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1、Hepatitis B,Patricia D. Jones, M.D. November 13, 2009,Hepatitis B,Prototype member of the Hepadnaviridae family DNA virus Outer lipoprotein envelope with 3 glycoproteins Hep B surface antigens (HBsAg) Viral nucleocapsid protein - Hep B core antigen (HBcAg) Soluble nucleocapsid protein-Hepatitis B e
2、antigen (HBeAg),http:/pathmicro.med.sc.edu/virol/hep-b5.jpg,Epidemiology,Worldwide: Affects 350-400 million persons Endemic areas: Asia, Africa 1 million worldwide deaths per year Acquired perinatally and in childhood United States: Affects 1.25 million persons 4000-5000 deaths per year Acquired via
3、 sexual activity, then IVDU and occupational exposure,http:/liver.stanford.edu/images/education/world_incidence.jpg,Primary Infection,Incubation Period 4-10 weeks During the prodromal period, patient may have a serum sickness-like syndrome. Constitutional symptoms, anorexia, nausea, RUQ discomfort a
4、nd jaundice. 30 % develop icteric hepatitis. 70% develop anicteric or subclinical hepatitis. 0.5-1% develop fulminant liver failure. Symptoms and jaundice disappear in 1-3 months, though fatigue may persist.,Infection in Children vs. Adults,Children In neonates, the immature immune system does not r
5、ecognize a difference between the virus and the host. Cellular immune responses to hepatocyte-membrane HBV proteins do not occur. Risk of developing chronic HBV infection is 90% in infants born to HBeAg positive mothers. In children under 5, risk is 25-30%. Adults: Tend to have a more vigorous immun
6、e response. Less than 5% of those infected develop continual viremia and persistent infection.,Serologic Diagnosis,http:/www.haps.nsw.gov.au/userData/img/hepB1.jpg,Chronic Hepatitis B Infection,Early Replicative Phase: Immune Tolerance Perinatally acquired infection High levels of HBV DNA, HBeAg pre
7、sent No liver diseasenormal ALT, asymptomatic, Stage 0-1 fibrosis Lasts 10-30 years Replicative Phase: Immune Clearance Spontaneous clearance of HBeAg Often characterized by periods of increased HBV DNA and increased ALT due to immune-mediated lysis of infected hepatocytes, i.e. flares Nonreplicatio
8、n Phase: Inactive Carrier State HBeAg negative, anti-Hep B e positive, HBV DNA undetectable ALT levels normalize, however some patients may have active inflammation,Chronic Hepatitis B Infection,HBeAg-negative Chronic Hepatitis Precore/Core Promoter Mutations Moderate levels HBV DNA Active liver dis
9、ease and elevated ALT Older patients Resolution Hallmark is the clearance of HbSAg Does not preclude development of cirrhosis, HCC or failure. Patients may still produce HBV DNA, which has implications in the immunosuppressed,Sequelae of Chronic HBV Infection,Cirrhosis Hepatocellular Carcinoma Hepat
10、ic Decompensation Extrahepatic Manifestations Death Prognosis is worse in endemic areas: Prolonged replicative phase Clearance of HBeAg causes a 2 fold decrease in death rate. Patients who reactivate have worse prognosis.,http:/pathmicro.med.sc.edu/lecture/images/hepato-b.jpg,Extrahepatic Manifestat
11、ions,Occur in 10-20% of patients with Chronic Hep B. Serum Sickness Polyarteritis Nodosa Membranous and Membranoproliferative Glomerulonephritis,Genotypes,Genotype B associated with HBeAg seroconversion at an earlier age, more sustained remission, less active hepatic necroinflammation, a slower rate
12、 of progression to cirrhosis and lower rate of HCC development when compared with Genotype C. Genotypes A and B are associated with higher rates of seroconversion with pegIFN-alpha than C and D.,Indications for Therapy,Acute Hepatitis One trial demonstrated no biochemical or clinical benefit in pati
13、ents treated with Lamivudine vs. placebo in 12 months. General Rule: Coagulopathy INR1.5 Persistent symptoms or marked jaundice (bilirubin 10 mg/dl) for more than 4 weeks after presentation Fulminant Hepatic Failure Concomitant infection with Hep C or D,Indications for Therapy,HBeAg-positive patient
14、s: HBeAg-positive patients with persistently normal ALT should be tested for ALT at 3-6 month intervals HBeAg status should be checked every 6-12 months. HBeAg positive with HBV DNA levels 20,000 IU/mL after a 3-6 month and ALT 1-2 x ULN OR are 40 years liver biopsy w/ treatment if biopsy shows mode
15、rate/severe inflammation or significant fibrosis. Patients who remain HBeAg positive with HBV DNAlevels20,000 IU/mL after a 3-6month period of elevated ALT levels 2 ULN should be considered for treatment. HBeAg-negative patients: HBeAg-negative patients with normal ALT and HBV DNA 2,000 IU/mL: Teste
16、d ALT q 3months during the first year to verify true “inactive carrier state” and then every 6-12 months.,http:/www.aasld.org/practiceguidelines/Documents/Bookmarked%20Practice%20Guidelines/Chronic_Hep_B_Update_2009%208_24_2009.pdf,http:/ JL. Hepatitis B Virus Infection. N Eng J Med 2008;359: 1486-500. Ganem D, Prince AM. Hepatitis B Virus InfectionNatural History and Clinical Consequences. N Eng J
