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  Infectious complications

4. Infection in the solid organ transplant recipient
• Epidemiologic exposures — detailed history of potential encounters
• Latent pathogens are often activated
• Bacterial and fungal pathogens Neutropenia
• Viral (eg CMV & intracellular (eg,TB) infections are more common with T
cell immune deficits
• Strongyloides stercoralis may reactivate after many years

6. Screening for latent TB
• Incidence  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 ≥5 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

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 infections toxoplasmosis, leishmaniasis & Chagas disease
• Geographic or endemic fungal infections Histoplasma
capsulatum, Coccidioides spp

12. 1 to 6 months after transplantation
• Viral pathogens 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 pneumonias pneumococcus, Legionella
• Less than adequate graft function 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
» posttransplant lymphoproliferative disorder (PTLD)
» squamous cell cancers of the skin or anogenital region

16. Cytomegalovirus (CMV)
• Cytomegalovirus (CMV)within the first year after SOT.
• Factors predisposing to CMV infection
– antilymphocyte antibody in addition to conventional
immunosuppression
– maintenance mycophenolate mofetil (MMF) therapy
– CMV-negative recipients who received a CMV-positive graft are at
the greatest risk of primary CMV infection

17. • Peak incidence 4 TO 6 MONTHS AFTER SOT
Fever
Malaise
Myalgia
Occasionally cough
Minor elevations of ALT
• CMV-DNA or antigen  Bloodstream
• Negative from blood  Intestinal biopsy
• Ganciclovir or Valganciclovir  Either post-transplant antiviral
prophylaxis or preemptive therapy
• Valganciclovir should not be used  Liver transplantation
• higher rate of tissue-invasive disease
• ganciclovir is recommended

18. A) Distal esophageal ulcerations caused by cytomegalovirus

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 disease continued high-level
immune suppression.
• B and T cell lymphomas can be seen

25. CT Findings lymphoproliferative disease following
solid organ transplant
Retroperitoneal mass (arrows) caused by an Epstein-Barr virus–positive 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 thrombosis recipients is 4%–12% in adults
42% in children
• mildly elevated liver enzymes
• fulminant hepatic failure.

28. • Prompt diagnosis of hepatic artery thrombosis early intervention
thrombectomy, hepatic artery reconstruction, or both
• Retransplantation
• After retransplantation, the mortality rate 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 stenosis5%–11% of liver transplant recipients
• Complication  site of anastomosis within 3 months after
transplantation
• Left untreated hepatic artery thrombosis hepatic ischemia biliary
stricture sepsis  graft loss
Causes
• 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
liquefaction infection.
Focal abscesses may be
a source of intermittent
or remittent sepsis.

34. • Portal vein thrombosis occurs in about 1%–2% of cases
• technical problems 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 ischemia
• Early  severe hepatic dysfunction
• Later  signs of portal hypertension
• Rarely, hepatic vein thrombosis and inferior vena cava
thrombosis/stenosis can create a Budd-Chiari–like syndrome.

38. • Most common biliary abnormalities  Biliary leakage (5%) & stricture
formation (anastomotic site)
• Anastomotic strictures two to six months post OLT
• Strictures and leaks in patients
duct-to-duct anastomoses amenable to endoscopic therapy
choledochojejunostomies percutaneous or surgical correction
• Biliary cast syndrome has decreased to 5% to 20%
• within the first year post OLT
• Clinical factors hepatic ischemia and biliary strictures
• Endoscopic and percutaneous therapy 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 Rejection Increased serum aminotransferases
• Liver biopsy is essential for differentiation
• Detection of CMV in the bloodstream
• Asymptomatic low-level CMV viremiaNO antiviral therapy
• Invasive fungal infections  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  Universal
• 75%signs of liver damage
• 25% cirrhosis within 5 years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 dyspepsia 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 HCV on patient and graft outcomes Controversial

42. POST KIDNEY/PANCREAS TRANSPLANTATION
• HBV antiviral therapy has improved clinical outcome
• HCV antiviral therapy with interferon alpha and ribavirin cannot be
used increased risk of allograft rejection.
• Cirrhotic patients who undergo KT have a significantly worse 10-year
survival (about 20% to 30%)
• Gastrointestinal CMV infection 7% of KT and KPT recipients, with
pancreas recipients at greater risk higher levels of
immunosuppression.
• About 4% develop intestinal fungal infections  candidal species.

43. POST KIDNEY/PANCREAS TRANSPLANTATION
• HSV infection post KT asymptomatic and self-limited
• stomatitis
• mononucleosis
• hepatitis
• pneumonia
• Cholecystitis is seen in KT recipients, and the incidence is higher
diabetic patients.
• gastrointestinal hemorrhageup to 20% of KT recipient  high
mortality
• APPROX 50% dyspepsia, and about 30% are colonized with
Helicobacter pylori

44. POST KIDNEY/PANCREAS TRANSPLANTATION
• Renal recipients are at particular riskIntestinal ischemia compared
with other SOT recipients
Incidence Low (<5%)
Etiology Multifactorial
• Recipients with polycystic kidney disease more often develop
intestinal ischemia and obstruction 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  related to medications and vagal nerve
injury during the operation
• Symptomatic gastroparesis
• 25% of LT recipients
• up to 80% in HLT recipients
Course  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 inhibitors Control reflux
• Unremitting 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 infection Pneumonitis
• LT and HLT recipients  highest incidence of fungal infection
Aspergillus > Candida species
• Patients undergoing LT for cystic fibrosis Pancreatic insufficiency, a
marker for severe cystic fibrosis, is common.
• Cystic fibrosis–Induced secondary biliary cirrhosis absorption of
cyclosporine.
• If severe liver disease prior to LT Lung-liver transplant

49. • Distal intestinal obstruction syndrome 20% = non-transplant
• Cystic fibrosis  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
– Viral & fungal esophagitis may underlie
• Candidal esophagitis
• Diabetes
• Broad-spectrum antibiotics
• High-dose immunosuppression
• Presence of a Roux-en-Y anastomosis in liver transplant recipients

51. • Severe necrotizing fungal esophagitis Perforation  fatal
• Esophageal infection
• Herpes viruses (CMV, HSV) Odynophagia, dysphagia
• Fungal species (Candida)
• Dysphagia secondary to pill esophagitis
• antibiotics
• antivirals
• potassium chloride
• bisphosphonates
• NSAIDs
• Severe esophageal infection Esophageal strictures

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 biopsy viral infections and drug
reactions can have a GHVD-like histologic pattern
• Symptomatic gastroparesis  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  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  Stool specimens
• Small intestinal involvement with CMV  profuse watery diarrhea
with protein-losing enteropathy (delayed diagnosis)
• Colonic involvement Inflammatory colitis 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 infection
Fulminant colitis
Toxic megacolon
• Prompt surgical intervention to prevent perforation and peritonitis
• Subtle Signs of colitis  Concomitant immunosuppression.
• 70% of patients respond Metronidazole;
• Persistent and more severe oral vancomycin
• Recurrence 20% of cases

58. Drug-related diarrhea
• Most common tacrolimus or sirolimus
• MMF watery diarrhea (30%) of patients reduction or
discontinuation.
• Antithymocyte globulin (ATG) and anti–T cell antibody (OKT3)
Diarrhea Lasts for three to four days  Resolves spontaneously
• Managed with dose manipulation Severe  Discontinuation
• Noninfectious diarrhea  increase the risk of graft loss and mortality

59. ABDOMINAL PAIN
• 30% of patients following SOT
• Early post-transplant period
• Intra-abdominal conditions  Urgent surgery
– abscess
– perforation
– severe colitis
– appendicitis
– intestinal obstruction
– intestinal ischemia
– acute cholecystitis

60. • Intestinal perforation < 5% of SOT recipients
• Incidence may be slightly higher  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 mortality 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 pain tissue-invasive CMV disease
• diffuse pattern of mucosal edema
• CMV focal ulceration
• perforation
• high-grade stricture
• intestinal obstruction
• The first manifestation of disseminated VZV infection severe
abdominal pain 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 ileus common after surgery
• RULE OUT CMV or VZV Intestinal nerve plexuses.
ABDOMINAL PAIN

63. ABDOMINAL PAIN
Noninfectious pseudo-obstruction 
• nasogastric decompression
• Electrolyte imbalance
• withdrawal of opiates
• Neostigmine Treatment of intestinal pseudo-obstruction
• Surgical intervention Massive colon dilation

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  Preemptive therapy
Lower doses of immune suppression
Rituximab

66. • PTLD Later than a year after transplant  Insidious
• Presents  Extranodal disease or visceral involvement
• Gastrointestinal PTLD can present with
• diarrhea
• intestinal obstruction
• bleeding
• perforation
• Mucosa-associated lymphoid tissue-type (MALT) lymphomas
• 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.
• Sirolimus dose-dependent elevations in serum aminotransferases.
• Bacterial sepsis severe cholestasis (cholangitis lenta)
• CMV infection Cholestatic or Hepatocellular picture.
• CMV hepatitis  frequent and severe in liver transplant recipients
• VZV and HSV  hepatitis and fulminant liver failure

69. Primary or recurrent disease HCV or HBV
• Immunosuppression Increase in HCV titers
Aggressive hepatic disease post-transplant
Cirrhosis 3 to 10 years
• INF-α disappointing
• HCV successfully treated renal transplant recipients
rate of renal graft failure related to INF-α is unacceptable
• Chronic HBV carriers 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  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 35%–50%
• Incidence of SOT–associated GVHD VARIES
• small intestine transplantation 5.6%
• followed by liver transplantation 1%–2%
• Approx 86 cases of liver transplant–associated GVHD since 1987
• Mortality rate 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  Clear
• Tissue injury
• surgery
• immunosuppressive agents TNF AND IL1
• chemotherapy
• irradiation
• Expression of adhesion molecules
• MHC molecules
• Costimulatory molecules
• ‘‘Priming’’ Activate host antigen presenting cells

74. PHASE 2
• Donor T cells are activated  APC
– Proliferate
– Differentiate Activated T cells
– Migrate
IL-2
Interferon g
MHC class II on epithelial cells & macrophages
Stimulates the activation of T cells & NK Cells

75. PHASE 3
• Effector phase
• Natural killer cell
• Antihost cytotoxic T-lymphocyte activity
Immune effector mechanisms
Induce Apoptosis in target cells

76. CLINICAL PRESENTATION
• SOT  Acute GVHD  2 to 6 weeks after liver transplantation
• Skin rash 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 cases Bullae & Vesicles

77. Upper GI system
• Anorexia
• Dyspepsia
• Intestinal bleeding
• Cramping abdominal pain (distal small bowel and colon)
• Diarrhea green, mucoid, watery, and mixed with exfoliated cells
forming fecal casts.
Hematopoietic System
• Liver transplantation 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  Increased crypt apoptosis
• Grade II Apoptosis with crypt abscess
• Grade III Crypt necrosis
• Grade IV Total denudation of mucosal areas
SKIN
• Grade I Vacuolization of the basal keratinocytes
• Grade II Dyskeratotic keratinocytes and basal cell vacuolization
• Grade III Increased keratinocyte necrosis and focal basal layer
clefting
• Grade IV  Necrosis of the entire epidermis & complete separation
from the dermis

80. DIAGNOSIS
• Demonstration of substantial donor lymphoid chimerism
• Donor lymphoid chimerism  very common following liver
transplantation
• usually disappears within 1 to 3 weeks
• Positive value > 20% more than 1-week post-transplant HIGHLY
specific
• Lower valueearly or subclinical GVHD.

81. TREATMENT
• Increasing immunosuppression
• Support of hematopoiesis with cytokines
• Discontinuation of antibiotics or any drugs Myelosuppression
• Mortality exceeds more than 75%
• Approx 86 cases since 1987
18 patients survived
13 of the survivors immunosuppression had been increased
5 other  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  high risk
• TMP-SMX OD [80 mg TMP/160 mg SMX] or one double-strength
tablet 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  cardiac transplantation
• seronegative recipients from seropositive donors 50 to 75 %
PRESENTATION:
• Myocarditis
• Cardiomyopathy
• brain abscess
• pneumonitis
• Empyema,

85. Toxoplasmosis
• Median time to presentation 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.

87. References