Solid Organ Transplantation Basics

Solid Organ Transplant: The Basics

• Over 42,000 people in the US received some form of transplant in 2022.
• Survival rates of transplanted grafts continue to improve.
• There are over 104,000 people currently on the waitlist for transplants.
• 90% of US adults support organ donation, but only 60% are registered.

Definitions

• Organ transplantation: the removal of organs from one person (donor) and the surgical implantation of those organs into another person (recipient).
• Immunosuppression: required to continue the healthy function of the donor organs, otherwise, the recipient risks rejection.
• Rejection: the activation of the recipient's immune system, targeting the donor organ.

History

• 1954: first successful renal transplant in North America.
• 1963: first lung transplant and first liver transplant.
• 1967: first successful heart transplant and first successful liver transplant.
• 1983: first successful lung transplant.
• 2022: the total number of organ transplants performed in the US reached one million.

What Gets Transplanted

• Organs and other tissues:
  • Heart
  • Lungs
  • Liver
  • Kidney
  • Intestine
  • Bone Marrow
  • Blood products
  • Corneas
  • Vascular Composite Allografts (VCAs):
    • Face
    • Hands
    • Uterus
    • Penis

Graft Survival

• Organ Type | 1 Year | 5 Year
  • Heart | 91% | 78%
  • Lung | 87.75% | 52.5%
  • Liver | 93.27% | 72%
  • Living Donor Kidney | 98.46% | 85%
  • Deceased Donor Kidney | 97.5% | 80%
  • Pancreas | 95% | 74.5%

VCA (Vascular Composite Allografts)

• Face: 18 total cranio-facial transplants performed from 2008-2020.
• Uterus: 39 transplants performed.
• Penile: 2 transplants performed.
• Limbs: 19 bilateral upper extremity, 18 unilateral.

Waitlist Stats

• Waitlist additions: 21,000.
• Waitlist mortality increased in 2020 for kidney, lung, and liver.

Who Gets Transplanted?

• Eligibility criteria:
  • End-stage organ disease despite best medical management.
  • Otherwise healthy.
  • Social support in place.
  • Medical need.
  • Geography.
• Contraindications:
  • Active substance use.
  • Active infection.
  • Active cancer.
  • Psycho-social issues.
  • Medical instability.
  • Obesity/cachexia.

Surgical Overview

• Kidney transplant: available at Mayo Clinic.
• Deceased donor liver transplant: available at Mayo Clinic.
• Living donor liver transplant: available at Mayo Clinic.
• Pancreas transplant: available at Mayo Clinic.
• Heart transplant: available at Mayo Clinic.
• Bilateral lung transplant: available at Emory University.
• Face transplant: available at Cleveland Clinic.
• Hand/arm transplant: available at Johns Hopkins University.
• Uterus transplant: available at Cleveland Clinic.
• Penile transplant: available at Johns Hopkins University.

Post-Surgical Support

• General: ICU vs. IMC, pain management, restore function, rehabilitation.
• Organ-specific:
  • Heart: hemodynamic support, pacemaker.
  • Lungs: pulmonary support, pulmonary toilet.
  • Kidney: fluids and electrolytes, bladder drainage.
  • Pancreas: blood glucose, bowel function.
  • Liver: LFTs, "other" LFTs, biliary drainage.

Possible Post-Surgical Complications

• Bleeding vs. thrombosis.
• Vascular stenosis.
• Wound infection.
• Interrupted lymphatics.
• Luminal disruption.
• Nerve injuries.
• Ischemia.
• Aspiration.

Medical Management: Immunosuppression

• Three phases:
  1. Induction: given in the peri-procedural timeframe.
  2. Maintenance: long-term graft survival.
  3. Rescue: treating rejection.

Induction

• Goal: massively suppress the immune system and delay recognition of the new organ as foreign.
• Agents:
  • Thymoglobulin (T-Cell Ab).
  • Campath (T cell Ab).
  • Basiliximab (IL 2 interceptor).
  • High-dose IV steroids.

Maintenance

• Goal: long-term graft survival.
• Agents:
  • Calcineurin inhibitors (tacrolimus, cyclosporin).
  • Mycophenolate mofetil (sometimes azathioprine).
  • Steroids.
  • mTOR inhibitors (rapamune, everolimus).

Prophylaxis

• Post-transplant infections:
  • PCP pneumonia.
  • Fungal infections.
  • CMV.

New and Coming Soon

• Hepatitis C positive donors.
• HIV positive donors.
• New immunosuppressive agents.

Rejection

• All transplanted patients will have some episode of rejection.
• Signs and symptoms:
  • Pain over graft site.
  • Lab abnormalities.
  • Failure to thrive.
  • Biopsy is the gold standard for diagnosis.
• Treatment:
  • Steroids.
  • Thymoglobulin.
  • Plasmapheresis.
  • Gamunex.

Other Complications

• Malignancy: 3-4 times increase in all types of cancer.
• PTLD (Post-Transplant Lymphoproliferative Disorder).
• Graft vs. Host.
• Non-compliance.

References

• List of sources cited in the original text, including journal articles, books, and online resources.

Hepatitis Overview

• Hepatitis is an inflammation of the liver, which can be caused by viral infections, autoimmune disorders, or exposure to toxins.
• It can be acute or chronic, and may lead to liver failure or cirrhosis.

Hepatitis A

• Caused by the Hepatitis A virus (HAV), which is transmitted through the fecal-oral route, contaminated food and water.
• Symptoms include fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, and jaundice.
• Diagnosis is made through serological tests for IgM and IgG anti-HAV antibodies.
• Treatment is supportive care, with no specific antiviral treatment.
• Prevention is possible through vaccination, proper hygiene, and sanitation.

Hepatitis B

• Caused by the Hepatitis B virus (HBV), which is transmitted through blood, semen, and other bodily fluids.
• Symptoms are similar to Hepatitis A, but can be more severe.
• Diagnosis is made through serological tests for HBsAg, anti-HBs, and anti-HBc antibodies.
• Treatment includes antiviral medications and interferon therapy.
• Prevention is possible through vaccination, safe sex practices, and screening of blood and organ donors.

Hepatitis C

• Caused by the Hepatitis C virus (HCV), which is transmitted through blood, organ transplantation, and vertical transmission.
• Symptoms are often asymptomatic, but can cause fatigue, loss of appetite, and nausea.
• Diagnosis is made through serological tests for anti-HCV antibodies and PCR for HCV RNA.
• Treatment includes antiviral medications, direct-acting antivirals (DAAs).
• There is no vaccine available, and prevention is through screening of blood and organ donors.

Liver Inflammation

• Characterized by liver cell necrosis, inflammation, and fibrosis.
• Causes include viral infections, autoimmune disorders, toxins, and metabolic disorders.
• Symptoms include fatigue, loss of appetite, nausea, vomiting, and abdominal pain.
• Diagnosis is made through liver function tests, imaging studies, and liver biopsy.

Viral Transmission

• Modes of transmission include fecal-oral, blood, and vertical transmission.
• Risk factors include unsafe sex, shared needles, tattooing, and piercing.
• Prevention is possible through vaccination, safe sex practices, screening of blood and organ donors, and proper hygiene.

Solid Organ Transplant

• Risk of transmission of Hepatitis B and C viruses through organ transplantation.
• Prevention is possible through screening of organ donors and antiviral prophylaxis.

Immunosuppression Therapy

• Increases risk of Hepatitis B and C reactivation.
• Prevention is possible through antiviral prophylaxis, monitoring of liver function and viral load.

Liver Failure

• Characterized by severe liver dysfunction, coagulopathy, and hepatic encephalopathy.
• Causes include acute liver inflammation, chronic liver disease, and cirrhosis.
• Symptoms include jaundice, fatigue, confusion, and bleeding.
• Treatment is supportive care, with liver transplantation as an option.

Cirrhosis

• Characterized by irreversible liver scarring, liver dysfunction, and portal hypertension.
• Causes include chronic liver disease, Hepatitis B and C, and alcohol abuse.
• Symptoms include fatigue, loss of appetite, nausea, vomiting, and abdominal pain.
• Treatment is liver transplantation, with management of complications such as portal hypertension and ascites.

Liver Failure

• Liver failure can be caused by various factors, including toxic agents, infections, mechanical injuries, and autoimmune diseases.
• Acute liver failure can develop in days to weeks, while chronic liver failure develops over a longer period of time (more than 6 months).
• Hepatitis is another word for liver inflammation, which can progress to fibrosis (scarring), cirrhosis (non-functional tissue), and eventually liver failure.

Diagnosis and Treatment

• Diagnosis involves laboratory tests, imaging studies, and liver biopsy.
• Laboratory tests include CBC, CMP, INR, and hepatitis serologies.
• Imaging studies include ultrasound, CT, and MRI liver protocols.
• Treatment involves supportive care, medications, and potential liver transplantation.
• Supportive care includes monitoring of INR, CBC, bilirubin, and liver function tests.
• Medications used to treat liver failure include lactulose, rifaximin, diuretics, midodrine, propranolol, and octreotide.

Prophylaxis

• Pantoprazole is used for GI prophylaxis.
• Cipro or other antibiotics are used for spontaneous bacterial peritonitis (SBP) prophylaxis.

Procedures

• Paracentesis is used to remove excess fluid from the abdomen and can help with breathing and patient comfort.
• Thoracentesis is used to remove excess fluid from the chest cavity.
• TIPS (transjugular intrahepatic portosystemic shunt) is a procedure used to create a shunt between the hepatic vein and the portal vein.
• ERCP (endoscopic retrograde cholangiopancreatography) and EGD (esophagogastroduodenoscopy) are used to diagnose and treat gastrointestinal disorders.
• Biopsy is used to diagnose liver disease.
• Transplant is a life-sustaining therapy that requires lifelong immunosuppression and has potential complications, such as cancer and cardiac disease.

Common Causes of Liver Failure

• Acute liver failure can be caused by medications, toxins, hepatitis A, B, and E, and other factors.
• Chronic liver failure can be caused by ETOH, NAFLD/NASH, chronic viral hepatitis, AIH, and other factors.

Epidemiology

• According to the CDC, approximately 4.5 million people in the US have chronic liver disease.
• Hepatitis C is the leading cause of liver disease, followed by ETOH, NAFLD/NASH, and hepatitis B.

Viral Prodrome

• Viral prodrome is a symptom complex that includes malaise, myalgia, arthralgia, fatigue, anorexia, nausea, vomiting, diarrhea, and fever.
• It can occur in patients with hepatitis B and other viral infections.

Icteric Phase

• The icteric phase is characterized by dark urine, clay-colored stool, and jaundice.
• It can occur in patients with liver disease and can be accompanied by other symptoms, such as fever, anorexia, and nausea.

Physical Findings

• Physical findings in patients with liver disease can include jaundice, ascites, vascular cephalization, caput medusae, and other signs of liver dysfunction.
• The "grimace" body habitus is a characteristic physical finding in patients with liver disease.

Hepatic Encephalopathy

• Hepatic encephalopathy is a complication of liver disease that can cause confusion, altered mental status, and other neurological symptoms.
• It can be graded from I to IV and can be provoked by various factors, including GI bleeding, electrolyte abnormalities, and dehydration.

Associated Pathophysiology

• Liver disease can be associated with various pathophysiological processes, including cardiovascular, respiratory, infectious, gastrointestinal, renal, hematological, oncological, endocrine, neurological, and dermatological disorders.