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Gi & hepatic complications of solid organ transplantation
1. GI & HEPATIC COMPLICATIONS
OF SOLID ORGAN
TRANSPLANTATION
PRESENTER:DR.ABHINAV KUMAR
2. OUTLINE
⢠Infection in the solid organ transplant recipient
⢠Post kidney/pancreas transplantation
⢠Liver transplantation
⢠Heart, lung, and heart/lung transplantation
⢠A problem-oriented approach to diagnosis in solid organ transplant
recipients
⢠Solid organ transplant-associated acute graft-versus-host disease
⢠Post-transplant prophylaxis
⢠Vaccination pre and post transplantation
3. COMPLICATIONS OF SOLID ORGAN
TRANSPLANTATION
⢠Gastrointestinal complaints after solid organ transplant (SOT) are
reported in 20% to 35% of recipients
⢠60% reported in India
⢠graft dysfunction,
⢠adverse effects of medications,
⢠opportunistic infections, or malignancy
⢠First six month ď Infectious complications
4. Infection in the solid organ transplant recipient
⢠Epidemiologic exposures â detailed history of potential encounters
⢠Latent pathogens are often activated
⢠Bacterial and fungal pathogensď Neutropenia
⢠Viral (eg CMV & intracellular (eg,TB) infections are more common with T
cell immune deficits
⢠Strongyloides stercoralis may reactivate after many years
5.
6. Screening for latent TB
⢠Incidence ď worldwide ranged from 0.35 to 15 %
8- to 100-fold increase
⢠tuberculin skin testing (TST) or TB interferon-gamma release assays
Pre-transplant anti-tuberculous prophylaxis
⢠Tuberculin reactivity of âĽ5 mm before transplantation
⢠History of tuberculin reactivity without adequate prophylaxis
⢠Recent conversion of tuberculin skin test to positive
⢠Radiographic evidence of old TB without prior prophylaxis
⢠History of inadequately treated TB
⢠Close contact with an individual with active pulmonary TB
⢠Receipt of an allograft from a donor with a history of untreated TB
7. Treatment after transplantation
⢠Compromised by drug toxicities and interactions
⢠Isoniazid or pyrazinamide hepatotoxicity, for example, may be
intolerable after liver transplantation.
⢠Rifampin will significantly reduce the serum level of calcineurin
inhibitors, an effect that persists for a number of weeks after
cessation of therapy.
⢠Therapy should be completed two to four weeks before
transplantation
8.
9.
10.
11. 1 to 6 months after transplantation
⢠opportunistic infections
⢠geographic and institutional variation
⢠Prophylaxis delays but does not eliminate the risk
Major infections
⢠Pneumocystis jirovecii (formerly P. carinii) pneumonia
⢠Latent infectionsď toxoplasmosis, leishmaniasis & Chagas disease
⢠Geographic or endemic fungal infectionsď Histoplasma
capsulatum, Coccidioides spp
12. 1 to 6 months after transplantation
⢠Viral pathogensď herpes group viruses,HBV & HCV
⢠Tuberculosis and, increasingly, nontuberculous mycobacteria
⢠Gastrointestinal parasites (Cryptosporidium and Microsporidium) and
viruses (cytomegalovirus [CMV], rotavirus) may be associated with
diarrhea.
13. More than 6 to 12 months after transplantation
⢠community-acquired pneumoniasď pneumococcus, Legionella
⢠Less than adequate graft functionď higher immunosuppressive
therapy
⢠Highest risk for opportunistic infections including PCP, cryptococcosis,
and nocardiosis.
⢠Prolonged antimicrobial prophylaxis
14. More than 6 to 12 months after transplantation
⢠Suffer rare infections in the late transplant period
⢠Infections are most often due to
⢠molds or Nocardia species
⢠late effects of viral infections manifest as malignancy
Âť posttransplant lymphoproliferative disorder (PTLD)
Âť squamous cell cancers of the skin or anogenital region
15.
16. Cytomegalovirus (CMV)
⢠Cytomegalovirus (CMV)ď within the first year after SOT.
⢠Factors predisposing to CMV infectionď
â antilymphocyte antibody in addition to conventional
immunosuppression
â maintenance mycophenolate mofetil (MMF) therapy
â CMV-negative recipients who received a CMV-positive graft are at
the greatest risk of primary CMV infection
17. ⢠Peak incidenceď 4 TO 6 MONTHS AFTER SOT
Fever
Malaise
Myalgia
Occasionally cough
Minor elevations of ALT
⢠CMV-DNA or antigen ď Bloodstream
⢠Negative from blood ď Intestinal biopsy
⢠Ganciclovir or Valganciclovir ď Either post-transplant antiviral
prophylaxis or preemptive therapy
⢠Valganciclovir should not be used ď Liver transplantation
⢠higher rate of tissue-invasive disease
⢠ganciclovir is recommended
19. C) Colon mucosa in cytomegalovirus
infection, showing focal ulceration (arrow)
and depressed ulceration and intramucosal
hemorrhage in surrounding mucosa.
D) Colon mucosa in cytomegalovirus infection
showing diffuse mucosal friability and
ulceration.
20. Herpes simplex virus (HSV)
⢠Second most commonly seen viral infection
⢠Reactivation of latent virus within the recipient
⢠two to four weeks after transplant
⢠HSV has tropism for squamous epithelium (nose, mouth, esophagus)
(intestine and liver) if not receiving prophylaxis
⢠Epstein-Barr virus (EBV)
⢠varicella-zoster virus (VZV) LESS COMMON
⢠human herpesvirus 6 (HHV-6)
⢠MMF immunotherapy may increase the risk of VZV dissemination.
21. B) Duodenal ulceration caused by herpes simplex virus, showing a deep,
irregular ulcer surrounded by edematous mucosa.
22. Fungal infections
⢠After the first month post-transplant
⢠Discontinued fungal prophylaxis
⢠Candida albicans
⢠Candida tropicalis MOST COMMON
⢠Aspergillus
⢠Zygomycetes EMERGING PATHOGENS
⢠Nocardia,
⢠Pneumocystis,
⢠Toxoplasma; LESS COMMON
⢠Strongyloides
23. Fungal infections
⢠Once beyond the first six months following SOT
⢠Opportunistic infections occur less frequently
⢠Recipients remain at risk for community-acquired infections.
⢠Post-transplant lymphoproliferative diseaseď continued high-level
immune suppression.
⢠B and T cell lymphomas can be seen
24.
25. CT Findings lymphoproliferative disease following
solid organ transplant
Retroperitoneal mass (arrows) caused by an Epstein-Barr virusâpositive B
cell lymphoma following liver transplantation.
26. CT Findings Lymphoproliferative Disease Following
Solid Organ Transplant
Distal small intestinal mass (arrows) following renal transplantation, caused
by a T cell lymphoma. The mass was causing intestinal obstruction, as
evidenced by the dilated loops of small intestine proximal to the mass.
27. LIVER TRANSPLANTATION
⢠Orthotopic liver transplant (OLT) are generally related to the surgery
⢠hemorrhage
⢠hepatic arterial stenosis or thrombosis
⢠biliary tract dysfunction
⢠bowel perforation
⢠bowel obstruction
⢠gastrointestinal bleeding
⢠Hepatic artery thrombosisď recipients is 4%â12% in adults
42% in children
⢠mildly elevated liver enzymes
⢠fulminant hepatic failure.
28. ⢠Prompt diagnosis of hepatic artery thrombosisď early intervention
thrombectomy, hepatic artery reconstruction, or both
⢠Retransplantation
⢠After retransplantation, the mortality rateď 30%
Risk factors
⢠significant difference in hepatic artery caliber
⢠interpositional conduit for the anastomosis
⢠previous stenotic lesion of the celiac axis
⢠excessive duration of cold ischemia time
⢠ABO blood type incompatibility
⢠cytomegalovirus infection
⢠acute rejection
29. Duplex Doppler US image obtained on the 4th postoperative day shows no
hepatic arterial flow at either color or pulsed Doppler imaging.
30. Maximum intensity projection image from
gadolinium-enhanced MR angiography
shows an abrupt cutoff of flow in the proper
hepatic artery (arrow), just beyond the
vessel origin.
Conventional angiogram helps confirm
hepatic artery thrombosis
31. Hepatic artery stenosisď 5%â11% of liver transplant recipients
⢠Complication ď site of anastomosis within 3 months after
transplantation
⢠Left untreatedď hepatic artery thrombosisď hepatic ischemiaď biliary
strictureď sepsis ď graft loss
Causesď
⢠clamp injury
⢠intimal trauma from a perfusion catheter
⢠disruption of the vasa vasorum with resultant ischemia of the arterial
ends
⢠Duplex Doppler US is the method of choice
32. Multidetector CT
angiograms help
confirm the presence
of hepatic artery
stenosis (arrow in b)
with reduced
intrahepatic perfusion
and collateral vessels
(arrowheads in c).
33. Ischemia and Infarction
⢠As a rule (in 85% of
cases), liver infarction in
transplant recipients is
associated with hepatic
artery complications;
less frequently, it results
from portal vein
occlusion
⢠Ischemic lesions have a
tendency to undergo
liquefactionď infection.
Focal abscesses may be
a source of intermittent
or remittent sepsis.
34. ⢠Portal vein thrombosis occurs in about 1%â2% of cases
⢠technical problemsď vessel misalignment, differences in the caliber of the anastomosed
vessels, or stretching of the portal vein at the anastomotic site
Stricture (arrow) at the site of the
portal anastomosis.
MR angiography demonstrates the stenosis (arrow)
with associated poststenotic dilatation of the intra-
hepatic portal vein.
35. LIVER TRANSPLANTATION
⢠Post-OLT, the biliary tree receives its entire blood supply from the
hepatic artery
⢠loss of flow results in bile duct necrosis
⢠leakage with development of bilomas & abscesses
Endoscopic retrograde
cholangiogram showing
an ischemic stricture of
the bile duct (arrow).
36. LIVER TRANSPLANTATION
Endoscopic retrograde cholangiogram
showing a bile leak (arrowhead) at the biliary
anastomosis (arrow).
Magnetic resonance cholangiogram of the
intrahepatic biliary system showing recurrent
sclerosing cholangitis in the liver graft. The
arrow points to a stricture, with upstream
biliary dilation.
37. LIVER TRANSPLANTATION
⢠Gradual loss of hepatic arterial flow can result in ductopenia, which is
indistinguishable from ductopenic rejection.
⢠Portal vein thrombosis can lead to hepatic ischemiaď
⢠Early ď severe hepatic dysfunction
⢠Later ď signs of portal hypertension
⢠Rarely, hepatic vein thrombosis and inferior vena cava
thrombosis/stenosis can create a Budd-Chiariâlike syndrome.
38. ⢠Most common biliary abnormalities ď Biliary leakage (5%) & stricture
formation (anastomotic site)
⢠Anastomotic stricturesď two to six months post OLT
⢠Strictures and leaks in patients
duct-to-duct anastomosesď amenable to endoscopic therapy
choledochojejunostomiesď percutaneous or surgical correction
⢠Biliary cast syndrome has decreased to 5% to 20%
⢠within the first year post OLT
⢠Clinical factorsď hepatic ischemia and biliary strictures
⢠Endoscopic and percutaneous therapyď successful in up to 70%, but
surgical intervention may be required (mortality 10% to 30%)
39. LIVER TRANSPLANTATION
⢠CMV hepatitis is more severe in OLT recipients
⢠CMV hepatitis V/S Rejectionď Increased serum aminotransferases
⢠Liver biopsy is essential for differentiation
⢠Detection of CMV in the bloodstream
⢠Asymptomatic low-level CMV viremiaď NO antiviral therapy
⢠Invasive fungal infections ď Commoner than other SOT recipients,
with a high mortality.
40. ⢠In the absence of prophylaxis
Intestinal colonization with Candida is nearly universal post OLT
⢠Candida accounts for the majority of all invasive fungal infections
following OLT
⢠Serum galactomannan assay is useful for detecting mold infections
⢠Recurrence of HCV in the liver allograft ď Universal
⢠75%ď signs of liver damage
⢠25% cirrhosis within 5 yearsď leads to increased graft loss
⢠HBV recurrence may be prevented with the use of HBIG & antiviral
⢠PBC recurs in about 26% of patients post-liver transplant.
41. POST KIDNEY/PANCREAS TRANSPLANTATION
⢠up to 50% of patients
⢠KT patients with GERD or dyspepsiaď increased risk of graft loss and
death
⢠Graft pancreatitis and graft duodenitis generally occur early after
kidney/pancreas transplant (KPT) and may lead to intra-abdominal
infection
⢠HCV or HBV infection ranges from 5% to 66% of KT and KPT
recipients, depending on country of origin.
⢠Effect of HCVď on patient and graft outcomesď Controversial
42. POST KIDNEY/PANCREAS TRANSPLANTATION
⢠HBV antiviral therapy has improved clinical outcome
⢠HCV antiviral therapy with interferon alpha and ribavirin cannot be
usedď increased risk of allograft rejection.
⢠Cirrhotic patients who undergo KT have a significantly worse 10-year
survival (about 20% to 30%)
⢠Gastrointestinal CMV infectionď 7% of KT and KPT recipients, with
pancreas recipients at greater riskď higher levels of
immunosuppression.
⢠About 4% develop intestinal fungal infections ď candidal species.
43. POST KIDNEY/PANCREAS TRANSPLANTATION
⢠HSV infection post KTď asymptomatic and self-limited
⢠stomatitis
⢠mononucleosis
⢠hepatitis
⢠pneumonia
⢠Cholecystitis is seen in KT recipients, and the incidence is higherď
diabetic patients.
⢠gastrointestinal hemorrhageď up to 20% of KT recipient ď high
mortality
⢠APPROX 50% dyspepsia, and about 30% are colonized with
Helicobacter pylori
44. POST KIDNEY/PANCREAS TRANSPLANTATION
⢠Renal recipients are at particular riskď Intestinal ischemia compared
with other SOT recipients
Incidenceď Low (<5%)
Etiologyď Multifactorial
⢠Recipients with polycystic kidney disease more often develop
intestinal ischemia and obstructionď high mortality.
⢠Ischemia should be considered in KT recipients with abdominal pain,
particularly older patients (>40 years of age) who have received a
cadaveric kidney
45. HEART, LUNG, AND HEART/LUNG
TRANSPLANTATION
⢠Most common complications
⢠Diarrhea,
⢠GERD,
⢠Dyspepsia,
⢠Nausea and vomiting,
⢠Abdominal pain,
⢠Pancreatitis,
⢠Herpesvirus infections (especially CMV),
⢠Cholelithiasis,
⢠Ulcers,
⢠Hepatobiliary disease
46. HEART, LUNG, AND HEART/LUNG
TRANSPLANTATION
⢠GERD and gastroparesis ď related to medications and vagal nerve
injury during the operation
⢠Symptomatic gastroparesis
⢠25% of LT recipients
⢠up to 80% in HLT recipients
Course ď waxing and waning
neuropathic
infectious (CMV)
medication-induced etiology
47. HEART, LUNG, AND HEART/LUNG
TRANSPLANTATION
⢠Development of obliterative bronchiolitis, which significantly
threatens the longevity of LT recipients.
⢠Proton pump inhibitorsď Control reflux
⢠Unremittingď laparoscopic fundoplication
⢠LT recipients may develop giant gastric ulcers (>3 cm in diameter)
that occur despite routine use of acid suppression.
⢠Associated with bilateral LT, high-dose NSAIDs after transplant, acute
rejection requiring high-dose glucocorticoids, and cyclosporine
immunosuppression.
48. ⢠Recipients of LT and HT > CMV infection 15% to 25%
⢠CMV infectionď Pneumonitis
⢠LT and HLT recipients ď highest incidence of fungal infectionď
Aspergillus > Candida species
⢠Patients undergoing LT for cystic fibrosisď Pancreatic insufficiency, a
marker for severe cystic fibrosis, is common.
⢠Cystic fibrosisâInduced secondary biliary cirrhosisď absorption of
cyclosporine.
⢠If severe liver disease prior to LTď Lung-liver transplant
49. ⢠Distal intestinal obstruction syndromeď 20% = non-transplant
⢠Cystic fibrosis ď cholecystitis, peptic ulcer disease, and GERD.
⢠Primary HCV infection following HT leads to significantly decreased
one- and three-year survival.
⢠Acquisition of HBV following HT does not appear to affect survival,
at least up to five years.
50. A PROBLEM-ORIENTED APPROACH TO DIAGNOSIS IN
SOLID ORGAN TRANSPLANT RECIPIENTS
⢠Upper Gastrointestinal Symptoms and Signs
⢠GERD is the most common cause of heartburn and midchest pain,
particularly following lung transplantation
â Viral & fungal esophagitis may underlie
⢠Candidal esophagitisď
⢠Diabetes
⢠Broad-spectrum antibiotics
⢠High-dose immunosuppression
⢠Presence of a Roux-en-Y anastomosis in liver transplant recipients
52. Anorexia, nausea, and/or vomiting
⢠Herpes virus infections or to medications
⢠Tacrolimus (Prograf) is a macrolide lactone
⢠Nausea ANOREXIA
⢠Abdominal pain WEIGHT LOSS
⢠Diarrhea
⢠Dose dependent and can be managed with dose reduction or, more
rarely, drug discontinuation.
⢠Sirolimus (Rapamune), a newer macrolide immunosuppressant, has a GI
side effect profile similar to tacrolimus.
53. ⢠MMF (CellCept) is an inhibitor of nucleic acid synthesis
⢠Nausea
⢠Vomiting
⢠Diarrhea
⢠Dosing modifications
⢠GVHD presents with fever, skin rash, and gastrointestinal symptoms,
particularly nausea, vomiting, and diarrhea.
⢠Endoscopic evaluation with biopsyď viral infections and drug
reactions can have a GHVD-like histologic pattern
⢠Symptomatic gastroparesis ď lung transplant > other solid organ
transplant.
54. ⢠CMV and VZV may rarely involve intestinal neural plexuses, leading to
intestinal dilation or gastroparesis.
⢠H. pylori infection may be associated
⢠symptomatic dyspepsia
⢠gastritis
⢠gastroduodenal ulceration
⢠No relationship between the use or degree of immunosuppression
and H. pylori colonization
⢠Incidence is similar to that seen in the non-transplant setting
55. Diarrhea and Constipation
⢠Diarrhea is commonly infectious
⢠fever
⢠abdominal pain (46%)
⢠nausea (32%)
⢠vomiting (22%)
⢠The microbes ď CMV and Clostridium difficile
wide range of organisms in SOT recipients
⢠adenovirus rotavirus coxsackievirus
⢠bacterial enteric pathogens
enterohemorrhagic E.coli, Yersinia enterocolitica
Giardia lamblia Candida species cryptosporidium
Isospora belli Strongyloides stercoralis
56. ⢠Diagnosis ď Stool specimens
⢠Small intestinal involvement with CMV ď profuse watery diarrhea
with protein-losing enteropathy (delayed diagnosis)
⢠Colonic involvementď Inflammatory colitisď bloody diarrhea and
fever, abdominal distention, and pain.
⢠Diagnosis of CMV may require mucosal biopsy, particularly if blood
specimens are negative for CMV DNA or antigen.
57. ⢠C. difficile infectionď
Fulminant colitis
Toxic megacolon
⢠Prompt surgical intervention to prevent perforation and peritonitis
⢠Subtle Signs of colitis ď Concomitant immunosuppression.
⢠70% of patients respondď Metronidazole;
⢠Persistent and more severeď oral vancomycin
⢠Recurrenceď 20% of cases
58. Drug-related diarrhea
⢠Most commonď tacrolimus or sirolimus
⢠MMFď watery diarrhea (30%) of patientsď reduction or
discontinuation.
⢠Antithymocyte globulin (ATG) and antiâT cell antibody (OKT3)
Diarrheaď Lasts for three to four days ď Resolves spontaneously
⢠Managed with dose manipulationď Severe ď Discontinuation
⢠Noninfectious diarrhea ď increase the risk of graft loss and mortality
59. ABDOMINAL PAIN
⢠30% of patients following SOT
⢠Early post-transplant periodď
⢠Intra-abdominal conditions ď Urgent surgery
â abscess
â perforation
â severe colitis
â appendicitis
â intestinal obstruction
â intestinal ischemia
â acute cholecystitis
60. ⢠Intestinal perforation < 5% of SOT recipients
⢠Incidence may be slightly higher ď Lung transplant
⢠Perforation may occur spontaneously without clear etiology
⢠colon diverticula in up to two thirds of cases
⢠ischemia in 15%
⢠Perforation, especially of a diverticulum, carries a mortalityď 55%
⢠Risk factors of colonic perforation
Diverticular disease Immunosuppression
CMV infection Fungal infections
Unrecognized lymphoma Colon cancer
Ischemia
61. ⢠SOT recipients also are at increased risk for cholelithiasis
Factors related to gallstones
⢠Cyclosporine
⢠Obesity
⢠Cystic fibrosis
⢠Abdominal painď tissue-invasive CMV disease
⢠diffuse pattern of mucosal edema
⢠CMVď focal ulceration
⢠perforation
⢠high-grade stricture
⢠intestinal obstruction
⢠The first manifestation of disseminated VZV infectionď severe
abdominal painď intestinal pseudo-obstruction & visceral neuropathy.
62. ⢠up to 19% of patients taking MMF
⢠Etiology of MMF-Local irritant and inflammatory effects
⢠interference with rapidly dividing intestinal cells
⢠Narcotic-induced ileusď common after surgery
⢠RULE OUTď CMV or VZVď Intestinal nerve plexuses.
ABDOMINAL PAIN
64. ABDOMINAL PAIN
Acute pancreatitis
⢠1% to 2% of renal transplant recipients
⢠up to 6% of liver transplant recipients
⢠up to 18% of heart transplant recipients
Association
⢠CMV infection hypercalcemia cholelithiasis
⢠biliary manipulation malignancy alcohol ingestion
Medications
⢠azathioprine, cyclosporine,
⢠tacrolimus, glucocorticoids.
65. Gastrointestinal Malignancy
⢠Post-transplant lymphoproliferative disorders (PTLDs)
⢠lymphoid proliferations 1 to 20 %
⢠lymphomas associated with EBV infection (EBV-LPD)
⢠Most PTLDs are of B cell origin EBV reactivation
Mononucleosis-like syndrome
Diffuse adenopathy
Fever
Detection of EBV DNA in the bloodstream ď Preemptive therapy
Lower doses of immune suppression
Rituximab
66. ⢠PTLDď Later than a year after transplant ď Insidious
⢠Presents ď Extranodal disease or visceral involvement
⢠Gastrointestinal PTLD can present with
⢠diarrhea
⢠intestinal obstruction
⢠bleeding
⢠perforation
⢠Mucosa-associated lymphoid tissue-type (MALT) lymphomasď
⢠Reduction in immunosuppression
⢠Antibiotics (if associated with H. pylori)
⢠Surgery
⢠Chemotherapy
67. Hepatobiliary Complications
⢠Azathioprine hepatotoxicity
⢠Elevation in serum aminotransferases (10%)
⢠Injury is generally cholestatic, with centrilobular hepatocyte damage.
Less common
⢠slow insidious development of sinusoidal obstruction syndrome
(veno-occlusive disease)
Portal hypertension
Regress with withdrawal of the drug
68. Hepatobiliary Complications
⢠Cyclosporine- or tacrolimus-induced cholestasis can occur when
blood levels are high.
⢠Sirolimusď dose-dependent elevations in serum aminotransferases.
⢠Bacterial sepsisď severe cholestasis (cholangitis lenta)
⢠CMV infectionď Cholestatic or Hepatocellular picture.
⢠CMV hepatitis ď frequent and severe in liver transplant recipients
⢠VZV and HSV ď hepatitis and fulminant liver failure
69. Primary or recurrent disease HCV or HBV
⢠Immunosuppressionď Increase in HCV titers
Aggressive hepatic disease post-transplant
Cirrhosis 3 to 10 years
⢠INF-Îąď disappointing
⢠HCVď successfully treated renal transplant recipients
rate of renal graft failure related to INF-Îą is unacceptable
⢠Chronic HBV carriersď Hepatitis flare following transplant
Responds to antiviral agents
70. Biliary Tract disease
⢠Acalculous cholecystitis Gallbladder sludge
⢠Thickened gallbladder wall Dilated bile ducts
⢠Cholelithiasis
⢠Pretransplant screening/prophylactic cholecystectomy remain
controversial.
Etiology of biliary tract disease
⢠obesity, total parenteral nutrition,
⢠fasting, biliary strictures
⢠Cyclosporine is excreted in the bile ď Increased incidence of
cholelithiasis and cholangitis.
71. Solid Organ Transplant-Associated Acute Graft-
Versus-Host Disease
⢠The occurrence of an immunologically mediated and injurious set of
reactions by cells genetically disparate to their host, otherwise known
as graft-versus-host disease (GVHD)
⢠Acute GVHD HSCT ď 35%â50%
⢠Incidence of SOTâassociated GVHD VARIES
⢠small intestine transplantation 5.6%
⢠followed by liver transplantation 1%â2%
⢠Approx 86 cases of liver transplantâassociated GVHD since 1987
⢠Mortality rateď 30% to more than 75%
72. ETIOLOGY AND PATHOGENESIS
⢠Risk factors
⢠Donor HLA homozygosity
⢠periorgan lymphoid tissue transfer
⢠relationship between recipient immunogenicity and the
immunosuppressive drug regimen
In liver transplant
⢠Autoimmune hepatitis
⢠alcoholic liver disease
⢠hepatocellular carcinoma Steatotic donor liver
⢠glucose intolerance
73. PHASE 1
⢠Mechanism of GVHD after solid organ transplants ď Clear
⢠Tissue injury
⢠surgery
⢠immunosuppressive agents TNF AND IL1
⢠chemotherapy
⢠irradiation
⢠Expression of adhesion molecules
⢠MHC molecules
⢠Costimulatory molecules
⢠ââPrimingââď Activate host antigen presenting cells
74. PHASE 2
⢠Donor T cells are activated ď APC
â Proliferate
â Differentiate Activated T cells
â Migrate
IL-2
Interferon g
MHC class II on epithelial cells & macrophages
Stimulates the activation of T cells & NK Cells
76. CLINICAL PRESENTATION
⢠SOT ď Acute GVHD ď 2 to 6 weeks after liver transplantation
⢠Skin rashď Initial presentation
⢠Characteristic maculopapular rashes are red to violet
⢠First appear on the palms of the hands and soles of the feet
⢠Coalesce and form confluent areas of involvement
⢠Severe casesď Bullae & Vesicles
77. Upper GI system
⢠Anorexia
⢠Dyspepsia
⢠Intestinal bleeding
⢠Cramping abdominal pain (distal small bowel and colon)
⢠Diarrheaď green, mucoid, watery, and mixed with exfoliated cells
forming fecal casts.
Hematopoietic System
⢠Liver transplantationď bone marrow is infiltrated by donor T cells
Severe neutropenia (100/ml)
Pancytopenia
⢠Dies of bleeding and infection from bone marrow failure
78. Histologic grading system
GI GVHD
⢠Grade I ď Increased crypt apoptosis
⢠Grade IIď Apoptosis with crypt abscess
⢠Grade IIIď Crypt necrosis
⢠Grade IVď Total denudation of mucosal areas
SKIN
⢠Grade Iď Vacuolization of the basal keratinocytes
⢠Grade IIď Dyskeratotic keratinocytes and basal cell vacuolization
⢠Grade IIIď Increased keratinocyte necrosis and focal basal layer
clefting
⢠Grade IV ď Necrosis of the entire epidermis & complete separation
from the dermis
79.
80. DIAGNOSIS
⢠Demonstration of substantial donor lymphoid chimerism
⢠Donor lymphoid chimerism ď very common following liver
transplantation
⢠usually disappears within 1 to 3 weeks
⢠Positive value > 20% more than 1-week post-transplantď HIGHLY
specific
⢠Lower valueď early or subclinical GVHD.
81. TREATMENT
⢠Increasing immunosuppression
⢠Support of hematopoiesis with cytokines
⢠Discontinuation of antibiotics or any drugsď Myelosuppression
⢠Mortality exceeds more than 75%
⢠Approx 86 cases since 1987
18 patients survived
13 of the survivorsď immunosuppression had been increased
5 other ď immunosuppression withdrawn.
82. POST-TRANSPLANT PROPHYLAXIS
⢠Vulnerable to nosocomial infections, especially in the early post-
transplant period
⢠Patients with prolonged hospitalizations or who require mechanical
ventilation are ď high risk
⢠TMP-SMX OD [80 mg TMP/160 mg SMX] or one double-strength
tabletď 3 TO 7 times/week
⢠Pneumocystis pneumonia (PCP)
⢠L. monocytogenes
⢠T. gondii
83. Pneumocystis pneumonia
⢠Incidence of infection was 10 to 15 percent in Most programs
⢠High as 70 to 88 percent in the lung transplant population
⢠Prophylaxis should be continued for six months to one year
⢠Patients allergic to sulfa-containing medications
⢠dapsone
⢠inhaled pentamidine
⢠Atovaquone
84. Toxoplasmosis
⢠Uncommon but highly morbid infection
⢠Found in muscle tissues (brain and phagocytic cells)
⢠greatest risk ď cardiac transplantation
⢠seronegative recipients from seropositive donorsď 50 to 75 %
PRESENTATION:
⢠Myocarditis
⢠Cardiomyopathy
⢠brain abscess
⢠pneumonitis
⢠Empyema,
85. Toxoplasmosis
⢠Median time to presentationď two months
⢠Prevention of toxoplasmosis has not been well studied
⢠One retrospective study suggests that TMP-SMX
⢠One double-strength tablet three times per week is sufficient for
both Pneumocystis and Toxoplasma prevention in cardiac transplant
recipients.