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Reshetnyak VI, Maev IV. Mechanism for development of malnutrition in primary biliary cholangitis. World J Meta-Anal 2022; 10:81-98. [DOI: 10.13105/wjma.v10.i3.81] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Revised: 04/14/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that is associated with impaired biliary excretion processes. Along with the development of cholestasis, there is a deficient flow of bile acids into the intestinal lumen causing malnutrition (MN) that is manifested in deficiencies of both macro- and micronutrients. The mechanism for development of trophological insufficiency is multifactorial. However, the trigger of MN in PBC is impaired enterohepatic circulation of bile acids. The ingress of bile acids with a detergent effect into the general bloodstream, followed by elimination via the kidneys and skin, triggers a cascade of metabolic disturbances, which leads to the gradual development and progression of calorie MN. The latter gradually transforms into protein-calorie MN (PСM) (as marasmus) due to the insufficient entry of bile acids into the duodenum, which is accompanied by a decrease in the emulsification, hydrolysis, and absorption of fats and fat-soluble vitamins, as well as disturbance of intestinal motility and bacterial overgrowth. Fat-soluble vitamin deficiencies complement PСM with vitamin and mineral MN. The development of hepatocellular failure enhances the progression of PСM due to the impaired protein synthetic function of hepatocytes in the advanced stage of PBC, which results in deficiency of not only the somatic but also the visceral pool of proteins. A mixed PСM form of marasmus and kwashiorkor develops. Early recognition of energy, protein, micronutrient, and macronutrient deficiencies is of great importance because timely nutritional support can improve liver function and quality of life in patients with PBC. In this case, it is important to know what type (energy, protein-calorie, vitamin, and vitamin-mineral) and form (marasmus, marasmus-kwashiorkor) of MN is present in the patient and how it is associated with the stage of the disease. Therefore, it is recommended to screen all patients with PBC for MN, from the early asymptomatic stage of the disease in order to identify and avoid preventable complications, such as fatigue, malaise, performance decrement, sarcopenia, osteoporosis, and hepatic encephalopathy, which will be able to provide appropriate nutritional support for correction of the trophological status.
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Affiliation(s)
- Vasiliy Ivanovich Reshetnyak
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
| | - Igor Veniaminovich Maev
- Department of Propaedeutic of Internal Diseases and Gastroenterology, A.I. Yevdokimov Moscow State University of Medicine and Dentistry, Moscow 127473, Russia
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You H, Ma X, Efe C, Wang G, Jeong SH, Abe K, Duan W, Chen S, Kong Y, Zhang D, Wei L, Wang FS, Lin HC, Yang JM, Tanwandee T, Gani RA, Payawal DA, Sharma BC, Hou J, Yokosuka O, Dokmeci AK, Crawford D, Kao JH, Piratvisuth T, Suh DJ, Lesmana LA, Sollano J, Lau G, Sarin SK, Omata M, Tanaka A, Jia J. APASL clinical practice guidance: the diagnosis and management of patients with primary biliary cholangitis. Hepatol Int 2022; 16:1-23. [PMID: 35119627 PMCID: PMC8843914 DOI: 10.1007/s12072-021-10276-6] [Citation(s) in RCA: 63] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 11/08/2021] [Indexed: 12/14/2022]
Affiliation(s)
- Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing, Mainland, China
| | - Xiong Ma
- Department of Gastroenterology and Hepatology, Renji Hospital, Shanghai Jiao Tong University, Shanghai, Mainland, China
| | - Cumali Efe
- Department of Gastroenterology, Gazi Yaşargil Education and Research Hospital, Diyarbakir, Turkey
| | - Guiqiang Wang
- Department of Infectious Diseases and Center for Liver Diseases, Peking University First Hospital, Beijing, Mainland, China
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seoul, South Korea
| | - Kazumichi Abe
- Department of Gastroenterology, Fukushima Medical University School of Medicine, Fukushima, Japan
| | - Weijia Duan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing, Mainland, China
| | - Sha Chen
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing, Mainland, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland, China
| | - Dong Zhang
- Experimental and Translational Research Center, Beijing Clinical Research Institute, Beijing, Mainland, China
| | - Lai Wei
- Hepatobiliary Pancreatic Center, Tsinghua Changgung Hospital, Tsinghua University, Beijing, Mainland, China
| | - Fu-Sheng Wang
- Treatment and Research Center for Infectious Diseases, The Fifth Medical Center of PLA General Hospial, Beijing, Mainland, China
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Jin Mo Yang
- Division of Hepatology, Department of Internal Medicine, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, South Korea
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Rino A. Gani
- Department of Internal Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Jakarta, Indonesia
| | - Diana A. Payawal
- Department of Medicine, Fatima University Medical Center, Manila, Philippines
| | | | - Jinlin Hou
- Department of Infectious Disease and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, Mainland, China
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - A. Kadir Dokmeci
- Department of Medicine, Ankara University School of Medicine, Ankara, Turkey
| | - Darrell Crawford
- School of Medicine, University of Queensland, Brisbane, Australia
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Teerha Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hatyai, Thailand
| | - Dong Jin Suh
- Department of Gastroenterology, University of Ulsan College of Medicine, Seoul, South Korea
| | | | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - George Lau
- Humanity and Health Clinical Trial Center, Humanity and Health Medical Group, Hong Kong SAR, China
| | - Shiv K. Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, India
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Tokyo, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, 95 Yong-an Road, Beijing, Mainland, China
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Jiang Y, Xu BH, Rodgers B, Pyrsopoulos N. Characteristics and Inpatient Outcomes of Primary Biliary Cholangitis and Autoimmune Hepatitis Overlap Syndrome. J Clin Transl Hepatol 2021; 9:392-398. [PMID: 34221925 PMCID: PMC8237146 DOI: 10.14218/jcth.2021.00008] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 02/23/2021] [Accepted: 02/26/2021] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND AND AIMS Primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH) are hepatobiliary diseases of presumed immune-mediated origin that have been shown to overlap. The aim of this retrospective trial was to use national data to examine the characteristics and outcomes of patients hospitalized with overlapping PBC and AIH (PBC/AIH). METHODS The National Inpatient Sample was used to identify hospitalized adult patients with PBC, AIH, and PBC/AIH from 2010 to 2014 by International Classification of Diseases-Ninth Edition Revision codes; patients with hepatitis B virus and hepatitis C virus infection were excluded. Primary outcomes measures were in-hospital outcomes that included mortality, respiratory failure, septic shock, length of stay, and total hospital charges. Secondary outcomes were the clinical characteristics of PBC/AIH, including the comorbid extrahepatic autoimmune disease pattern and complications of cirrhosis. RESULTS A total of 3,478 patients with PBC/AIH were included in the study. PBC/AIH was associated with higher rates of Sjögren's syndrome (p<0.001; p<0.001), lower rates of Crohn's disease (p<0.05; p<0.05), and higher rates of cirrhosis-related complications when compared to PBC or AIH alone. There were similar rates of mortality between the PBC/AIH, PBC, and AIH groups. The PBC/AIH group had higher rates of septic shock when compared to the PBC group (p<0.05) and AIH group (p<0.05) after adjusting for possible confounders. CONCLUSIONS PBC/AIH is associated with a lower rate of Crohn's disease, a higher rate of Sjögren's syndrome, higher rates of cirrhosis-related complications, and significantly increased risk of septic shock compared to PBC and AIH individually.
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Affiliation(s)
- Yi Jiang
- Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Bing-Hong Xu
- Liver Center & Center for Asian Health, RWJBH-Saint Barnabas Medical Center, Florham Park, New Jersey, USA
| | - Brandon Rodgers
- Department of Medicine, Rutgers New Jersey Medical School, Newark, New Jersey, USA
| | - Nikolaos Pyrsopoulos
- Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, New Jersey, USA
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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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Oya A, Umezu T, Ogawa R, Nishiwaki T, Niki Y, Nakamura M, Matsumoto M, Kanaji A. Short-Term Outcomes of Total Hip Arthroplasty after Liver Transplantation. Arthroplast Today 2021; 8:11-14. [PMID: 33665276 PMCID: PMC7906880 DOI: 10.1016/j.artd.2021.01.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 12/02/2020] [Accepted: 01/03/2021] [Indexed: 02/07/2023] Open
Abstract
Background Idiopathic osteonecrosis of the femoral head (ONFH) frequently occurs after liver transplantation (LT) because of lifelong administration of corticosteroids or immunosuppressants and often requires total hip arthroplasty (THA). This study examines patient characteristics and short-term outcomes of THA after LT. Methods We observed 9 hips in 7 patients who underwent THA from August 2015 to December 2017 for ONFH after LT (group L). Cementless implants were inserted in all hips. Medical records were retrospectively reviewed to reveal reasons for LT, type of donor, and period from LT to THA. Preoperative laboratory data, operative time, intraoperative blood loss, complication rates, and Harris Hip Score were compared with a control group of 27 cementless THAs in 27 patients with ONFH. Results Causative diseases were liver cirrhosis (n = 4), type B fulminant hepatitis (n = 1), congenital biliary atresia (n = 1), and iatrogenic biliary tract injury (n = 1). Four livers were from living donors and 3 from cadavers. Mean time from LT to THA was 10.4 (1-20) years. Preoperative blood test showed a significant decrease in platelet count (178 vs 268 [∗103/μl]) and rise in total bilirubin (1.1 vs 0.7 [mg/dL]) in group L. There was no significant difference in operative time (86 vs 100 [minutes]), but intraoperative blood loss (303 vs 163 [mL]) increased significantly in group L. There were no significant differences in complication incidence or Harris Hip Score between the 2 groups. Conclusion THA after LT requires caution because risks for bleeding increase. However, short-term outcomes appear to be equivalent to normal THA.
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Affiliation(s)
- Akihito Oya
- Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Taro Umezu
- Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Ryo Ogawa
- Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Toru Nishiwaki
- Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Yasuo Niki
- Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Masaya Nakamura
- Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Morio Matsumoto
- Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Arihiko Kanaji
- Department of Orthopedic Surgery, Keio University School of Medicine, Tokyo, Japan
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Dysregulation of Circulating FGF19 and Bile Acids in Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1934541. [PMID: 32626734 PMCID: PMC7306076 DOI: 10.1155/2020/1934541] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 04/19/2020] [Accepted: 05/12/2020] [Indexed: 12/14/2022]
Abstract
Background Primary biliary cholangitis-autoimmune hepatitis overlap syndrome (PBC-AIH OS), which exhibits features between autoimmune hepatitis and cholestasis, is a common condition and usually shows a progressive course toward cirrhosis and liver failure without adequate treatment. Synthesis of bile acids (BAs) plays an important role in liver injury in cholestasis, and the process is regulated by fibroblast growth factor 19 (FGF19). The overall role of circulating FGF19 in BA synthesis and PBC-AIH OS requires further investigation. Methods We analyzed BA synthesis and correlated clinical parameters with serum BAs and FGF19 in 35 patients with PBC-AIH OS. Serum concentrations of 7alpha-hydroxycholest-4-en-3-one (C4) were used to quantify the synthesis of BA directly. Results Serum FGF19 levels were higher, while C4 levels were substantially lower in PBC-AIH OS patients than those in healthy controls. Circulating FGF19 levels strongly correlated with C4 (r = −0.695, p < 0.0001), direct bilirubin (r = 0.598, p = 0.0001), and total bile acids (r = 0.595, p = 0.002). Moreover, circulating FGF19 levels strongly correlated with the model for end-stage liver disease score (r = 0.574, p = 0.0005) and Mayo risk score (r = 0.578, p = 0.001). Conclusions Serum FGF19 is significantly increased in patients with PBC-AIH OS, while BA synthesis is suppressed. Circulating FGF19 primarily controls the regulation of BA synthesis in response to cholestasis and under cholestatic conditions. Therefore, modulation of circulating FGF19 could provide a promising targeted therapy for patients with PBC-AIH OS.
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Ehnert S, Aspera-Werz RH, Ruoß M, Dooley S, Hengstler JG, Nadalin S, Relja B, Badke A, Nussler AK. Hepatic Osteodystrophy-Molecular Mechanisms Proposed to Favor Its Development. Int J Mol Sci 2019; 20:2555. [PMID: 31137669 PMCID: PMC6566554 DOI: 10.3390/ijms20102555] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Revised: 05/14/2019] [Accepted: 05/22/2019] [Indexed: 02/07/2023] Open
Abstract
Almost all patients with chronic liver diseases (CLD) show altered bone metabolism. Depending on the etiology, this manifests in a severe osteoporosis in up to 75% of the affected patients. Due to high prevalence, the generic term hepatic osteodystrophy (HOD) evolved, describing altered bone metabolism, decreased bone mineral density, and deterioration of bone structure in patients with CLD. Once developed, HOD is difficult to treat and increases the risk of fragility fractures. Existing fractures affect the quality of life and, more importantly, long-term prognosis of these patients, which presents with increased mortality. Thus, special care is required to support the healing process. However, for early diagnosis (reduce fracture risk) and development of adequate treatment strategies (support healing of existing fractures), it is essential to understand the underlying mechanisms that link disturbed liver function with this bone phenotype. In the present review, we summarize proposed molecular mechanisms favoring the development of HOD and compromising the healing of associated fractures, including alterations in vitamin D metabolism and action, disbalances in transforming growth factor beta (TGF-β) and bone morphogenetic protein (BMP) signaling with histone deacetylases (HDACs) as secondary regulators, as well as alterations in the receptor activator of nuclear factor kappa B ligand (RANKL)-osteoprotegerin (OPG) system mediated by sclerostin. Based on these mechanisms, we give an overview on the limitations of early diagnosis of HOD with established serum markers.
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Affiliation(s)
- Sabrina Ehnert
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Romina H Aspera-Werz
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Marc Ruoß
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Steven Dooley
- Department of Medicine II, Molecular Hepatology, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany.
| | - Jan G Hengstler
- IfADo-Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, 44139 Dortmund, Germany.
| | - Silvio Nadalin
- Department of General, Visceral and Transplant Surgery, University Hospital Tuebingen, 72076 Tuebingen, Germany.
| | - Borna Relja
- Department of Trauma, Hand and Reconstructive Surgery, University Hospital Frankfurt, Goethe University, 60590 Frankfurt, Germany.
| | - Andreas Badke
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
| | - Andreas K Nussler
- Siegfried Weller Research Institute, Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
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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: 218] [Impact Index Per Article: 31.1] [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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9
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Zakharia K, Tabibian A, Lindor KD, Tabibian JH. Complications, symptoms, quality of life and pregnancy in cholestatic liver disease. Liver Int 2018; 38:399-411. [PMID: 28921801 DOI: 10.1111/liv.13591] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Accepted: 09/12/2017] [Indexed: 12/11/2022]
Abstract
Cholestatic liver diseases (CLDs) encompass a variety of disorders of bile formation and/or flow which generally result in progressive hepatobiliary injury and ultimately end-stage liver disease. Many patients with CLD are diagnosed between the ages of 20-50 years, a particularly productive period of life professionally, biologically and in other respects; it is not surprising, thus, that CLD is often associated with impaired health-related quality of life (HRQOL) and uncertainty regarding implications for and outcomes of pregnancy. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most prominent CLDs, both having considerable morbidity and mortality and representing major indications for liver transplantation. These disorders, as a consequence of their complications (eg ascites, hepatic osteodystrophy), associated conditions (eg inflammatory bowel disease) and symptoms (eg pruritus and fatigue), can significantly impair an array of domains of HRQOL. Here we review these impactful clinical aspects of PSC and PBC as well as the topics of fertility and pregnancy.
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Affiliation(s)
- Kais Zakharia
- Internal Medicine Residency Program, Beaumont Health - Dearborn, Dearborn, MI, USA
| | - Anilga Tabibian
- Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA
| | - Keith D Lindor
- Arizona State University, Phoenix, AZ, USA
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
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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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Fat-Soluble Vitamin Deficiency in Pediatric Patients with Biliary Atresia. Gastroenterol Res Pract 2017; 2017:7496860. [PMID: 28690638 PMCID: PMC5485346 DOI: 10.1155/2017/7496860] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Accepted: 05/07/2017] [Indexed: 02/06/2023] Open
Abstract
Objective To analyze the levels of fat-soluble vitamins (FSVs) in pediatric patients with biliary atresia (BA) before and after the Kasai procedure. Methods Pediatric patients with obstructive jaundice were enrolled in this study. The FSV levels and liver function before, 2 weeks after, and 1, 3, and 6 months after the Kasai procedure were measured. Results FSV deficiency was more obvious in patients with BA than in patients with other cholestatic liver diseases, especially vitamin D deficiency. 25-Hydroxy vitamin D (25-(OH)D) deficiency was more pronounced in younger patients before surgery. The 25-(OH)D level was significantly higher in patients with than without resolution of jaundice 3 months after surgery. At 6 months after surgery, the 25-(OH)D level was abnormally high at 8.76 ng/ml in patients with unresolved jaundice. Conclusions Preoperative FSV deficiency, particularly vitamin D deficiency, is common in patients with BA. 25-(OH)D deficiency is more pronounced in younger children before surgery. Postoperative FSV deficiency was still prevalent as shown by the lower 25-(OH)D levels in patients with BA and unresolved jaundice. This required long-term vitamin AD supplementation for pediatric patients with BA and unresolved jaundice after surgery.
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12
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Ali AH, Carey EJ, Lindor KD. The management of autoimmunity in patients with cholestatic liver diseases. Expert Rev Gastroenterol Hepatol 2016; 10:73-91. [PMID: 26523975 DOI: 10.1586/17474124.2016.1095088] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cholestatic liver diseases are rare diseases that often lead to cirrhosis and its consequent complications. In addition to liver-related morbidity, patients with cholestatic liver diseases often suffer from autoimmune diseases that affect several organs and tissues. The robust and efficient data collection and collaboration between hepatologists and rheumatologists have led to significant advancements in understanding the relationship between the cholestatic liver diseases and associated autoimmune diseases. In this paper, we discuss the cholestatic liver diseases (primary biliary cirrhosis, primary sclerosing cholangitis and immunoglobulin G4 associated cholangitis) and associated autoimmune diseases.
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Affiliation(s)
- Ahmad H Ali
- a 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Elizabeth J Carey
- a 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Keith D Lindor
- a 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA.,b 2 Arizona State University, College of Health Solutions, Phoenix, AZ, USA
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13
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Alves SC, Fasano S, Isenberg DA. Autoimmune gastrointestinal complications in patients with systemic lupus erythematosus: case series and literature review. Lupus 2016; 25:1509-1519. [PMID: 27329649 DOI: 10.1177/0961203316655210] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Accepted: 05/25/2016] [Indexed: 02/06/2023]
Abstract
The association of systemic lupus erythematosus (SLE) with gastrointestinal autoimmune diseases is rare, but has been described in the literature, mostly as case reports. However, some of these diseases may be very severe, thus a correct and early diagnosis with appropriate management are fundamental. We have analysed our data from the SLE patient cohort at University College Hospital London, established in 1978, identifying those patients with an associated autoimmune gastrointestinal disease. We have also undertaken a review of the literature describing the major autoimmune gastrointestinal pathologies which may be coincident with SLE, focusing on the incidence, clinical and laboratory (particularly antibody) findings, common aetiopathogenesis and complications.
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Affiliation(s)
- S Custódio Alves
- Internal Medicine Unit, Department of Medicine, Hospital de Cascais, Cascais, Portugal
| | - S Fasano
- Rheumatology Unit, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy
| | - D A Isenberg
- Centre for Rheumatology, Department of Medicine, University College London, London, UK
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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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15
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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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16
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Abstract
Overlap syndrome in hepatology is emerging as a diagnostic and therapeutic challenge, which is further complicated by the present gaps in the information regarding the immunopathogenesis of these diseases. The present review represents a concise review of literature on overlap syndromes with emphasis on prevalence, etiopathogenesis, clinical presentation, diagnosis, and management of true overlap syndromes.
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Affiliation(s)
- Pooja Dhiman
- Department of Biochemistry, JIPMER, Dhanvantari Nagar, Puducherry, India
| | - Sharad Malhotra
- Department of Medical Gastroenterology, Batra Hospital and Medical Research Centre, New Delhi, India,Address for correspondence: Dr. Sharad Malhotra, Consultant, Medical Gastroenterology, Batra Hospital and Medical Research Centre, New Delhi, India. E-mail:
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17
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Purnak T, Beyazit Y, Ozaslan E, Efe C, Hayretci M. The evaluation of bone mineral density in patients with nonalcoholic fatty liver disease. Wien Klin Wochenschr 2012; 124:526-531. [PMID: 22850810 DOI: 10.1007/s00508-012-0211-4] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2012] [Accepted: 07/01/2012] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Nonalcoholic fatty liver diseases (NAFLD) are a clinical spectrum of disorders, of which nonalcoholic steatohepatitis (NASH) is the most strongly associated with inflammation. Inflammation is a known risk factor for low bone mass in the body. The primary goal of the present study was to evaluate the association between bone mineral density and liver function in patients with NASH. MATERIALS AND METHODS Consenting patients with a diagnosis of NAFLD were included in the study. Extent of fatty change was graded based on ultrasonographic appearance (Grade 1, mild; Grade 2, moderate; Grade 3, severe). Bone mineral density was measured using the dual-energy x-ray absorptiometry method. ALT and hs-CRP were considered as noninvasive marker of NASH. According to ALT levels, patients were divided into two subgroups. RESULTS A total of 102 patients with NAFLD and 54 healthy controls participated in the study. None of the patients with NAFLD had an abnormal bone mineral density. Furthermore, there was no difference between groups with regard to serum vitamin D levels. A subgroup analysis revealed that female patients with elevated serum ALT level had significantly lower bone mineral densities and higher hsCRP levels than female patients with normal ALT levels. The difference in vitamin D levels and body mass indices between the same subgroups was statistically insignificant. CONCLUSIONS Simple steatosis of the liver does not affect bone mineral density. However, in a subgroup of patients with NAFLD, the presence of elevated serum ALT and hs-CRP levels, which are suggestive of NASH, was associated with lower bone mineral densities. Better understanding of the biological basis and the complex interactions between NAFLD and bone mass may help guide the clinical management of bone diseases associated with inflammation of the liver.
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Affiliation(s)
- Tugrul Purnak
- Department of Gastroenterology, Ankara Numune Education and Research Hospital, Talatpasa Bulvari, Samanpazari, 06100, Ankara, Turkey.
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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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Abstract
Primary biliary cirrhosis is a chronic autoimmune inflammatory disease of the liver with a striking female preponderance. It has an insidious onset and typically affects middle-aged women. The disease manifests gradually with symptoms of fatigue, pruritis, and increased alkaline phosphatase levels on laboratory evaluation. The hallmark of the disease is the circulating antimitochondrial antibody. Histology is characterized by inflammation of the bile ducts, destruction of cholangiocytes, and subsequent cholestasis, progressing to biliary cirrhosis. The standard treatment for primary biliary cirrhosis is ursodeoxycholic acid, which improves survival, but the disease can still lead to cirrhosis and liver failure over decades.
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Affiliation(s)
- Bhavik M Bhandari
- Division of Gastroenterology & Hepatology, Drexel University College of Medicine, 219 North Broad Street, Fifth Floor, Philadelphia, PA 19107, USA.
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Kayaniyil S, Vieth R, Harris SB, Retnakaran R, Knight JA, Gerstein HC, Perkins BA, Zinman B, Hanley AJ. Association of 25(OH)D and PTH with metabolic syndrome and its traditional and nontraditional components. J Clin Endocrinol Metab 2011; 96:168-75. [PMID: 20980431 DOI: 10.1210/jc.2010-1439] [Citation(s) in RCA: 89] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/12/2023]
Abstract
CONTEXT Emerging evidence suggests that 25-hydroxy vitamin D [25(OH)D] and PTH may play a role in the etiology of the metabolic syndrome (MetS). However, evidence to date is limited and inconsistent, and few studies have examined associations with nontraditional MetS components. OBJECTIVE The objective of the study was to examine the association of vitamin D and PTH with MetS and its traditional and nontraditional components in a large multiethnic sample. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, we examined 654 participants from London and Toronto, Ontario, Canada, aged 30 yr and older with risk factors for type 2 diabetes. MAIN OUTCOME MEASURES Presence of MetS and its traditional and nontraditional components was measured. RESULTS Approximately 43% of the study participants were classified as having MetS. Higher 25(OH)D was significantly associated with a reduced presence of MetS after adjustment for age, sex, season, ethnicity, supplement use, physical activity, and PTH (odds ratio 0.76, 95% confidence interval 0.62-0.93). PTH was not associated with the presence of MetS after multivariate adjustment. Multivariate linear regression analyses indicated significant adjusted inverse associations of 25(OH)D with waist circumference, triglyceride level, fasting insulin, and alanine transaminase (P < 0.041). Elevated PTH was positively associated with waist circumference and high-density lipoprotein cholesterol (P < 0.04). Other associations between PTH and MetS components were attenuated after adjustment for adiposity. CONCLUSIONS Serum 25(OH)D, but not PTH, was significantly associated with MetS as well as a number of MetS components after multivariate adjustment. These results suggest that low 25(OH)D may play a role in the etiology of the MetS.
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Affiliation(s)
- Sheena Kayaniyil
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
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21
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Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Primary biliary cirrhosis. Hepatology 2009; 50:291-308. [PMID: 19554543 DOI: 10.1002/hep.22906] [Citation(s) in RCA: 891] [Impact Index Per Article: 55.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Keith D Lindor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA.
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22
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Muratori P, Granito A, Pappas G, Pendino GM, Quarneti C, Cicola R, Menichella R, Ferri S, Cassani F, Bianchi FB, Lenzi M, Muratori L. The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Am J Gastroenterol 2009; 104:1420-1425. [PMID: 19491855 DOI: 10.1038/ajg.2009.126] [Citation(s) in RCA: 76] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES During the last decade patients with concomitant clinical, biochemical, immunoserological, and histological features of both autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) were sporadically described, but definite diagnostic criteria and specific serological markers to support the diagnosis of AIH/PBC overlap syndrome (AIH/PBC OS) are still lacking. METHODS Clinical, biochemical, and histological features, autoantibody profile, and treatment response of 15 patients with coexistent hepatitic and cholestatic liver damage, all fulfilling strict diagnostic criteria for both AIH and PBC, were compared with those of 120 patients with pure PBC and 120 patients with pure AIH. RESULTS At diagnosis, the AIH/PBC OS patients' median age was 51 years, similar to that of the PBC patients (52 years, P=NS), but significantly higher than that of the AIH patients (40 years, P=0.04). Anti-dsDNA antibodies were detected in 60% of AIH/PBC OS patients, but only in 4% of PBC patients and 26% of AIH patients (P<0.0001 and 0.01, respectively). Double positivity for antimitochondrial antibodies (AMA) and anti-dsDNA was present in 47% of those with AIH/PBC OS, but only in 2% of the pathological controls (P<0.0001; specificity: 98; 95% confidence interval (CI): 97-99.2; positive likelihood ratio: 28; 95% CI: 9.8-79.4). Combined therapy (ursodeoxycholic acid (UDCA) plus steroids) achieved biochemical response in 77% of AIH/PBC OS patients. CONCLUSIONS Concomitant AMA/anti-dsDNA seropositivity can be considered the serological profile of AIH/PBC OS. The combination of UDCA and steroids is effective in achieving persistent biochemical amelioration in most AIH/PBC OS patients.
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MESH Headings
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Antinuclear/immunology
- Biopsy
- Child
- Child, Preschool
- Female
- Fluorescent Antibody Technique, Indirect
- Hepatitis, Autoimmune/complications
- Hepatitis, Autoimmune/diagnosis
- Hepatitis, Autoimmune/immunology
- Humans
- Liver/pathology
- Liver Cirrhosis, Biliary/complications
- Liver Cirrhosis, Biliary/diagnosis
- Liver Cirrhosis, Biliary/immunology
- Male
- Middle Aged
- Mitochondria, Liver/immunology
- Prognosis
- Radiography, Abdominal
- Retrospective Studies
- Syndrome
- Young Adult
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Affiliation(s)
- Paolo Muratori
- Department of Clinical Medicine, Alma Mater Studiorum, University of Bologna, Policlinico Sant'Orsola-Malpighi, via Massarenti, 9, Bologna, Italy.
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23
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Abstract
Vitamin D and calcium are critical for skeletal health. Their absorption from the intestine is negatively impacted by a number of gastrointestinal diseases and surgical procedures, leading to osteoporosis and/or osteomalacia. Diseases of the liver can impact the metabolism of vitamin D to its circulating form, 25(OH)D, as well as the production of carrier proteins, albumin and vitamin D-binding protein, that may alter the delivery of 25(OH)D and its active metabolite 1,25(OH)(2)D to target tissues, including the skeleton, again leading to bone disease. The clinician evaluating a patient with apparent osteoporosis and vitamin D deficiency/ insufficiency needs to consider a gastrointestinal etiology. Similarly, the clinician evaluating a patient with a gastrointestinal disorder needs to evaluate that patient for vitamin D deficiency and bone disease. Treatment involves adequate vitamin D and calcium supplementation to achieve normal serum 25(OH)D, PTH, and serum and urine calcium levels.
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24
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Affiliation(s)
- Keith Lindor
- Division of Gastroenterology and Hepatology, Fiterman Center for Digestive Disease, Mayo Clinic, Rochester, MN 55905, USA.
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25
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Reshetnyak VI. Concept on the pathogenesis and treatment of primary biliary cirrhosis. World J Gastroenterol 2006; 12:7250-7262. [PMID: 17143938 PMCID: PMC4087480 DOI: 10.3748/wjg.v12.i45.7250] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2006] [Revised: 07/28/2006] [Accepted: 09/04/2006] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic, progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis, leading to liver failure in the absence of treatment. Little is known about the etiology of PBC. PBC is characterized by anti-mitochondrial antibodies and destruction of intra-hepatic bile ducts. The serologic hallmark of PBC is the presence of auto-antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex (PDC). Current theories on the pathogenesis of PBC favor the hypothesis that the disease develops as a result of an inappropriate immune response following stimulation by an environmental or infectious agent. Some reports suggest that xenobiotics and viral infections may induce PBC. The pathogenetic mechanism is believed to be caused by a defect in immunologic tolerance, resulting in the activation and expansion of self-antigen specific T and B lymphocyte clones and the production of circulating autoantibodies in addition to a myriad of cytokines and other inflammatory mediators. This leads to ductulopenia and persistent cholestasis, by developing end-stage hepatic-cell failure. In this review are given our own and literary data about mechanisms of development of intrahepatic cholestasis and possible ways of its correction.
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26
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Associations between serum 25-hydroxyvitamin D3 concentrations and liver histology in patients with non-alcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2006; 17:517-24. [PMID: 16928437 DOI: 10.1016/j.numecd.2006.04.002] [Citation(s) in RCA: 320] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2006] [Revised: 03/22/2006] [Accepted: 04/14/2006] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM To explore associations between serum 25-hydroxyvitamin D(3) [25(OH)D] concentrations and liver histology in patients with non-alcoholic fatty liver disease (NAFLD). METHODS AND RESULTS We studied 60 consecutive patients with biopsy-proven NAFLD, and 60 healthy controls of comparable age, sex and body mass index (BMI). NAFLD patients had a marked decrease in winter serum 25(OH)D concentrations (51.0+/-22 vs. 74.5+/-15 nmol/L, P<0.001) compared with controls. Metabolic syndrome (MetS; as defined by the Adult Treatment Panel III criteria) and its individual components occurred more frequently among NAFLD patients. The marked differences in 25(OH)D concentrations observed between the groups were little affected by adjustment for age, sex, BMI, creatinine, calcium, homeostasis model assessment (HOMA)-insulin resistance, and the presence of the MetS. Interestingly, among NAFLD patients, decreased 25(OH)D concentrations were closely associated with the histological severity of hepatic steatosis, necroinflammation and fibrosis (P<0.001 for all) independent of age, sex, BMI, creatinine, calcium, HOMA-insulin resistance, and presence of the MetS. CONCLUSIONS Compared with controls, NAFLD patients have a marked decrease in serum 25(OH)D concentrations, which is closely associated with histopathological features of NAFLD. Further investigation into whether vitamin D(3) may play a role in the development and progression of NAFLD appears to be warranted.
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Davis GL. Thoughts on Nutrition and Liver Disease. Nutr Clin Pract 2006; 21:243-4. [PMID: 16772541 DOI: 10.1177/0115426506021003243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Gary L Davis
- Division of Hepatology and Transplant Medicine, Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246, USA.
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Affiliation(s)
- Marshall M Kaplan
- Division of Gastroenterology, Tufts-New England Medical Center, Boston, MA 02111, USA.
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Strassburg CP, Manns MP. [Primary biliary liver cirrhosis and overlap syndrome. Diagnosis and therapy]. Internist (Berl) 2004; 45:16-26. [PMID: 14735240 DOI: 10.1007/s00108-003-1127-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Primary biliary cirrhosis represents a chronic cholestatic liver disease of unknown etiology. It primarily affects females, is associated with extrahepatic immune-mediated syndromes, shows an immunogenetic association with HLA DR8, and displays serum autoantibodies, which makes an autoimmune etiology likely. The diagnosis is reached in patients with elevated alkaline phosphatase, gamma glutamyl transferase and bilirubin levels who exhibit normal bile ducts upon ultrasound examination, and in whom specific antimitochondrial autoantibodies are detectable. Half of all PBC patients additionally show specific antinuclear autoantibodies. Immunosuppressive therapy is ineffective; steroids, transplant immunosuppressants, colchicine, d-penicillamine and methotrexate are of limited clinical benefit. Ursodeoxycholic acid has few side effects and leads to a biochemical response and a delay of disease progression in most cases. When ursodeoxycholic acid therapy is ineffective an overlap syndrome with autoimmune hepatitis can be present, which can respond to steroid treatment. The only curative option is liver transplantation which should be considered when bilirubin levels exceed 100 microM/l.
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Affiliation(s)
- C P Strassburg
- Abteilung für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover.
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