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GI Grand Rounds

Explore the demographics, risk factors, treatment, and outcomes of severe acute HBV. Learn about acute HBV incidence and the management of severe cases.

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GI Grand Rounds

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  1. GI Grand Rounds Johanna Chan Gastroenterology Fellow Baylor College of Medicine 6/27/13

  2. No conflicts of interestNo financial disclosures

  3. HPI • RFC: abnormal liver function tests • 39yo transvestite man with DM1, frequent hospitalizations for DKA • Admitted to hospital 4/4/13 with DKA • ALT 765, AST 629, total bilirubin 0.5, alk phos 229, albumin 3.4 • No documented hypotension, no available INR, no other specific GI symptoms • Referred to GI clinic for follow up of LFTs

  4. Past Medical History • DM1, diagnosed in his 20s • poorly controlled (Hgb A1c 13.7%) • frequent hospitalizations for DKA • complicated by peripheral neuropathy • chronic early satiety and nausea (?gastroparesis) • HTN • HLD • Hypothyroid

  5. Medications • Insulin • Gabapentin • Enalapril • Esomeprazole 20 mg PO daily • Simvastatin 40 mg PO QHS (stopped after 4/2013) • Levothyroxine 100 mcg PO daily • Tylenol 500 mg PO BID (stopped after 4/2013) • No herbs or supplements

  6. HPI continued • Presents to GI clinic approximately 6 weeks post-hospitalization • Malaise, poor appetite, nausea, vomiting of clear yellow emesis, early satiety • Clearly now markedly jaundiced, scleral icterus • No abdominal pain, change in stools • 60 lb unintentional weight loss over the past 10 years

  7. Other history • Family history • Mother DM2 • Brother DM1, HTN, HLD • No rheumatologic or other autoimmune disease • No family history of liver disease • Social history • Complete EtOH abstinence • No history of IVDA or tobacco • No blood transfusions or tattoos • Unprotected sex (MSM) • “Black market” hormone injections, Mexico, 1990s

  8. Exam • T 98.2, BP 113/72, HR 85, RR 12, O2 sat 99% RA • 5’8”, 189 lbs • Gen: markedly jaundiced, AAOx4, NAD, groomed casually in women’s clothing • HEENT: marked scleral icterus • Neck: supple, no LAD • CV: RRR no m/r/g • Chest: no spider angiomata, no gynecomastia • Lungs: CTAB no wheezes/rales/rhonchi • Abd: S/NT/ND, NABS, no fluid wave • Ext: no edema

  9. Available labs HIV negative HAV IgM negative HBsAg positive (negative in 2008) HBcAb IgM positive (negative in 2008) HBV DNA PCR 108,000,000 HBV DNA log 10 8.04 HCV IgG negative

  10. Labs in clinic 100 15 13 137 144 4.8 200 4.1 27 0.9 38.2 68% PMNs MCV 89 Total protein 7.1 Albumin 3.3 Total bili 8.8 ALT 2143 AST 1302 Alk phos 193 INR 1.1 PTT 39.9 TSH 3.02 HCV DNA PCR negative HDV Ab negative

  11. LFT trend

  12. Imaging • RUQ U/S: mild hepatomegaly (17cm at right mid-clavicular line) with normal echogenicity, smooth contour; small sludge, CBD 0.3cm

  13. Management?

  14. LFT trend

  15. Clinical questions • Who is getting acute HBV in the U.S.? • What is severe acute HBV? • How and when should we treat severe acute HBV?

  16. Acute HBV demographics • Acute HBV incidence has declined 82% since 1990 • 8.5 cases per 100,000 in 1990 • 1.5 cases per 100,000 in 2007 (the lowest rate ever recorded) • Declines in all age groups, but especially in children <15 yrs, attributable to vaccination (national vaccination strategy implemented in 1991) Daniels et al. MMWR Surveill Summ. 2009 May 22;58(3):1-27.

  17. Acute HBV demographics • In 2007, 4,519 acute symptomatic cases reported (43,000 additional new infections, asymptomatic) • Risk factors for infection: 38% multiple sex partners, 11% MSM, 6% sexual contact with a person known to have hepatitis B. IVDU reported for 15% of persons. • 2007 reports: 76% had jaundice, 40% were hospitalized, and 2% died. Daniels et al. MMWR Surveill Summ. 2009 May 22;58(3):1-27.

  18. Acute HBV incidence Daniels et al. MMWR Surveill Summ. 2009 May 22;58(3):1-27.

  19. Acute HBV incidence Daniels et al. MMWR Surveill Summ. 2009 May 22;58(3):1-27.

  20. Acute HBV incidence Daniels et al. MMWR Surveill Summ. 2009 May 22;58(3):1-27.

  21. Management of severe acute HBV

  22. Typical acute HBV clearance Tillman et al. Liver Int. 2012 Apr;32(4):544-53.

  23. Acute hepatitis B • In approximately 1% of cases, acute HBV progresses to liver failure with need for transplantation

  24. Treatment with lamivudine for severe acute HBV • Large series of 37 patients (multicenter) • Definition of severe acute hepatitis: • Bilirubin >=10 mg/dl • INR > 1.6 • Presence of hepatic encephalopathy • Transplant-free survival with lamivudine for severe/acute to fulminant hepatitis B was 78.3% (29 of 37 patients) compared with 21.6% of historic controls (p < 0.001). Tillman HL et al. J Viral Hepat 2006; 13:256-63.

  25. Treatment with newer antivirals for acute HBV • Prospective study, 6 patients in Germany with HBV-related acute liver failure • Entecavir 1 mg/day within 1-18 days of admission, continued for at least 3 months • Normalization of INR, ALT, and bilirubin within 3 months • 1 patient went on to develop chronic hepatitis B Jochum C et al. Digestion 2009; 80:235-40.

  26. Risk of increasing chronicity with treating acute HBV • 57 patients hospitalized with acute HBV acquired in adulthood in Japan • 7 of 57 patients developed persistence (HBsAg positive 6 months after index hospitalization) • 6 of the 7 received prednisolone or glycyrrhizin during acute illness, 1 did not • Infection persisted in 86% of patients who received treatment vs. 2% of patients who did not (p = 0.01) Kobayashi M et al. J Med Virol 2002; 68:522-8.

  27. Take home points • Fortunately, frequency of severe acute to fulminant liver failure in acute HBV is low • For acute severe to fulminant HBV-related liver failure, lamivudine has shown benefits in transplant-free survival • Small case series promising for entecavir in the setting of acute severe to fulminant HBV-related liver failure

  28. References • Daniels D, Grtydal S, Wasley A; Centers for Disease Control and Prevention. Surveillance for acute viral hepatitis – United States, 2007. MMWR Surveill Summ. 2009 May 22;58(3):1-27. • De Socio GV et al. Severe acute hepatitis B treated with entecavir. Mediterr J hematol Infect Dis. 2011;3(1):32011010. • Jochum C et al. Hepatitis B-associated acute liver failure: immediate treatment with entecavir inhibits hepatitis B virus replication and potentially its sequelae. Digestion 2009; 80:235-40. • Kobayashi M et al. Viral genotypes and resonse to interferon in patients with acute prolonged hepatitis B virus infection of adulthood in Japan. J Med Virol 2002; 68:522-8. • Kumar M et al. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology. 2007 Jan; 45(1):97-101.

  29. References continued • Tillman HL, Zachou K, Dalekos GN. Management of severe acute to fulminant hepatitis B: to treat or not to treat or when to treat? Liver Int. 2012 Apr;32(4):544-53. • Tillman HL et al. Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience. J Viral Hepat 2006; 13:256-63. • Yu JW et al. The study of efficacy of lamivudine in patients with severe acute hepatitis B. Dig Dis Sci. 2010 Mar; 55(3):775-83. • Yu JW et al. Lamivudine treatment is associated with improved survival in fulminant hepatitis B. Liver Int 2011; 31:499-506.

  30. Questions?

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