肝移植術(shù)后管理課件

1、Long-Term Management of the Successful Adult Liver Transplant (2012 Practice Guideline),感染內(nèi)科科內(nèi)業(yè)務(wù)學(xué)習(xí)陳洪濤2016-03-17,,Background------中國(guó)肝移植現(xiàn)狀,,Background------中國(guó)肝移植現(xiàn)狀,,Background------中國(guó)肝移植現(xiàn)狀,,Background------中國(guó)肝移植現(xiàn)狀,

2、,Background------中國(guó)肝移植現(xiàn)狀,,Background------中國(guó)肝移植現(xiàn)狀,,Background------中國(guó)肝移植現(xiàn)狀,,Background------中國(guó)肝移植現(xiàn)狀,,Background------中國(guó)肝移植現(xiàn)狀,Survival >85%, 4years >75%, 5yearsRecurrence 8%, 4ye

3、ars,,Background------中國(guó)肝移植現(xiàn)狀,杭州標(biāo)準(zhǔn),,Background------美國(guó)肝移植現(xiàn)狀,,Background------美國(guó)肝移植現(xiàn)狀,Characteristics of adult liver transplant recipients, 2002 & 2012,,Background,Liver Transplantation (LT) as a Treatment for End-

4、stage Liver Disease / Mortality After LT / Morbidity After LTComplications of Portal Hypertension After LTLiver Tests / Vascular ThrombosisImmunosuppressionLate RejectionPromoting Health After LTBone Health.,,Conte

5、nts,Systemic DiseaseNutrition and ObesityOncologyReproductive HealthInfectious DiseaseImmunizationsHepatitis（Viral, PBC/PSC, AIH, ALD, NASH/NAFLD ）,,Contents,,Recommendations and Rationales Morbidity After LT,Cli

6、nical 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

7、 vein. The late emergence of hepatic encephalopathy suggests the development of clandestine cirrhosis or a persistent portosystemic shunt Late-onset ascites or peripheral edema may indicate stenosis of the inferior ve

8、na cava or portal vein anastomosis.,,Recommendations and Rationales Complications of Portal Hypertension After LT,,Recommendations and Rationales LIVER TESTS,,Recommendations and Rationales Vascular Thrombosis,Hepa

9、tic 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 to as bilomas

10、ischemic 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 1

11、50 ng/mL Sirolimus --- 5 ng/ mL.,,Recommendations and Rationales Late Rejection,Cellular rejection (also known as acute cellular rejection and late-onset rejection) Liver tests nonspecific abnormalities with a

12、rise in serum bilirubin and aminotransferases Histologically, cellular rejection is characterized by the triad of inflammatory bile duct damage, subendothelial inflammation of the portal, central, or perivenular veins,

13、 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 Rej

14、ection,Cellular rejection--Risk factors Reduction of immunosuppression (whether iatro- genic or due to noncompliance). Pre-LT autoimmune liver disease. Concurrent administration of interferon (for HCV treatment). T

15、he differential diagnosis includes infection, recurrent and de novo autoimmune disease, and drug toxicity,,Recommendations and Rationales Late Rejection,Cellular rejection--TreatmentMild : an increase in maintenance

16、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 baseline imm

17、unosuppression 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,Duc

18、topenic rejection --Risk factors Recurrent and unresponsive cellular rejection.Transplantation for autoimmune disease.Exposure to interferon Loss of a previous graft to ductopenic rejection. The differential diagno

19、sis includes recurrent disease (PBC or PSC) and drug toxicity.,,Recommendations and Rationales Late Rejection,Ductopenic rejection –Treatmentncreased immunosuppression, and an increase in or switch to tacrolimus may b

20、e 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 re

21、duces the risk of infection with 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 s

22、hould be worn for activities that will involve soil exposure and tick exposure and also to avoid unnecessary sun exposure During periods of maximal immunosuppression, LT recipients should avoid crowds to minimize exposu

23、res 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 and RationalesPromotin

24、g 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-

25、risk pets All LT recipients should be educated about the importance 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

26、encouraged to examine their skin on a regular basis and report any suspicious or concerning lesions to their physicians the sustained cessation of smoking is the most important pre- ventative intervention,,Recommendatio

27、ns 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 wi

28、th normal 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 fact

29、ors for bone loss; in particular, this should include an assessment of calcium intake and 25-hydroxy- vitamin D levels, an evaluation of gonadal and thyroid function, a full medication history, and thoracolumbar radiogra

30、phy The osteopenic LT recipient should perform regular weight-bearing exercise and receive calcium and vitamin D supplements,,Recommendations and RationalesSystemic Disease,Kidney Disease Urinary protein quantificati

31、on 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 t

32、he development of CKD in LT recipientsMetabolic Syndrome Metabolic Syndrome,,Recommendations and RationalesSystemic Disease,Metabolic Syndrome The treatment of DM after LT should aim for an HBA1c target goal of <

33、;7.0% with a combination of lifestyle modifications and pharmacological agents as appropriateMetformin or sulfonylureas may be used in LT recipients with normal renal function, whereas sulfonylureas such as glipizide an

34、d glimepiride are preferable if there is any deterioration of renal function Consideration can be given to the conversion of immunosuppression from tacrolimus to cyclosporine in LT recipients with poor glycemic control

35、,,Recommendations and RationalesSystemic Disease,Hypertension The treatment of hypertension should aim for a target goal of 130/80 mm Hg with a combination of lifestyle modifications and pharmacologi- cal agents as app

36、ropriate amlodipine and nifedipine may be more effective in LT recipients because they counteract the vasoconstrictive effect of CNIs non-dihydropyridine calcium channel blockers (verapamil and diltiazem) should be use

37、d with caution because they may increase the bioavailability of CNIs significantly Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and direct renin inhibitors should be used as first-line antihy

38、pertensive therapy in LT recipients with DM, CKD, and/or significant proteinuria,,Recommendations and RationalesSystemic Disease,Hyperlipidemia,,Recommendations and RationalesONCOLOGY,,,Recommendations and RationalesO

39、NCOLOGY All LT recipients should see a dermatologist after transplantation to assess cutaneous lesions, with at least an annual evaluation by a derma- tologist 5 years or more after transplantation Patients with PSC an

40、d inflammatory bowel disease or other established risk factors for colorectal cancer should undergo an annual screening colonoscopy with biopsies. Colectomy, including continence-preserving pouch operations, should be co

41、nsidered when colonic biopsy reveals dysplasia,,Recommendations and RationalesONCOLOGY For patients without prior HCC who develop recurrent cirrhosis of the allograft, surveillance for de novo HCC should be undertaken

42、with abdominal imaging every 6 to 12 months An immunosuppressant regimen that includes sirolimus (started several weeks after trans- plantation) should be considered for patients undergoing transplantation for HCC Rese

43、ction or ablation is usually the treatment of choice for a solitary extrahepatic metastasis or an intrahepatic recurrence of HCC,,Recommendations and RationalesREPRODUCTIVE HEALTH the female LT recipients postpone conc

44、eption until At least 1 year after LT. Allograft function is stable. Medical comorbidities such as diabetes and hypertension are well controlled. Immunosuppression is at a low level.,,Recommendations and RationalesR

45、EPRODUCTIVE HEALTH,The ideal immunosuppression for pregnancy is tacrolimus monotherapy, which should be maintained at therapeutic levels throughout pregnancy; cyclosporine, azathioprine, and prednisone may also be used i

46、f they are necessary Allograft function and CNI serum levels are monitored every 4 weeks until 32 weeks, then every 2 weeks, and then weekly until delivery,,Recommendations and RationalesINFECTIOUS DISEASE,,,Recommend

47、ations and RationalesINFECTIOUS DISEASE CMV,The treatment of LT recipients with CMV should be maintained until viremia and all symptoms have resolved Prophylaxis against CMV should be resumed whenever LT recipients re

48、ceive anti-lymphocyte therapy for the treatment of rejection and should be continued for 1 to 3 months after the treatment of rejection Resistant virus should be suspected in patients with a history of prolonged gancicl

49、ovir or valgan ciclovir exposure who have a persistent or progressive infection despite treatment with high- dose intravenous ganciclovir In such instances, genotypic assays should be performed, and consideration should

50、 be given to the initiation of foscarnet with or in substitution for ganciclovir,,Recommendations and RationalesINFECTIOUS DISEASE EBV/PTLD,PTLD should be considered in LT recipients (especially high-risk individuals)

51、who present with unexplained fever, lymphadenopathy, or cytopenias Although EBV may be associated with the de- velopment of PTLD, the detection of EBV viremia is not diagnostic for PTLD; a histopathological diagnosis is

52、 required,,Recommendations and RationalesINFECTIOUS DISEASE Fungal Infections,Risk factors pre- operative fungal colonization,massive transfusion requirements (>40 U of blood products),Choledocho-jejunostomy, re

53、operation, retransplantation,hepatic iron overload,renal replacement therapyextended intervals of intensive care,,Recommendations and RationalesINFECTIOUS DISEASE Fungal Infections,Blood cultures are most helpful fo

54、r the diagnosis of Candida bloodstream infections and Blastomyces Cryptococcal antigen testing of cerebrospinal fluid or blood is most helpful for the diagnosis of Cryptococcus Urinary histoplasmosis and Blastomyces an

55、tigens are useful for the diagnosis of disseminated histoplasmosis and blastomycosis, respectively,,Recommendations and RationalesINFECTIOUS DISEASE Pneumocystis jirovecii,All LT recipients should receive prophylaxis

56、against P. jirovecii with 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

57、the preferred alternatives for patients who are intolerant of tri- methoprim sulfamethoxazole,,Recommendations and RationalesINFECTIOUS DISEASE Tuberculosis,Because of the risk of a marked reduction in CNI and mTOR in

58、hibitor 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 impact on drug levels, or no

59、n–rifampin-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

60、 frequent monitoring of CNI levels because of the significant interaction between antiretrovirals and CNIs Standard prophylaxis for CMV is recommended for HIV-infected LT recipients receiving HAART, and lifelong Pneumoc

61、ystis pneumonia prophy laxis is the norm,,Recommendations and RationalesINFECTIOUS DISEASE,,,Recommendations and RationalesIMMUNIZATIONS,,,Recommendations and RationalesIMMUNIZATIONS,,All LT recipients should receive

62、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 va