scholarly journals Primary Biliary Cholangitis and Bile Acid Farnesoid X Receptor Agonists

Diseases ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 20
Author(s):  
Ludovico Abenavoli ◽  
Anna Caterina Procopio ◽  
Sharmila Fagoonee ◽  
Rinaldo Pellicano ◽  
Marco Carbone ◽  
...  
Keyword(s):  
Farnesoid X Receptor ◽  
Drop Out ◽  
Future Perspective ◽  
Primary Biliary Cholangitis ◽  
First Line ◽  
Obeticholic Acid ◽  
Intrahepatic Bile Ducts ◽  
Protective Actions ◽  
Line Drug

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by the progressive destruction of the intrahepatic bile ducts. Currently, the first line drug for PBC is ursodeoxycholic acid (UDCA) characterized by anti-apoptotic, anti-inflammatory and protective actions on cholangiocytes. Despite its recognized therapeutic action, 30–40% of PBC patients only partially benefit from UDCA therapy. This has led to the identification of the role of the farnesoid x receptor (FXR) in cholestatic liver diseases and, consequently, to the development of obeticholic acid (OCA), a steroid FXR agonist that has been recently approved for the treatment of PBC. OCA though is not effective in all patients and can cause itch, which eventually induces treatment drop out. Therefore, the search for new therapeutic strategies for PBC has begun. This review, in addition to summarizing the current treatments for PBC, provides overview of the chemical characteristics of new steroid FXR agonist candidates that could represent a future perspective for the treatment of PBC.

scholarly journals Obeticholic acid—a new therapy in PBC and NASH

2020 ◽  
Vol 133 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Roger W Chapman ◽  
Kate D Lynch
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Ursodeoxycholic Acid ◽  
Farnesoid X Receptor ◽  
Primary Biliary Cholangitis ◽  
Second Line ◽  
Obeticholic Acid ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Introduction Obeticholic acid (OCA) is a semi-synthetic hydrophobic bile acid (BA) analogue that is highly selective agonist of farnesoid X receptor (FXR), a key nuclear BA receptor, which induces expression of gut-derived hormones, in particular fibroblast growth factor 19. The resulting beneficial effects of OCA on glucose and lipid metabolism and particularly hepatic inflammation make it a candidate for the treatment of a variety of conditions including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). Sources of data In PBC patients who have not initially responded to ursodeoxycholic acid, OCA has been shown in double-blind controlled clinical trials to significantly reduce serum alkaline phosphatase. To date, OCA is the only therapy licensed by the FDA, EMA and endorsed by NICE as second line therapy for PBC. No medications are currently approved in Europe or the USA for the treatment of NASH. In recent clinical trials, OCA has been shown encouraging results by improving liver blood tests and reducing liver fibrosis with no worsening of NASH. Areas of agreement OCA is the established second line therapy for PBC in those patients who fail to adequately respond to ursodeoxycholic acid. Areas of controversy The main side effects of OCA treatment in both PBC and NASH is that of dose-dependent pruritis which can lead to treatment discontinuation in ~1–10% of patients. In addition, OCA-treated patients may also exhibit (reversible) alterations in serum lipid levels; most notably a small decrease in high density lipoprotein cholesterol. It is not yet known whether these changes carry a long-term cardiovascular risk in NASH. In addition, the relatively high cost of OCA may limit its use in cash-limited health systems. Growing Points Additional clinical trials are in progress to ascertain the long-term effects of OCA on survival in PBC and NASH. Areas timely for developing research New FXR agonists with a lower rate of side effects are being developed and trialed. Combination therapy with other agents may offer increased efficacy.

scholarly journals Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel

2019 ◽  
Vol 6 (1) ◽  
pp. e000256 ◽  
Author(s):  
Jennifer Pate ◽  
Juilo A Gutierrez ◽  
Catherine T Frenette ◽  
Aparna Goel ◽  
Sonal Kumar ◽  
...  
Keyword(s):  
Liver Disease ◽  
Patient Adherence ◽  
Treated Patient ◽  
Management Strategies ◽  
Primary Biliary Cholangitis ◽  
Cholestatic Liver Disease ◽  
Common Symptom ◽  
Obeticholic Acid ◽  
Intrahepatic Bile Ducts ◽  
Patient Health

Background and aimsThis article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment.MethodsIn May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice.ResultsThese recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms.ConclusionsPruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.

scholarly journals Diagnostic accuracy of BAL Gene Xpert compared to BAL AFB staining in Sputum negative Pulmonary Tuberculosis Suspects

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 1935-1938
Author(s):  
Sowmitha S G ◽  
Ashok Kumar Aradhyula ◽  
Gangadharan V ◽  
Sathish Kumar M
Keyword(s):  
Human Life ◽  
Diagnostic Testing ◽  
Smear Microscopy ◽  
First Line ◽  
Microbiological Profile ◽  
The World ◽  
Study Population ◽  
Smear Negative ◽  
Line Drug

Tuberculosis has stood the test of time over the millennia and still wreaks havoc on human life all over the world. We have studied the role of bronchoscopy in smear negative PTB suspects and have compared the results of BAL Gene Xpert with BAL AFB staining among the study population. We have also determined the microbiological profile in cases who are MTB negative. We retrospectively reviewed the respiratory samples (sputum and BAL) of 82 sputum negative PTB suspects from july 2018 – july 2019 for ZN stain and Gene Xpert. 25 cases were detected by Gene Xpert additionally to the 11 cases detected by BAL afb staining alone. Out of the 36 cases detected on gene Xpert 3(8%) were RIF resistant. These 5 samples which were positive on BAL AFB and negative on Gene Xpert,are suspected to be NON TB mycobacteria. Out of the remaining 41 samples, non TB culture results showed 8 Acinetobacter, 10 pseudomonas, 12 klebsiella, 2 e.coli,2 candida, 7 no growth on culture. According to our study, the bronchoscopic samples when subjected to Gene Xpert detect a higher number of cases which would go undetected otherwise compared to BAL AFB staining. Hence, bronchoscopy must be performed on such smear negative suspects and Gene Xpert could replace smear microscopy as initial diagnostic testing. It also helps in detecting first line drug resistance in addition.

Primary biliary cholangitis

2020 ◽  
pp. 3127-3135
Author(s):  
Jessica K. Dyson ◽  
David E.J. Jones
Keyword(s):  
Alkaline Phosphatase ◽  
Liver Disease ◽  
Serum Alkaline Phosphatase ◽  
Disease Diagnosis ◽  
Immunosuppressive Drug ◽  
Primary Biliary Cholangitis ◽  
Line Treatment ◽  
Antimitochondrial Antibodies ◽  
First Line ◽  
Intrahepatic Bile Ducts

Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a chronic, cholestatic liver disease in which the biliary epithelial cells lining the small intrahepatic bile ducts are the target for immune-mediated damage, leading to progressive ductopenia and cholestasis. The cause is unknown but presumed to be autoimmune. The disorder affects women (>90% of cases) and usually has an insidious onset in middle age. Younger patients are less common but have a more aggressive disease course. Fatigue and pruritus are the most common presenting symptoms. Findings on examination vary widely, ranging from no abnormality to jaundice with hyperpigmentation, scratch marks, and rarely the features of advanced liver disease. Diagnosis of PBC is based on three criteria: (1) cholestatic liver function tests, with increases in serum alkaline phosphatase and γ‎-glutamyl transferase, (2) presence of serum antimitochondrial antibodies (found in more than 95% of cases), and (3) compatible liver histology. Many asymptomatic patients are recognized following the incidental discovery of antimitochondrial antibodies or elevated levels of serum alkaline phosphatase. First-line treatment is with ursodeoxycholic acid which can lead to significant improvement in liver biochemical values. Second-line treatment is with obeticholic acid. No immunosuppressive drug regimen has been proven effective. Progression may be slow, but eventually patients can develop cirrhosis. Cholestyramine is used as first line to treat pruritus. There is no recognized treatment for fatigue. Liver transplantation is indicated in some cases.

scholarly journals Obeticholic Acid: A New Era in the Treatment of Nonalcoholic Fatty Liver Disease

2018 ◽  
Vol 11 (4) ◽  
pp. 104 ◽  
Author(s):  
Ludovico Abenavoli ◽  
Tetyana Falalyeyeva ◽  
Luigi Boccuto ◽  
Olena Tsyryuk ◽  
Nazarii Kobyliak
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Hepatic Metabolism ◽  
Lifestyle Changes ◽  
Farnesoid X Receptor ◽  
Primary Biliary Cholangitis ◽  
Obeticholic Acid ◽  
Nonalcoholic Fatty Liver

The main treatments for patients with nonalcoholic fatty liver disease (NAFLD) are currently based on lifestyle changes, including ponderal decrease and dietary management. However, a subgroup of patients with nonalcoholic steatohepatitis (NASH), who are unable to modify their lifestyle successfully, may benefit from pharmaceutical support. Several drugs targeting pathogenic mechanisms of NAFLD have been evaluated in clinical trials for the treatment of NASH. Farnesoid X receptor (FXR) is a nuclear key regulator controlling several processes of the hepatic metabolism. NAFLD has been proven to be associated with abnormal FXR activity. Obeticholic acid (OCA) is a first-in-class selective FXR agonist with anticholestatic and hepato-protective properties. Currently, OCA is registered for the treatment of primary biliary cholangitis. However, promising effects of OCA on NASH and its metabolic features have been reported in several studies.

scholarly journals Obeticholic Acid

2017 ◽  
Vol 33 (2) ◽  
pp. 66-71
Author(s):  
Susan M. Smith ◽  
Angela H. Pegram
Keyword(s):  
Phase Ii ◽  
Data Extraction ◽  
Farnesoid X Receptor ◽  
Phase Iii ◽  
Primary Biliary Cholangitis ◽  
Biliary Cirrhosis ◽  
Efficacy And Safety ◽  
Obeticholic Acid ◽  
Clinical Role ◽  
Ongoing Research

Objective: To review the pharmacology, efficacy, and safety of obeticholic acid (OCA) and determine its clinical role relative to other agents in the treatment of patients with primary biliary cholangitis (PBC). Data Sources: A PubMed search (1946 to November 2016) was conducted using the terms INT-747, obeticholic acid, OCA, farnesoid X receptor agonists, FXR agonists, primary biliary cirrhosis, and primary biliary cholangitis. Study Selection and Data Extraction: Phase II and III studies evaluating the use of OCA in PBC patients were included in this review. Data Synthesis: OCA, a farnesoid X receptor (FXR) agonist, is indicated for adult patients with PBC in combination with ursodeoxycholic acid (UDCA) or as monotherapy if unable to tolerate UDCA. Two clinical trials were identified evaluating OCA for the treatment of PBC. Study end points utilized biochemical markers (alkaline phosphatase [ALP] and bilirubin). A phase II study (n = 165) to determine efficacy and safety of OCA at 3 different doses (10 mg, 25 mg, 50 mg) demonstrated statistically significant reductions in ALP ( P < .0001 for all OCA groups versus placebo) after 12 weeks. A phase III trial (n = 217) assessed lower OCA doses (5 mg and 10 mg) with a longer study duration (12 months). Statistically significant differences ( P < .001) between the 5 to 10 mg group (46%) and the 10 mg group (47%) compared to the placebo group (10%) were found. The primary adverse effect reported in both trials was pruritus. Conclusions: OCA is the first FXR agonist approved for the treatment of PBC. Ongoing research to evaluate clinical outcomes with OCA is currently underway.

scholarly journals DEVELOPMENT OF MDR TB IN SHORT DURATION IN A PATIENT RECEIVING TREATMENT FOR SIMPLE TB: A CASE REPORT

2016 ◽  
Vol 21 (4) ◽  
pp. 301
Author(s):  
Muhammad Kashif Munir ◽  
Sana Rehman ◽  
Rizwan Iqbal ◽  
Muhammad Saqib Saeed
Keyword(s):  
Early Diagnosis ◽  
Disease Burden ◽  
Diagnostic Techniques ◽  
Team Work ◽  
First Line ◽  
Mdr Tb ◽  
Prompt Diagnosis ◽  
Line Drug ◽  
Available Resources

AbstractMultidrug resistant (MDR) tuberculosis (TB) is becoming more cumbersome especially in developing countries. Already supportive infrastructures are weak as compared to disease burden. Numerous diagnostic techniques for early diagnosis of TB and MDR TB have brought incremental improvements however; the technical intricacies of these assays and their reliance on enthusiastic laboratory infrastructure have restricted their implementation, particularly in low resource and high burden settings. Recently introduced GeneXpert MTB / RIF assay simultaneously detects the presence of MTB, and its susceptibility to the important first line drug rifampicin. Aim of this report is to understand the role of physician in prompt diagnosis and its control in spread of MDR TB and conversion of normal TB to MDR TB using available resources. Watchfulness of physician is an important factor in treating TB patients and early diagnosis of MDR TB using available resources. A good skilled team work is necessary to locate such cases in early stages and pro-mpt treatment can save many lives and ultimately serve as a big barrier in spreading primary MDR TB.Keywords:MDR TB, Tuberculosis, Prompt Diagnosis, GeneXpert.

Social Representations and Commitment

2018 ◽  
Vol 23 (3) ◽  
pp. 233-249 ◽  
Author(s):  
Eric Bonetto ◽  
Fabien Girandola ◽  
Grégory Lo Monaco
Keyword(s):  
Social Representations ◽  
Social Representation ◽  
Second Line ◽  
Review Of The Literature ◽  
First Line ◽  
Research Perspectives ◽  
The Social ◽  
Bibliographic Search ◽  
English Articles

Abstract. This contribution consists of a critical review of the literature about the articulation of two traditionally separated theoretical fields: social representations and commitment. Besides consulting various works and communications, a bibliographic search was carried out (between February and December, 2016) on various databases using the keywords “commitment” and “social representation,” in the singular and in the plural, in French and in English. Articles published in English or in French, that explicitly made reference to both terms, were included. The relations between commitment and social representations are approached according to two approaches or complementary lines. The first line follows the role of commitment in the representational dynamics: how can commitment transform the representations? This articulation gathers most of the work on the topic. The second line envisages the social representations as determinants of commitment procedures: how can these representations influence the effects of commitment procedures? This literature review will identify unexploited tracks, as well as research perspectives for both areas of research.

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