Case Report 1

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Case Report (1)

• Chief Complaint
• Jaundice for two weeks.
• Clinical Course
• A 39-year-old female uremic patient.
• Received allograft renal transplantation on
  2001-1-10 in Mainland China (????).
• Delayed graft function was noted after
  transplantation, and steroid pulse therapy was
  given.

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Causes of Acute Renal Failure after Renal
Transplantation

• Prerenal
• Hypovolemia.
• Arterial stenosis or thrombosis.
• Venous thrombosis.
• Renal
• Acute tubular necrosis.
• Hyperacute or acut rejection.
• Nephrotoxicity.
• Postrenal
• Ureteral obstruction, Urinary leak, Hematoma.

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Case Report (2)

• The patient came back to Taiwan with sCr around
  1.3 mg/dL.
• FK506 2mg po. Bid. Cellcept 500 mg po. Bid.
  Prednisolone 20 mg po. QD. were used as
  immunosuppressive therapy for 2 months.
• Hypertension was treated by Diovan 80 mg po. Qd.
  for 1 month.

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Immunosuppressive Therapy

• Cyclosporin
• Inhibits IL-2 secretion from helper T cells.
• FK506 (Tacrolimus)
• Inhibits IL-2 secretion by helper T cells.
• Mycophenolate Mofetil (Cellcept)
• Inhibit GTP synthesis in activated immune cells.
• Steroids
• Inhibits cytokine secretion from immune cells.

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Case Report (3)

• The First Admission
• On 2001-3-12.
• FK506 was replaced by cyclosporin (CsA) due to
  hyperglycemia.
• Diabetes was noted before hemodialysis.
• Family History ().
• Cyclosporin (Sandimmun Neoral) 100mg po. Bid. was
  given after discharge.

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Case Report (4)

• The First Admission
• Very high C2 levels were noted.
• Glurenorm was used for hyperglycemia.
• No liver function test was done during this
  admission.
• The patient was discharged on 2001-3-19.

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Serum C2 Levels
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Target C2 Levels in Renal Transplant Recipients
(BioDrugs 200115(5)279-290)
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Case Report (5)

• Medications at discharge
• Cyclosporin 100 mg Bid.
• Cellcept 500 mg Bid.
• Prednisolone 15 mg Qd.
• Diovan 1 Qd.
• Glurenorm 1.5 Bid.
• Glucophage 1 Qd.

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Case Report (6)

• OPD on 90-4-12
• Impaired liver function was noted.
• SGOT 80 U/L, SGPT 124 U/L.
• Cr 1.5 mg, Glucose AC 150 mg.
• BP 150/96 mmHg.
• Stopped Diovan.
• Doxaben 0.5 Bid. was added.

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Case Report (7)

• OPD on 90-5-3
• SGOT 48 U/L, SGPT 79 U/L.
• Cr 1.7 mg.
• BP 160/110 mmHg
• Cellcept dosage was increased to 1000 mg Bid.
• Tenormin 100 mg Bid. was added.

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Case Report (8)

• OPD on 90-5-31
• SGOT 45 U/L, SGPT 63 U/L.
• Cr 1.5 mg. T. Bil 1.3
• BP 120/80 mmHg.
• Anti-HCV (), HBsAg(), Anti-HBsAb(-).
• Insulin injection was given (unknown dosage).

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Case Report (9)

• OPD on 90-6-28
• SGOT 107 U/L, SGPT 151 U/L.
• Cr 1.6 mg/dL, T. Bil 5.2 mg/dL
• BP 130/90 mmHg.
• Anti-HCV (), HBsAg(), Anti-HBsAb(-).
• Jaundice(), Dyspnea().
• Admitted on 90-7-2.

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Case Report (10)

• The Second Admission (90-7-2 )
• Generalized weakness and edema.
• UTI with E. Coli infection was noted.
• Markedly prolongation of PT and APTT was also
  found.
• Sudden onset of leukopenia and thrombocytopenia
  occurred on 90-7-3.

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Case Report (11)

• 2001-7-3
• The patient was transferred to ICU due to
  impeding hepatic failure.
• No active lung lesion.
• Lamivudine was given.
• 2001-7-4
• Conscious disturbance, shock, and high fever
  occurred.
• The patient expired.

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Hepatology Profiles
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Major Problems of This Patient

• Acute liver failure.
• Leukopenia.
• Thrombocytopenia.

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Causes of Acute Hepatic Failure (1)(J
Gastroenterol Hepatol 200015480-8)

• Viral
• Hepatitis A, B(D), C, E. ?
• Haemorrhagic fever viruses. ?
• Cytomegalovirus. ?
• Herpes simplex viruses. ?
• Adenovirus. ?

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Causes of Acute Hepatic Failure (2)(J
Gastroenterol Hepatol 200015480-8)

• Drugs/Toxins
• Acetaminophen
• Carbon tetrachloride
• Amanita phalloides poisoning
• Bacillus cereus (???) emetic toxin.
• Cyanobacteria microcystins.
• Isoniazid, halothane, troglitazone.
• Herbal medicines.
• Idiosyncratic reactions.

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Drugs Inducing Idiosyncratic Liver Injury (1)

• Infrequent Causes
• Isoniazid
• Valproate
• Halothane
• Phenytoin
• Sulfonamides
• Propylthiouracil
• Amiodarone
• Disulfiram
• Dapsone

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Drugs Inducing Idiosyncratic Liver Injury (2)

• Rare Causes
• Carbamazepine
• Ofloxacin
• Ketoconazole
• Lisinopril
• Niacin
• Labetalol
• Etoposide (VP-16)
• Imipramine
• Interferon alfa
• Flutamide

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Causes of Acute Hepatic Failure (3)(J
Gastroenterol Hepatol 200015480-8)

• Metabolic/Genetic
• Galactosaemia.
• Fructose intolerance.
• Tyrinosaemia.
• Neonatal iron storage disease.
• Wilsons disease.
• Alpha-1-antitrypsin deficiency.
• Neoplastic
• Lymphoma, metastatic malignancies.

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Causes of Acute Hepatic Failure (4)(J
Gastroenterol Hepatol 200015480-8)

• Pregnancy-related
• Acute fatty liver of pregnancy.
• HELLP syndrome (haemolysis, impaired liver
  function, low platelet)
• Heat stroke
• Vascular
• Budd-Chiari syndrome.
• Veno-occlusive disese.
• Ischemic shock liver.

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Possible Causes of AHF

• Viral infection
• Hepatitis virus B or C.
• Haemorrhagic fever viruses.
• Cytomegalovirus.
• Herpes simplex viruses.
• Adenovirus.

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Long-Term Impact of Hepatitis B, C Virus
Infection on Renal Transplantation(Am J Nephrol
200121300-306)

• 477 patients from 1984 to 1999.
• Age 6-67 years old.
• Follow-up period 4 months to 15 years.
• Cyclosporin-based immunotherapy.

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Prevalence of Chronic Liver Disease
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Prevalence of Hepatoma
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Prevalence of Liver Cirrhosis/Hepatic Failure
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10-year Patient Survival Rate
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10-year Graft Survival Rate
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Lamivudine Therapy for Severe Acute Hepatitis B
Virus Infection after Renal Transplantation(Trans
plantation Proceedings 2001332948-2949)

• 56 positive outcome in immunosuppressed
  patients.
• Higher positive outcome in patients with renal
  transplantation.
• Should be given as early as possible.
• Long time treatment is reasonable.
• No risk of rejection.

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HCV Transmission by Organ Transplantation

• 96 in 26 organ recipients. (N Eng J Med
  1992327910-915)
• 56 in 37 kidney recipients. (Transplantation
  199457826-813)
• 0 in 6 kidney recipients. (Transplantation
  199455674-675)
• 57 in 14 kidney recipients. (Nephron
  199571249-253)

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Hepatitis C Progression after Renal
Transplantation (1)

• Liver disease is more aggressive in RT recipients
  who acquire HCV at the time of transplantation.
• 12 jaundice patients in 15 RT recipients during
  21?12 months. (NDT 1998133103-3107)
• 6 of 14 RT recipients died. (Kidney Int
  199751981-999)

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Hepatitis C Progression after Renal
Transplantation (2)

• Chronic hepatitis and cirrhosis occurred more
  frequently in RT recipients with HBV and HCV
  coinfection than those with HCV alone.
• 26 vs 10 (NDT 1995(suppl 6)10S122-S124)
• 50 vs 25.5 (NDT 199510125-128)
• No difference in the death rate from liver diease.

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Hepatitis C Progression after Renal
Transplantation (3)

• 10-year patient survival rate was 91 in 16
  HCV-positive recipients.
• (Transplant Proc 1998302100-2101)
• The use of azathioprine, antilymphocyte globulin,
  and anti-CD3 antibodies (OKT3) is linked wih more
  frequent liver disease.
• (N Eng J Med 1991325454-460)

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Viral Hemorrhagic Fevers(D.Amstrong Infectious
Disease,1999)

• An acute onset of high fever.
• High mortality rate.
• Bleeding tendency.
• Prolonged APTT.
• Pulmonary edema.
• Thrombocytopenia.
• Impaired liver function, AST/ALT gt 1.
• Death due to shock or ARDS.

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RNA Viruses Causing VHF
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Viral Hemorrhagic Fevers(Infectious Disease,
Donald Amstrong,1999)

• Diagnosis
• Isolating the virus from serum.
• Demonstrating a 4-fold rise in antibody titer.
• Demonstrating high-titer IgG antibody with
  virus-specific IgM antibody in association with
  compatible clinical disease.

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Key Clinical Features of VHF
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Yellow Fever

• Mosquito-mediated.
• The 1st phase
• Lasts for 72 hours.
• Headache, malaise, weakness, nausea, vomiting.
• The 2nd phase
• No symptoms for 24 48 hours.
• The 3rd phase
• High fever, bradycardia, bleeding.
• Hepatic failure, renal failure.

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Hantavirus Infection

• Febrile phase
• High fever, chills, headache, malaise, myalgia,
  elevated WBC, rising hematocrit.
• Hypotensive phase
• Hypotension, shock, hemorrhage, pulmonary edema,
  thrombocytopenia, renal failure.

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Dengue Hemorrhagic Fever

• No classical progressive phases in adult
  patients.
• May have a stormy and fatal course.
• Elevated liver enzymes.
• Hypotension.
• Gastrointestinal bleeding.

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Posttransplantation Viral Infection

• Cytomegalovirus (the most common).
• Herpes Simplex Virus.
• Varicella Zoster
• Epstein-Barr Virus.
• Human Immunodeficiency Virus.

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Cytomegalovirus (CMV) Infection

• Asymptomatic
• Positive CMV culture.
• More than 4x rise in anti-CMV antibody titer.
• Symptomatic
• Fever. Usually between 4th and 10th weeks.
• Neutropenia, Splenomegaly.
• Pneumonia, Hepatitis, pancreatitis.
• Arthralgia, Myalgia.
• Gastrointestinal ulceration.
• Chorioretinitis. (4 6 months later)

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Anti-CMV Ab in This Patient

• CMV antibody 1 16 (). (2000-9-7)
• CMV IgM antibody negative. (2000-9-7)

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Types of CMV Disease
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Herpes Simplex Virus (HSV) Infection

• Oropharyngeal ulceration.
• Epidermal infection.
• Gastrointestinal tract disease.
• Fulminant hepatitis.
• Pneumonia.
• Encephalitis.

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• Varicella Zoster Infection
• Localized zoster.
• Epstein-Barr Virus Infection
• Acute lymphoproliferative syndrome.
• Human Immunodeficiency Virus
• Persistent leukopenia.

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Neutropenia

• Definition
• Neutrophil count lt 1,500/cumm.
• Etiology
• Bone marrow injury.(radiation, drugs, hepatitis,
  malignancies)
• Maturation defects (poor nutrition).
• Increased margination (endotoxin)
• Accelerated consumption. (severe sepsis)
• Accelerated destruction. (Drugs, immune
  mechanisms)

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Thrombocytopenia (1)

• Definition
• Platelet count lt 70,000/cumm.
• Etiology
• Congenital.
• Acquired (decreased production).
• Aplastic anemia.
• Marrow infiltration.
• Radiation toxicity
• Chemotherapy.
• Drug toxicity (thiazides, alcohol, estrogens)

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Thrombocytopenia (2)

• Nutritional deficiency.
• Viral infection.
• Splenic problem.
• Increased platelet destruction
• Infection.
• Disseminated intravascular coagulation (DIC).
• Drug-induced.
• Posttransfusion.

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Final Diagnosis

• Acute liver failure due to Viral Infection
• Hepatitis B or/and C virus.
• Hantavirus, Dengue virus, Cytomegalovirus, Herpes
  simplex virus, Adenovirus. (??????)