The detrimental effects of Donor Specific HLA alloantibodies (DSA) on outcomes following liver organ transplantation have been known for many years.
Liver transplantation is an exception but some evidence has been recently highlighted, showing that DSA could be associated with acute antibody-mediated rejection, chronic rejection, plasma cell hepatitis, anastomotic biliary stricture, NRH, fibrosis progression... The prevalence of preformed donor specific DSA is about 20% and the incidence of de novo DSA is about 10% in Liver transplantation (LT). DSA are associated with several graft diseases, mainly AMR but diagnosis was made on histological features+/-C4d staining. De novo DSA and preformed class II DSA, especially with high MFI, seem to pejoratively influence outcomes after LT. When associated with HCV, DSA worsen fibrosis progression. Thanks to antiviral IFN-free regimen, therapeutic strategies of DSA positivity and/or AMR will not differ from HCV- recipients, but need to be evaluated in prospective studies.
Conférence du Professeur Philippe Mathurin (Hôpital Universitaire Claure Huriez, Lille, France), Juin 2014. Le "Binge Drinking" est un des enjeux de santé publique majeur dans tous les pays occidentaux. Une augmentation de la mortalité par cirrhose alcoolique est constatée dans les pays où l'alcoolisme chronique et le Binge Drinking sont les plus répandus.
Conférence du Dr. Maximiliano GELLI (Chirurgien hépatique, AP-HP Hôpital Paul Brousse, Villejuif, France) aux Journées de Chirurgie Hépato-Biliaire, juin 2014, Paris.
Suppléance hépatique : comment et pour qui ?
Pr Didier Samuel et Pr Saliba Faouzi
Les journées du Centre Hépato-Biliaire - JCHB 2019
Journées de l'hépatologie
Conférence du Professeur Philippe Mathurin (Hôpital Universitaire Claure Huriez, Lille, France), Juin 2014. Le "Binge Drinking" est un des enjeux de santé publique majeur dans tous les pays occidentaux. Une augmentation de la mortalité par cirrhose alcoolique est constatée dans les pays où l'alcoolisme chronique et le Binge Drinking sont les plus répandus.
Conférence du Dr. Maximiliano GELLI (Chirurgien hépatique, AP-HP Hôpital Paul Brousse, Villejuif, France) aux Journées de Chirurgie Hépato-Biliaire, juin 2014, Paris.
Suppléance hépatique : comment et pour qui ?
Pr Didier Samuel et Pr Saliba Faouzi
Les journées du Centre Hépato-Biliaire - JCHB 2019
Journées de l'hépatologie
Présentation du Dr. Revault, médecin Coordinateur du COMEDE au Staff d'Hépatologie (CHU Paul-Brousse, Villejuif, France) - 25 fev 2015.
1. Présentation du Comité pour la santé des exilés
2. Principales caractéristiques des populations accompagnées et soignées
3. Difficultés d'accès aux soins, dispositifs de couverture maladie et droit au séjour pour raison médicale
Présentation du Dr. Revault, médecin Coordinateur du COMEDE au Staff d'Hépatologie (CHU Paul-Brousse, Villejuif, France) - 25 fev 2015.
1. Présentation du Comité pour la santé des exilés
2. Principales caractéristiques des populations accompagnées et soignées
3. Difficultés d'accès aux soins, dispositifs de couverture maladie et droit au séjour pour raison médicale
Publier en Medecine et Science de la vie : Tirer parti de l'offre de publicat...Mony Claire
Les publications scientifiques se multiplient et évoluent. L'Open Access a pris en 15 ans une véritable ampleur et offre au chercheur de nouvelles possibilités pour valoriser son travail.
Conférence du Dr. Florent ARTRU, Réanimateur (Hôpital Universitaire Paul Brousse, Centre hépato-Biliaire), Juin 2014. Résultats des greffes hépatiques en cas de cirrhose grave.
Conférence du Prof. Gilles Pelletier présentant les règles d'attribution des greffons hépatiques pour les patients souffrant d'un cancer primaire du foie (CHC). Conférence donnée en juin 2014. France.
Les traitements de l'hépatite C chronique en 2014, pour les patients cirrhotiques et transplantés : Nouvelles molécules, Résultats, Traitement selon le génotype, Telaprevir, Boceprevir, Sofosbuvir, Simeprevir, Daclatasvir, Ledipasvir, Ombitasvir, Asunaprevir... Conférence du Dr. Audrey COILLY, Hépatologue à l'Hôpital Paul Brousse (France), aux Journées Hépato-Biliaire (13 Juin 2014, Paris).
Les tests de dépistage rapide de l'Hépatite C : Quel impact sur la prise en charge de nos patients ? Conférence du Dr. Pascal Mélin (Centre Hospitalier de Saint-Dizier, France)
Conférence du Professeur Didier Samuel (Hépatologue, Hôpital Paul Brousse, France). Stratégie thérapeutique pour l'élimination de l'antigène HBs (AgHBs) chez les patients porteurs d'une hépatite B chronique.
Conférence du Pr. Vincent Leroy (Hôpital Universitaire de Grenoble, France), Juin 2014. Prise en charge de l'Hépatite C à l'aide des nouveaux antiviraux Sofosbuvir, Daclatasvir, Siméprévir, en combinaison ou non avec l'Interféron pégylé et la Ribavirine.
Conférence du Dr. Bruno Roche (Hépatologue, Hôpital Paul Brousse, France). Physiopathologie, Facteurs de risque, incidence et prise en charge de la réactivation virale B après négativation du virus.
William Dean Wallace Lung Summary Banff 2013 Meeting in BrazilKim Solez ,
Lung summary from 12th Banff Conference on Transplant Pathology from the meeting in Comandatuba-Bahia, Brazil on August 23rd, 2013 http://cybernephrology.ualberta.ca/banff/2013
Liver transplant (LT) is becoming the need of the hour and often the last ray of hope for many of our cirrhotic patients. The dearth of deceased donors, acceptance of living-related donors, better operative skills, and post transplant outcomes have played an important role is making LT accessable to more and more needy people. However, for best outcome it is important to stick to the established criteria laid down for listing a patient for LT for both best outcomes and better distribution of donor livers.
Anemia Indian scenario In Chronic Kidney Disease Patients Dr Ashutosh Ojha
this is a comprehensive presentation in Post Doctoral Certificate in Nephrology training program. At Gauhati Medical College Hospital ,Dept Of Nephrology.
2014 06-05 Pretransplant Evaluation for Kidney Transplantation - Pretransplan...Maarten Naesens
Short overview of evidence-based decisions for the pre transplant evaluation of kidney transplant recipients. Pretransplantbilan onderzoeken niertransplantatie UZ Leuven.
Is routine thromboprophylaxis warranted in all patients of tibial fracture ma...iosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Sydney Sexual Health Centre Journal Club presentation by Gwamaka E.M. on The Journal of Infectious Diseases Volume 214 Issue 10, published in November 2016.
The Journal of Infectious Diseases has been published continuously since 1904 and describes itself as "the premier global journal for original research on infectious diseases". Research published in the JID includes studies in microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.
The Sydney Sexual Health Centre Journal Club allows our team to stay up-to-date with what is being published in the field of sexual health. Staff members take turns to read, review and share the contents of an allocated journal. Journal Club encourages knowledge sharing and discussion about topics raised.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Couples presenting to the infertility clinic- Do they really have infertility...
Donor specific HLA alloantibodies and Hepatitis C Virus in Liver Transplantation - Breackthrough to achieve long-term survival
1. Breakthrough to achieve long-term survival
DSA & HCV in liver transplantation
Audrey Coilly, MD
Centre Hepato-Biliaire
Paul Brousse Hospital, Villejuif, France
2. DISCLOSURES
Audrey Coilly, MD
Centre Hepato-Biliaire
AP-HP Hopital Paul-Brousse, Villejuif, France
I have relevant financial relationships with respect to the content of this
session as follows:
1.Speaker Bureau: Gilead France
2.Grant: Novartis France
3.Consultancy and Teaching: Astellas, MSD, BMS, Janssen
3. How to improve long term survival in liver transplantation?How to improve long term survival in liver transplantation?
Watt, KD. Am J Transpl. 2010Watt, KD. Am J Transpl. 2010
% death according to time after liver
transplantation
% death according to time after liver
transplantation
50%
20%
• Register study, n=798
4. How to improve long term survival in liver transplantation?How to improve long term survival in liver transplantation?
Watt, KD. Am J Transpl. 2010Watt, KD. Am J Transpl. 2010
• Register study, n=798
• From 8-years post-LT, the
first cause of death is
liver-related
5. HCV recurrence is the first cause of death and graft loss when patients
are transplanted with a positive HCV RNA
HCV recurrence is the first cause of death and graft loss when patients
are transplanted with a positive HCV RNA
Forman, LM. Gastroenterology. 2002Forman, LM. Gastroenterology. 2002
Patient survival Graft survival
11,036 patients (UNOS registry)
11,791 LT from 1992 to 1998
1.00
0.75
0.50
0.25
0.00
1 2 3 4 5
Follow-up (years)
Proportionofpatientssurviving
Log-rank X2
=19.7
P<0.0001
HCV -
HCV +
1.00
0.75
0.50
0.25
0.00
1 2 3 4 5
Follow-up (years)
HCV -
HCV +
Log-rank X2
=52.85
P<0.0001Proportionofallograftssurviving
0 0
6. • The detrimental effects of DSA on outcomes following solid organ
transplantation have been known for many years1
• Liver transplantation is an exception but some evidence has been recently
highlighted, showing that DSA could be associated with2
:
Spectrum of diseases related to donor-specific HLA alloantibodies (DSA)
in liver transplantation
Spectrum of diseases related to donor-specific HLA alloantibodies (DSA)
in liver transplantation
1- Angaswamy, N. Human Immunology. 2013 2- O’Leary, JG. Am J Transpl. 20141- Angaswamy, N. Human Immunology. 2013 2- O’Leary, JG. Am J Transpl. 2014
7. 1. What are the prevalence and incidence of DSA after LT and
are they impacted by HCV replication?
2. How to diagnose acute antibody-mediated rejection (AMR)?
When associated with HCV recurrence?
3. What are the consequences of DSA on LT outcomes and on
HCV recurrence?
4. How to prevent? When and How to treat AMR?
AgendaAgenda
8. 1. What are the prevalence and incidence of DSA after LT and
are they impacted by HCV replication?
2. How to diagnose acute antibody-mediated rejection (AMR)?
When associated to HCV recurrence?
3. What are the consequences of DSA on LT outcomes and on
HCV recurrence?
4. How to prevent? When and How to treat AMR?
AgendaAgenda
9. Preformed DSA is quite common in LT contextPreformed DSA is quite common in LT context
1- Castillo-Rama, M. Liver Transpl. 2008 2- Kozlowski, T. Liver Transpl. 2011 3- Muro, M. Transpl Immuno.
2005 4- Fontana, M. Transpl Int. 2010 5- Taner, T. Am J Transpl. 2012
1- Castillo-Rama, M. Liver Transpl. 2008 2- Kozlowski, T. Liver Transpl. 2011 3- Muro, M. Transpl Immuno.
2005 4- Fontana, M. Transpl Int. 2010 5- Taner, T. Am J Transpl. 2012
• Several reports of monocentric, retrospective, cross-match
studies in liver transplant recipients showed prevalence of
DSA ranging from 5.2% to 24.2%1-4
• A prospective monocentric study5
was consistent with these
reports, as DSA was found in 22.2%
10. In most cases, preformed DSA disappear after liver transplantationIn most cases, preformed DSA disappear after liver transplantation
1- Taner, T. Am J Transpl. 2012 2- Dar, W. Am J Transpl. 20111- Taner, T. Am J Transpl. 2012 2- Dar, W. Am J Transpl. 2011
Among the 20 patients, only 3
had persistent DSA at 4 months
post-LT1
Some reports suggest that Class
I DSA were preferentially
cleared*2
*In recipients of SLKT
11. While preformed DSA disappear,
liver recipients may develop de novo DSA
While preformed DSA disappear,
liver recipients may develop de novo DSA
1- Kaneku, H. Am J Transpl. 2013 2- Del Bello, A. Am J Transpl. 20141- Kaneku, H. Am J Transpl. 2013 2- Del Bello, A. Am J Transpl. 2014
• In a large retrospective cohort study of 749 liver transplant recipients,
8.1% developed de novo DSA 1 year post-LT1
• Another large retrospective study enrolling 267 patients have shown an
incidence of de novo DSA of 9.1% (median follow-up: 110 months)2
• In both studies, de novo DSA were mainly Class II DSA (Anti-DQ)
12. Risk factors of de novo DSA appearanceRisk factors of de novo DSA appearance
1- Kaneku, H. Am J Transpl. 2013 2- Del Bello, A. Am J Transpl. 20141- Kaneku, H. Am J Transpl. 2013 2- Del Bello, A. Am J Transpl. 2014
At one year post-LT1
In the French study, the sole predictive factor for the emergence of de
novo DSAs was retransplantation (OR 3.75; 95% CI 1.28-11.05, p=0.025)2
13. Risk factors of de novo DSA appearanceRisk factors of de novo DSA appearance
1- Kaneku, H. Am J Transpl. 2013 2- Del Bello, A. Am J Transpl. 20141- Kaneku, H. Am J Transpl. 2013 2- Del Bello, A. Am J Transpl. 2014
At one year post-LT1
In the French study, the sole predictive factor for the emergence of de
novo DSAs was retransplantation (OR 3.75; 95% CI 1.28-11.05, p=0.025)2
14. Risk factors of de novo DSA appearanceRisk factors of de novo DSA appearance
1- Kaneku, H. Am J Transpl. 2013 2- Del Bello, A. Am J Transpl. 20141- Kaneku, H. Am J Transpl. 2013 2- Del Bello, A. Am J Transpl. 2014
At one year post-LT1
In the French study, the sole predictive factor for the emergence of de
novo DSAs was retransplantation (OR 3.75; 95% CI 1.28-11.05, p=0.025)2
• None of these studies have shown differential prevalence or incidence of
DSA in HCV positive patients
• The use of pegylated interferon α was not a predictor of DSA appearence2
15. 1. What are the prevalence and incidence of DSA after LT and
are they impacted by HCV replication?
2. How to diagnose acute antibody-mediated rejection (AMR)?
When associated with HCV recurrence?
3. What are the consequences of DSA on LT outcomes and on
HCV recurrence?
4. How to prevent? When and How to treat AMR?
AgendaAgenda
16. The diagnosis of AMR is challengingThe diagnosis of AMR is challenging
• Abnormalities of liver test are inconstant and non specific
• In the majority of patients, the presence of DSA is not
associated with rejection
– Variability of DSA testing techniques
– Screening: Solid-phase immunoassays (Luminex®)
– The presence and specificity of antibodies is then detected
using a spectrophotometer
– The mean fluorescence intensity (MFI) allows a
normalization and a quantification of the results
17. There is no consensus concerning threshold of MFI to be considered
positive
There is no consensus concerning threshold of MFI to be considered
positive
Musat, AI. Liver Transpl. 2013Musat, AI. Liver Transpl. 2013
• Ranging from >300 to >10 000
• Prospective study enrolling 109 LT patients
– Aimed to determine cut-off of MFI with the best PPV and NPV for
acute rejection (<90d post-LT)
-- Class I or II MFI≥300
-- Class I and II MFI<300
18. Pathological examination is important to assess diagnosis of AMRPathological examination is important to assess diagnosis of AMR
O’Leary, JG. Liver Transpl. 2014O’Leary, JG. Liver Transpl. 2014
• Until recently, there was no consensus concerning histological fearures of
AMR
• Most of the time, AMR is followed by ACR
AMR - ACRAMR - ACR
Persistent ARPersistent AR
Chronic rejectionChronic rejection
Graft LossGraft Loss
21. Does C4d staining assist the histopathological diagnosis in liver
transplantation?
Does C4d staining assist the histopathological diagnosis in liver
transplantation?
1- Colvin, RB. J Am Soc Nephrol 2007 2- Bellamy CO. Histopathology. 2007 3- Jain, A. Clin transp. 2006
4- Bouron-Dal Soglio, D. Hum Pathol 2008 5- Lunz, J. Am J Transplant. 2012
1- Colvin, RB. J Am Soc Nephrol 2007 2- Bellamy CO. Histopathology. 2007 3- Jain, A. Clin transp. 2006
4- Bouron-Dal Soglio, D. Hum Pathol 2008 5- Lunz, J. Am J Transplant. 2012
• C4d staining is well validated to
diagnose AMR in kidney
transplantation1
• In LT, interpretation of C4d staining
and practical utility is less clear2
– More sensitive in fresh tissue
– C4d deposits are often seen in other
liver insults as HCV recurrence3-4
• Only obvious and diffuse staining
(strong portal vein, capillary,
periportal sinusoids)5 O’Leary, JG. Liver Transplant. 2014
25. De novo DSAs decrease both patient and graft survivalDe novo DSAs decrease both patient and graft survival
• Patients with de novo DSA develop AMR in 23.8%1
1- Del Bello, A. Am J Transpl. 2014 2- Kaneku, H. Am J Transpl. 20131- Del Bello, A. Am J Transpl. 2014 2- Kaneku, H. Am J Transpl. 2013
Patient survival2
Graft survival2
28. DSA are associated with fibrosis progression in HCV positive recipientsDSA are associated with fibrosis progression in HCV positive recipients
• In this monocentric retrospective study analyzing 507 LT patients
• Preformed Class I and II DSAs were associated with lower survival
• de novo DSA are limit but unsignificant regarding fibrosis progression
O’Leary, JG. Liver Transplant. 2014O’Leary, JG. Liver Transplant. 2014
29. 1. What are the prevalence and incidence of DSA after LT and
are they impacted by HCV replication?
2. How to diagnose acute antibody-mediated rejection (AMR)?
When associated with HCV recurrence?
3. What are the consequences of DSA on LT outcomes and on
HCV recurrence?
4. How to prevent? When and How to treat AMR?
AgendaAgenda
30. « Prevention is better than cure »: Before liver transplantation« Prevention is better than cure »: Before liver transplantation
1- Curry, MP. ILTS 2014. Oral #137 2- O’Leary, JG. Am J Transpl. 20131- Curry, MP. ILTS 2014. Oral #137 2- O’Leary, JG. Am J Transpl. 2013
HCV: Achieve SVR before LT
• Not always possible with
IFN-based regimen
• Most of patients will be
able to achieve SVR before
LT
• Post-LT SVR12: 70%
Preformed DSA
Liver transplant
(up to 48 weeks)
SOF 400 mg/day +
RBV 1000–1200 mg/day
SOF 400 mg/day +
RBV 1000–1200 mg/day
Undergoing LT
for HCC
2° to HCV1
N=61
Undergoing LT
for HCC
2° to HCV1
N=61
• Evidence does not advocate
to contraindicate LT when
there is a positive
crossmatch, nor to delay LT
awaiting the results
• Avoid preformed Class II
DSA in combined liver-
kidney transplantation
(MFI>10,000)2
31. « Prevention is better than cure »: After liver transplantation« Prevention is better than cure »: After liver transplantation
• In my opinion, treating HCV recurrence based on IFN-free regimen is
mandatory without waiting a significant fibrosis on the liver graft
Preformed DSA
Strict monitoring:
-Liver test when tapering IS
-Retest DSA: timing?
-Protocol liver biopsies: 1, 2 and 5 years
32. « Prevention is better than cure »: After liver transplantation« Prevention is better than cure »: After liver transplantation
• In my opinion, treating HCV recurrence based on IFN-free regimen is
mandatory without waiting a significant firbrosis on the liver graft
De novo or persistent DSA
*Anti-humoral agents and techniques as plasmapheresis, IV immune globuline, rituximab, bortezomib*Anti-humoral agents and techniques as plasmapheresis, IV immune globuline, rituximab, bortezomib
33. • The prevalence of preformed DSA is about 20% and the
incidence of de novo DSA is about 10% in LT
• DSA are associated with several graft diseases, mainly AMR
but diagnosis was made on histological features+/-C4d
staining
• De novo DSA and preformed class II DSA, especially with high
MFI, seem to pejoratively influence outcomes after LT
• When associated with HCV, DSA worsen fibrosis progression
• Thanks to antiviral IFN-free regimen, therapeutic strategies of
DSA positivity and/or AMR will not differ from HCV-
recipients, but need to be evaluated in prospective studies
ConclusionConclusion
Editor's Notes
Early and late stage as well
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Utiliser DSA against Class I, etc…
Bien parlé de la prevention: eviter tf, adherence etc