Liver transplantation current status, controversies and mythsAbhishek Yadav
Details the present status, indications, techniques about liver transplantation. Also dispels some common myths surrounding liver transplantation. #liver transplantation # living donor liver transplantation #liver cirrhosis #liver failure#transplantation#live donor#drabhishekyadav.com#liversurgeon#myths#livedonorlivertransplantation#organtransplantation#alcohololiverdisease
Basics of kidney_transplant and donor_recepient evaluationJosephN7
This contains basic information on kidney transplant, benefits of transplant , donor_recepient evaluation, immunosuppressive drugs and risk factors
for update on my new presentations follow and leave a comment on any topic.
follow me on social media for related content (IG "mulebajoseph" and Pinterest "Joseph N Muleba" twitter "joseph n muleba"
Liver transplantation; notes of DM/DNB/SpecialistsPratap Tiwari
Liver transplantation; extensive notes of DM/DNB/Specialists. This was my notes for my exam compiled from several sources, credit goes to original authors. This is just for quick revision
Liver transplantation current status, controversies and mythsAbhishek Yadav
Details the present status, indications, techniques about liver transplantation. Also dispels some common myths surrounding liver transplantation. #liver transplantation # living donor liver transplantation #liver cirrhosis #liver failure#transplantation#live donor#drabhishekyadav.com#liversurgeon#myths#livedonorlivertransplantation#organtransplantation#alcohololiverdisease
Basics of kidney_transplant and donor_recepient evaluationJosephN7
This contains basic information on kidney transplant, benefits of transplant , donor_recepient evaluation, immunosuppressive drugs and risk factors
for update on my new presentations follow and leave a comment on any topic.
follow me on social media for related content (IG "mulebajoseph" and Pinterest "Joseph N Muleba" twitter "joseph n muleba"
Liver transplantation; notes of DM/DNB/SpecialistsPratap Tiwari
Liver transplantation; extensive notes of DM/DNB/Specialists. This was my notes for my exam compiled from several sources, credit goes to original authors. This is just for quick revision
History of liver transplant.
Why and When liver need to be transplant ?
What at basic requirements in LT.
Success and Failure %age
Global statistics of organ donation
A very simple yet comprehensive presentation to understand the concept of CRRT and its implementation in Intensive Care Unit. Intended for the very beginners in ICU. After going through the presentation you will be able to say "Now I know it!"
History of liver transplant.
Why and When liver need to be transplant ?
What at basic requirements in LT.
Success and Failure %age
Global statistics of organ donation
A very simple yet comprehensive presentation to understand the concept of CRRT and its implementation in Intensive Care Unit. Intended for the very beginners in ICU. After going through the presentation you will be able to say "Now I know it!"
Hepatocellular carcinoma—role of interventional radiologist Dr. Muhammad Bin ...Dr. Muhammad Bin Zulfiqar
In these presentation we will discuss the merits, demrits and outcomes of various interventional radiology modalities for the treatment of hepatocellular carcinoma
Best Liver Transplantation, Liver Treatment and Liver Transplant Hospitals in Hyderabad, Bangalore, Chennai and Mumbai
Global Hospitals India’s leading Multi-Specialty, Multi-Organ Transplant Centre with locations in Hyderabad, Chennai, Bangalore and Mumbai. The hospital is home to the Institute of Liver, Pancreases Diseases and Transplants that is the foremost liver transplant facilities in the country with expertise for both live-donor and cadaver transplants.
The hospitals offers state-of-the-art infrastructure alongside a team of high-skilled doctors - with competencies to treating a wide array of liver-related ailments and emergencies.
Global Hospitals is the leading tertiary healthcare provider and has pioneered several advanced liver transplant surgeries. Acomprehensive liver disease and transplant centre - the institute has successfully performed over 600 transplants.
Comprising of some of the best known transplant surgeons, the state-of-the-art infrastructure facility delivers best post-operative care for complex hepatology cases and Hepatobiliary Surgeries, including Hepatitis C, Liver Cirrhosis, Fatty Liver Disease and others
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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
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
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.
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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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Surgical Site Infections, pathophysiology, and prevention.pptx
Liver transplantation an update
1. Liver Transplantation: An Update
Mahmoud El-Meteini, MD
General Secretary of PALTS
Professor of HPB & Liver Transplant Surgery, Ain Shams University.
Director of Ain-Shams Center for Organ Transplant (ASCOT)
Ain Shams University, Cairo - Egypt
2. History of Orthotopic Liver Transplantation (OLTx)
• 1963: 1st Unsuccessful attempt (Denver)
• 1967: 1st Long term survivor
• 1970’s: 1 year pt Survival: 35%
• 1980’s: 5 year pt Survival: 70%
• 1984: Reduced Liver Tx
• 1989: Split Liver Tx
• 1989/1990: 1st successful LDLT (Brazil/ Australia)
• 1994: 1st AALDLT (Japan)
• 1993: 1st Unsuccessful LDLT (Egypt)
• 1996: Undisciplined trial OLT (Egypt)
• 2001: 1st Real LDLT Program (Egypt)
3. 3
Patient survival after liver transplantation
has shown continued improvement
• The last 10 yrs have seen steady
improvements in pt survival in
Europe, the US, Australia & New
Zealand1–3
– 1-year post-transplant
survival of ≈ 90%
– These improvements are due
to advances in peri-operative
care, perfection of surgical
technique, introduction of
potent immunosuppressants,
antibiotics & antiviral drugs4
1. European Liver Transplant Registry, ELTR. 2010. Available at: http://www.eltr.org/spip.php?article152, accessed 28 October 2011. 2.
US Organ Procurement and Transplantation Network, OPTN. 2008. Available at:
http://optn.transplant.hrsa.gov/ar2008/Preface_Contributors.htm?cp=1, accessed 28 October 2011; 3. Lynch SV, Balderson GA. ANZLTR
Registry Report. Australia and New Zealand Liver Transplant Registry. Available at: http://www.anzltr.org/thisYear/report.pdf, 28
October 2011.4. Braun F et al. Transplant Proc 2009;41:2564-66
European patient survival (%) following liver
transplantation has improved over the past 25 years1
0
20
40
60
80
100
0 1 2 3 4 5 6 7 8 9 10
18
46
56
61
66
79
22
34
64
81
85
86
52
65
1995–99: 18162
<1985: 519 1985–89: 4129 1990–94: 12007
2000–2004: 22945 >2004: 18786
Time Post-transplant (years)
PercentageSurvival(%)
8. 8
In Egypt: HCV & HCC are the main indications
65%
30%
5%
HCV
HCC
Other
9. 200 Million People Infected With HCV Worldwide
2.5%–10%
>10%
1%–2.5%
Prevalence of infection
Global Burden of HCV Working Group. J Clin Pharmacol. 2004;4420-4429.
WHO. Wkly Epidemiol Rec. 2002;77:41-48.
Not available
10. Global Incidence of Hepatocellular carcinoma
• HCC is the 3rd cancer related mortalitiy worldwide.³
• Its the 5th common malignancey in males, the 9th among females.²
• Main cause of mortalitiy in cirrhotic patients.4
• Its annual incidence is 560,000, and annual mortality of 550,000.5
1. Perz JF, et al. J Hepatol. 2006;45:529-38. 2. Jelic S. Ann Oncol. 2009;Suppl 4:iv41-5.
3. Garcia M, et al. American Cancer Society. 2007. www.cancer.org. Accessed Jan 2010.
4. Llovet J, J Hepatol. 2000;33:423-9. 5. Marrero CR, Marrero JA. Arch Med Res. 2007;38:612-20.
11. Survival of the 3 Leading Indications for
LTx (01/1988 - 06/2002)
Cirrhosis : 24227
Cancers : 4608
63
66
71
75
82
4144
49
58
74
55
56
5961
65
0
20
40
60
80
100
1 2 3 4 5 6 7 8 9 10
(%)
Yrs
p Log Rank :
Acute Hepatic Failure vs Cirrhosis : 0.0001
Cancers vs Cirrhosis : 0.0001
Acute Hepatic Failure vs Cancers : 0.0001 (Wilcoxon test)
12. 12
1197 1018 984 1070
638
5124
121 14 29 23 192
0
1000
2000
3000
4000
5000
6000
Brazil Germany Italy Spain UK USA
Numberoflivertransplantations
Whole liver (deceased donor) Liver (living donor)
More than 20,000 liver transplants are now
performed annually worldwide
1. US Organ Procurement and Transplantation Network, OPTN. 2008. Available at:
http://srtr.org/annual_reports/current/905_li.htm, accessed 28 October 2011; 2. European Liver Transplant Registry, ELTR.
2010. Available at: http://eltr.org, accessed 28 October 2011; 3. Van Gelder F et al. Organs,Tissues & Cells 2010;13:5-8.
NA
In the US, the incidence of liver transplantation was 21.6 ppm in 20071
In Europe, there were 6120 transplants during 2007, compared with only 531 in 19862
IRODaT 2009 preliminary data3
14. WL: Problems/ Management
• OLTx is the only treatment that improves Survival rate in pts. with
ESLD.
• OLTx is the only treatment with potential for cure in pts. with HCC in
Cirrhotic liver.
• Globally, 1.4 million deaths occur annually as a result of chronic liver
diseases.
• UNOS Waiting List:as of April 27th,2011
Liver 16,171
<30 days 854
30 to < 90 days 1,439
90 to 6 months 1,539
Total 3832
(23.6%)
15. Liver Tx Waiting List is growing
& Waiting times are now longer
0
2,000
4,000
6,000
8,000
10,000
12,000
The liver waiting list has grown by
23% since 1998
0
2
4
6
8
10
12
14
Medianmonthstotransplant
Time on the liver transplant
waiting list has increased by 54%
since 2005
Numberofpatients
US Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients Annual Report 2011,
Available at: http://srtr.transplant.hrsa.gov/annual_reports/2011/default.aspx. Accessed February 2013.
16. Gap between supply and demand
1000
1500
2000
2500
3000
2007 2008 2009 2010 2011
Numberofpatients
Number of donors Patients active on waiting list
In the UK, about 14% of all waiting list patients die or become too sick to undergo the
transplant procedure2
Eurotransplant International Foundation Annual Report 2012, Figure 6.5, Available at: http://statistics.eurotransplant.org/.
Accessed April 2013; 2. van der Meulen JH, et al. Transplantation 2007;84:572–579.
17.
18.
19. 19
In the face of donor organ shortage, Organ
Allocation is determined by MELD score
• MELD scale provides a predictive measure of short-term mortality risk &
prognosis in patients with ESLD1,2
– MELD score is based on laboratory indicators of renal dysfunction (serum
creatinine), liver disease (serum bilirubin) and bleeding risk (INR for
prothrombin time)
• The higher the MELD score, the higher the priority for a liver transplant
• In the MELD era, patients with ESLD and poor renal function have
become increasingly common candidates for liver
transplantation3
• Allocation of donor livers is based on MELD scores in most countries
ESLD, end stage liver disease; MELD, Model for End-stage Liver Disease; INR, international normalized ratio
1. Malinchoc M et al. Hepatology 2000;31:864-871;
2. Kamath PS et al. Hepatology 2001;33:464-470;
3. Sharma P et al. Liver Tranpl 2009;15:1142-48
20. MELD score: 6- 40
• Serum , serum Creatinine & INR to predict survival
• Patients twice within the last 7 days, value for serum
creatinine should be 4.0
Hepatology, 2001
22. • T1 no extra MELD points
• T2 (within Milan) MELD 22
Freeman RB, et al. Am J Transplant. 2006;6:1416-21.
Freeman RB, et al. Liver Transpl. 2004;10:7-15.
The 2004 MELD for HCC in USA
23. Extended Criteria Donors (ECD)
Marginal Donors
• Ideal Donor: Age<40, trauma as cause of death, donation after
brain death (DBD), haemodynamic stability at time of procurement,
no steatosis or any underlying liver disease & no transmissible
diseases (infectious/ malignant).
• ECD: Any donor who does not fit these criteria
SRTR Data: increased utilization of elderly donors, DCD
& donors with positive markers of HBV & HCV
• Implications:
1ry graft nonfunctioning
Early graft poor function
Transmission of donor derived disease
Death or need for re-transplantation
24. Donor after Cardiac Death (DCD)
• Def. Organ procurement after a standoff period of 5 min.
after death is certified
• Implications: variable period of warm ischemia time
that may result in early poor function, non-function of the
graft or diffuse cholangiopathy
• Measures to halt deleterious effects on graft function:
judicious donor selection (age<40, no steatosis), use of
heparinized perfusate, use of extracorporeal oxygenation,
short WIT (<15 min) & short CIT (<10 hrs)
Deshpande R, Heaton N: J.Hepatology 2006; 45: 499
25.
26. Donor Assessment
• Age 18-50
• BMI < 30
• No Co-morbid disease
• Phase I: ABO blood group compatibility & Blood
chemistry (CBC, Liver and Kidney function)
• Phase II: Virology markers (e.g. Anti HCV antibodies,
Anti HBV antibodies, etc)
• Phase III: CT scan anatomy & Volumetry.
• Phase IV: Liver biopsy, Medical consultation (e.g.
Cardiac , Chest & Psychiatric consultation)
28. Recipient Assessment
• History
– Etiology of liver disease
– Previous liver transplantation
– GIT hemorrhage
– Ascites
– History of SBP
– History of encephalopathy
– Surgical history
– Medical history eg, diabetes, hypertension,
ischemic heart disease
• Child-Pugh & MELD score
36. Surgical procedures
• The two surgical techniques are performed simultaneously;
the donor procedure last 6-8 hrs while the recipient
procedure 10-12 hrs
• The donor spend the first 24- 48 hrs post-op in the ICU & an 6-
10 days in hospital
• The two half-livers (both in donor and recipient) grow back to
80% of their size in 3-4 weeks
37. 0
10
20
30
40
50
60
70
80
90
100
Kidney-CD Kidney-LD Pancreas SPK Liver Heart
%Graftsurvival
1 year 5 years 10 years
Excellent short-term but poor long-term
survival
CD, cadaver donor; LD, living donor; SPK, simultaneous pancreas and kidney transplant.
Levy, GA, Lake, JR, Holt, DW, Wallemacq P. Current Trends in Transplantation: Drug Therapy and Monitoring, Abbott
Laboratories, Abbott Park, USA, 1–157 (2009). Published in July 2009 37
Organ type
38. Infections, malignancies and CVD are leading causes
of death among liver transplant patients
CVD, cardiovascular disease
US Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients Annual Report 2008;
Available at: http://optn.transplant.hrsa.gov/ar2008/Preface_Contributors.htm?cp=1, accessed 28 September 2012 38
0
50
100
150
200
4 12 20 28 36 44 52 60 68 76 84 92
Infection
Malignancy
CVD
Other
Unknown
Deathsper100patient-yearswith
afunctioninggraft
Time posttransplant, months
39. 39
LTx pts had the 2nd-highest Cumulative
Incidence of “chronic renal failure” at 5 yrs
Ojo AO et al. N Engl J Med 2003;349:931-40
Incidence of CRF in a study of >60,000 non-renal organ transplant recipients
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0 12 24 36 48 60 72 84 96 108 120
Cumulativeincidenceof
chronicrenalfailure
Months since Transplantation
Intestine
Liver
Lung
Heart
Heart-lung
40. 40
Liver transplant recipients are becoming;
Older with Higher MELD scores
MELD, Model for End-stage Liver Disease ;CRF, chronic renal failure
1. US Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients Annual Report 2008; Available at:
http://optn.transplant.hrsa.gov/ar2008/Preface_Contributors.htm?cp=1, accessed 28 October 2011;
2. Sharma P et al. Liver Transpl 2009;15:1142-8
0
2
4
6
8
10
12
Deceased donor transplant
Living donor transplant
Patients(%)
0
5
10
15
20
25
30
Deceased donor transplant
Living donor transplant
Age >65 years1 MELD score 21–301
US data show that 24% of recipients of deceased donor transplants have MELD score
>20, compared with 9% of recipients of living donor transplants1
41. 41
HCV recurrence post-transplant is a key
unmet need in HCV patients
HCV, hepatitis C virus; CNI, calcineurin inhibitor
1. Berenguer M et al. Hepatology 2002;36:202-10; 2. Prieto M et al. Hepatology 1999;29:250-256; 3. Berenguer M et al. J Hepatol 2001;35:666-
78; 4. Berenguer M et al. J Hepatol 2000;32:673-684. 5. Firpi RJ et al. Liver Transpl 2009;15:1063-71; 6. Bhat I, Mukherjee S. Panminerva Med
2009;51:235-47
Liver transplant
Recurrence of infection: >98%
Acute hepatitis: 25–45%
• HCV-related chronic hepatitis: 80–100%
• HCV-related graft cirrhosis: 8–30%
• Cholestatic hepatitis: 2–8%
Follow-up: 3.5 months
(1–13 months)
Follow-up: 5 years
• HCV reinfection is “Universal”1–5
• Early & aggressive HCV recurrence
significantly accelerates the progression of
the disease, compared with HCV in the non-
transplant population1–5
• HCV Recurrence after LTx is associated with
– Accelerated fibrosis progression
– Accelerated graft cirrhosis
– Reduced graft survival
– Reduced pt survival
• Reducing the use of CNIs & Steroids
appears to slow the progression of
HCV6
42. 42
HCV recurrence is associated with
Reduced Patient Survival
HCV, hepatitis C virus.
Berenguer M et al. Hepatology. 2002;36:202-10
Log-rank p=0.0001
HCV–
HCV+
0.0
Time post-transplant (years)
1 2 3 4 5 6 7 8 9
20
40
60
80
100
0
Patientsurvival(%)
HCV+
77
65
61
55
HCV–
87
83
76
70
Year
1
3
5
7
Patient survival (%)
Prospective, single-centre study of 522 pts who underwent liver transplant
between 1991 and 2000
43. Portal pressure/
bilirubin
HCC
PEI/RFA Sorafenib
Stage 0
PST 0, Child–Pugh A
Very early stage (0)
1 HCC < 2 cm
Carcinoma in situ
Early stage (A)
1 HCC or 3 nodules
< 3 cm, PST 0
End stage (D)
Liver transplantation TACEResection Symptomatic
treatment (20%)
Survival < 3 months
Curative treatments (30%)
5-year survival (40–70%)
Palliative treatments (50%)
Median survival 11–20 months
Associated diseases
YesNo
3 nodules ≤ 3 cm
Increased
Normal
1 HCC
Stage D
PST > 2, Child–Pugh C
Intermediate stage (B)
Multinodular,
PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
Stage A–C
PST 0–2, Child–Pugh A–B
Adapted from Bruix J, Sherman M. Hepatology. 2010.
AASLD = American Association for the Study of Liver Diseases;
PEI = percutaneous ethanol injection; PST = Performance
Status test; RFA = radiofrequency ablation;
TACE = transarterial chemoembolization.
BCLC Staging System Treatment Strategy
(AASLD guidelines updated 2010)
46. Bhoori S, et al. Transplant International. 2010;23:712-22.
Proposals of Expansion of Conventional
Criteria in Liver Tx for HCC
Author (year), centre Expanded criteria
5-yr specific survival for
exceeding Milan criteria
Yao et al. (2001), San Francisco
1 HCC 6.5 cm or 3 HCC 4.5 cm with
cumulated diameter 8 cm
73%
Herrero et al. (2001), Pamplona 1 HCC 6 cm or 3 HCC 5 cm 73%
Onaca et al. (2007), Dallas 1 HCC 6 cm or 4 HCC 5 cm N/A
*Kwon (2007), Seoul
HCC 5 cm, no number restriction AFP
400 ng/mL
80% (including Milan)
*Jonas et al. (2007), Berlin
Any number, each 6 cm with cumulated
diameter 15 cm
62% at 3 years
*Takada et al. (2007), Kyoto
10 HCC, each 5 cm PIVKA-II < 400
mAU/mL
67%
*Soejima et al. (2007), Fukuoka Any number, each 5 cm 74%
*Sugawara et al. (2007), Tokyo 5 HCC 5cm 70% (at 3 years)
Zheng et al. (2008), Hangzhou
Total tumor diameter 8cm or HCC grade
I/II and AFP 400 ng/mL
72.3%
*Lee et al. (2008), Asan 6 HCC 5 cm 76.3%
Silva et al. (2008), Valencia
3 HCC 5 cm with cumulated diameter
10 cm
67%
Toso et al. (2008), Edmonton TTV 115 cm3 72%
Mazzaferro et al. (2009), Milan
Number of HCC nodules maximum
diameter (cm) 7
71% (if microvascular
invasion absent)
*LDLT = living donor liver transplantation.
AFP = alpha-fetoprotein; PIVKA-II = protein-induced by vitamin K
47. Contour plot of 5-yr survival according to size & number of tumors
Mazzaferro V, et al. Lancet Oncology. 2009;10:35-43.
Size of largest tumor in mm
*1,112 patients exceed Milan criteria.
Liver Transplantation: 5-yr survival in
an Exploratory Analysis of 1,556* HCC pts
Numberoftumors
48. Mazzaferro V, et al. Lancet Oncology. 2009;10:35-43.
Patients beyond Milan criteria &
exceeding “up-to-7”criteria have
a poor overall survival of < 50%
Liver Transplantation: Overall Survival in an
Exploratory Analysis of 1,556 HCC patients
• 444 patients within Milan criteria .
• 283 patients beyond Milan criteria and within “up-to-7” criteria.
• 829 patients beyond Milan criteria and exceeding “up-to-7” criteria
• More HCC pts could be candidates for transplant if precise survival estimation using
individual tumor characteristics and “up-to-7” criteria is employed
0.8
0.6
0.4
0.2
0.0
0 12 24 36 48 60 72
Months
Survival
probability
1.0
Exceeding “up-to-7” criteria (N = 829)
Beyond Milan – “up-to-7” criteria (N = 283)
Milano IN (N = 444)
73%
71%
48%
49. Are Neo-Adjuvant Locoregional Treatment
Indicated in pts listed for LT ?
• Bridge Therapy: No recommendation could
be made on bridging therapy in pts with
UNOS T1 HCC .
• A cost-effective analysis based on Markov
model & the review of cohort studies indicate
a benefit for bridging therapies if the
waiting time is expected to be > 6 months
to avoid TP.
50. Definitions of Down-staging before
transplantation
Toso C, et al. J Hepatology. 2010;52:930-6.
Neo-adjuvant
treatment
Down-staging
To decrease tumor progression
and hence dropout from the
waiting list
To improve long-term results To select pts with good
long-term outcomes among
poor risks pts.
(Response to ttt & observation time
used as a surrogate markers for
favorable biology)
To bring patient whose tumor
burden is outside accepted
criteria for Tx to within acceptable
criteria.
Before transplantation
51. Which is the best neo-adjuvant treatment in Pts
considered for LT?
Locoregional
therapy Indications Risks Benefits
RFA Small HCC (usually 3 cm),
away from the liver surface,
away from major vessels
HCC seeding (1–2%)
liver rupture (small)
• OK even in case of
decreased liver function
• Only one session usually
required
• Complete necrosis in
90% of cases
TACE Any HCC size preserved liver
function (Child–Pugh A-B)
uptake of contrast
Liver failure
arterial injury (2%)
• OK even for large HCCs
TARE Any HCC preserved liver
function (Child–Pugh A-B),
absence of intra-hepatic
shunt, uptake of contrast
Off-target embolization
arterial injury
• OK even for large HCCs
(up to 10 cm?)
• OK even in case of portal
vein thrombosis more
efficient than TACE (to be
confirmed)
• Shorter time to response
(to be confirmed)
Toso C, et al. J Hepatology. 2010;52:930-6.
52. Response to therapy is a potentially effective tool for prioritizing HCC patients for
liver transplantation
Vitale A, et al. Ann Surg Oncol. 2010;17:2290-302.
Siegel AB, et al. Hepatology. 2010;52:360-9.
Response to therapy as a criterion for awarding priority
to patients with HCC awaiting liver transplantation
Months post-liver transplantation
Intention-to-treat survival
1.0
0.8
0.6
0.4
0.2
0 12 24 36 48 60
Responder (n = 85)
Non-responder (n = 62)
p < 0.01
Months
Freedomfromrecurrence
53. Increased HCC recurrence & lower survival
are linked to Several Factors
Higher exposure to CNIs1
Portal vein thrombus3 Pretransplant
AFP levels1,3
Vascular invasion1
TNM staging3Tumor biology1,2
AFP, alpha fetoprotein; CNI, calcineurin inhibitor; HCC, hepatocellular carcinoma; TNM, tumor node metastasis.
1. Vivarelli M, et al. Ann Surg. 2008;248:857862; 2. Vakili K, et al. Liver Transpl. 2009;15:18611866;
3. Wang ZX, et al. Clin Transplant. 2010;24:752757. 53
54. 54
100
75
50
25
0
HCC Recurrence post transplantation is a key
unmet need in HCC pts
HCC, hepatocellular carcinoma; OLT, orthotopic liver transplant
1. Valdivieso A et al. Transplant Proc 2010;42:660-2; 2. Lee KK et al. J Surg Oncol. 2010;101:47-53
Cumulative post-transplant survival for patients with and without HCC recurrence1
SurvivalafterOLT(%)
0 1 2 5 10
No HCC recurrence (n=159)
HCC recurrence (n=23)
Years
p<0.001
3 4
HCC recurrence following transplantation ranges from 10–35%1,2
Pts with HCC recurrence have a poorer prognosis
55. Drinking coffee cuts liver cancer risk ??
Drinking three cups of coffee daily can reduce the risk of
developing liver cancer by more than 50 per cent, a new
study has claimed.
57. The incidence of acute transplant
rejection is declining. . .
0%
10%
20%
30%
40%
50%
60%
US Organ Procurement and Transplantation Network and Scientific Registry of Transplant Recipients Annual Reports 2003 &
2005, Available at: http://www.srtr.org/annual_Reports/default.aspx. Accessed March 2013.
Acuterejection[%]
Percentage of liver transplant patients who received antirejection
medication by 1-year posttransplant from 1992–2003
58. CNI minimization in liver transplant patients
…… but High level exposure to CNIs is a well-recognized risk
factor for chronic kidney disease in liver transplant recipients1
Attempts to withdraw CNI have
lead to increased risk of
acute rejection2,3
CNI minimization can help tip the
balance between adequate
immunosuppression and
exposure to CNIs2
CNI, calcineurin inhibitor.
1. Kong Y, et al. PLoS One. 2011;6:e24387; 2. De Simone P, et al. Am J Transplant. 2012;12:3008–3020;
3. Schlitt HJ, et al. Lancet. 2001;357:587591. 58
59. 59
Everolimus + low Tac demonstrated a Comparable Safety
profile with standard Tac
aThe incidence of clinically relevant proteinuria above 3 g/day in the everolimus + low Tac group was
comparable to that in the standard Tac group. Patients with proteinuria ≥0.5 g/24 hrs at one month post-
transplant had no progression to more severe proteinuria with everolimus + low Tac.
Incidence rates of selected adverse
events
Everolimus +
low Tac (n=245)
Standard Tac
(n=241)
Hyperlipidemia 23.7% 9.5%
Hypertension 17.1% 15.8%
New Onset DM 19.6% 16.6%
Proteinuriaa
17.6% 0.8%
Peripheral edema 2.9% 10.8%
Stomatitis, Mouth Ulceration 9.4% 1.2%
Tremor 9.4% 12.0%
Wound Healing Complications 11% 7.9%
Tac, Tac, tacrolimus
DeSimone P et al. Am J Transpl. 2012
60.
61.
62. Both Sirolimus (P≤ 0.05) & Anti-CD25 Antibody induction
(P≤ 0.01) demonstrated significantly improved survivals
after LTx for HCC.
63. HR (95% CI) to compare Risk of Mortality after LTx using diff. immunosuppress. protocols.
Results corrected for MELD, Tx year, Primary Liver Disease (non-HCC), Age at Tx
& when applicable: TTV, AFP & PreTx HCC ttt.
*Significant variables
64. Use of Everolimus as a Rescue
Immunosuppressive therapy in Liver
Transplant Patients with Neoplasms
Gomez-Camarero J et al, Transplantation 2007;84: 786–791
65. Father of Modern Transplantation
Thomas Starzl
First successful human liver
transplant in 1967 (Denver,
U.S.A.)
No sense of accomplishment
can exceed that of seeing a
robust LT recipient who, a
few weeks earlier, was
seemingly near death from
ESLD.
66. Summary
• Successful LTx requires optimal patient selection and timing of Tx.
• Indications across most centers are similar, however, a regional
difference exists with HCC & metabolic reasons being on the rise.
• To date, MELD score is the most accurate to predict early outcome
of LTx & to prioritize organ allocation including that for HCC
patients.
• Organ shortage is currently tackled by: ECD & Surgical innovation.
• Current unmet needs following LTx include: minimizing CNI toxicity,
CKD, HCV & HCC recurrence.
• Introduction of new immunosuppressant with less severe AEs and
equivalent anti-rejection efficacy are urgently needed with mTORi
emerging as a new player in this context.