1 / 43

Fibrosis After Liver Transplantation

Fibrosis After Liver Transplantation. Amany A.Maqsod Sholkamy Professor of Internal Medicine &Hepatology Faculty of Medicine Cairo University Consultant Liver Transplantation Kasr AlAiny H Supervisor of the Liver ICU French H Cairo University.

gus
Download Presentation

Fibrosis After Liver Transplantation

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Fibrosis After Liver Transplantation Amany A.MaqsodSholkamy Professor of Internal Medicine &Hepatology Faculty of Medicine Cairo University Consultant Liver Transplantation Kasr AlAiny H Supervisor of the Liver ICU French H Cairo University

  2. NAFLD and HCV are the most common indications of liver transplantation worldwide. Amany A.Maqsoud APASL 2014

  3. Post transplant HCV related fibrosis Amany A.Maqsoud APASL 2014

  4. The problem: • Recurrence of HCV in the graft occur immediately after its implantation. • Studies showed that approximately 10–30% of HCV patients develop cirrhosis within 5y post transplant. • The majority of HCV patients develop graft cirrhosis by 9–12 years post transplant. Amany A.Maqsoud APASL 2014

  5. Risk factors: • Metabolic syndrome • Type of immunosuppressive drugs • High viral load • Advanced donor age • Prolonged warm ischemia time Modifiable factors such as donor age metabolic syndrome…. etc should be avoided whenever possible. Amany A.Maqsoud APASL 2014

  6. When to treat….? Amany A.Maqsoud APASL 2014

  7. When to start ttt ? • Pre-emptive treatment is not recommended because of the side effects of antiviral drugs and drug-drug interactions with the immunosupressives. • So, ttt should be for selected patients. Those showing fibrosis progression, choestasis or significant necroinflammation. Specially in the first post Tx year. Amany A.Maqsoud APASL 2014

  8. To biopsy or not? …That is the question! • The issue is when to biopsy and what to interpret as an indication to start ttt before loosing the graft. • Scheduled annual, every 2y, or on demandbiopsyprotocols ??. The rate of progression. • The ideal surveillance interval is not known. • Complexities of biopsy interpretation is a major issue of concern. And hence the looking for another “non invasive” tool. Amany A.Maqsoud APASL 2014

  9. Non invasive tools/lab.: • Traditional indirect markers: platelets, albumin, GGT, and liver enzymes. • Combinations of serologies and markers of extracellular matrix turnover. • However, all showed variable accuracy in determining the stage of disease or predicting progression. None of these are routinely used. Amany A.Maqsoud APASL 2014

  10. Non invasive tools/elastography: • US and MRI elstography have been studied in the post transplant (HCV/NASH) settings for assessment of fibrosis progression and deciding ttt. • Many post transplant graft copathologies (inflammation, steatosis, B obstruction) can interfere with their accuracy. Amany A.Maqsoud APASL 2014

  11. What findings indicate ttt ? • Clinically, the occurrence of signs of portal hypertension in the subsequent postTx year is a grave sign indicating significant graft fibrosis demanding urgent ttt. • However, this may occur so far after fibrosis/cirrhosis are advanced. • Earlier interference is shown to be better by many researches. Amany A.Maqsoud APASL 2014

  12. What findings indicate ttt: • Treatment is currently recommended only for patients with histologically significant recurrence, who are generally defined as individuals with: • At least grade 2 of 4 necroinflammation. • Stage F0-1 or 1-2/4 fibrosis. ??? • The cholestatic variant of HCV. Amany A.Maqsoud APASL 2014

  13. To my opinion, … • The presence of one or more of the risk factors, the alteration of graft functions, the cumulative dose of steroids used and biopsy results each should have a certain weight in decision to start ttt. • Elstography may come as a complementary step in follow up of borderline histologic findings. Amany A.Maqsoud APASL 2014

  14. Post transplant NAFLD associated fibrosis Amany A.Maqsoud APASL 2014

  15. Post liver transplantation NAFLD may be a recurrence of the pretransplant NAFLD or may occur de novo, even after Tx of other organs. • Post Tx NAFLD imposes no effect on allover mortality or graft related deaths. • Cirrhosis estimated to be 5% 5y after Tx. Amany A.Maqsoud APASL 2014

  16. Risk factors for development: • Metabolic syndrome “the coming pandemic”. • Type and dose of immunosupressives • Donor steatosis. • The steatogenic, and cytotoxic effect of HCV. Amany A.Maqsoud APASL 2014

  17. AASLD 2009 reported: • The prevalence of postTx metabolic syndrome (PTMS) and its individual components has been found to be higher post-LT versus a comparable population without LT. • The development of NAFLD after liver transplantation for non-NAFLD cirrhosis is also being increasingly recognized. Amany A.Maqsoud APASL 2014

  18. Risk factors in PTMS: Amany A.Maqsoud APASL 2014

  19. Metabolic effects of common immunosupressives Amany A.Maqsoud APASL 2014

  20. Donor’s steatosis: • One of the adverse impacts of the world epidemic of obesity/MS is the limited availability of suitable donors. • Studies showed that steatosis of 30% (15% in LDLT) are not accepted and carries the danger of early graft loss. ??? fibrosis • Again, studies showed that biopsy is the gold standard in assessing donor’s steatosis. Amany A.Maqsoud APASL 2014

  21. Diagnosis: • Clinically; the presence of one or more of the risk factors should raise a high index of suspicion. • NAFLD may be clinically silent. • Alteration of liver enzymes (if present) may occur in the posttransplant setting due to many factors. Amany A.Maqsoud APASL 2014

  22. Diagnosis: • Biopsy protocol: No standard posttransplant interval biopsy protocol. Amany A.Maqsoud APASL 2014

  23. Biopsy protocol • The variability in the time points at which postTx biopsy procedures were performed makes comparisons across studies more difficult. Furthermore, NAFLD is usually asymptomatic and may be clinically silent, and a biopsy sample taken at a single point in time may not be representative of the spectrum of fatty liver disease. Moreover, …… Amany A.Maqsoud APASL 2014

  24. Diagnosis: biopsy protocol • Moreover, a patient’s metabolic profile can change over time, and this may be reflected in the histological findings encountered at different time intervals. • This brings us to the 2 immortal “till now” questions: • Biopsy schedule • Efficacy of non-invasive tools of diagnosis. Risk factors tailored Amany A.Maqsoud APASL 2014

  25. Hematoxylin and eosin–stained liver biopsy section demonstrating macrovesicularsteatosis with foci of lobular inflammation. H&E stained liver allograft biopsy section 2.5 years after transplantation for NASH-related cirrhosis. Hepatocytes show ballooning degeneration and Mallory hyaline inclusions. Trichrome-stained liver allograft biopsy sample highlighting foci of perisinusoidal fibrosis Amany A.Maqsoud APASL 2014

  26. Treatment: • Medical: • Prophylaxis • Definitive • Surgical Amany A.Maqsoud APASL 2014

  27. Treatment: • Prophylaxis is of utmost importance. • Scheduled biopsy protocol can also identify pts with steatosis that impose critical control of metabolic risk factors and modification of type/dose of immunosupressives. • Until now, no specific trials assessed a specific drug therapy for post Tx steatosis. Amany A.Maqsoud APASL 2014

  28. Surgical Treatment: • Bariatric surgery through limited series and case reports studies showed good results. • Risks of exacerbation of NASH after bariatric surgery due to excessive weight loss as well as risks of impaired drug absorption and bacterial overgrowth that can impact post-transplant outcomes. Amany A.Maqsoud APASL 2014

  29. Consensus: • Avoidance of the risk factors for RFP in post transplant HCV is important in the management of these patients. (1A) Amany A.Maqsoud APASL 2014

  30. Consensus: • Data regarding relative risk of different immunosuppressive drugs remain conflicting, and further studies are required before current protocols are modified. (2c) Amany A.Maqsoud APASL 2014

  31. Consensus: • Liver biopsy is the 'gold standard' for diagnosis and follow up of fibrosis and implementing specific antiviral therapy. Protocol liver biopsy is of utmost importance in the posttransplant care of these patients. (1A) Amany A.Maqsoud APASL 2014

  32. Consensus: • Significant fibrosis or portal hypertension one year after transplantation predict rapid disease progression and graft loss, and indicate more urgent antiviral treatment. (1B) Amany A.Maqsoud APASL 2014

  33. Consensus: • Transient elstography for replacing biopsy in the assessment and diagnosis of fibrosis progression still needs validation through large scale clinical studies. (2C) Amany A.Maqsoud APASL 2014

  34. Consensus statements: • Diagnosis depends mainly on liver biopsy. However, the alteration in liver enzymes, plus the imaging modalities and the presence of risk factors are all collectively important (beside liver biopsy) for making the diagnosis and assessing the degree of inflammation and fibrosis. (1B) Amany A.Maqsoud APASL 2014

  35. Consensus statements: • Prophylaxis is important to avoid progression of fibrosis and graft dysfunction. This is confirmed through scheduled liver biopsy and follow up program tailored according to the presence of risk factors. (1A) Amany A.Maqsoud APASL 2014

  36. Consensus statements: • For the treatment of post liver Tx NAFLD, Vit. E as recommended for the non transplant situation is also applied. (C2) • Insulin sensitizers need further clinical studies. (2C) Amany A.Maqsoud APASL 2014

  37. Consensus statements: • Weight loss and treatment of metabolic syndrome and its individual components are the definite treatment available till now. (1A). • Modification of the type and dose of immunosuppressives is important although data are still lacking (1B) Amany A.Maqsoud APASL 2014

  38. Consensus statements: • Although data supporting a role for the metabolic syndrome in post transplantation HCV-mediated RFP are preliminary, current data suggest that strict strategies to reduce weight gain and the adverse metabolic profile post-transplant should be implemented. (1B) Amany A.Maqsoud APASL 2014

  39. Consensus statements: • Biopsy is the gold standard for assessing the presence and degree of steatosis in the donor graft. (1C) • Steatosis of more than 30% of the donor graft is associated with high risk of primary non-function.(1A) Amany A.Maqsoud APASL 2014

  40. Mother to Daughter Brother to Brother Brother to Brother Mother to Son Mother to Son Father to Son Son to Father Mother to Daughter Son to Mother

  41. Kasr AlAyni Liver Tx Program

  42. Annual Conference Amany A.Maqsoud 2014

  43. Thank you Amany A.Maqsoud 2014

More Related