Hepatitis B and Acute Liver Failure

1. Hepatitis B andAcute Liver Failure Jack Kuritzky, PGY-2 UNC Internal Medicine Morning Report 3/12/10

2. HEP B - NATURAL HISTORY • Mode of Infection • Perinatal most common worldwide • In US, most commonly transmitted by sexual contact or IVDU • Incubation period 1-4 months • Symptoms • Anorexia • Constitutional symptoms • Jaundice • Nausea • RUQ disomfort

3. HEP B – ACUTE PHASE • Subclinical or anicteric hepatitis (70%) • Icteric hepatitis (30%) • Fulminant Hepatitis (0.1% - 0.5%) • Acute Liver Failure: Rapid development of severe acute liver failure with impaired synthetic function and encephalopathy in a patient who previously had a normal liver or well compensated liver disease • Development of encephalopathy within 8 weeks of symptoms in a pt w/o liver disease • Development of encephalopathy within 2 weeks of jaundice

4. ACUTE LIVER FAILURE Goldberg, E and Chopra, S. Acute liver failure: Definition; etiology; and prognostic indicators. UpToDate, Sept. 2009.

5. CAUSES OF ACUTE LIVER FAILURE • Data from 17 US sites, 308 consecutive patients with acute liver failure (Ostapowicz G, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002 Dec 17;137(12):947-54.) • Acetaminophen overdose (39 percent) • Indeterminate (17 percent) • Drug reactions (13 percent) • Viral hepatitis A or B (12 percent) • survival at 3 weeks was 67%. • 29% had liver transplantation and 43% survived without transplantation

6. HEP B – RESOLUTION OF INFECTION • Previous infection without further virologic, biochemical, or histologic evidence of disease • Symptoms typically improve in 1-3 months • >95% of cases resolve in adults • >90% progress in neonatal hepatitis and 20-50% progress in patients 1-5 yrs old

7. HEP B – CHRONIC PHASELess than 5% of infected adults • Asymptomatic carrier state • HBsAg+ but no chronic, active inflammatory damage • Chronic hepatitis • Chronic "necroinflammatory infection", subdivided with HBeAg positive and HBeAg negative • HBeAg is a marker of viral replication and infectivity • 12-20% progress cirrhosis • Cirrhosis • 6-15% of compensated cirrhosis progress to HCC • Hepatocellular carcinoma

8. HEP B - TREATMENT • SUPPORTIVE • Antiviral options: lamivudine, adefovir, entecavir, telivudine, and tenofivir  • Who to treat--Acute HepB: • Trial of 71 patients with lamivudine for acute HepB (Kumar, et al. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology. 2007 Jan;45(1):97-101.) • No difference in clinical or biochemical outcomes • No difference in patients with severe disease, though numbers limited • Fulminant HepB, immunocompromised, prolonged course (>4 weeks), pre-existing liver disease, coinfection with HepC/D • Who to treat--Chronic HepB • Compensated cirrhosis w/HBV DNA >2,000 IU/mL • Decompensated cirrhosis w/detectable viral load

9. HEP B - VACCINE • Series of 3 injections at time 0, 1 month, and 6 months • Indicated for health-care workers, dialysis patients, patients w/chronic liver disease, patients with high-risk sexual practices, and IV drug users • Good response is determined by an anti-HepB surface Ag titer of  >10 mIU/mL • Available US vaccines are 95% effective in healthy adults • Post vaccination testing only recommended for health-care workers, dialysis patients, and other selected patient populations • Non-responders should complete a second 3-dose regimen (successful in 50-70% of patients)

10. SOURCES • Goldberg, E and Chopra, S. Acute liver failure: Definition; etiology; and prognostic indicators. UpToDate, Sept 2009. • Kumar, et al. A randomized controlled trial of lamivudine to treat acute hepatitis B. Hepatology. 2007 Jan;45(1):97-101 • Lok, A. Clinical manifestations and natural history of hepatitis B virus infection. UpToDate, Sept 2009. • Ostapowicz G, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med 2002 Dec 17;137(12):947-54.

11. QUESTIONS?