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hepatitis B infection

Etiology: 1) hepatitis B virus 2) associated disorders a) membranoproliferative glomerulonephritis [1] b) polyarteritis nodosa c) cryoglobulinemia type 2 d) cryoglobulinemia type 3 Epidemiology: 1) accounts for 50% of cases of acute viral hepatitis in USA 2) heterosexual transmission 40% 3) injection drug abuse 20% 4) homosexual transmission 10% 5) mode of transmission unknown in 30-40% 6) semen & blood & perhaps other body fluids are infectious 7) transmission from mother to fetus during delivery 8) 1 in 1000 unimmunized travelers become infected [3] 9) asymptomatic carriers (HBsAg+, HBeAg-) a) without increased mortality [4] b) 32% convert to HBsAg- 10) increases acute hepatitis B infection in Kentucky, Tennessee, & West Virginia 2006-2013 [28] 11) 2/3 of U.S. deaths in patients with hepatitis B 2000-2019 occurred in patients born in U.S. - U.S.-born decedents more frequently had nonliver disease as the underlying cause of death than non-US-born decedents 12) worldwide high prevelance regions - Africa, Southeast Asia, the Middle East, Eastern Europe, eastern & northern countries in South America Pathology: 1) HBV is NOT directly hepatocytopathic 2) liver injury occurs secondary to cytotoxic T-cell response against HBcAg on surface of infected cells 3) hepatocyte necrosis & clearance of HBV are determined by vigor of T-cell response 4) HbeAg negative precore mutants a) associated with a point mutation resulting in a stop codon b) cases associated with fulminant hepatitis 5) clearance rates are low regardless of therapy [33] - seropositivity for HbeAg lowers clearance further Genetics: - susceptibility linked to: - CTLA4, defects in IFNAR2, IL10RB, MBL2, TNF-slpha Clinical manifestations: - most cases are asymptomatic - prodromal syndrome may be characterized by - rapid-onset symmetric polyarthritis often present prior to jaundice - maculopapular rash (trunk, legs) - right upper quadrant pain [1] - fatigue, malaise, anorexia, nausea/vomiting, jaundice Laboratory: 1) abnormal liver function tests a) serum AST is increased (20-50 fold elevations common) b) serum ALT is increased - monitor in hepatitis B carriers every 6 months [40] 2) hepatitis B serology (serologic diagnosis) a) hepatitis B surface antigen in serum (HBsAg) - negative in resolved infection - conversion to HBsAg negative persists long-term in 95% [36] b) hepatitis B surface antibody in serum (HBsAb) - positive in persons - immunized with hepatitis B vaccine - persons with resolved hepatitis B infection c) hepatitis B e antigen in serum (HBeAg) - positive in active hepatitis B infection (acute or chronic) - use HBV DNA to monitor infectivity [19] d) hepatitis B core antigen in tissue (HBcAg) e) hepatitis B core antibody in serum (HBcAb) - hepatitis B core IgM in serum for acute prodrome - hepatitis B core IgG in serum positive for - resolved hepatitis B infection - chronic hepatitis B infection (all forms) - negative for persons immunized with hepatitis B vaccine 6) hepatitis B virus DNA by PCR a) levels identify chronic hepatitis B subtypes - immune tolerant: > 1,000,000 U/L - immune active: > 2000 U/L HBeAg-; > 20,000 U/L HBeAg+ - inactive: < 2000 U/L (hepatitis B carriers) b) hepatitis B virus DNA level predicts 1] risk of hepatocellular carcinoma 2] infectivity [19] c) monitor hepatitis B carriers with hepatitis B DNA every 6-12 months [40] d) see management section for treatment threshold [1] 7) serum AST/platelet count ratio index [24] 8) serum alpha-fetoprotein not routinely recommended [40] 9) see ARUP consult [18] Special laboratory: - transient elastography (FibroScan) [24] - screen for heptocellular carcinoma in at risk patients with ultrasound every six months [1] - all patients with cirrhosis - Asian male hepatitis B carriers > 40 years of age - Asian female hepatitis B carriers > 50 years of age - any hepatitis B carrier with a family history of hepatocellular carcinoma - African & North American Black hepatitis B carriers Complications: 1) chronic active hepatitis - persistent HBV viral replication 6 months after exposure 2) cirrhosis - risk factors - older age - longer duration of infection - high hepatitis B virus DNA - high serum ALT - long-term alcohol use - HIV1 infection - hepatitis C virus or hepatitis D virus coinfection - smoking 3) hepatocellular carcinoma - cirrhosis - HBV genotype C - conversion from HBeAg(-) to HBeAg(+) - male - family history of hepatocellular carcinoma - may develop in the absence of cirrhosis [1] - screen for heptocellular carcinoma in at risk patients with ultrasound every six months [1] 4) polyarteritis nodosa [1] Management: 1) hepatitis B immune globulin a) passive immunization b) post exposure: needle stick, sexual & household contacts c) prevention of maternal to fetal transmission d) infants born to hepatitis B positive mothers should be given hepatitis B immune globulin & hepatitis B vaccine within 12 hours of birth [31] 2) hepatitis B vaccine: a) active immunization b) give with hepatitis B immune globulin (post exposure) c) infants weighing < 2 kg born to hepatitis B negative mothers should be given hepatitis B vaccine either at 1 month of age or hospital discharge, whichever occurs first [31] d) not effective in patients already infected [1] 3) use barrier protection for sexual activity 4) intimate contacts should receive HBV immune globulin (acute HBV contacts) & hepatitis B vaccine (acute & chronic HBV contacts) 5) do NOT treat immune tolerant patients without liver inflammation, i.e. normal serum transaminases [1] ***** (MKSAP) 6) in general, do not treat acute hepatitis B - acute hepatitis B infection will resolve spontaneously within 6 months in 90% of adults [1] - serial monitoring of serum transaminases & INR 7) chronic hepatitis B - treat chronic hepatitis B only if (or) [1] - acute liver failure - immune active chronic hepatitis B - HBV DNA > 2000 IU/mL HBeAg- - HBV DNA > 20,000 IU/mL HBeAg+ - cirrhosis - prolonged acute hepatitis B - immunosuppression - initiate tenofovir or entecavir prior to immunosuppressive chemotherapy [40] - continue tenofovir or entecavir during immunosuppressive therapy & for 6 months after [40] - see chronic hepatitis B for investigational treatment [39] 8) antiviral therapy (NOT immune tolerant) a) treatment with entecavir or tenofovir indefinitely after renal transplantation to prevent reactivation hepatitis B [1] b) tenofovir (HBeAg+ or HBeAg- patients) (NCG, NICE [10]) - improves, survival, reverses cirrhosis at 5 years [20] - may diminish incidence of hepatocellular carcinoma c) tenofovir & entecavir are preferred antiviral agents for chronic hepatitis B infection [24] - emtricitabine/tenofovir for HIV1 coinfection [1] d) do NOT treat immune tolerant patients with normal serum ALT [1] e) lamivudine of no benefit [5,6,14] f) entecavir (Baraclude) better than lamivudine [11,12,17] 1] effectively suppresses hepatitis B virus [21] 2] improves clinical outcomes in patients with cirrhosis [21] 3] hepatitis B-related polyarteritis nodosa [1] g) adefovir (long-term), > 48 weeks [7,12] h) emtricitabine (Emtriva) i) telbivudine (Tyzeka) j) interferon-alpha (peginterferon alfa 2a, Pegasys) - older treatment - **risk of exacerbating liver inflammation** [1] - indicated for immune-mediated necro-inflammatory activity in the liver (ALT > 100 U/L) - goal is low circulation HBV DNA levels (< 200 pg/mL) - duration of treatment = 1 year - may be transient rise in ALT after initiation of therapy - **contraindicated** with - **acute hepatitis B** - decompensated cirrhosis (i.e. encephalopathy, variceal hemorrhage, ascites) unless liver transplant is available - other active autoimmune disorder - depression [1] 9) only a minority of patients sustain response after treatment is stopped [7] 10) follow-up survelliance: - monitor serum transaminases every 3-6 months in patients asymptomatic patients with immune tolerance or in hepatitis B carriers [1] - monitor hepatitis B carriers with hepatitis B DNA every 6-12 months - monitor high-risk patients for hepatocellular carcinoma - RUQ abdominal ultrasound every 6 months - cirrhosis, Asian men > 40 years, Asian women > 50 years - persons from sub-Saharan Africa >= 20 years - persons with family history of hepatocellular carcinoma [1] 11) liver transplantation a) encephalopathy b) cirrhosis 12) prevention: - hepatitis B vaccine reduces prevalence of hepatitis B infection [1] - prevention of vertical transmission during pregnancy - MKSAP guidelines recommend treatment of pregnant women with HBV DNA > 200,000 IU/mL at 24-28 weeks gestation with tenofovir, lamivudine, or telbivudine to prevent vertical transmission to the infant [1,35] - treatment of HBsAg-positive pregnant women high viral load (HBV DNA > 200,000 IU/mL) with tenofovir 300 mg PO QD from 30-32 weeks' gestation until postpartum week 4 reduces transmission of HBV to infant 5% vs 18% [29] - tenofovir does not reduce vertical transmission [32] - infants should receive hepatitis B immune globulin shortly after birth & HBV vaccination at birth & 1, 2, 4, & 6 months Notes: - HBV infection should not disqualify infected individuals from practicing surgery, dentistry, or medicine [19] - patients do not need to be routinely informed of provider or student HBV status; disclosure may be counterproductive to public health [19] - current threshold for health care providers allowed to participate in higher-risk healthcare-associated procedures is 1000 IU/mL for HBV DNA [37]

Interactions

disease interactions

Related

chronic hepatitis hepatitis B immune globulin (H-BIG, Hep-B-Gammagee, HyperHep) hepatitis B vaccine (Engerix-B, Recombivax HB, Heplisav-B, Dynavax, PreHevbrio) hepatitis B virus (HBV) hepatitis B virus (HBV) serology hepatitis B virus DNA screening for hepatitis B

Specific

chronic hepatitis B hepatitis B carrier

General

viral hepatitis

Database Correlations

OMIM 610424

References

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