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4C1 Case discussion of suspected flared up HBV-related Fulminent hepaic failure

4C1 Case discussion of suspected flared up HBV-related Fulminent hepaic failure. Ri 王經凱 林煒莎. A 65 year-old woman complained of general malaise since 12/26/2005. Brief history(1). Breast cancer, infiltrating ductal carcinoma, T2N0M0 s/p MRM at 新店

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4C1 Case discussion of suspected flared up HBV-related Fulminent hepaic failure

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  1. 4C1 Case discussion of suspected flared up HBV-related Fulminent hepaic failure Ri 王經凱 林煒莎

  2. A 65 year-old woman complained of general malaise since 12/26/2005.

  3. Brief history(1) • Breast cancer, infiltrating ductal carcinoma, T2N0M0 s/p MRM at 新店 慈濟H. on 10/21/2005 s/p chemotherapy on 11/2005, 12/05/2005, and 12/26/2005 • HBV carrier, regular OPD follow up • DM(-), hypertension(-) • Alcohol(-), smoking(-) • Allergy(-)

  4. Brief history(2) • Drug hx: C/T(: cyclophosphamide, 5-FU, doxorubicin); dexamethasone, tropisetron(navoban), famotidine, diphenhydramine • Travel history: nil

  5. Brief history(3) • General malaise and yellow skin appearance were noted since 12/26/2005 • Leukocytopenia and abnormal liver function(AST/ALT:573/1081, ammonia100, T-bil 12.67)was noted at OPD  admitted to 新店慈濟H. • HBV DNA>3.8*108 • After admission, rapidly progressive loss of consciousness despite conservative treatment  transfer to NTUH

  6. Physical examination • Consciousness: E1M2-3V1; general yellowish skin • BP: 152/61, HR: 74, BT 37.2 • HEENT: sclerae: icteric; neck: supple; grossly normal • Chest: symmetrically expansion, breathing sound: clear, port-a insertion on left subclavian area • Abdomen: soft, distention, no skin rash • Extremity: pitting edema

  7. Lab data s/p P.E. s/p P.E. s/p P.E. s/p P.E.

  8. Tentative diagnosis • Fulminent hepatic failure, suspect HBV flare up induced • Breast cancer, infiltrating ductal carcinoma, T2N0M0

  9. Etiology of Fulminent Hepatitis • Whether chemotherapy induce fulminent hepatitis ? • Chemotherapy in patients with hepatitis B • Prognosis of fulminent hepatitis

  10. Etiology of Fulminent Hepatitis • The most frequent etiologies were 1. acetaminophen (20 percent), 2. cryptogenic (15 percent) 3. drug reactions (12 percent), 4. hepatitis B (10 percent) 5. hepatitis A (7 percent). From United States that included 295 patients seen in 13 transplant centers between 1994 and 1996

  11. The reason of liver function test (LFT) abnormalities after chemotherapy 1. the chemotherapy drug 2. progressive tumor (metastasis ?) 3. coexisting hepatic disease ( Ex : hepatitis B) 4. pre-existing medical conditions 5. taking multiple medications

  12. # The diagnosis of drug-induced liver injury can be difficult. # Although rarely necessary, liver biopsy may be required in this setting to exclude tumor metastasis and confirm the impression of drug-induced changes

  13. #Biopsy findings may be nonspecific, but in general, they depend on the underlying etiology. #Idiosyncratic medication-induced hepatitis ->Panlobular necrosis . #Viral hepatitis typically shows a panlobular injury and may be difficult to distinguish from medication-induced hepatitis

  14. Whether chemotherapy induce fulminent hepatitis ? • Cyclophosphamide • 5-fluorouracil (5-FU) • Doxorubicin CAF

  15. Cyclophosphamide #cyclophosphamide is infrequently hepatotoxic #recommend a 25 to 30 percent dose reduction for patients with a serum bilirubin 3.1 to 5 mg/dL or aspartate transaminase (AST) 180 IU/L, with omission of the drug if the bilirubin is 5 mg/dL

  16. 5-fluorouracil (5-FU) #Only rare reports of hepatotoxicity have been noted with intravenous 5-FU . #more hepatotoxicity is noted when intravenous 5-FU is administered in combination with some immunostimulant agent #Oral derivatives of 5-FU have not been reported to cause liver damage.

  17. Doxorubicin • Hepatotoxicity from doxorubicin is rare • idiosyncratic reaction attributable to doxorubicin. • The need for doxorubicin dose reduction in patients with impaired liver function is a controversial area

  18. COMBINATION CHEMOTHERAPY REGIMENS • Approximately one-half to three-fourths of women receiving adjuvant CAF (cyclophosphamide, doxorubicin and 5-FU) develop transient mild abnormalities in LFTs . • These usually appear within the first three months of therapy, and normalize within a year of treatment cessation

  19. CONCLUSIONS — Chemotherapeutic agents, alone and in combination with other drugs and radiation, may cause indirect or direct hepatotoxicity. • Abnormal liver function may alter drug metabolism and increase the risk of extrahepatic toxicity. Guidelines on dose modification in hepatic disease are largely empiric.

  20. Chemotherapy in patients with hepatitis B

  21. Chemotherapy in patients with hepatitis B • HBV reactivation in pts under chemotherapy ~risk : 20-50% ~risk factors for HBV reactivation with chemotherapy: 1. HBsAg positive, particularly those who are HBeAg positive or have high levels of HBV DNA 2. male 3. use of corticosteroids

  22. ~In the presence of corticosteroids: HBV replication increases. serum aminotransferases tend to decline. ~ Corticosteroids withdrawal: viral replication declines aminotransferases increase . The peak rise in aminotransferases typically occurs four to six weeks after withdrawal

  23. Chemotherapy in patients with hepatitis B #A growing number of studies have demonstrated that prophylactic lamivudine can reduce both the incidence of reactivation and its severity in patients who are HBsAg positive.

  24. Prognosis of fulminent hepatitis

  25. Prognosis of fulminent hepatitis • Prognosis factor: 1. degree of encephalopathy 2. the patient's age 3. the cause of FHF 4. severity of SIRS 5. Alpha fetoprotein (AFP) levels 6. ratios of factor VIII and factor V 7. liver histology 8. CT scanning of the liver 9. cytokine levels 10. serum phosphate levels 11. adrenal insufficiency

  26. Spontaneous recovery is more likely with lower grades of encephalopathy : •     Grade I to II — 65 to 70 percent    Grade III — 40 to 50 percent    Grade IV — <20 percent

  27. Prognosis • Patients presenting in grade III or IV encephalopathy were less likely than those patients presenting in grade I or II encephalopathy to survive without receiving a liver graft. • The most significant predictor of outcome : due to acetaminophen, hepatitis A, shock liver, or pregnancy-related disease showed 50 percent transplant free survival, while all other etiologies showed <25 percent transplant-free survival

  28. Prognosis of fulminent hepatitis • King's College Criteria — developed for predicting the outcome in patients with FHF • a cohort of 588 patients with acute liver failure who were managed medically between 1973 and 1985 • This criteria is better able to predict patients with a poor prognosis than those with a good prognosis. • Recommendations for liver transplantation in FHF were proposed based upon the results

  29. Prognosis of fulminent hepatitis • Currently available prognostic scoring systems do not adequately predict outcome and determine candidacy for liver transplantation. • The only therapy proven to improve patient outcome in FHF is liver transplantation, which is associated with one-year survival rates of greater than 80 percent

  30. Thank you for your attention!

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