1、Long-Term Management of the Successful Adult Liver Transplant (2012 Practice Guideline),感染内科科内业务学习陈洪涛2016-03-17,Background-中国肝移植现状,Background-中国肝移植现状,Background-中国肝移植现状,Background-中国肝移植现状,Background-中国肝移植现状,Background-中国肝移植现状,Background-中国肝移植现状,Background-中国肝移植现状,Background-中国肝移植现状,Survival 85%, 4ye
2、ars 75%, 5yearsRecurrence 8%, 4years,Background-中国肝移植现状,杭州标准,Background-美国肝移植现状,Background-美国肝移植现状,Characteristics of adult liver transplant recipients, 2002 & 2012,Background,Liver Transplantation (LT) as a Treatment for End-stage Liver Disease / Mortality After LT / Morbidity After LTComplications
3、 of Portal Hypertension After LTLiver Tests / Vascular ThrombosisImmunosuppressionLate RejectionPromoting Health After LTBone Health.,Contents,Systemic DiseaseNutrition and ObesityOncologyReproductive HealthInfectious DiseaseImmunizationsHepatitis（Viral, PBC/PSC, AIH, ALD, NASH/NAFLD ）,Contents,Reco
4、mmendations and Rationales Morbidity After LT,Clinical features of liver failure and portal hypertension resolve rapidly after LT. The exception is splenomegaly, which may persist for years Variceal hemorrhage is very unusual unless the patient has an occluded portal vein. The late emergence of hepa
5、tic encephalopathy suggests the development of clandestine cirrhosis or a persistent portosystemic shunt Late-onset ascites or peripheral edema may indicate stenosis of the inferior vena cava or portal vein anastomosis.,Recommendations and Rationales Complications of Portal Hypertension After LT,Rec
6、ommendations and Rationales LIVER TESTS,Recommendations and Rationales Vascular Thrombosis,Hepatic artery thrombosis (HAT) or stenosis may present clinically after 3 months, as : intrahepatic non-anastomotic strictures and/or sterile or infected fluid collections within the liver, sometimes referred
7、 to as bilomasischemic cholangiopathy or biliary cast syndrome.,Recommendations and Rationales Immunosuppression,the target levels after 3 months, whole blood trough levels Tacrolimus - 5 to 10 ng/mL Cyclosporine-100 to 150 ng/mL Sirolimus - 5 ng/ mL.,Recommendations and Rationales Late Rejection,Ce
8、llular rejection (also known as acute cellular rejection and late-onset rejection) Liver tests nonspecific abnormalities with a rise in serum bilirubin and aminotransferases Histologically, cellular rejection is characterized by the triad of inflammatory bile duct damage, subendothelial inflammation
9、 of the portal, central, or perivenular veins, and a predominantly lymphocytic portal inflammatory infiltrate with neu- trophils and eosinophils in addition Ductopenic rejection (also known as vanishing bile duct syndrome),Recommendations and Rationales Late Rejection,Cellular rejection-Risk factors
10、 Reduction of immunosuppression (whether iatro- genic or due to noncompliance). Pre-LT autoimmune liver disease. Concurrent administration of interferon (for HCV treatment). The differential diagnosis includes infection, recurrent and de novo autoimmune disease, and drug toxicity,Recommendations and
11、 Rationales Late Rejection,Cellular rejection-TreatmentMild : an increase in maintenance levels of immunosuppression Moderate or severe: a short course of increased immunosuppression (eg, methyl predni- sone at 500 mg/day or prednisolone at 200 mg/day for 3 days) followed by an increase in the basel
12、ine immunosuppression Only approximately half of patients, with approximately 25% developing a further episode of cellular rejection and 25% developing ductopenic rejection.,Recommendations and Rationales Late Rejection,Ductopenic rejection -Risk factors Recurrent and unresponsive cellular rejection
13、.Transplantation for autoimmune disease.Exposure to interferon Loss of a previous graft to ductopenic rejection. The differential diagnosis includes recurrent disease (PBC or PSC) and drug toxicity.,Recommendations and Rationales Late Rejection,Ductopenic rejection Treatmentncreased immunosuppressio
14、n, and an increase in or switch to tacrolimus may be effective in some early cases. when fewer than 50% of the portal tracts contain bile ducts, the condition progresses to graft failure.,Recommendations and RationalesPromoting Health After LT,Frequent handwashing reduces the risk of infection with
15、pathogens acquired by direct contact, including Clostridium difficile, community-acquired viral infections, and pathogens found in soil Shoes, socks, long-sleeve shirts, and long pants should be worn for activities that will involve soil exposure and tick exposure and also to avoid unnecessary sun e
16、xposure During periods of maximal immunosuppression, LT recipients should avoid crowds to minimize exposures to respiratory illnesses Work in high-risk areas, such as construction, animal care settings, gardening, landscaping, and farming, should be reviewed with the transplant team,Recommendations
17、and RationalesPromoting Health After LT,LT recipients should avoid the consumption of water from lakes and rivers LT recipients should avoid unpasteurized milk products and raw and undercooked eggs and meats LT recipients should avoid high-risk pets All LT recipients should be educated about the imp
18、ortance of sun avoidance and sun protection through the use of a sun block with a sun protection factor of at least 15 and protective clothing. They should be encouraged to examine their skin on a regular basis and report any suspicious or concerning lesions to their physicians the sustained cessati
19、on of smoking is the most important pre- ventative intervention,Recommendations and RationalesBone Health,Recommendations and RationalesBone Health,In the first 5 years after transplantation, screening by BMD should be done yearly for osteopenic patients and every 2 to 3 years for patients with norm
20、al BMD; thereafter, screen- ing depends on the progression of BMD and on risk factors If osteopenic bone disease is confirmed or if atraumatic fractures are present, then patients should be assessed for risk factors for bone loss; in particular, this should include an assessment of calcium intake an
21、d 25-hydroxy- vitamin D levels, an evaluation of gonadal and thyroid function, a full medication history, and thoracolumbar radiography The osteopenic LT recipient should perform regular weight-bearing exercise and receive calcium and vitamin D supplements,Recommendations and RationalesSystemic Dise
22、ase,Kidney Disease Urinary protein quantification using the concentration ratio of protein to creatinine in a spot urine specimen should be evaluated at least once yearly The reduction or withdrawal of CNI-associated immunosuppression is an appropriate response to the development of CKD in LT recipi
23、entsMetabolic Syndrome Metabolic Syndrome,Recommendations and RationalesSystemic Disease,Metabolic Syndrome The treatment of DM after LT should aim for an HBA1c target goal of 40 U of blood products),Choledocho-jejunostomy, reoperation, retransplantation,hepatic iron overload,renal replacement thera
24、pyextended intervals of intensive care,Recommendations and RationalesINFECTIOUS DISEASE Fungal Infections,Blood cultures are most helpful for the diagnosis of Candida bloodstream infections and Blastomyces Cryptococcal antigen testing of cerebrospinal fluid or blood is most helpful for the diagnosis
25、 of Cryptococcus Urinary histoplasmosis and Blastomyces antigens are useful for the diagnosis of disseminated histoplasmosis and blastomycosis, respectively,Recommendations and RationalesINFECTIOUS DISEASE Pneumocystis jirovecii,All LT recipients should receive prophylaxis against P. jirovecii with
26、trimethoprim-sulphame- thoxazole (single strength daily or double strength 3 times per week) for a minimum of 6 to 12 months after transplantation (grade 1, level A). Atovaquone and dapsone are the preferred alternatives for patients who are intolerant of tri- methoprim sulfamethoxazole,Recommendati
27、ons and RationalesINFECTIOUS DISEASE Tuberculosis,Because of the risk of a marked reduction in CNI and mTOR inhibitor levels with rifampin coadministration, the doses of CNIs will need to be increased 2- to 5-fold at the initiation of treatment.Rifabutin may be substituted for rifampin to reduce the
28、 impact on drug levels, or nonrifampin-containing regimens can be consid- ered, although the duration of treatment will need to be extended.,Recommendations and RationalesINFECTIOUS DISEASE HIV,HIV-infected LT recipients receiving HAART require frequent monitoring of CNI levels because of the signif
29、icant interaction between antiretrovirals and CNIs Standard prophylaxis for CMV is recommended for HIV-infected LT recipients receiving HAART, and lifelong Pneumocystis pneumonia prophy laxis is the norm,Recommendations and RationalesINFECTIOUS DISEASE,Recommendations and RationalesIMMUNIZATIONS,Rec
30、ommendations and RationalesIMMUNIZATIONS,All LT recipients should receive an annual influenza vaccination All LT recipients should avoid live virus vac- cines (grade 1, level A).Re-immunization is indicated for some vac- cines, notably the influenza vaccine (annually) and the pneumococcal vaccine (every 3-5 years; no class or level provided),THANKS!,
