Liver Transplantation for the Primary Care Provider. Atif Zaman MD MPH Oregon Health & Sciences University

Transcription

1 Liver Transplantation for the Primary Care Provider Atif Zaman MD MPH Oregon Health & Sciences University

2 Disclosures 1. The speaker/planner Atif Zaman, MD MPH have no relevant financial relationships to disclose. 2. The speaker/planner Lauren Myers, MMSc, PA-C have no relevant financial relationships to disclose

3 Objectives Why is LT done? How will it help my patient? Who should be referred for LT evaluation, and when? Medical considerations Psychosocial consideration What is the LT process? Referral Evaluation Transplant Post-transplant Expectations for PCPs of patients who need/get LT

4 Why is LT done? How will it help my patient? Increased survival! 5 year survival (overall) post-lt is about 80% 5 year survival for a patient with Child s Class C cirrhosis is < 20%

5 Decompensated cirrhosis is deadlier than many cancers D Amico J Hepatology 2006

6 Problems for which LT is not done Fatigue Sleeping problems Pain Elevated aminotransferases (ALT/AST)

7 LT is not as rosy as it might seem One year survival after LT (all-comers, US average) is about 90% This number has been improving over time, and 90% is considered good by those it the business It also means that there s a 10% chance an LT will kill the patient! If your chances of dying in one year are < 10%, you don t want an LT

8 How bad is cirrhosis? Will it kill me? D Amico J Hepatology 2006

9 Living with LT is better than dying but several downsides Life-long immune suppression Daily pills and frequent blood monitoring Complications of immune suppression Increased risk of cancer and rare (bad) infections Progressive renal dysfunction (and possibly failure) Cost Recurrence of original liver disease HCV infection 100% HBV infection 100% PBC/PSC 15-25% Alcohol?

10 Who should be considered for LT? Patients in whom the liver disease poses an imminent threat to life, and for whom LT could be expected to increase survival. Practically speaking: 1. Decompensated cirrhosis 2. Acute liver failure 3. Hepatocellular Carcinoma (HCC) confined to the liver

11 Reasons why patients got LT in the US in 2011 (SRTR db) Primary Cause of Disease Percentage of LT 2011 Decompensated cirrhosis 51% Acute Liver Failure 4% Liver cancer 21% Other 24%

12 MELD score MELD = Model for End-stage Liver Disease A patient s MELD score is calculated in a complex formula (available on internet, phone app) based on lab values INR Total Bilirubin Creatinine MELD range is 6 to 40 and reflects the severity of liver disease (and chance of dying)

13 MELD score and the LT list All US liver transplant centers waitlists are stratified by MELD scores Reflects a sickest first paradigm Assumes that the MELD score accurately predicts the patient s risk of dying due to liver disease

14 Reason to refer for LT consideration: Decompensated Cirrhosis This is the largest and most obvious group of patients that need LT consideration Typically have one or more symptoms/episodes Ascites Hepatic encephalopathy Variceal bleeding Fatigue

15 Reason to refer for LT consideration: Decompensated Cirrhosis This is the group for whom the MELD score makes the most sense Timing to refer the patient for LT consideration can best be achieved by paying attention to the MELD score Rule of thumb: when a patient s MELD reaches about 15, this is a good time to refer for LT evaluation MELD scores at the top of our list is are the mid-20s A MELD of 15 would put a patient about 40 th on our transplant list (so this is in plenty of time)

16 Patient with decompensated cirrhosis is sicker than MELD indicates The MELD score is not perfect! (It s ~ 85% predictive) If a patient seems very sick but the MELD score is not that high (say <15), this is a good time to run the case by a transplant hepatologist May simply need specialty help in treating complications May reflect a special consideration for LT despite low MELD May reflect non-liver disease that is causing clinical troubles LT not helpful if the liver is not the problem!

17 Reason to refer for LT consideration: Acute Liver Failure Rare (~2000 cases per year in the US) Deadly (very high mortality in absence of LT) Need specialty care immediately MELD score not used on LT list for this group

18 Acute Liver Failure (ALF) Coagulopathy (INR > 1.5) Encephalopathy No prior liver disease ( acute ) Noted abnormalities are due to the liver Liver function failing (coagulopathy + encephalopathy) Not elevated AST/ALT

19 Acute Liver Failure (ALF) Coagulopathy (INR > 1.5) Encephalopathy No prior liver disease ( acute ) Noted abnormalities are due to the liver Liver function failing (coagulopathy + encephalopathy) Not elevated AST/ALT Contact a transplant hepatologist immediately

20 Hepatocellular Carcinoma (HCC) Screening for HCC All patients with cirrhosis Selected patients with chronic HBV infection

21 Liver Transplantation for HCC Why transplant for HCC? 1. HCC is deadly (very) 2. HCC is usually (~90% of the time) non-resectable (not curable) 3. In selected patients, LT cures HCC (as well as the usuallycirrhotic liver)

22 Liver Transplantation for HCC Patients with HCC usually have cirrhosis, but often the cirrhosis is not advanced HCC patients often have low MELD scores If HCC patients were listed by their biological MELD score, they would be near the bottom of lists, and likely die from HCC progression before LT

23 Liver Transplantation for HCC Patients on the LT list who have HCC are thus given a MELD exception of 22 once they have been listed for 6 months MELD Increases if not transplanted within 3 months This allocation strategy is favoring patients with HCC over patients with decompensated cirrhosis May change, but who knows when?

24 Management of HCC Very complicated, really must have multi-disciplinary team (ideally one that includes LT as an option) PCP role: understand indications for screening for HCC, be diligent about screening Seek feedback from go-to Multi-D HCC group if HCC is detected on screening

25 Exceptions to MELD-based stratification on LT list The way it works: Any LT center can list any patient at any time Stratification on the list, however, is by MELD score (law) If a center wants a particular patient higher on the list than the patient s MELD indicates, an exception can be requested This request goes to other LT centers in the region for a vote, and if the vote is aye then the patient gets the requested MELD score

26 Typical successful requests for MELD exceptions HCC (most common by far) Primary Biliary Cirrhosis: itching Primary Sclerosing Cholangitis: recurrent cholangitis Hepatopulmonary Syndrome: pao 2 < 60 mmhg

27 Summary: medical reasons to request LT evaluation Decompensated cirrhosis, MELD > 15 Acute liver failure HCC

28 Other parts of the LT package: what you patient does and doesn t need Overall medical condition (outside of the liver) Substance abuse issues Social support and compliance Financial capability

29 Medical condition outside the liver In general, as the number of medical co-morbidities increase, the chances of having a successful outcome peri/post-lt decrease Really big problems: Significant cardiac or pulmonary disease Diabetes mellitus Renal failure

30 Nutrition and state of conditioning Patients with poor nutrition and physically debilitated do poorly after LT

31 Substance abuse and LT Huge problem In general, LT programs do not transplant patients with active or recently active substance abuse problems

32 Typical requirement for LT listing around the country 6 months abstinence from alcohol and drugs

33 Portland VA and OHSU requirements (also fairly typical) If patient has a drug/alcohol problem: Six months abstinence minimum Successful completion of substance abuse rehabilitation program Ongoing recovery support No tobacco use at all If using, cessation followed by 4 consecutive weekly neg screens

34 LT psychosocial considerations LT programs want to determine whether the patient and his/her environment will support LT All comes down to ability to comply with post-lt regimen Without this compliance, allografts (and patients) don t make it!

35 What psychosocial considerations affect pre- and post-lt compliance? Drug and alcohol problems Significant psychiatric disease Including personality disorders Inadequate social support Inadequate financial resources/stability

36 What psychosocial considerations affect pre- and post-lt compliance? Drug and alcohol problems Significant psychiatric disease Including personality disorders Inadequate social support Inadequate financial resources/stability Psychosocial difficulties are the main reasons why patients are denied listing for LT

37 The process: LT referral Can be initiated by PCP or specialist Goes through initial medical and administrative review If no red flags, evaluation is scheduled and prioritized depending on medical urgency

38 The process: LT referral Can be initiated by PCP or specialist Goes through initial medical and administrative review If no red flags, evaluation is scheduled and prioritized depending on medical urgency This does not mean the patient is on the list!

39 The process: LT evaluation Usually takes several days to a week (if outpatient) The patient typically sees Transplant surgeon Transplant hepatologist Social worker Psychologist/psychiatrist Dietician Transplant coordinator nurse May see a chaplain May see an addictions specialist

40 The process: LT evaluation Medical work-up includes Blood work (lots of it) Assessment for CAD (some kind of stress test) Assessment of pulmonary function (PFTs, ABG) Contrast scan of the abdomen Looking for HCC as well as assessment of hepatic vasculature Other things that may have been identified during the referral Consult with ID (if positive PPD or other reason) Consult with Cardiology (if prior heard problem identified)

41 LT evaluation: inpatient or outpatient? Inpatient is for patients who are hospitalized, very ill and not expected to leave the hospital without LT Inpatient evaluations are difficult on everyone (especially the patient) and should be avoided if possible Chances of getting listed are lower Evaluation may reveal some aspect that needs work before listing, and there may not be sufficient time in the hospitalized patient

42 The process: LT evaluation After evaluation meetings and testing, the patient is presented at a weekly Transplant Selection Conference Three outcomes from Transplant Selection Conference 1. Accept (the patient will be put on the list) 2. Decline (the patient will not be put on the list) 3. Defer (the patient will be put on the list after doing X,Y &Z)

43 Details for deferment Easy things to do Get a vaccination Get a neurology (derm, renal, etc) consult Get a colonoscopy See the dentist Hard things to do Successfully complete a drug/alcohol rehab, develop ongoing recovery support Get an adequate social support person (or backup) Get adequate insurance Stop smoking

44 Details often needing completing before listing not done at LT center EGD and colonoscopy (if not already done) Vaccinations PPD Dental clearance Drug/alcohol rehab (can be done through VA)

45 Details often needing completing before listing not done at LT center EGD and colonoscopy (if not already done) Vaccinations PPD Dental clearance Drug/alcohol rehab (can be done through VA) Usually the job of the referring physician to assist the patient in such requirements

46 The process: patient listed for LT Patient is on the LT list corresponding to blood type Thus, 4 lists (O, A, B, AB) Stratified according to MELD score Either biological or exception (HCC or other) Where am I on the list? A frequent question by patients and providers, and very difficult to answer (because list changes daily due to new patients and changing illness severity of listed patients) 1. At the top 2. In the top five 3. In the top half 4. In the bottom half

47 The process: patient listed for LT Patient must have MELD re-verified periodically Labs every 3 months minimum Cardiac status must be re-verified periodically Echo, maybe stress test yearly if near top of list Patient must be seen by team (hepatologist) periodically Frequency depends on illness of patient Patient must have imaging periodically Usually every 6 months, US/CT/MRI or some alternating combo

48 The process: transplant The Organ Procurement Organization (OPO) calls the transplant surgeon: We have a liver for Mr. X Prior to this call, the donor patient has been determined to be brain dead or no chance of survival Donor consent (often through family) obtained Risk factors for prior liver disease assessed Blood testing for liver function done Testing for HIV, Hepatitis B and C done

49 The process: transplant Surgeon, hepatologist, or nurse coordinator calls patient Are you okay? No new complications that might preclude transplant Do you want this liver? Risk factors for the donor liver discussed briefly Any physical obstacles to coming to LT center immediately?

50 The process: transplant After agreement that the patient wants the liver, s/he starts for the hospital immediately Transplant team goes to hospital to harvest donor organ Patient admitted to the hospital Brief clinical assessment, labs, sometimes a scan Donor organ arrives at hospital, patient taken to OR, liver transplant done 4 to 12 hours

51 Post-LT to hospital discharge Takes usually 1-2 weeks in the hospital Infrequently serious complications arise, and patients can be hospitalized for months, or die in this period After hospital discharge, patients are seen 1-2 times weekly in the transplant clinic Cannot leave the city Seeing transplant surgeons in the clinic After 1-2 months, can leave city At 3 months, switched from seeing surgeons back to the hepatologists (indefinitely)

52 Post-LT three to six months Still on prophylactic medications due to the profound immune suppression PCP prophylaxis for 6 months (Septra, Bactrim, Pentamidine) CMV prophylaxis (Valgancyclovir) Fungal prophylaxis (Fluconazole) Immune suppression Usually off prophylactic medications by 6 months, and on stable immune suppression

53 Post-LT: immune suppression Backbone Tacrolimus Cyclosporin Sirolimus Anti-metabolite Azathioprine Mycophenolate Corticosteroids Prednisone

54 Expectations for the PCP: pre-lt Recognize when the patient needs to be evaluated for LT Work with LT center on items to complete so that the patient can be listed for LT Help the LT center to get tests as the need arises in order to keep the patient on the list Consult the LT center when something (medically or psychosocially) changes in the patient s status

55 Expectations for the PCP: post-lt Facilitate recurring labs for the post-lt patient Always emphasize that labs should be drawn an hour or less prior to when the patient takes his/her immunosuppressives! Help the patient with routine medical problems that may be brought on/exacerbated by LT Diabetes mellitus (very common) HTN Osteoporosis Yearly skin exams