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LIVER transplantation Present SCENARIO in India… Dr. PARVIDER S. LUBANA MS; D.N.B. FAMAS; FICS (USA) Fellow Liver Transplant Surgery Memorial Sloan Ketterin Cancer Center Newyork Fellow Liver surgery Singapore General Hospital, SINGAPORE. Consultant & Asst. Professor Hepato-Pan-Biliary & Colo-Rectal Services M.G.M. Medical College & M.Y.Hospital
ANATOMY…… Eight segments, based on arterial and portal venous inflow. Segment 1 -caudate lobe. Independent lobe. Segments 2-4 segments of the left lobe Segments 5-8 are segments of the right lobe
Structures in the Hilum of the Liver: HDL : Common Bile duct, Hepatic artery, portal vein.
Functions of the liver… Detoxification Storage of iron, Production of chemicals vitamins, of bile minerals ManufactureStorage of energy Production of proteins and blood clotting factors
Physiology of liver … Maintaining core body temprature ph balance and corection of lactic acidosis Synthesis of clotting factors. Glucose metabolism, glycolysis and gluconeogenesis. Urea formation from protien catabolism. Bilirubin formation from Hb degradaion Drug and hormone metabolism Removal of gut endotoxins and foreign antigen
HOWEVER……IF…. The functioning of the liver is inadequate to meet the requirements of the body liver failure
CAUSES OF LIVER FAILURE…oo 1. Inflammation of the liver over a prolonged time period.o 2. Chronic alcohol intake, eventually leading to cirrhosis and liver failure.o 3. Autoimmune disorder -primary biliary cirrhosis.o 4. Biliary atresia Structural abnormality with absence or a closure of the bile duct opening.o 6. Congenital disorders of copper metabolism, leading to excess deposition of copper. (Wilsons disease, Menkes disease).o 7. Liver (HCC) & Bile D cancer (CC).
LIVER TRANSPLANTATION“The only option for people whose liver can no longer function”
In the last 40 years, Liver transplantationhas evolved from an experimental procedureconfined to laboratory to a clinicallytherapeutic intervention that is appliedworld wide to virtually all form of end stageliver disease.• In 2010 alone 9040 Liver Transplants weredone in 157 Transplant centers world wide.• In India the rate is 120-125 Transplants ayear at various centers.
Since early times, the idea of tissue andorgan Transplantation has captured theimagination of the successive generation andover the centuries numerous fancifuldescriptions of successful transplants havebeen recorded.One of most widely cited early example isthat of Christian Arab Saints Cosmos andDamian performing a miraculoustransplantation of the leg.
MILESTONES IN ORGAN TRANSPLANTATION…..1954 Joe Murray performed successful kidney Transplant between identical twins.1962 Roy Calne demonstrated the efficacy of azathioprine in preventing rejection of Kidney allografts.1963 Tom Starzl performed the first human liver transplant.1966 Lilehei & Kelly-Human Pancreas Transplant.1967 Sir Christiaan Bernard performed first human heart Transplant(Cape Town S.A.).1968 Fritz Derom performed first successful human lung Transplant(Ghent Belgium).
1978 - Roy Calne introduced cyclosporin into clinical practice.1981- Bruce Reitz & Normann Shumway performed first successful Heart-Lung Transplant (Stanford U.S.A. )1987- Fokert Belzer developed university of wisconsin ( UW) Solution – a new Liver & Pancreas preservation solution.1989- Tom Starzl demonstrated clinical efficacy of FK506 (Tacrolimus).
Chronic Liver Disease is 10th leading cause of death in India.. 25000 deaths annually. (3rd National Health & Nutrition examination Survey) ALD is the most common indication for LTx in India. (67%) World wide HCV is most common indication for LTx(40%)
INDICATIONS FOR LTx:Fulminant Hepatic Failure :o Alcoholic Liver Diseaseo Chronic Hepatitis C & Hepatitis B infection.o Non-alcoholic steatohepatitiso Autoimmune Hepatitiso Primary Biliary Cirrhosiso Primary Sclerosing Cholangitiso Hepatic tumorso Metabolic and genetic disorders
Ideal Candidate FOR LIVER TRANSPLANTATION …o Presence of irreversible liver disease and a life expectancy of less than 12 months with no effective medical or surgical alternatives to transplantation.o Chronic liver disease that has progressed to the point of significant interference with the patients ability to work or with his quality of life.o Progression of liver ds that will predictably results in mortality exceeding that of transplantation.
CROSS SECTION OF A NORMAL LIVER. The Holes Are Bile Ducts.
“FATTY LIVER” –ALCOHOLIC LIVER DISEASE.NOTICE THE YELLOW COLOUR AND SWOLLENAPPEARANCE
LIVER WITH CIRRHOSIS DUE TO ALCOHOLCONSUMPTION . NOTICE THE SMALL NODULES.
CONTRAINDICATIONS TO LTXo Presence of a malignancy in any other part of the body.o Presence of an active infection.o Presence of advanced cancer of the liver.o Presence of severe heart, lung or kidney disease.o Presence of advanced HIV disease.
DEFINITIONS OF COMMON TERMS ALLOGRAFT – an Organ or Tissue Transplanted from one individual to another. SYNGENEIC GRAFT (Isograft) - a Transplant between two identical twins. ORTHOTOPIC GRAFT - a graft placed in its normal anatomical position . HETEROTOPIC GRAFT - a graft placed in a site different from that where the organ is normally located. XENOGRAFT - a graft performed between different species.
Where does a Liver for a transplant come from ? There are two types of LTX options: Living donor transplantation This involves removing a segment of liver from a healthy living donor & implanting it into a recipient. Both the donor and recipient liver segment will grow to normal size in a few weeks. Cadaveric transplantation The ideal donor is a Young, previously healthy, Brain dead, Heart beating victim of an Road traffic accident.
LIVER TRANSPLANTATION- DONORS Live related donors: The patient’s blood relative. Rate of success is better if the liver is obtained from a first degree relative (father, mother, brother or sister) Living unrelated donors: This can be done only after an approval by the hospital appointed committee members. Cadaveric (deceased) donors: Usually seen following a road traffic accident or an irreversible injury to the brain. In these individuals, a part of the brain known as the brain stem fails to function and the patient is brain dead.
RECIPIENT PROCEDURES Most difficult part of LTX. Hepatectomy with removal of corresponding abd. Aorta & IVC. During ANHEPATIC PHASE venovenous bypass is used to return blood from IVC & portal vein to SVC. Donor liver size can be reduced or split grafts can be made.
PRE Opr. INVESTIGATIONS….o Computed tomography.o Ultrasound to determine blood flow to the liver.o Echocardiogram to evaluate cardiac function.o Pulmonary function studies (PFT) to determine the functioning of the lungs.o Blood tests. (LFT, coagulation profile)o Test for HIV and hepatitis
PRE OPERATIVE VOLUMETRIC DETERMINATIONOF LIVER Helical CT Used to directly measure liver volumes Formula for association with BSATOTAL LIVER VOLUME = 706.2 X BSA (in m2) + 2.4
SELECTION CRITERIA FOR ORGAN ALLOCATION…o United Network for Organ Sharing (UNOS) governing body for organ allocation utilizes MELD score.o Model for End Stage Liver Disease (MELD) Score 0.957 x loge (creatinine) + 0.378 x loge (bilirubin mg/dL) + 1.12 x loge (INR) + 0.643 x 10 [Range from 10 to 40]
PROCEDURE…. In liver transplant surgery the diseased liver is removed through an incision made in the upper abdomen. The new liver is put in place and attached to the patients blood vessels and bile ducts.
Normalanatomicallocation Right upper quadrant of theof the abdomenLiver…
No… Not the Entire Liver-just a portion of the normal live donor Liver is required . ( Liver has an amazing regenerative capacity) * Prometheus A fit patient with a healthy Liver will regenerate a 75 % resection within three months. Diseased Healthy Liver Liver Of Segment the From receipient donor
POST OPERATIVE COMPLICATIONS… Right pleural effusion Hepatic edema secondary to aggressive resuscitation & increased intravascular volume. o Electrolyte Derangements o Thrombocytopenia o Biliary leak o Hepatic artery thrombosis o Allograft rejection
OUTCOMELTx improves the quality and duration of life in most recipients. Overall LTX outcome has improved progressively over the last two decades. Improved outcome after LTX is due to better immunosuppression, organ preservation, chemoprophylaxis ,technical advances & wonderful Pre-Postoperative care of the patient. Graft survival after LTX is around 85% at 1 year and 70% at 5 years.
Overall the future of LTX remainspromising.The potential future obstacles in India includes: Organ shortage Expanding recipient pool Financial constraints Religious myths. Rigid govt. policies* *Chinese model
TYPES OF GRAFT REJECTIONHYPERACUTE: Immediate graft destruction due to pre formed anti HLA/ABO anti bodies. Characterized by intravascular thrombosis. Very rare in LTX.
ACUTE /CELLULAR REJECTION Occurs during first 6 mths, mediated by T cell dependent immune response. Reversible in majority by increasing immunosuppression. Characterized by mononuclear cell infiltration. Enlarged tender liver, pyrexia, deranged LFTs.
CHRONIC ALLOGRAFT REJECTION .. Occurs after first 6 months. Most common cause of graft failure. Non immune factors may contribute to pathogenesis. Myointimal proliferation of hep. arteries-bile duct destruction. Inflammation is usually absent. Retransplantation is the only treatment.
HLA ANTIGENS Are the most common cause of graft rejection Their physiological function is as antigen recognition units. Are highly polymorphic (amino acids sequence differs between individuals). HLA – A , - B (class 1) & - DR (class 2) are most important in organ transplantation. Anti – HLA antibodies may cause hyperacute rejection.
IMMUNOSUPPRESSIVE THERAPYMost immunosuppressive protocol use a combination of immunosuppressive drugs.Individual drugs can be classified according to their principle mode of action in preventing the T – cell dependent rejection response.Azathioprine, Cyclosporin, Tacrolimus(FK506), Rapamycin, OKT3 & Anti – CD25 are commonly used combination.
• Watch those drugs ! • All drugs are chemicals, and when you mix them up without a doctors advice you could create something poisonous that could damage me badly. I scar easily.. and those scars, called "cirrhosis" are permanent. Medicine is sometimes necessary. But taking pills when they arent necessary is a bad habit. All those chemicals can really hurt a liver.
• Dont eat too much fatty food… I make the cholesterol your body needs, and I try to make the right amount. Give me a break…. Eat a good, well balanced nourishing diet. If you eat the right stuff for me, Ill really do my stuff for you!
• Dont drown me in beer, alcohol or wine! Even one drink is too much for some people and could scar me for life.
• Be careful with aerosol sprays! • Remember, I have to detoxify what you breathe in, too. So when you are cleaning with aerosol cleaners, make sure the room is ventilated, or wear a mask.• That goes double for bug sprays, mildew sprays, paint sprays and all those other chemical sprays you use.• Be careful what you breathe!
WARNING: I cant and wont tell you Im in trouble untilIm almost at the end of my rope... and yours.Remember: I am a non-complainer. Overloading me with drugs, alcohol and other junk can destroy me! This may be the only warning you will ever get. Your….. Liver