecol 2005; 192:2088-9. [PMID: 15970907 DOI: 10.1016/j.ajog.2005.01.048] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Pruritus associated with intrahepatic cholestasis of pregnancy (ICP) is usually mild but some cases are refractory to medical treatment. We report a case of intractable ICP that was successfully treated with plasmapheresis. Plasmapheresis should be considered for ICP that is refractory to traditional therapies.
Collapse
Affiliation(s)
- Jennifer E Warren
- Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, 84132, USA
| | | | | |
Collapse
|
|
39
|
Parés A, Cisneros L, Salmerón JM, Caballería L, Mas A, Torras A, Rodés J. Extracorporeal albumin dialysis: a procedure for prolonged relief of intractable pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol 2004; 99:1105-10. [PMID: 15180733 DOI: 10.1111/j.1572-0241.2004.30204.x] [Citation(s) in RCA: 80] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Pruritus is a distressing symptom in patients with primary biliary cirrhosis, and when uncontrollable it is an indication for liver transplantation. Since pruritus can result from unknown substances that accumulate systemically as a consequence of impaired biliary secretion, we have assessed whether a new extracorporeal albumin dialysis (ECAD) procedure, the molecular-adsorbing recirculating system-MARS, has any effect on pruritus of cholestasis. METHODS Four patients with primary biliary cirrhosis and resistant pruritus were treated with two 7-h ECAD sessions 1 day apart. Pruritus was recorded from 15 days before the first session, before and after each session, and during the follow-up using a visual analogue scale (VAS). Standard liver tests as well as serum bile acid levels were also measured. RESULTS There was a clear association between ECAD treatment and relief of itching, which promptly disappeared in two patients, or decreased markedly in the other two. One patient was free of pruritus for 18 months except for short periods with mild pruritus. The second patient experienced amelioration of itching, which almost disappeared completely and recurred mildly 4 months later. In the other two patients pruritus was alleviated markedly after ECAD but gradually recurred. These two patients were treated again 9 and 7 months later with favorable effects on pruritus. The scratching skin lesions improved or disappeared in parallel with the alleviation of itching. The albumin dialysis procedure did not result in liver test changes, except for circulating bile acids, which decreased in all the patients. No significant adverse effects were observed. CONCLUSIONS The ECAD procedure seems to be an effective alternative for the treatment of patients with pruritus of cholestasis who do not respond to other therapeutic methods.
Collapse
Affiliation(s)
- Albert Parés
- Liver Unit, Institut Clínic de Malalties Digestives, Hospital Clínic, Barcelona, Spain
| | | | | | | | | | | | | |
Collapse
|
|
40
|
Abstract
Pruritus is a complication of liver disease. It can have a marked negative impact on quality of life; when intractable, it is an indication for liver transplantation. The cause of this type of pruritus is unknown. There is, however, evidence to suggest that the pruritus associated with liver disease is mediated, at least in part, by endogenous opioids. A central mechanism has been proposed. Therapeutic interventions have concentrated on the removal of presumed and unknown pruritogens from the circulation, hepatic enzyme induction, and, over the past decade, opiate antagonists, the first specific treatment for the pruritus of cholestasis. Other pharmacologic interventions that change neurotransmission have recently been reported to decrease the pruritus in patients with liver disease, as has a newly developed system that applies albumin-based dialysis. These interventions are promising, but they must be tested in properly controlled behavioral trials.
Collapse
Affiliation(s)
- Nora V Bergasa
- Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, 630 West 168th Street, P&S 10- 508, New York, NY 10032, USA.
| |
Collapse
|
|
41
|
Abstract
Liver transplantation is the accepted treatment for patients with end-stage liver disease or intractable symptoms secondary to primary biliary cirrhosis (PBC), and has proven survival benefit. Indications for transplantation are an unacceptable quality of life or anticipated death in less than 1 year. Although there are a number of prognostic models, serum bilirubin provides the simplest guide to transplantation timing. Those grafted for PBC are at greater risk of developing chronic rejection, and are less likely to be successfully weaned from immunosuppression than those grafted for other indications. Following transplantation, antimitochondrial antibodies persist and histological features of recurrent PBC may be seen in the allograft in up to 50% by 10 years; however, at least in the medium-term, this rarely causes clinical problems.
Collapse
|
|
42
|
Abstract
Pruritus and fatigue are the most common symptoms of patients with PBC, and both have marked negative impact on quality of life. Over the past decade, evidence has emerged supporting a role of the central nervous system in the pathogenesis of these two common manifestations of PBC. There is no evidence that the pruritus of cholestasis is mediated in the skin. Clinical and laboratory data do support a role of the opioid neurotransmitter system in the mediation of the pruritus of cholestasis; a central mechanism has been proposed. Treatment with opiate antagonist is thus a specific alternative. Studies of the behavioral consequence of the pruritus of cholestasis, scratching activity, allow for the design of clinical trials with objective end-points. The etiology of fatigue is unknown. A central component is being considered. The identification of objective alterations in fatigue and the adoption of a definition that incorporates the perception and the behavioral consequences of fatigue should facilitate the development of objective methodology. The potential role of various neurotransmitter systems, including the serotonin system and the opioid system, in the mediation of the fatigue of PBC seems to merit further investigation.
Collapse
Affiliation(s)
- Nora V Bergasa
- Division of Digestive and Liver Diseases, College of Physicians and Surgeons of Columbia University, 630 West 168th Street, P & S 10-508, New York, NY 10032, USA.
| |
Collapse
|
|
43
|
Abstract
Pruritus is often the most troublesome symptom in patients with chronic liver disease, particularly when cholestasis is a prominent feature. The exact pathogenesis is unknown, but empirical treatment, such as cholestyramine, based on a liver-based origin of pruritus, has been used for many years. Recently, evidence for a central mechanism for pruritus has been obtained and opioid antagonists have been tried clinically with some benefit, but their use is not widespread. In addition, the pruritus associated with intrahepatic cholestasis of pregnancy can now be alleviated in many cases by ursodeoxycholic acid. As it also improves foetal outcome, this should become first-line therapy. We review the pathogenesis and therapy of pruritus, highlighting practical aspects to help with patients with seemingly intractable pruritus.
Collapse
Affiliation(s)
- M Mela
- Liver Transplantation and Hepatobiliary Unit, Royal Free Hospital, London, UK
| | | | | |
Collapse
|
|
44
|
Terg R, Coronel E, Sordá J, Muñoz AE, Findor J. Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study. J Hepatol 2002; 37:717-22. [PMID: 12445410 DOI: 10.1016/s0168-8278(02)00318-5] [Citation(s) in RCA: 106] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
BACKGROUND/AIMS To assess the efficacy and safety of naltrexone for the short and long term treatment of pruritus of cholestasis. METHODS Twenty patients with pruritus and cholestasis were included. A baseline pruritus score was obtained over 1 week. Patients were then randomized to receive 50 mg/day of naltrexone or placebo for 2 weeks. Subsequently, a 1-week washout period ensued and patients were crossed over to the other therapy for 2 additional weeks. Pruritus was assessed daily with a visual analogue scale (VAS) from 0 to 10. Patients whose pruritus decreased >50% of basal with naltrexone received naltrexone 50 mg/day for 2 additional months. RESULTS Mean basal VAS was similar in both groups. VAS showed greater and more significant changes with naltrexone than with placebo (P<0.0003). In nine out of 20 patients (45%) receiving naltrexone, pruritus decreased >50% compared to basal value, including five whose pruritus disappeared completely. No significant changes were observed in serum biochemistry. Most of the adverse events that occurred during the first 48 h of naltrexone therapy were consistent with opioid withdrawal-like phenomena and spontaneously disappeared 2 days after starting treatment. CONCLUSIONS Naltrexone can be considered as an alternative option to treat pruritus of cholestasis. In the current study, side effects were transient and did not require specific medication.
Collapse
Affiliation(s)
- Rubén Terg
- Unidad de Hepatología, Hospital de Gastroenterología Bonorino Udaondo, Escuela de Medicina, Universidad del Salvador, Avenida Caseros, 2061 (1264), Buenos Aires, Argentina.
| | | | | | | | | |
Collapse
|
|
45
|
Abstract
Guidelines for clinical practice are intended to indicate preferred approaches to medical problems as established by scientifically valid research. Double blind, placebo-controlled studies are preferable, but reports and expert review articles are also utilized in a thorough review of the literature conducted through the National Library of Medicine's MEDLINE. When only data that will not withstand objective scrutiny are available, a recommendation is identified as a consensus of experts. Guidelines are applicable to all physicians who address the subject, without regard to specialty training or interests, and are intended to indicate the preferable but not necessarily the only acceptable approach to a specific problem. Guidelines are intended to be flexible and must be distinguished from standards of care that are inflexible and rarely violated. Given the wide range of specifics in any health care problem, the physician must always choose the course best suited to the individual patient and the variables in existence at the moment of decision. Guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee and approved by the Board of Trustees. Each has been intensely reviewed and revised by the Committee, other experts in the field, physicians who will use them, and specialists in the science of decision of analysis. The recommendations of each guideline are therefore considered valid at the time of their production based on the data available. New developments in medical research and practice pertinent to each guideline will be reviewed at an established time and indicated at publication to assure continued validity.
Collapse
Affiliation(s)
- Young-Mee Lee
- Division of Gastroenterology, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
| | | |
Collapse
|
|
46
|
Abstract
Pruritus is experienced by about 80% of patients with primary biliary cirrhosis. It can have a marked negative impact on the quality of life of patients, and it can be an indication for liver transplantation. There is evidence to suggest that the pruritus of cholestasis is mediated, at least in part, by endogenous opioids. A central component has been proposed. Behavioural data have shed light on the pathogenesis of this form of pruritus. Fatigue affects the majority of patients with primary biliary cirrhosis. It interferes with work performance and family life. An idea is emerging that suggests that fatigue in primary biliary cirrhosis also may be mediated centrally. Research tools need to be developed to study fatigue objectively in patients with primary biliary cirrhosis.
Collapse
Affiliation(s)
- N V Bergasa
- Division of Digestive and Liver Diseases, College of Physicians and Surgeons of Columbia University, 630 W 168 St, P & S 10-508, New York, New York, 10032, USA
| | | | | |
Collapse
|
|
47
|
Yerushalmi B, Sokol RJ, Narkewicz MR, Smith D, Karrer FM. Use of rifampin for severe pruritus in children with chronic cholestasis. J Pediatr Gastroenterol Nutr 1999; 29:442-7. [PMID: 10512405 DOI: 10.1097/00005176-199910000-00013] [Citation(s) in RCA: 77] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Rifampin has been proposed to reduce pruritus in children and adults with chronic cholestasis; however, there is a paucity of published data regarding the use of rifampin in children. METHODS In an open trial, 24 children were evaluated during a 6-year period. Diagnoses included 13 patients with extrahepatic biliary atresia (54%), six with Alagille's syndrome, three with Byler's disease, and one each with primary sclerosing cholangitis and alpha1-antitrypsin deficiency. All patients had severe pruritus that had not responded adequately to at least 2 months of therapy with ursodeoxycholic acid, diphenhydramine, or phenobarbital and local skin care measures. Treatment was initiated with rifampin, 10 mg/kg per day in two divided doses for 18+/-20 months, and the effect on the severity of pruritus was assessed by a clinical scoring system. RESULTS Ten patients showed a complete response, 12 a partial response, and 2 no response. Complete response was more common in extrahepatic cholestasis (64% vs. 10%), whereas partial response was more common in intrahepatic cholestasis (80% vs. 29%). Treatment was associated with reduction of gamma-glutamyl transpeptidase. No clinical or biochemical toxicity of rifampin was observed. CONCLUSIONS We conclude that for more than 90% of children with chronic cholestasis and severe pruritus unresponsive to other treatments, rifampin appears to be a safe and effective therapy.
Collapse
Affiliation(s)
- B Yerushalmi
- Pediatric Liver Center, Department of Pediatrics, University of Colorado School of Medicine and The Children's Hospital, Denver 80218, USA
| | | | | | | | | |
Collapse
|
|
48
|
Abstract
Several drugs have been evaluated in the treatment of primary biliary cirrhosis over a number of years. These drugs have immunosuppressive, antiinflammatory, cupruretic, antifibrotic and bile acid properties. Ursodeoxycholic acid has been shown to improve survival free of transplantation in a conclusive fashion. This drug is the single agent that can be recommended for the treatment of primary biliary cirrhosis. Corticosteroid therapy and ursodeoxycholic acid have been evaluated in a few patients with autoimmune cholangitis. This article reviews a large number of studies that have been published assessing different drugs in the treatment of these two entities, particularly in the treatment of primary biliary cirrhosis.
Collapse
Affiliation(s)
- P Angulo
- Division of Gastroenterology and Hepatology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA
| | | |
Collapse
|
|
49
|
Bergasa NV, Jones EA. The pruritus of cholestasis: evolving pathogenic concepts suggest new therapeutic options. Clin Liver Dis 1998; 2:391-405, x. [PMID: 15560039 DOI: 10.1016/s1089-3261(05)70014-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Pruritus is a distressing symptom experienced by a large proportion of patients with cholestasis. The cause of this form of pruritus is unknown, and therapy tends to be empirical and unsatisfactory. This article discusses the emerging role of the brain and neurotransmitter systems in the pathogenesis of the pruritus of cholestasis and emphasizes the importance of the application of quantitative methodology in clinical trials of therapies for the pruritus of cholestasis.
Collapse
Affiliation(s)
- N V Bergasa
- Division of Gastroenterology and Liver Disease, Beth Israel Medical Center, New York, USA
| | | |
Collapse
|
|
50
|
Abstract
Plasmapheresis is the process by which plasma containing components causing or thought to cause disease is removed from the circulation, and the remaining blood components are returned with plasma or a harmless plasma substitute to the donor. It primarily removes protein-bound solutes or high-molecular-weight solutes such as circulating protein-bound toxins, autoantibodies, immune complexes, or other abnormally occurring molecules. Plasmapheresis has been used in the treatment of more than 100 diseases in human medicine, including immune-mediated diseases, neoplasia, infectious diseases, sepsis, hyperlipidemia, thyrotoxicosis, and removal of toxins. In immune-mediated disease, it is most useful to rapidly decrease plasma concentrations of antibodies or immune complexes, whereas other immunosuppressive measures are used to prolong the effect.
Collapse
Affiliation(s)
- J W Bartges
- Department of Small Animal Medicine, Veterinary Teaching Hospital, University of Georgia, Athens 30602, USA
| |
Collapse
|