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1
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Faisal MS, Gonzalez HC, Gordon SC. Primary Biliary Cholangitis: Epidemiology, Diagnosis, and Presentation. Clin Liver Dis 2024; 28:63-77. [PMID: 37945163 DOI: 10.1016/j.cld.2023.06.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Using ursodeoxycholic acid as a standard treatment and for its ability to test for antimitochondrial antibody to accelerate diagnosis, survival of primary biliary cholangitis patients has approached that of the general population, leading to a change in nomenclature from primary biliary cirrhosis to primary biliary cholangitis to more accurately describe the disease.
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Affiliation(s)
- Muhammad Salman Faisal
- Department of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA
| | - Humberto C Gonzalez
- Department of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA
| | - Stuart C Gordon
- Department of Gastroenterology and Hepatology, Henry Ford Health, 2799 West Grand Boulevard, Detroit, MI 48202, USA; Wayne State University School of Medicine, 540 East Canfield Street, Detroit, MI 48201, USA.
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2
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Sarcopenia and Frailty in Cirrhosis. Med Clin North Am 2023; 107:589-604. [PMID: 37001955 DOI: 10.1016/j.mcna.2022.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
Abstract
Sarcopenia and frailty are frequent in cirrhosis, and both contribute to increased morbidity and mortality. The complex pathogenesis of sarcopenia in cirrhosis is mainly determined by hyperammonemia and malnutrition. Sarcopenia/frailty screening and reevaluation should be undertaken in all cirrhotic patients. Frailty tests are useful in the ambulatory setting, whereas the computed tomography scan is the diagnostic gold standard for sarcopenia. To manage sarcopenia/frailty, a multidisciplinary team should develop a personalized comprehensive care plan that includes patient education, protein/calorie intake goals, late evening meals, exercise programs, and micronutrient replenishment. In selected patients, branched-chain amino acid and testosterone supplements may also be beneficial.
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3
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Borel P, Dangles O, Kopec RE. Fat-soluble vitamin and phytochemical metabolites: Production, gastrointestinal absorption, and health effects. Prog Lipid Res 2023; 90:101220. [PMID: 36657621 DOI: 10.1016/j.plipres.2023.101220] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 12/12/2022] [Accepted: 01/12/2023] [Indexed: 01/18/2023]
Abstract
Consumption of diets rich in fruits and vegetables, which provide some fat-soluble vitamins and many phytochemicals, is associated with a lower risk of developing certain degenerative diseases. It is well accepted that not only the parent compounds, but also their derivatives formed upon enzymatic or nonenzymatic transformations, can produce protective biological effects. These derivatives can be formed during food storage, processing, or cooking. They can also be formed in the lumen of the upper digestive tract during digestion, or via metabolism by microbiota in the colon. This review compiles the known metabolites of fat-soluble vitamins and fat-soluble phytochemicals (FSV and FSP) that have been identified in food and in the human digestive tract, or could potentially be present based on the known reactivity of the parent compounds in normal or pathological conditions, or following surgical interventions of the digestive tract or consumption of xenobiotics known to impair lipid absorption. It also covers the very limited data available on the bioavailability (absorption, intestinal mucosa metabolism) and summarizes their effects on health. Notably, despite great interest in identifying bioactive derivatives of FSV and FSP, studying their absorption, and probing their putative health effects, much research remains to be conducted to understand and capitalize on the potential of these molecules to preserve health.
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Affiliation(s)
- Patrick Borel
- C2VN, INRAE, INSERM, Aix-Marseille Univ, Marseille, France.
| | | | - Rachel E Kopec
- Human Nutrition Program, Department of Human Sciences, Foods for Health Discovery Theme, The Ohio State University, Columbus, OH 43210, USA.
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4
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Shah ND, Barritt AS. Nutrition as Therapy in Liver Disease. Clin Ther 2022; 44:682-696. [DOI: 10.1016/j.clinthera.2022.04.012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/27/2022] [Accepted: 04/27/2022] [Indexed: 12/12/2022]
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5
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Saadati S, Salehi-sahlabadi A, Hosseini-Oskouiee F, Aghamohammadi V, Ramezani M, Askari B, Sayyah A, Sadeghi A, Hekmatdoost A. Dietary Total Antioxidant Capacity and Risk of Gall Stone: A Case-Control Study. Int J Prev Med 2021; 12:178. [PMID: 37663404 PMCID: PMC10472078 DOI: 10.4103/ijpvm.ijpvm_245_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 08/07/2020] [Indexed: 11/04/2022] Open
Abstract
Background Since the relation between dietary total antioxidant capacity (DTAC) and the occurrence of gallstone disease (GSD) remains unclear, we conducted, for the first time, a case-control study to clarify this association in the Iranian population. Methods In the present case-control study, convenience Sampling was performed. A total of 600 participants (300 case and 300 control) were included. Anthropometric, demographic, physical activity, and nutrient intakes data were obtained from each subject. DTAC was calculated using the US Department of Agriculture's database. The odds ratio (OR) and 95% confidence intervals were assessed using unconditional logistic regression. Results The participants in the highest quartile of DTAC had a significantly lower OR for gallstone than the lowest quartile, which remained significant after further adjustment for age, sex, and education (model 2: OR, 0.34; 95% CI, 0.16-0.71). In addition, after adjustment for age, sex, education, BMI, physical activity, and energy, the results revealed that participants with the highest quartile of DTAC had 71% lower odds of gallstone than those with the lowest quartile (model 3: OR, 0.29; 95% CI, 0.11-0.78). Conclusions The results of the present study demonstrated that the DTAC had an inverse association with GSD incident. However, interventional approaches are needed to confirm the relation between DTAC and GSD prevention.
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Affiliation(s)
- Saeede Saadati
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ammar Salehi-sahlabadi
- Student Research Committee, Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Hosseini-Oskouiee
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Mortaza Ramezani
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Askari
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Sayyah
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology, Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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6
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Lai JC, Tandon P, Bernal W, Tapper EB, Ekong U, Dasarathy S, Carey EJ. Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology 2021; 74:1611-1644. [PMID: 34233031 PMCID: PMC9134787 DOI: 10.1002/hep.32049] [Citation(s) in RCA: 377] [Impact Index Per Article: 94.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Accepted: 06/23/2021] [Indexed: 12/13/2022]
Affiliation(s)
- Jennifer C Lai
- Department of Medicine, University of California, San Francisco, San Francisco, CA
| | - Puneeta Tandon
- Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Albert, Canada
| | - William Bernal
- Liver Intensive Therapy Unit, Institute of Liver Studies, Kings College Hospital, London, UK
| | - Elliot B Tapper
- Division of Gastroenterology, University of Michigan, Ann Arbor, MI
| | - Udeme Ekong
- Georgetown University School of Medicine, Medstar Georgetown Transplant Institute, Washington, DC
| | - Srinivasan Dasarathy
- Department of Gastroenterology and Hepatology, Inflammation and Immunity, Lerner Research Institute, Cleveland Lerner Research Institute, Cleveland Clinic, Cleveland, OH
| | - Elizabeth J Carey
- Division of Gastroenterology and Hepatology, Mayo Clinic in Arizona, Phoenix, AZ
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7
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Pieters A, Gijbels E, Cogliati B, Annaert P, Devisscher L, Vinken M. Biomarkers of cholestasis. Biomark Med 2021; 15:437-454. [PMID: 33709780 DOI: 10.2217/bmm-2020-0691] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Cholestasis is a major pathological manifestation, often resulting in detrimental liver conditions, which occurs in a variety of indications collectively termed cholestatic liver diseases. The frequent asymptomatic character and complexity of cholestasis, together with the lack of a straightforward biomarker, hampers early detection and treatment of the condition. The 'omics' era, however, has resulted in a plethora of cholestatic indicators, yet a single clinically applicable biomarker for a given cholestatic disease remains missing. The criteria to fulfil as an ideal biomarker as well as the challenging molecular pathways in cholestatic liver diseases advocate for a scenario in which multiple biomarkers, originating from different domains, will be assessed concomitantly. This review gives an overview of classical clinical and novel molecular biomarkers in cholestasis, focusing on their benefits and drawbacks.
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Affiliation(s)
- Alanah Pieters
- Department of In Vitro Toxicology & Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium
| | - Eva Gijbels
- Department of In Vitro Toxicology & Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium
| | - Bruno Cogliati
- Department of Pathology, School of Veterinary Medicine & Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva 87, Cidade Universitária, SP, 05508-270, Brazil
| | - Pieter Annaert
- Drug Delivery & Disposition, Department of Pharmaceutical & Pharmacological Sciences, Katholieke Universiteit Leuven, ON II Herestraat 49, Box 921, Leuven, 3000, Belgium
| | - Lindsey Devisscher
- Basic & Applied Medical Sciences, Gut-Liver Immunopharmacology Unit, Faculty of Medicine & Health Sciences, Ghent University, C Heymanslaan 10, Ghent, 9000, Belgium
| | - Mathieu Vinken
- Department of In Vitro Toxicology & Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium
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8
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Chan KH, O'Sullivan M, Farouji I, Are G, Slim J. Sensory Axonopathy Associated With Vitamin E Deficiency. Cureus 2021; 13:e13389. [PMID: 33754112 PMCID: PMC7971715 DOI: 10.7759/cureus.13389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Vitamin E deficiency can be observed in patients with malabsorption syndromes or inherited diseases such as ataxia. It is unusual for it to be a result of dietary insufficiency due to its presence in a wide variety of foods. Patients with vitamin E deficiency can present with neuromuscular disorders such as ataxia, hyporeflexia, spinocerebellar syndrome, as well as loss of vibration and proprioceptive sensation. Herein, we are presenting a case in which a previously healthy adult with no family history of genetic defects and malabsorption syndrome presented with a characteristic sensory axonopathy associated with vitamin E deficiency without any evidence of fat malabsorption. Patient reported a markedly improvement of symptoms after three-month supplementation of vitamin E. The unique part of this case was that the patient presented with neuropathic pain associated with vitamin E deficiency without any family history of inherited deficiency or any malabsorption syndrome.
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Affiliation(s)
- Kok Hoe Chan
- Internal Medicine, Saint Michael's Medical Center, Newark, USA
| | - Michael O'Sullivan
- Internal Medicine, University of New England College of Osteopathic Medicine, Maine, USA
| | - Iyad Farouji
- Internal Medicine, Saint Michael's Medical Center, Newark, USA
| | - Gowthami Are
- Internal Medicine, Saint Michael's Medical Center, Newark, USA
| | - Jihad Slim
- Infectious Diseases, Saint Michael's Medical Center, Newark, USA
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9
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Leung KK, Deeb M, Hirschfield GM. Review article: pathophysiology and management of primary biliary cholangitis. Aliment Pharmacol Ther 2020; 52:1150-1164. [PMID: 32813299 DOI: 10.1111/apt.16023] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/13/2020] [Accepted: 07/18/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Primary biliary cholangitis (PBC), an immune-mediated disease characterised by destruction of intrahepatic bile ducts, results in progressive damage to the biliary tree, cholestasis and ultimately advanced liver disease. In the last decade, advances in practice have improved clinical care, driven novel therapeutic options and improved risk stratification tools. AIMS To provide an overview of the disease characteristics of PBC and review a patient-centred management approach for the clinical team caring for those with PBC. METHODS We reviewed the current literature and guidelines on PBC with a focus on management and therapies. RESULTS A confident diagnosis of PBC is usually made based on serum liver tests and immune serology. Management of PBC should focus on three main 'process' pillars: (a) treat and risk-stratify through use of biochemical and prognostic criteria; (b) manage concurrent symptoms and other associated diseases; and (c) stage disease, monitor progression and prevent complications. With ongoing complexities in management, including a newly licensed therapy (obeticholic acid) and alternative non-licensed treatments and ongoing clinical trials, discussion with PBC expert centres is encouraged. CONCLUSIONS PBC is a dynamic disease wherein current treatment goals have become appropriately ambitious. Goals of care should prioritise prevention of end-stage liver disease and amelioration of patient symptom burden for all.
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Affiliation(s)
- Kristel K Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.,Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Maya Deeb
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.,Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Gideon M Hirschfield
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Toronto, Toronto, ON, Canada.,Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, Ontario, Canada
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10
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Send SR. Nutritional Management of Cholestasis. Clin Liver Dis (Hoboken) 2020; 15:9-12. [PMID: 32104570 PMCID: PMC7041952 DOI: 10.1002/cld.865] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 06/27/2019] [Indexed: 02/04/2023] Open
Abstract
http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-1-reading-abdel-send a video presentation of this article http://aasldpubs.onlinelibrary.wiley.com/hub/journal/10.1002/(ISSN)2046-2484/video/15-1-interview-send the interview with the author Answer questions and earn https://www.wileyhealthlearning.com/Activity/7025317/disclaimerspopup.aspx.
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Affiliation(s)
- Stephanie R. Send
- Department of Food and Nutrition ServicesRush University Medical CenterChicagoIL
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11
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Bunchorntavakul C, Reddy KR. Review article: malnutrition/sarcopenia and frailty in patients with cirrhosis. Aliment Pharmacol Ther 2020; 51:64-77. [PMID: 31701570 DOI: 10.1111/apt.15571] [Citation(s) in RCA: 125] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 05/20/2019] [Accepted: 10/13/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Malnutrition/sarcopenia and frailty are common in patients with cirrhosis and are associated with poor outcomes. AIM To provide an overview of data on the importance, assessment and management of malnutrition/sarcopenia and frailty in cirrhosis. METHODS A literature search was conducted in PubMed and other sources, using the search terms "sarcopenia," "muscle," "malnutrition," "cirrhosis," "liver" and "frailty" from inception to April 2019, to identify the relevant studies and international guidelines. RESULTS The prevalence of malnutrition/sarcopenia in cirrhosis is 23%-60%. Frailty generally overlaps with malnutrition/sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition/sarcopenia in cirrhosis is complex/multifactorial and not just reduction in protein/calorie intake. Hyperammonemia appears to be the main driver of sarcopenia in cirrhosis through several molecular signalling pathways. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched-chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality- and liver-related events, they, and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long-term ammonia-lowering agents and myostatin antagonists, are currently under investigation. CONCLUSIONS Malnutrition/sarcopenia and frailty are unique, inter-related and multi-dimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.
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Affiliation(s)
- Chalermrat Bunchorntavakul
- Division of Gastroenterology and Hepatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand
| | - K Rajender Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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12
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Farnesoid X receptor and bile acids regulate vitamin A storage. Sci Rep 2019; 9:19493. [PMID: 31862954 PMCID: PMC6925179 DOI: 10.1038/s41598-019-55988-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 11/29/2019] [Indexed: 12/18/2022] Open
Abstract
The nuclear receptor Farnesoid X Receptor (FXR) is activated by bile acids and controls multiple metabolic processes, including bile acid, lipid, carbohydrate, amino acid and energy metabolism. Vitamin A is needed for proper metabolic and immune control and requires bile acids for efficient intestinal absorption and storage in the liver. Here, we analyzed whether FXR regulates vitamin A metabolism. Compared to control animals, FXR-null mice showed strongly reduced (>90%) hepatic levels of retinol and retinyl palmitate and a significant reduction in lecithin retinol acyltransferase (LRAT), the enzyme responsible for hepatic vitamin A storage. Hepatic reintroduction of FXR in FXR-null mice induced vitamin A storage in the liver. Hepatic vitamin A levels were normal in intestine-specific FXR-null mice. Obeticholic acid (OCA, 3 weeks) treatment rapidly reduced (>60%) hepatic retinyl palmitate levels in mice, concurrent with strongly increased retinol levels (>5-fold). Similar, but milder effects were observed in cholic acid (12 weeks)-treated mice. OCA did not change hepatic LRAT protein levels, but strongly reduced all enzymes involved in hepatic retinyl ester hydrolysis, involving mostly post-transcriptional mechanisms. In conclusion, vitamin A metabolism in the mouse liver heavily depends on the FXR and FXR-targeted therapies may be prone to cause vitamin A-related pathologies.
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Abstract
PURPOSE OF REVIEW The goal of this chapter is to educate clinicians on the neurologic manifestations of certain nutritional deficiencies in order to promptly identify and appropriately treat these patients. RECENT FINDINGS Many vitamin and nutritional deficiencies have been described dating back to the early days of neurology and medicine. Some are very rare and thus, there are no randomized controlled studies to assess supplementation or dosage; however, there are reviews of case reports that can assist clinicians in choosing treatments. While endemic vitamin and nutritional deficiencies may be rarely encountered in many countries, vulnerable populations continue to be at risk for developing neurologic complications. These populations include those with diseases causing malabsorption, the elderly, chronic alcohol users, as well as pregnant mothers with hyperemesis gravidarum to name a few. It is important to recognize syndromes associated with these nutritional deficiencies, as prompt identification and treatment may prevent permanent neurologic damage.
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Affiliation(s)
- Kristin L Miller
- Department of Neurology and Rehabilitation, University of Illinois at Chicago College of Medicine, 912 S Wood St, Chicago, IL, 60612, USA.
| | - Gabriela Trifan
- Department of Neurology and Rehabilitation, University of Illinois at Chicago College of Medicine, 912 S Wood St, Chicago, IL, 60612, USA
| | - Fernando D Testai
- Department of Neurology and Rehabilitation, University of Illinois at Chicago College of Medicine, 912 S Wood St, Chicago, IL, 60612, USA
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14
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Abstract
Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune disease with a variable progressive course. PBC can cause debilitating symptoms including fatigue and pruritus and, if left untreated, is associated with a high risk of cirrhosis and related complications, liver failure, and death. Recent changes to the PBC landscape include a name change, updated guidelines for diagnosis and treatment as well as new treatment options that have recently become available. Practicing clinicians face many unanswered questions when managing PBC. To assist these healthcare providers in managing patients with PBC, the American College of Gastroenterology (ACG) Institute for Clinical Research & Education, in collaboration with the Chronic Liver Disease Foundation (CLDF), organized a panel of experts to evaluate and summarize the most current and relevant peer-reviewed literature regarding PBC. This, combined with the extensive experience and clinical expertise of this expert panel, led to the formation of this clinical guidance on the diagnosis and management of PBC.
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15
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Characteristics and Outcomes of Liver Transplantation for Primary Biliary Cholangitis in Young Patients: Analysis of the United Network for Organ Sharing Database. Transplantation 2018; 103:1191-1198. [PMID: 30376552 DOI: 10.1097/tp.0000000000002501] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Primary biliary cholangitis (PBC) in younger patients has been suggested to require liver transplantation (LT) in early adulthood, but data is limited on its outcomes. We aimed to evaluate the characteristics and outcome of LT in young patients with PBC in comparison with older adults. METHODS The United Network for Organ Sharing database was analyzed for all patients with PBC who underwent LT between 2000 and 2012. Based on age at the time of LT, subjects were divided into 2 groups: young patients (≤40 y) and older adults (≥41 y). Baseline demographics, clinical parameters, and outcomes of LT were then compared between the 2 groups. Univariable and multivariable analyses were performed to assess the factors associated with outcomes of LT. RESULTS A total of 2084 patients with PBC were included in the analysis with 158 young patients. Compared with older adults, younger patients were more likely to be male (27.2% versus 15.4%) and nonwhite (43.7% versus 21.5%), but they were less likely to have obesity, diabetes, or hypertension (P < 0.05) and had a lower mortality (8.2% versus 15.1%) but higher retransplantation rate (14.6% versus 4.7%) (P < 0.001). On multivariable analysis, older age, dialysis or ventilator use, and lower albumin were associated with high post-LT mortality. CONCLUSIONS Compared with older adults, early-onset PBC in younger patients requiring LT had higher percentage of males and nonwhites and had a lower prevalence of metabolic comorbidities but higher retransplantation rates. Further studies are warranted to confirm these findings.
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Takitani K, Kishi K, Miyazaki H, Koh M, Tamaki H, Inoue A, Tamai H. Altered Expression of Retinol Metabolism-Related Genes in an ANIT-Induced Cholestasis Rat Model. Int J Mol Sci 2018; 19:ijms19113337. [PMID: 30373117 PMCID: PMC6274878 DOI: 10.3390/ijms19113337] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 10/19/2018] [Accepted: 10/23/2018] [Indexed: 11/16/2022] Open
Abstract
Cholestasis is defined as a reduction of bile secretion caused by a dysfunction of bile formation. Insufficient bile secretion into the intestine undermines the formation of micelles, which may result in the reduced absorption of lipids and fat-soluble vitamins. Here, we investigated the retinol homeostasis and the alterations of retinol metabolism-related genes, including β-carotene 15,15′ monooxygenase (BCMO), lecithin:retinol acyltransferase (LRAT), aldehyde dehydrogenase (ALDH), cytochrome P450 26A1 (CYP26A1), and retinoic acid receptors (RAR) β, in a α-naphthyl isothiocyanate (ANIT)-induced cholestasis rat model. Moreover, we examined the expression of the farnesoid X receptor (FXR) target genes. Our results showed that plasma retinol levels were decreased in ANIT rats compared to control rats. On the contrary, hepatic retinol levels were not different between the two groups. The expression of FXR target genes in the liver and intestine of cholestasis model rats was repressed. The BCMO expression was decreased in the liver and increased in the intestine of ANIT rats compared to control rats. Finally, the hepatic expression of LRAT, RARβ, and ALDH1A1 in cholestatic rats was decreased compared to the control rats, while the CYP26A1 expression of the liver was not altered. The increased expression of intestinal BCMO in cholestasis model rats might compensate for decreased circulatory retinol levels. The BCMO expression might be regulated in a tissue-specific manner to maintain the homeostasis of retinol.
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Affiliation(s)
- Kimitaka Takitani
- Department of Pediatrics, Osaka Medical College, Osaka 569-8686, Japan.
| | - Kanta Kishi
- Department of Pediatrics, Osaka Medical College, Osaka 569-8686, Japan.
| | - Hiroshi Miyazaki
- Department of Pediatrics, Osaka Medical College, Osaka 569-8686, Japan.
- Department of Pediatrics, Osaka Rosai Hospital, Osaka 591-8025, Japan.
| | - Maki Koh
- Department of Pediatrics, Osaka Medical College, Osaka 569-8686, Japan.
| | - Hirofumi Tamaki
- Department of Pediatrics, Osaka Medical College, Osaka 569-8686, Japan.
- Department of Medicine, Shinseikai Daiichi Hospital, Aichi 468-0031, Japan.
| | - Akiko Inoue
- Department of Pediatrics, Osaka Medical College, Osaka 569-8686, Japan.
| | - Hiroshi Tamai
- Department of Pediatrics, Osaka Medical College, Osaka 569-8686, Japan.
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17
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Hirschfield GM, Dyson JK, Alexander GJM, Chapman MH, Collier J, Hübscher S, Patanwala I, Pereira SP, Thain C, Thorburn D, Tiniakos D, Walmsley M, Webster G, Jones DEJ. The British Society of Gastroenterology/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut 2018; 67:1568-1594. [PMID: 29593060 PMCID: PMC6109281 DOI: 10.1136/gutjnl-2017-315259] [Citation(s) in RCA: 213] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Revised: 01/22/2018] [Accepted: 01/23/2018] [Indexed: 12/12/2022]
Abstract
Primary biliary cholangitis (formerly known as primary biliary cirrhosis, PBC) is an autoimmune liver disease in which a cycle of immune mediated biliary epithelial cell injury, cholestasis and progressive fibrosis can culminate over time in an end-stage biliary cirrhosis. Both genetic and environmental influences are presumed relevant to disease initiation. PBC is most prevalent in women and those over the age of 50, but a spectrum of disease is recognised in adult patients globally; male sex, younger age at onset (<45) and advanced disease at presentation are baseline predictors of poorer outcome. As the disease is increasingly diagnosed through the combination of cholestatic serum liver tests and the presence of antimitochondrial antibodies, most presenting patients are not cirrhotic and the term cholangitis is more accurate. Disease course is frequently accompanied by symptoms that can be burdensome for patients, and management of patients with PBC must address, in a life-long manner, both disease progression and symptom burden. Licensed therapies include ursodeoxycholic acid (UDCA) and obeticholic acid (OCA), alongside experimental new and re-purposed agents. Disease management focuses on initiation of UDCA for all patients and risk stratification based on baseline and on-treatment factors, including in particular the response to treatment. Those intolerant of treatment with UDCA or those with high-risk disease as evidenced by UDCA treatment failure (frequently reflected in trial and clinical practice as an alkaline phosphatase >1.67 × upper limit of normal and/or elevated bilirubin) should be considered for second-line therapy, of which OCA is the only currently licensed National Institute for Health and Care Excellence recommended agent. Follow-up of patients is life-long and must address treatment of the disease and management of associated symptoms.
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Affiliation(s)
- Gideon M Hirschfield
- NIHR Birmingham Biomedical Research Centre, Birmingham, UK
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Jessica K Dyson
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
- NIHR Newcastle Biomedical Research Centre, Newcastle, United Kingdom
| | - Graeme J M Alexander
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
| | - Michael H Chapman
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - Jane Collier
- Translational Gastroenterology Unit, Oxford University Hospitals, University of Oxford, Oxford, UK
| | - Stefan Hübscher
- Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Imran Patanwala
- Department of Gastroenterology, Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
- University of Liverpool, Liverpool, UK
| | - Stephen P Pereira
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | | | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | | | - George Webster
- Department of Gastroenterology, University College London Hospitals NHS Foundation Trust, London, UK
| | - David E J Jones
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
- NIHR Newcastle Biomedical Research Centre, Newcastle, United Kingdom
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18
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Abstract
Patients with primary biliary cholangitis (PBC) are at risk for various harmful consequences of chronic cholestasis. These include fat-soluble vitamin deficiency, even in the setting of macronutrient sufficiency, as well as metabolic bone disease, including osteoporosis with fractures. Hyperlipidemia is often present and less commonly associated with risk of cardiovascular event; however, the long-term effect of new emerging therapies for PBC remains to be determined. Patients with PBC also have infrequent but notable risk of portal hypertension despite early-stage disease. This review discusses the background, evaluation, and practical management of these complications of chronic cholestasis.
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Affiliation(s)
- David N Assis
- Department of Medicine, Section of Digestive Diseases, Yale University School of Medicine, 333 Cedar Street, 1080 LMP, New Haven, CT 06510, USA.
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19
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Patterns of disease progression and incidence of complications in primary biliary cholangitis (PBC). Best Pract Res Clin Gastroenterol 2018; 34-35:71-83. [PMID: 30343713 DOI: 10.1016/j.bpg.2018.06.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 06/08/2018] [Indexed: 02/07/2023]
Abstract
Clinical outcome for patients with primary biliary cholangitis (PBC) is dictated by development of cirrhosis, portal hypertension and its associated complications; including for some, a predisposition toward hepatocellular carcinoma. However rates of clinical progression vary, and accurately identifying disease course is of critical importance to patients, clinicians, as well as industry, who are committed to developing new effective and life-prolonging therapy as well as treating symptoms that appear disproportionate to underlying disease severity. Patients seek reassurance and guidance as to their own prognosis, and clinicians wish to confidently recognise those at highest risk of poor outcomes as equally as they strive to reassure individuals with a more favourable disease trajectory. International registries have facilitated a much greater knowledge of disease incidence and heterogeneity of presenting phenotypes. In so doing they highlight the opportunity to provide a more individualized estimate of the clinical course that patients experience, and have led to a renewed approach to risk stratification; both in terms of 'hard outcomes' and also disease-associated complications in PBC specifically.
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20
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Guañabens N, Parés A. Osteoporosis in chronic liver disease. Liver Int 2018; 38:776-785. [PMID: 29479832 DOI: 10.1111/liv.13730] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 02/19/2018] [Indexed: 12/15/2022]
Abstract
Osteoporosis is a frequent complication in patients with chronic liver disease, especially in end-stages and in chronic cholestasis, in addition to non-alcoholic fatty liver disease, haemochromatosis and alcoholism. Mechanisms underlying osteoporosis are poorly understood, but osteoporosis mainly results from low bone formation. In this setting, sclerostin, a key regulator of the Wnt/β-catenin signalling pathway which regulates bone formation, in addition to the effects of the retained substances of cholestasis such as bilirubin and bile acids on osteoblastic cells, may influence the decreased bone formation in chronic cholestasis. Similarly, the damaging effects of iron and alcohol on osteoblastic cells may partially explain bone disease in haemochromatosis and alcoholism. A role for proinflammatory cytokines has been proposed in different conditions. Increased bone resorption may occur in cholestatic women with advanced disease. Low vitamin D, poor nutrition and hypogonadism, may be contributing factors to the full picture of bone disorders in chronic liver disease.
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Affiliation(s)
- Núria Guañabens
- Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
| | - Albert Parés
- Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, University of Barcelona, Barcelona, Spain
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21
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Waniek S, di Giuseppe R, Esatbeyoglu T, Ratjen I, Enderle J, Jacobs G, Nöthlings U, Koch M, Schlesinger S, Rimbach G, Lieb W. Association of Circulating Vitamin E (α- and γ-Tocopherol) Levels with Gallstone Disease. Nutrients 2018; 10:nu10020133. [PMID: 29382041 PMCID: PMC5852709 DOI: 10.3390/nu10020133] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 01/20/2018] [Accepted: 01/23/2018] [Indexed: 12/22/2022] Open
Abstract
In addition to well-established risk factors like older age, female gender, and adiposity, oxidative stress may play a role in the pathophysiology of gallstone disease. Since vitamin E exerts important anti-oxidative functions, we hypothesized that circulating vitamin E levels might be inversely associated with prevalence of gallstone disease. In a cross-sectional study, we measured plasma levels of α- and γ-tocopherol using high performance liquid chromatography in a community-based sample (582 individuals; median age 62 years; 38.5% women). Gallstone disease status was assessed by ultrasound. Multivariable-adjusted logistic regression models were used to estimate the association of circulating α- and γ-tocopherol/cholesterol ratio levels with prevalent gallstone disease. Lower probabilities of having gallstone disease were observed in the top (compared to the bottom) tertile of the plasma α-tocopherol/cholesterol ratio in multivariable-adjusted models (OR (Odds Ratio): 0.31; 95% CI (Confidence Interval): 0.13–0.76). A lower probability of having gallstone disease was also observed for the γ-tocopherol/cholesterol ratio, though the association did not reach statistical significance (OR: 0.77; 95% CI: 0.35–1.69 for 3rd vs 1st tertile). In conclusion, our observations are consistent with the concept that higher vitamin E levels might protect from gallstone disease, a premise that needs to be further addressed in longitudinal studies.
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Affiliation(s)
- Sabina Waniek
- Institute of Epidemiology, University of Kiel, 24105 Kiel, Germany.
| | | | - Tuba Esatbeyoglu
- Institute of Human Nutrition and Food Science, University of Kiel, 24118 Kiel, Germany.
| | - Ilka Ratjen
- Institute of Epidemiology, University of Kiel, 24105 Kiel, Germany.
| | - Janna Enderle
- Institute of Epidemiology, University of Kiel, 24105 Kiel, Germany.
| | - Gunnar Jacobs
- Institute of Epidemiology, University of Kiel, 24105 Kiel, Germany.
- Biobank PopGen, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
| | - Ute Nöthlings
- Department of Nutrition and Food Science, University of Bonn, 53113 Bonn, Germany.
| | - Manja Koch
- Institute of Epidemiology, University of Kiel, 24105 Kiel, Germany.
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
| | - Sabrina Schlesinger
- Institute for Biometrics and Epidemiology, German Diabetes Center (DDZ) at Heinrich Heine University Duesseldorf, 40225 Duesseldorf, Germany.
| | - Gerald Rimbach
- Institute of Human Nutrition and Food Science, University of Kiel, 24118 Kiel, Germany.
| | - Wolfgang Lieb
- Institute of Epidemiology, University of Kiel, 24105 Kiel, Germany.
- Biobank PopGen, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
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22
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Saeed A, Dullaart RPF, Schreuder TCMA, Blokzijl H, Faber KN. Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients 2017; 10:nu10010029. [PMID: 29286303 PMCID: PMC5793257 DOI: 10.3390/nu10010029] [Citation(s) in RCA: 145] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Revised: 12/13/2017] [Accepted: 12/19/2017] [Indexed: 12/22/2022] Open
Abstract
Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A’s functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central role in vitamin A metabolism: (1) it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2) it produces retinol binding protein 4 (RBP4) that distributes vitamin A, as retinol, to peripheral tissues; and (3) it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs). In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH); it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M) is the most prominent heritable factor associated with NAFLD. Interestingly, PNPLA3 harbors retinyl ester hydrolase activity and PNPLA3-I148M is associated with low serum retinol level, but enhanced retinyl esters in the liver of NAFLD patients. Low circulating retinol in NAFLD may therefore not reflect true “vitamin A deficiency”, but rather disturbed vitamin A metabolism. Here, we summarize current knowledge about vitamin A metabolism in NAFLD and its putative role in the progression of liver disease, as well as the therapeutic potential of vitamin A metabolites.
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Affiliation(s)
- Ali Saeed
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
- Institute of Molecular Biology & Bio-Technology, Bahauddin Zakariya University, Multan 60800, Pakistan.
| | - Robin P F Dullaart
- Department of Endocrinology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
| | - Tim C M A Schreuder
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
| | - Klaas Nico Faber
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
- Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
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23
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Freund C, Gotthardt DN. Vitamin A deficiency in chronic cholestatic liver disease: Is vitamin A therapy beneficial? Liver Int 2017; 37:1752-1758. [PMID: 28371374 DOI: 10.1111/liv.13433] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 03/22/2017] [Indexed: 02/07/2023]
Abstract
Chronic cholestatic diseases are progressive diseases of the biliary tract that cause hepatic fibrosis and ultimately lead to liver failure. Liver transplantation is the sole curative option currently available, and because of high morbidity and mortality rates of these diseases, new therapeutic approaches are needed. Vitamin A is a nutrient essential for health as it regulates many processes, including epithelial growth and immunological processes. Vitamin A is primarily stored in hepatic stellate cells, and during liver injury, through an unknown mechanism, these cells lose vitamin A and convert into collagen-producing myofibroblasts, which contributes to hepatic fibrosis. Vitamin A deficiencies in chronic cholestatic diseases have been frequently reported, and therefore, retinoid metabolism has attracted a lot of attention. Retinoids have been shown to attenuate or even prevent hepatic fibrosis, and to regulate hepatic immunological response to cholestatic injury in different rodent models of chronic cholestasis. Recently, their potential as therapeutic drugs in primary sclerosing cholangitis patients was analyzed. The aim of this review is to summarize the existing knowledge and hypotheses about vitamin A role and the disease progression in cholestatic liver disease.
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Affiliation(s)
- Cora Freund
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany
| | - Daniel N Gotthardt
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany
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24
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Burman BE, Jhaveri MA, Kowdley KV. An Update on the Treatment and Follow-up of Patients with Primary Biliary Cholangitis. Clin Liver Dis 2017; 21:709-723. [PMID: 28987258 DOI: 10.1016/j.cld.2017.06.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by chronic granulomatous lymphocytic cholangitis of the small bile ducts. PBC was a leading indication for liver transplant in the United States; with early diagnosis and treatment, the majority of patients with PBC have a normal life expectancy. Pathogenesis involves inflammatory damage of bile duct epithelium secondary to innate and adaptive immune responses, and toxicity from accumulated bile acids. Cholestasis and disease progression can lead to cirrhosis. Extrahepatic complications include dyslipidemia, metabolic bone disease, and fat-soluble vitamin deficiency. Ursodeoxycholic acid is a well-established therapy. Novel targeted therapeutics are being developed.
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Affiliation(s)
- Blaire E Burman
- Division of Gastroenterology and Hepatology, Virginia Mason Medical Center, 1100 Ninth Avenue, Seattle, WA 98101, USA
| | - Manan A Jhaveri
- Department of Organ Transplant & Liver Center, Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, 1124 Columbia Street, WA 98101, USA
| | - Kris V Kowdley
- Department of Organ Transplant & Liver Center, Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, 1124 Columbia Street, WA 98101, USA.
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25
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Al-Abboodi Y, Ridha A, Fasullo M, Naguib TH. Risks of PEG tube placement in patients with cirrhosis-associated ascites. Clin Exp Gastroenterol 2017; 10:211-214. [PMID: 28979154 PMCID: PMC5589105 DOI: 10.2147/ceg.s142644] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
This study examined the safety of placing percutaneous endoscopic gastrostomy (PEG) tube in people with liver cirrhosis. The target population was further subdivided into people with ascites (case group) and people without ascites (control). We compare the morbidity and the mortality difference of PEG placement in cirrhotic patients with ascites vs cirrhotic patients without ascites. We then examined multiple factors including sex, race, chronic illness including hypertension, congestive heart failure, and others and their influence on the inpatient mortality of all cirrhotic patients who had PEG placement. A total of 38,175 inpatient PEG tube placements were identified. Only 583 patients out of 38,175 had a history of cirrhosis. One hundred seven had ascites and the rest did not. Mean age of the patients was 61.14 years. Patient demography included (65.2%) male and the rest were female, 359 were white (64.4%), 90 black (14.8%), 84 Hispanic (13.7%), 23 Asians (3.3%), 7 Native Americans (0.4%), and 20 others (3.5%). Complications from PEG procedure in cirrhosis with ascites vs non-ascites included bleeding of 4 (0.8%) vs 2 (1.9%) (P=0.35), surgical site infection 2 (0.4%) vs 1 (0.9%) (P=0.51), and urinary tract infection 105 (22.1%) vs 34 (23.8%) (P=0.34), respectively. There was no colonic injury in either group. The total inpatient mortality was 75 out of the 583. Fifty-six (11.8%) were in the ascites group and 19 (17.8%) in the non-ascites group (P=0.097). Factors including ascites, postsurgical bleeding, and surgical site infection did not have influence on the inpatient mortality and there were no statistical differences between the two groups.
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Affiliation(s)
- Yasir Al-Abboodi
- Internal Medicine Department, Saint Davis Round Rock Medical Centre, Round Rock, TX, USA
| | - Ali Ridha
- Internal Medicine Department, University of Arkansas for Medical Science, Little Rock, AR, USA
| | - Matthew Fasullo
- Internal Medicine Department, Umass Memorial Medical Center, Worcester, MA, USA
| | - Tarek H Naguib
- Internal Medicine Department, Texas Tech University Health and Sciences Center, Amarillo, TX, USA
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26
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Abstract
Purpose of Review Nutritional status in patients with cirrhosis is very frequently associated with macro- and micronutrient deficiencies. Cirrhosis itself is the cause of malnutrition and nutritional deficiencies but these conditions have to be identified and addressed properly as they can worsen the prognosis of cirrhosis. The goals of this review are to 1) identify and describe the challenges associated with nutritional assessment in cirrhosis and 2) describe recent advancements when using clinical, laboratory, and instrumental tools in the evaluation of malnourished patients with liver diseases. Recent Findings The most promising tools for nutritional assessment in cirrhosis include the evaluation of body composition with phase angle obtained by bioelectrical impedance analysis, computed tomography transverse images at the level of third lumbar vertebra. The Royal-Free Hospital global assessment algorithm appears to be helpful but needs further validation. Summary Nutritional assessment in cirrhosis is challenging as several factors, including edema, can interfere with it and because of lack of a validated gold standard. Regardless, nutritional assessment methods have been developed in recent years and should gain relevance in the clinical practice.
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27
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Hirschfield GM, Beuers U, Corpechot C, Invernizzi P, Jones D, Marzioni M, Schramm C. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67:145-172. [PMID: 28427765 DOI: 10.1016/j.jhep.2017.03.022] [Citation(s) in RCA: 879] [Impact Index Per Article: 109.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 03/23/2017] [Indexed: 02/07/2023]
Abstract
Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune cholestatic liver disease, which when untreated will culminate in end-stage biliary cirrhosis. Diagnosis is usually based on the presence of serum liver tests indicative of a cholestatic hepatitis in association with circulating antimitochondrial antibodies. Patient presentation and course can be diverse and risk stratification is important to ensure all patients receive a personalised approach to their care. The goals of treatment and management are the prevention of end-stage liver disease, and the amelioration of associated symptoms. Pharmacologic approaches in practice, to reduce the impact of the progressive nature of disease, currently include licensed therapies (ursodeoxycholic acid and obeticholic acid) and off-label therapies (fibric acid derivatives, budesonide). These clinical practice guidelines summarise the evidence for the importance of a structured, life-long and individualised, approach to the care of patients with PBC, providing a framework to help clinicians diagnose and effectively manage patients.
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28
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Pollock G, Minuk GY. Diagnostic considerations for cholestatic liver disease. J Gastroenterol Hepatol 2017; 32:1303-1309. [PMID: 28106928 DOI: 10.1111/jgh.13738] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Accepted: 01/16/2017] [Indexed: 12/17/2022]
Abstract
Cholestatic liver disease results from insufficient bile synthesis, secretion and/or flow through the biliary tract. Common presenting features include fatigue, pruritus, and cholestatic liver enzyme abnormalities wherein elevations of serum alkaline phosphatase and gamma-glutamyltransferases levels exceed those of alanine and aspartate aminotransferases. With prolonged cholestasis, fat soluble vitamin deficiencies, fibrosis, cirrhosis, and, on occasion, carcinoma of the biliary tract or liver can occur. Once mechanical obstruction to bile flow has been ruled out, the majority of causes can be classified as immune-mediated, infectious, or miscellaneous. Because specific therapeutic options are increasing for many causes of cholestasis, an accurate diagnosis is an important first step towards treatment. Thus, this review focuses on the diagnostic features of non-mechanical causes of cholestasis.
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Affiliation(s)
- Galia Pollock
- Section of Hepatology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Gerald Y Minuk
- Section of Hepatology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
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29
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Chascsa D, Carey EJ, Lindor KD. Old and new treatments for primary biliary cholangitis. Liver Int 2017; 37:490-499. [PMID: 28371104 DOI: 10.1111/liv.13294] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2016] [Accepted: 10/27/2016] [Indexed: 02/13/2023]
Abstract
Primary biliary cholangitis (formerly primary biliary cirrhosis) is a rare progressive cholestatic liver disease, whose hallmark features include a persistently elevated alkaline phosphatase level, presence of anti-mitochondrial antibodies and characteristic histology. Since 1998, ursodeoxycholic acid (UDCA), a bile acid, has been the only available therapeutic agent. Primary biliary cholangitis is associated with the development of end-stage liver disease, increased morbidity and mortality. UDCA has been shown to improve serum biochemistries, histology and delay the need for liver transplantation. The clinical issue is that approximately 25%-40% of patients do not respond to this standard therapy. In recent years, many trials have investigated alternative and adjunctive treatments, leading to the recent approval of obeticholic acid, an analogue of chenodeoxycholic acid, which has shown significant and sustained reductions in alkaline phosphatase levels in combination with UDCA. Obeticholic acid has rapidly been embraced as a new agent to improve the biochemical profile in refractory patients, in addition to being approved for use as monotherapy in patients who cannot tolerate UDCA. There are several other studies and targets which are being investigated. This review is intended to highlight the benefits of UDCA, educate the reader on the newly available obeticholic acid, and to summarize the many ongoing trials and therapeutic targets being investigated in attempts to control and cure primary biliary cholangitis.
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Affiliation(s)
- David Chascsa
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Elizabeth J Carey
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Keith D Lindor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA.,College of Health Solutions, Arizona State University, Phoenix, AZ, USA
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30
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Saeed A, Hoekstra M, Hoeke MO, Heegsma J, Faber KN. The interrelationship between bile acid and vitamin A homeostasis. Biochim Biophys Acta Mol Cell Biol Lipids 2017; 1862:496-512. [PMID: 28111285 DOI: 10.1016/j.bbalip.2017.01.007] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Revised: 01/04/2017] [Accepted: 01/18/2017] [Indexed: 12/12/2022]
Abstract
Vitamin A is a fat-soluble vitamin important for vision, reproduction, embryonic development, cell differentiation, epithelial barrier function and adequate immune responses. Efficient absorption of dietary vitamin A depends on the fat-solubilizing properties of bile acids. Bile acids are synthesized in the liver and maintained in an enterohepatic circulation. The liver is also the main storage site for vitamin A in the mammalian body, where an intimate collaboration between hepatocytes and hepatic stellate cells leads to the accumulation of retinyl esters in large cytoplasmic lipid droplet hepatic stellate cells. Chronic liver diseases are often characterized by disturbed bile acid and vitamin A homeostasis, where bile production is impaired and hepatic stellate cells lose their vitamin A in a transdifferentiation process to myofibroblasts, cells that produce excessive extracellular matrix proteins leading to fibrosis. Chronic liver diseases thus may lead to vitamin A deficiency. Recent data reveal an intricate crosstalk between vitamin A metabolites and bile acids, in part via the Retinoic Acid Receptor (RAR), Retinoid X Receptor (RXR) and the Farnesoid X Receptor (FXR), in maintaining vitamin A and bile acid homeostasis. Here, we provide an overview of the various levels of "communication" between vitamin A metabolites and bile acids and its relevance for the treatment of chronic liver diseases.
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Affiliation(s)
- Ali Saeed
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Institute of Molecular biology & Bio-technology, Bahauddin Zakariya University, Multan, Pakistan.
| | - Mark Hoekstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
| | - Martijn Oscar Hoeke
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
| | - Janette Heegsma
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; Laboratory Medicine, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
| | - Klaas Nico Faber
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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31
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Huang YQ. Recent advances in the diagnosis and treatment of primary biliary cholangitis. World J Hepatol 2016; 8:1419-1441. [PMID: 27957241 PMCID: PMC5124714 DOI: 10.4254/wjh.v8.i33.1419] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 07/26/2016] [Accepted: 08/29/2016] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients.
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Agmon-Levin N, Kopilov R, Selmi C, Nussinovitch U, Sánchez-Castañón M, López-Hoyos M, Amital H, Kivity S, Gershwin EM, Shoenfeld Y. Vitamin D in primary biliary cirrhosis, a plausible marker of advanced disease. Immunol Res 2015; 61:141-6. [PMID: 25424577 DOI: 10.1007/s12026-014-8594-0] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Vitamin D immune-modulating effects were extensively studied, and low levels have been linked with autoimmune diseases. The associations of vitamin D with autoimmune diseases of the liver, and particularly primary biliary cirrhosis (PBC), are yet to be defined. Hence, in this study, serum levels of vitamin D were determined in 79 patients with PBC and 70 age- and sex-matched controls by the LIAISON chemiluminescent immunoassays (DiaSorin-Italy). Clinical and serological parameters of patients were analyzed with respect to vitamin D status. Mean levels of vitamin D were significantly lower among patients with PBC compared with controls (16.8 ± 9 vs. 22.1 ± 9 ng/ml; p = 0.029), and vitamin D deficiency (≤10 ng/ml) was documented in 33% of patients with PBC versus 7% of controls (p < 0.0001). Vitamin D levels inversely correlated with advanced liver damage and the presence of concomitant autoimmune diseases. In contrast, higher levels of vitamin D were observed among patients with PBC treated with ursodeoxycholic acid (UDCA). In conclusion, low vitamin D levels are common among patients with PBC and correlate with advanced disease, lack of UDCA therapy and autoimmune comorbidity. This alludes to the plausible roles of vitamin D as a prognostic marker of PBC severity, and as a potential player in this disease pathogenesis. While further studies are awaited, monitoring vitamin D in patients with PBC and use of supplements may be advisable.
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Affiliation(s)
- Nancy Agmon-Levin
- The Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel
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Abstract
Primary biliary cirrhosis is a chronic cholestatic liver disease characterised by destruction of small intrahepatic bile ducts, leading to fibrosis and potential cirrhosis through resulting complications. The serological hallmark of primary biliary cirrhosis is the antimitochondrial antibody, a highly disease-specific antibody identified in about 95% of patients with primary biliary cirrhosis. These patients usually have fatigue and pruritus, both of which occur independently of disease severity. The typical course of primary biliary cirrhosis has changed substantially with the introduöction of ursodeoxycholic acid (UDCA). Several randomised placebo-controlled studies have shown that UDCA improves transplant-free survival in primary biliary cirrhosis. However, about 40% of patients do not have a biochemical response to UDCA and would benefit from new therapies. Liver transplantation is a life-saving surgery with excellent outcomes for those with decompensated cirrhosis. Meanwhile, research on nuclear receptor hormones has led to the development of exciting new potential treatments. This Seminar will review the current understanding of the epidemiology, pathogenesis, and natural history of primary biliary cirrhosis, discuss management of the disease and its sequelae, and introduce research on new therapeutic options.
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Affiliation(s)
- Elizabeth J Carey
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Ahmad H Ali
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Keith D Lindor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA; Arizona State University, College of Health Solutions, Phoenix, AZ, USA.
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34
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Reshetnyak VI. Primary biliary cirrhosis: Clinical and laboratory criteria for its diagnosis. World J Gastroenterol 2015; 21:7683-7708. [PMID: 26167070 PMCID: PMC4491957 DOI: 10.3748/wjg.v21.i25.7683] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Revised: 04/07/2015] [Accepted: 06/10/2015] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic granulomatous, and destructive inflammatory lesion of small intralobular and septal bile ducts, which is likely to be caused by an autoimmune mechanism with a the presence of serum antimitochondrial antibodies and a potential tendency to progress to cirrhosis. Despite the fact that the etiology of this disease has been unknown so far, there has been a considerable body of scientific evidence that can reveal the clinical and laboratory signs of PBC and the individual components of its pathogenesis and elaborate diagnostic criteria for the disease and its symptomatic therapy. Deficiencies in autoimmune tolerance are critical factors for the initiation and perpetuation of the disease. The purpose of this review is to summarize the data available in the literature and the author's findings on clinical and laboratory criteria for the diagnosis of PBC. This review describes the major clinical manifestations of the disease and the mechanisms of its development. It presents the immunological, biochemical, and morphological signs of PBC and their significance for its diagnosis. A great deal of novel scientific evidence for the problem of PBC has been accumulated. However, the inadequate efficiency of therapy for the disease lends impetus to the quest for its etiological factors and to further investigations of its pathogenetic mechanisms and, on this basis, to searches for new methods for its early diagnosis.
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35
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Guo GY, Shi YQ, Wang L, Ren X, Han ZY, Guo CC, Cui LN, Wang JB, Zhu J, Wang N, Zhang J, Cai Y, Han Y, Zhou XM, Fan DM. Serum vitamin D level is associated with disease severity and response to ursodeoxycholic acid in primary biliary cirrhosis. Aliment Pharmacol Ther 2015; 42:221-30. [PMID: 25982180 DOI: 10.1111/apt.13244] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2014] [Revised: 12/13/2014] [Accepted: 04/25/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Serum vitamin D levels are associated with bone complications in patients with primary biliary cirrhosis (PBC). Increasing evidence suggests a nonskeletal role of vitamin D in various autoimmune and liver diseases. AIM To investigate the clinical relevance of vitamin D levels in PBC, especially their association with the therapeutic effects of ursodeoxycholic acid (UDCA). METHODS Consecutive PBC patients were retrospectively reviewed. 25-hydroxyvitamin D [25(OH)D] levels were determined in frozen serum samples collected before initiation of UDCA treatment. Response to UDCA was evaluated by Paris-I and Barcelona criteria. Logistic regressions were performed to identify the treatment response-associated parameters. RESULTS Among 98 patients, the mean serum 25(OH)D concentration was 17.9 ± 7.6 ng/mL. 25(OH)D levels decreased with increasing histological stage (P = 0.029) and were negatively correlated with bilirubin and alkaline phosphatase levels. After 1 year of UDCA therapy, 31 patients failed to achieve complete response according to Paris-I criteria. The baseline 25(OH)D level was significantly lower in nonresponders (14.8 ± 6.4 vs. 19.3 ± 7.6 ng/mL, P = 0.005). Vitamin D deficiency at baseline was associated with an increased risk of incomplete response independent of advanced stages (OR = 3.93, 95% CI = 1.02-15.19, P = 0.047). Similar results were obtained when biochemical response was evaluated by Barcelona criteria. Furthermore, 25(OH)D levels were lower in patients who subsequently suffered death or liver transplantation (12.1 ± 4.6 vs. 18.4 ± 7.6 ng/mL, P = 0.023). CONCLUSIONS 25(OH)D level is associated with biochemical and histological features in PBC. Pre-treatment vitamin D status is independently related to subsequent response to UDCA. Our results suggest that vitamin D status may have important clinical significance in PBC.
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Affiliation(s)
- G-Y Guo
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - Y-Q Shi
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - L Wang
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - X Ren
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - Z-Y Han
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - C-C Guo
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - L-N Cui
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - J-B Wang
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - J Zhu
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China
| | - N Wang
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - J Zhang
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - Y Cai
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - Y Han
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - X-M Zhou
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
| | - D-M Fan
- Division of Hepatology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.,State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, China
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36
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Marchioni Beery RM, Vaziri H, Forouhar F. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective. J Clin Transl Hepatol 2014; 2:266-84. [PMID: 26357630 PMCID: PMC4521232 DOI: 10.14218/jcth.2014.00024] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Revised: 10/15/2014] [Accepted: 10/19/2014] [Indexed: 12/12/2022] Open
Abstract
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are two major types of chronic cholestatic liver disease. Each disorder has distinguishing features and variable progression, but both may ultimately result in cirrhosis and hepatic failure. The following offers a review of PBC and PSC, beginning with a general overview of disease etiology, pathogenesis, diagnosis, clinical features, natural course, and treatment. In addition to commonly associated manifestations of fatigue, pruritus, and fat-soluble vitamin deficiency, select disease-related topics pertaining to women's health are discussed including metabolic bone disease, hyperlipidemia and cardiovascular risk, and pregnancy-related issues influencing maternal disease course and birth outcomes. This comprehensive review of PBC and PSC highlights some unique clinical considerations in the care of female patients with cholestatic liver disease.
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Affiliation(s)
- Renée M. Marchioni Beery
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Renée M. Marchioni Beery, DO, Division of Internal Medicine, Department of Gastroenterology and Hepatology, 263 Farmington Avenue, Farmington, CT 06030-1845, USA. Tel: +01-860-679-3158, Fax: +01-860-679-3159. E-mail:
| | - Haleh Vaziri
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Faripour Forouhar
- Department of Pathology and Lab Medicine, University of Connecticut Health Center, Farmington, CT, USA
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37
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Ali AH, Carey EJ, Lindor KD. Diagnosis and management of primary biliary cirrhosis. Expert Rev Clin Immunol 2014; 10:1667-78. [DOI: 10.1586/1744666x.2014.979792] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Abstract
The care of the patient with cholestasis hinges on identifying the etiology, treating reversible causes, and managing chronic cholestatic processes. PBC and PSC are important causes of chronic cholestasis, and are the most common causes of cholestatic liver disease. Effective therapy is available for patients with PBC, whereas none exists for patients with PSC. Awareness of the complications that may be associated with cholestasis and implementing the appropriate management are essential.
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Affiliation(s)
- Andrea A Gossard
- Cholestatic Liver Disease Study Group, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
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39
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Abstract
Cholestasis is defined as impairment of bile formation or bile flow. Care of the patient with cholestatic features is dependent on identifying the cause of the cholestasis, initiating appropriate treatment of reversible conditions, and the recognition and management of cholestasis-specific complications. Cholestasis may include extrahepatic ducts and intrahepatic bile ducts, or may be limited to one or the other. Jaundice and pruritus are the hallmarks of cholestasis clinically but biochemical evidence may, and often does, precede the clinical manifestations.
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Affiliation(s)
- Andrea A Gossard
- Cholestatic Liver Disease Study Group, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55901, USA.
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40
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Abstract
OBJECTIVE Fat-soluble vitamin (FSV) deficiencies are common complications in pediatric patients with chronic cholestasis. The aim of the present study was to evaluate the status of FSV deficiencies in patients under present practice and to test the effect of an oral, absorbable, fat-soluble vitamin formulation (OAFSV) in these patients. METHODS We recruited a total of 23 pediatric patients receiving conventional FSV supplementation in a single medical center, with diagnosis of biliary atresia (10), progressive familial intrahepatic cholestasis (9), Alagille syndrome (2), and other conditions (2). Ten patients switched to OAFSV and continued for 3 months. Plasma levels of vitamins A, D, and E and an international normalized ratio (INR) for prothrombin time (PT), a surrogate marker for vitamin K deficiency, were measured. RESULTS The proportion of patients with FSV A, D, E, and K deficiencies under conventional supplementation was 73.9%, 81.8%, 91.3%, and 20.0%, respectively. In patients with total bilirubin levels ≥3.0 mg/dL, the proportion of at least 1 FSV deficiency was 100%; and the deficiency rates of vitamin A, D, E, and K were 78.6%, 100.0%, 100.0% and 21.4%, respectively. Of the 10 patients receiving standard daily dose of OAFSV for 3 months, no adverse events or overdose effects were found. The rates of vitamin A, D, and E deficiency in the patients receiving OAFSV decreased from 80.0%, 100%, and 100%, respectively, to 70.0%, 60.0%, and 60.0% after 3 months of oral supplementation. CONCLUSIONS High rates of FSV deficiency were found in pediatric patients with chronic cholestasis under present follow-up. OAFSV supplementation is safe and potentially effective in pediatric patients with cholestasis.
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41
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Harrison E, Herrick AL, McLaughlin JT, Lal S. Malnutrition in systemic sclerosis. Rheumatology (Oxford) 2012; 51:1747-56. [PMID: 22850183 DOI: 10.1093/rheumatology/kes160] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
SSc is a chronic multi-system disease with wide-reaching consequences. Gastrointestinal features are present in over 90% of cases and these, together with other disease manifestations, may lead to nutritional decline. This produces substantial morbidity, including reliance on enteral support and even parenteral nutrition-dependent intestinal failure. These complications carry an associated mortality. Up to 18% of patients with SSc are reported to be at high risk of malnutrition [as assessed by Malnutrition Universal Screening Tool (MUST) criteria], with risk increasing with disease severity. Little is known about this decline, its rate of progression and how it affects the individual. Few case series report on nutritional interventions. Most current interventions are based on experience in other diseases. The development of specialist knowledge of SSc-related gastrointestinal disease management and nutritional screening and interventions is required. This paper reviews current knowledge relating to malnutrition and its management in SSc.
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Affiliation(s)
- Elizabeth Harrison
- Department of Gastroenterology, Salford Royal NHS Foundation Trust, Salford, UK.
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43
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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.
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Affiliation(s)
- Asma Siddique
- Department of Gastroenterology, Center for Liver Disease, Digestive Disease Institute, Seattle, WA 98111, USA
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44
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Cheung K, Lee SS, Raman M. Prevalence and mechanisms of malnutrition in patients with advanced liver disease, and nutrition management strategies. Clin Gastroenterol Hepatol 2012; 10:117-25. [PMID: 21893127 DOI: 10.1016/j.cgh.2011.08.016] [Citation(s) in RCA: 235] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2011] [Revised: 07/22/2011] [Accepted: 08/24/2011] [Indexed: 02/07/2023]
Abstract
Malnutrition is prevalent among cirrhotic patients and is an important prognostic factor. Etiologic factors include hypermetabolism, malabsorption, altered nutrient metabolism, and anorexia. It is a challenge to manage nutrition in cirrhotic patients because of alterations to metabolic and storage functions of the liver; use of traditional assessment tools, such as anthropometric and biometric measures, is difficult because of complications such as ascites and inflammation. In addition to meeting macro- and micronutrient requirements, the composition and timing of supplements have been proposed to affect efficacy of nutrition support. Studies have indicated that branched chain aromatic acid can be given as therapeutic nutrients, and that probiotics and nocturnal feeding improve patient outcomes.
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Affiliation(s)
- Kally Cheung
- Alberta Health Services, Calgary, Alberta, Canada
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45
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Yamashiki N, Sugawara Y, Tamura S, Kaneko J, Yoshida H, Aoki T, Hasegawa K, Akahane M, Ohtomo K, Fukayama M, Koike K, Kokudo N. Diagnostic accuracy of α-fetoprotein and des-γ-carboxy prothrombin in screening for hepatocellular carcinoma in liver transplant candidates. Hepatol Res 2011; 41:1199-1207. [PMID: 21917089 DOI: 10.1111/j.1872-034x.2011.00871.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM Although hepatocellular carcinoma (HCC)-specific serum tumor markers, α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), are used in the screening for HCC, their utility in pre-transplantation evaluation is not well established. This study aimed to evaluate the accuracy of AFP and DCP measurement for the diagnosis of HCC in liver transplant candidates. METHODS A total of 315 consecutive adult patients (174 men and 141 women, mean age 52 years), who were to receive liver transplantation for end-stage liver diseases, were enrolled. The pre-transplant levels of AFP and DCP were compared with the histopathology of explanted liver. RESULTS Hepatocellular carcinoma was present in the explanted liver of 106 recipients (median number of nodules 2, mean diameter 2.5 cm). The area under receiver operating characteristic curve for the diagnosis of HCC was 0.83 (95% confidence interval, 0.78-0.88) for AFP and 0.47 (0.41-0.54) for DCP. With the cut-off value of 100 mAU/mL, 20/106 (18.9%) patients with HCC and 54/194 (27.8%) patients without HCC were positive for DCP. DCP positivity was associated with vascular invasion, tumor differentiation and size among patients with HCC, which was associated with albumin level among patients without HCC. Vitamin K was administered prior to transplantation to 20 patients who were positive for DCP (two with and 18 without HCC), resulting in a decrease in DCP levels in 19 of them. CONCLUSIONS Serum DCP levels may be raised in end-stage liver disease patients without HCC, and cannot be used as a reliable marker for HCC among liver transplant candidates.
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Affiliation(s)
- Noriyo Yamashiki
- Department of Gastroenterology The Artificial Organ and Transplantation Division, Department of Surgery Department of Radiology Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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46
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Abstract
The liver plays a central role in hemostasis, as it is the site of synthesis of clotting factors, coagulation inhibitors, and fibrinolytic proteins. The most common coagulation disturbances occurring in liver disease include thrombocytopenia and impaired humoral coagulation. Therapy's overall goal is not to achieve complete correction of laboratory value abnormalities but to gain hemostasis. Therapy with vitamin K may be a useful option in patients with increased prothrombin time due to vitamin K deficiency; in patients with malnutrition; in patients using antibiotics; and in patients with cholestatic liver disease, particularly prior to invasive procedures. Infusion of fresh frozen plasma is more often effective and is recommended in patients with liver disease before invasive procedures or surgery, as such patients require transient correction in their prothrombin time. Therapy with plasma exchange may be considered in patients who cannot be treated with fresh frozen plasma due to volume overload risk. In patients with severe coagulopathy and hypofibrinogenemia, cryoprecipitate therapy is ideal. Therapy with prothrombin-complex concentrate is seldom pursued in patients with liver disease due to high risk of thrombotic complications. Transfusions of platelets are appropriate for patients with thrombocytopenia (< 50,000/mm(3)) associated with active bleeding or before invasive procedures in which a short-term platelet count increase is noted. Trial with desmopressin may be considered before invasive procedures in patients with liver disease and with refractory and prolonged bleeding time. Recombinant activated factor VIIa administration is suggested for patients with significantly prolonged prothrombin time and contraindications to fresh frozen plasma therapy; however, this is expensive. Thrombopoietin and interleukin-11 are currently investigational for patients with thrombocytopenia of chronic liver disease. Liver transplantation completely restores impaired coagulation abnormalities and is the ultimate intervention that corrects coagulopathy of advanced liver disease and liver failure.
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Affiliation(s)
- Wojciech Blonski
- K. Rajender Reddy, MD Division of Gastroenterology, Hospital of the University of Pennsylvania, 3400 Spruce Street, 2 Dulles, Philadelphia, PA 19104, USA.
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Cash WJ, McCance DR, Young IS, McEneny J, Cadden IS, McDougall NI, Callender ME. Primary biliary cirrhosis is associated with oxidative stress and endothelial dysfunction but not increased cardiovascular risk. Hepatol Res 2010; 40:1098-106. [PMID: 20977566 DOI: 10.1111/j.1872-034x.2010.00717.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM Primary biliary cirrhosis (PBC) is a chronic cholestatic disease which is associated with hypercholesterolaemia. Further, cholestatic diseases are associated with deficiencies of anti-oxidant vitamins. Despite these associations PBC is not associated with an increase in cardiovascular mortality. The aim of this study is to assess if primary biliary cirrhosis is associated with oxidative stress, endothelial dysfunction and alteration of vascular compliance which is a surrogate marker for cardiovascular risk. METHODS Fifty-one PBC patients and 34 control subjects were studied. Lipid soluble vitamins A, and E in addition to ascorbate and carotenoids were measured to assess anti-oxidant status. C-reactive protein, hydroperoxides and adhesion molecules sICAM-l/sVCAM-l were assessed as serological measures of endothelial function. Finally, measures of vascular compliance were assessed by applanation tonometer. RESULTS CRP, sICAM and sVCAM were all significantly higher in PBC patients (469.14 vs 207.13, P < 0.001; 768.12 vs 308.03,P < 0.001; 708.40 vs 461.31, P < 0.001) whilst anti-oxidant vitamin levels were lower in PBC patients, with ascorbate, vitamin E and vitamin A all significantly lower in PBC patients (39.91 vs 72.68, P < 0.001; 2.63 vs 3.14, P = 0.02; 1.08 vs 1.81, P < 0.001). Despite these findings PBC patients have a lower pulse wave velocity than control subjects (8.22 m/s vs 8.78 m/s, P = 0.022). CONCLUSION PBC patients appear to have reduced vascular risk as assessed by pulse wave velocity but concurrently have evidence of endothelial dysfunction, inflammation and anti-oxidant deficiency.
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Affiliation(s)
- William J Cash
- Liver Unit Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital Department of Medicine, Queen's University, Belfast, UK
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48
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Disturbances of parathyroid hormone-vitamin D axis in non-cholestatic chronic liver disease: a cross-sectional study. Hepatol Int 2010; 4:634-40. [PMID: 21063488 DOI: 10.1007/s12072-010-9194-2] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2009] [Accepted: 07/09/2010] [Indexed: 12/14/2022]
Abstract
PURPOSE Liver has an important role in metabolism of vitamin D. This study aimed to evaluate the patterns of vitamin D-parathyroid hormone (PTH) disturbance and correlate it in patients with non-cholestatic chronic liver disease (CLD). METHODS A total of 40 healthy controls and 90 consecutive patients with evidence of non-cholestatic CLD due to hepatitis C (n = 28), hepatitis B (n = 26), autoimmune hepatitis (n = 19), and cryptogenic causes (n = 17) were enrolled. Cirrhosis was evident in 51 patients. Serum concentrations of 25-hydroxy vitamin D, PTH, calcium, phosphate, and liver enzymes were measured. Child-Pugh classification was determined in cirrhotic patients. RESULTS Vitamin D deficiency (<50 nmol/l) was found in 46 (51.1%) patients and vitamin D insufficiency (50-80 nmol/l) in 15 (16.7%) patients. Secondary hyperparathyroidism (serum PTH > 6.8 pmol/l) was present in 6 (6.7%) patients. The prevalence of vitamin D deficiency was significantly higher in cirrhotic versus noncirrhotic patients (76.5 vs. 17.9%; P < 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. Child-Pugh class B and C patients had significantly lower vitamin D level compared with class A patients (P < 0.001), whereas there was no significant difference in serum calcium, phosphate, and PTH levels. No significant correlation was seen between vitamin D and PTH, calcium or phosphate levels. Lower serum level of vitamin D was associated with coagulopathy, hyperbilirubinemia, hypoalbuminemia, anemia, and thrombocytopenia. CONCLUSIONS Vitamin D inadequacy and the severity of liver dysfunction move in parallel in patients with non-cholestatic CLD. Vitamin D assessment and replacement should be considered in the management of patients with non-cholestatic CLD.
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Affiliation(s)
- Salman Waqar
- West of England Eye Unit, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
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Abbas G, Lindor KD. Pharmacological treatment of biliary cirrhosis with ursodeoxycholic acid. Expert Opin Pharmacother 2010; 11:387-92. [PMID: 20102304 DOI: 10.1517/14656560903493460] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
IMPORTANCE OF THE FIELD Primary biliary cirrhosis is a cholestatic liver disease that at one time was the leading indication for liver transplantation. Treatment with ursodeoxycholic acid has clearly improved the natural history of primary biliary cirrhosis. AREAS COVERED IN THIS REVIEW The treatment of primary biliary cirrhosis with a focus on ursodeoxycholic acid is covered. Papers related to treatment of primary biliary cirrhosis and associated conditions, using a variety of drugs but with a focus on ursodeoxycholic acid, are included. The papers reviewed date from 1984 - 2009. WHAT WILL THE READER GAIN The reader will gain an up-to-date understanding of current treatment strategies for primary biliary cirrhosis using ursodeoxycholic acid and an appreciation of what conditions are improved with this therapy and what associated conditions are not. TAKE-HOME MESSAGE Ursodeoxycholic acid in a dose of 13 - 15 mg/kg/day should be considered in all patients with primary biliary cirrhosis who have abnormal liver enzymes.
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Affiliation(s)
- Ghulam Abbas
- Mayo Clinic, Division of Gastroenterology and Hepatology, 20 First Street SW, Rochester, MN 55905, USA
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