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

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

3. HEP B – ACUTE PHASE Subclinical or anicteric hepatitis (70%) Subclinical or anicteric hepatitis (70%) Icteric hepatitis (30%) Icteric hepatitis (30%) Fulminant Hepatitis (0.1% - 0.5%) 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 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 8 weeks of symptoms in a pt w/o liver disease Development of encephalopathy within 2 weeks of jaundice 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.) 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) Acetaminophen overdose (39 percent) Indeterminate (17 percent) Indeterminate (17 percent) Drug reactions (13 percent) Drug reactions (13 percent) Viral hepatitis A or B (12 percent) Viral hepatitis A or B (12 percent) survival at 3 weeks was 67%. survival at 3 weeks was 67%. 29% had liver transplantation and 43% survived without transplantation 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 Previous infection without further virologic, biochemical, or histologic evidence of disease Symptoms typically improve in 1-3 months Symptoms typically improve in 1-3 months >95% of cases resolve in adults >95% of cases resolve in adults >90% progress in neonatal hepatitis and 20-50% progress in patients 1-5 yrs old >90% progress in neonatal hepatitis and 20-50% progress in patients 1-5 yrs old

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

8. HEP B - TREATMENT SUPPORTIVE SUPPORTIVE Antiviral options: lamivudine, adefovir, entecavir, telivudine, and tenofivir Antiviral options: lamivudine, adefovir, entecavir, telivudine, and tenofivir Who to treat--Acute HepB: 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.) 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 clinical or biochemical outcomes No difference in patients with severe disease, though numbers limited 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 Fulminant HepB, immunocompromised, prolonged course (>4 weeks), pre-existing liver disease, coinfection with HepC/D Who to treat--Chronic HepB Who to treat--Chronic HepB Compensated cirrhosis w/HBV DNA >2,000 IU/mL Compensated cirrhosis w/HBV DNA >2,000 IU/mL Decompensated cirrhosis w/detectable viral load Decompensated cirrhosis w/detectable viral load

9. HEP B - VACCINE Series of 3 injections at time 0, 1 month, and 6 months 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 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 Good response is determined by an anti-HepB surface Ag titer of >10 mIU/mL Available US vaccines are 95% effective in healthy adults 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 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) 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 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. 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. 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?