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General Reference ⬇

Nejm 1997;337:1733

Pathophys and Cause ⬆ ⬇

Cause:Hepatitis B virus

Pathophys:Percutaneous, perimucosal, perinatal and sexual transmission into blood.

Acute phase: 4-6 wk, viral replication, inflammatory response with cytopathic reaction; hepatic failure in 0.1-0.5% through massive autoimmune lysis of infected hepatocytes.

Chronic phase: host able to target infected hepatocytes, viral replication ceases, aminotransferase levels normalize, HBV DNA no longer detectable; integration of HBV into hepatocyte DNA.

Epidemiology ⬆ ⬇

Primarily spread venereally or via blood and blood products (transfusion risk = 1/63 000—Nejm 1996;334:1685), fresh, dry, or frozen. Transmitted by mucous membranes but not by urine and feces (Nejm 1969;281:1375), and via eczematous skin (Ann IM 1976;85:573)

Signs and Symptoms ⬆ ⬇

Sx:60- to 160-d incubation period; arthralgias/arthritis (Nejm 1978;298:185; Ann IM 1971;74:207; 1971;75:29), cryoglobulins (Ann IM 1977;87:287), urticaria and other rashes (Ann IM 1978;89:34)

Si:Many cases anicteric

Course ⬆ ⬇

Acute hepatitis, leads to:

  • Benign course, recover or have relapsing, or portal mild hepatitis; or
  • Acute liver necrosis, all of whom die w/o transplant; or
  • Submassive hepatic necrosis (bridging) of whom 60% die or go on to postnecrotic cirrhosis, the balance recover completely; or
  • Chronic active hepatitis, controlled with medications, eventually with a progressive downhill course; or
  • Asymptomatic carrier state in ~90% newborns, 20% school age children, <1% young healthy adults (Nejm 1987;316:965)

Complications ⬆ ⬇

Hepatocellular carcinoma, hepatoma, 2% after 10 yr (Ann IM 2001;135:759), higher w higher hep B DNA levels (Jama 2006;295:65), 10% higher if hep BeAg present (Nejm 2002;347:168); chronic active hepatitis (10%) (Hepatitis C); delta (delta.gif) agent infection (hepatitis D), an RNA viral parasite of hep B virus, only can replicate if hep B around, leads to acute hepatitis itself or severe chronic active hepatitis (Nejm 1987;317:1256); fasting hypoglycemia (Nejm 1972;286:1436); serum sickness (20%), polyarteritis, nephritis, esp membranous GN (Nejm 1991;324:1457)

Lab and Xray ⬆ ⬇

Lab:

Chem:Typical hepatitis enzyme picture w ALT (SGPT) > AST (SGOT) > LDH > alkaline phos levels; get CPK to r/o myopathy if LDH > AST (SGOT) > ALT (SGPT)

Path:Liver bx in patient with new dx, nl ALT to distinguish HBeAg-negative chronic hepatitis B from inactive HBsAg carrier; bx showing active disease would prompt tx of chronic hep B.

Serol:Core IgM antibody always up by time of 1st sx (Nejm 1978;298:1379); HBsAg (Ann IM 1982;96:193) elevated; e-antigen elevation correlates with infectivity; anti-HBsAg appears shortly after sx develop, but there may be a window of infectivity when HBsAg and antibody is negative but core (c) antibody is positive which, if IgM, can be distinguished from remote infection where there is attenuation of all but IgG core antibody. Follow hep B viral DNA log titers; suppress to <1000/cc

Treatment ⬆

Rx:

Prevention

  • Body fluid precautions including wearing gloves (Ann IM 1981;95:133)
  • Monitor Hep B-pos health workers but let work unless surgeons doing high-exposure surgery, then should not work if Hep BeAg positive or documented transmissions (Nejm 1997;336:178)
  • Screen all pregnant women for HBsAg (Ann IM 1987;107:412) so can prophylax and immunize their infants
  • Hep B immune globulin (HBIG) prophylaxis 0.05 cc/kg × 2, 30 d apart within 24-72 h of exposure, $160/dose; for newborns of HBsAg-pos mothers 0.5 cc within 12 h of birth along w vaccine
  • Immunization w recombinant vaccine (Nejm 1997;336:196; Med Let 1985;27:118), lasts >15 yr (Ann IM 2005;142:333); cmplc: rare postvaccine alopecia (Jama 1997;278:1176), no incr in later MS (Nejm 2001;344:319, 327), perhaps other autoimmune diseases (RA?)
  • Adults/children w 20 µgm q 1 mo × 2 then 3rd dose in 6-12 mo like dT, or q1yr × 3 doses also works; $100; neither vaccine nor HBIG necessary if anti-HBc present
  • Newborns, all w 10 µgm at birth, 1 and 6 mo (Jama 1995;274:1201) esp to SE Asian children to prevent 7% incid of child-to-child transmisssion (Jama 1996;276:906; Nejm 1989;321:1301); for newborns of HBsAg-pos mothers (Med Let 1992;34:69), vaccinate and give HBIG as above. Vaccination has halved Taiwan rate of childhood hepatoma (Nejm 1997;336:1855)

of chronic disease (ACP J Club 2006;145:18; Nejm 2006;354:1001, 1011, 1071; 2005;352:2743), chronic suppression to prevent cirrhosis progression and/or hepatoma:

  • 1st: Interferon-image2a or peginterferon-image2a (Nejm 2005;353:2682) × 4-6 mo may permanently help 30-40% if given early on, certainly for chronic delta.gif-agent infection (Nejm 1994;330:88), and for chronic hep B (Nejm 1994;330:137), esp if e-antigen pos (Nejm 1996;334:1422); $2000/mo
  • 2nd: Lamivudine (3TC) 100+ mg po q d ×1 yr (Nejm 2004;351:1521, 1567; 2002;346:1706) or similar telbivudine (Nejm 2007;357:2576), but resistance develops so multidrug regimens, eg w pegylated interferon-image2b (Ann IM 2005;142:240) or dipivoxil; $260/mo
  • 3rd: Entecuvir 0.5 mg po qd; better than lamivudine; alone since resistance development rare; $725/mo
  • 3rd: Adefovir (Hepsera) (Nejm 2005;352:2673; 2003;348:800, 808; Med Let 2002;44:105) 10 mg po qd if hep B Ag positive; used if lamivudine resistance (Ann IM 2005;142:821). Renal toxicity, drug resistance develops in 6%. $675/mo
  • No steroids (Nejm 1976;294:722)