hepatitis B infection
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Etiology
- hepatitis B virus
- associated disorders
Epidemiology
- accounts for 50% of cases of acute viral hepatitis in USA
- heterosexual transmission 40%
- injection drug abuse 20%
- homosexual transmission 10%
- mode of transmission unknown in 30-40%
- semen & blood & perhaps other body fluids are infectious
- transmission from mother to fetus during delivery
- 1 in 1000 unimmunized travelers become infected[3]
- asymptomatic carriers (HBsAg+, HBeAg-)
- increases acute hepatitis B infection in Kentucky, Tennessee, & West Virginia 2006-2013[28]
- 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
- worldwide high prevelance regions
- Africa, Southeast Asia, the Middle East, Eastern Europe, eastern & northern countries in South America
Pathology
- HBV is NOT directly hepatocytopathic
- liver injury occurs secondary to cytotoxic T-cell response against HBcAg on surface of infected cells
- hepatocyte necrosis & clearance of HBV are determined by vigor of T-cell response
- HbeAg negative precore mutants
- associated with a point mutation resulting in a stop codon
- cases associated with fulminant hepatitis
- clearance rates are low regardless of therapy[33]
- seropositivity for HbeAg lowers clearance further
Genetics
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
- abnormal liver function tests
- serum AST is increased (20-50 fold elevations common)
- serum ALT is increased
- monitor in hepatitis B carriers every 6 months[40]
- hepatitis B serology (serologic diagnosis)
- hepatitis B surface antigen in serum (HBsAg)
- hepatitis B surface antibody in serum (HBsAb)
- positive in persons
- immunized with hepatitis B vaccine
- persons with resolved hepatitis B infection
- positive in persons
- hepatitis B e antigen in serum (HBeAg)
- hepatitis B core antigen in tissue (HBcAg)
- 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
- hepatitis B virus DNA by PCR
- 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)
- hepatitis B virus DNA level predicts
- risk of hepatocellular carcinoma
- infectivity[19]
- monitor hepatitis B carriers with hepatitis B DNA every 6-12 months[40]
- see management section for treatment threshold[1]
- levels identify chronic hepatitis B subtypes
- serum AST/platelet count ratio index[24]
- serum alpha-fetoprotein not routinely recommended[40]
- see ARUP consult[18]
Diagnostic procedures
- 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
- chronic active hepatitis
- 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
- risk factors
- 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]
- polyarteritis nodosa[1]
Management
- hepatitis B immune globulin
- passive immunization
- post exposure: needle stick, sexual & household contacts
- prevention of maternal to fetal transmission
- infants born to hepatitis B positive mothers should be given hepatitis B immune globulin & hepatitis B vaccine within 12 hours of birth[31]
- hepatitis B vaccine:
- active immunization
- give with hepatitis B immune globulin (post exposure)
- 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]
- not effective in patients already infected[1]
- use barrier protection for sexual activity
- intimate contacts should receive HBV immune globulin (acute HBV contacts) & hepatitis B vaccine (acute & chronic HBV contacts)
- do NOT treat immune tolerant patients without liver inflammation, i.e. normal serum transaminases[1] ***** (MKSAP)
- 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
- chronic hepatitis B
- treat chronic hepatitis B only if (or)[1]
- acute liver failure
- immune active chronic hepatitis B
- 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]
- initiate tenofovir or entecavir prior to immunosuppressive chemotherapy[40]
- see chronic hepatitis B for investigational treatment[39]
- treat chronic hepatitis B only if (or)[1]
- antiviral therapy (NOT immune tolerant)
- treatment with entecavir or tenofovir indefinitely after renal transplantation to prevent reactivation hepatitis B[1]
- tenofovir (HBeAg+ or HBeAg- patients) (NCG, NICE[10])
- improves, survival, reverses cirrhosis at 5 years[20]
- may diminish incidence of hepatocellular carcinoma
- tenofovir & entecavir are preferred antiviral agents for chronic hepatitis B infection[24]
- do NOT treat immune tolerant patients with normal serum ALT[1]
- lamivudine of no benefit[5][6][14]
- entecavir (Baraclude) better than lamivudine[11][12][17]
- effectively suppresses hepatitis B virus[21]
- improves clinical outcomes in patients with cirrhosis[21]
- hepatitis B-related polyarteritis nodosa[1]
- adefovir (long-term), > 48 weeks[7][12]
- emtricitabine (Emtriva)
- telbivudine (Tyzeka)
- 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]
- only a minority of patients sustain response after treatment is stopped[7]
- 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]
- liver transplantation
- 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]
More general terms
More specific terms
Additional terms
- 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
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ Journal Watch 22(9):71, 2002 Goldstein ST et al Incidence and risk factors for acute hepatitis B in the United States, 1982-1998: implications for vaccination programs. J Infect Dis 185:713, 2002 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11920288
- ↑ 3.0 3.1 Prescriber's Letter 9(7):40 2002
- ↑ 4.0 4.1 Journal Watch 24(21):162, 2004 Manno M, Camma C, Schepis F, Bassi F, Gelmini R, Giannini F, Miselli F, Grottola A, Ferretti I, Vecchi C, De Palma M, Villa E. Natural history of chronic HBV carriers in northern Italy: morbidity and mortality after 30 years. Gastroenterology. 2004 Sep;127(3):756-63. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15362032
- ↑ 5.0 5.1 Journal Watch 24(21):162-63, 2004 Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, Lu ZM, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Button P, Pluck N; Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004 Sep 16;351(12):1206-17. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15371578
- ↑ 6.0 6.1 Journal Watch 25(4):30-31, 2005 Janssen HL, van Zonneveld M, Senturk H, Zeuzem S, Akarca US, Cakaloglu Y, Simon C, So TM, Gerken G, de Man RA, Niesters HG, Zondervan P, Hansen B, Schalm SW; HBV 99-01 Study Group; Rotterdam Foundation for Liver Research. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005 Jan 8;365(9454):123-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15639293
- ↑ 7.0 7.1 7.2 Journal Watch 25(16):130, 2005 Hadziyannis SJ, Tassopoulos NC, Heathcote EJ, Chang TT, Kitis G, Rizzetto M, Marcellin P, Lim SG, Goodman Z, Ma J, Arterburn S, Xiong S, Currie G, Brosgart CL; Adefovir Dipivoxil 438 Study Group. Long-term therapy with adefovir dipivoxil for HBeAg- negative chronic hepatitis B. N Engl J Med. 2005 Jun 30;352(26):2673-81. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15987916
Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, Gane E, Fried MW, Chow WC, Paik SW, Chang WY, Berg T, Flisiak R, McCloud P, Pluck N; Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study Group. Peginterferon Alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005 Jun 30;352(26):2682-95. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15987917
Lok AS. The maze of treatments for hepatitis B. N Engl J Med. 2005 Jun 30;352(26):2743-6. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15987924 - ↑ Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, Moyer LA, Bell BP, Alter MJ; Advisory Committee on Immunization Practices (ACIP). A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005 Dec 23;54(RR-16):1-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16371945
- ↑ Lim SG et al, A double-blind placebo-controlled study of emtricitrabine in chronic hepatitis B Arch Intern Med 2006; 166:49 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16401810
- ↑ 10.0 10.1 Chen C-J, Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295:65 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16391218
- ↑ 11.0 11.1 Chang T-T et al, A comparison of entacavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 2006; 354:1001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16525137
Lai C-L et al, Entacavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B N Engl J Med 2006; 354:1011 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16525138 - ↑ 12.0 12.1 12.2 Kanwal F et al, Treatment alternatives for hepatitis B cirrhosis: A cost effective analysis. Am J Gastroenterol 2006, 101:2076 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16968510
- ↑ Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, Moyer LA, Bell BP, Alter MJ; Advisory Committee on Immunization Practices (ACIP). A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents. MMWR Recomm Rep. 2005 Dec 23;54(RR-16):1-31. Erratum in: MMWR Morb Mortal Wkly Rep. 2006 Feb 17;55(6):158-9. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/16371945 <Internet> http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5416a1.htm
- ↑ 14.0 14.1 Kumar M et al, A randomized controlled trial of lamividine to treat acute hepatitis B. Hepatology 2007, 45:97 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17187417
- ↑ Weinbaum CM et al, Centers for Disease Control and Prevention (CDC) Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008 Sep 19;57(RR-8):1-20. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18802412
- ↑ Sorrell MF et al. National Institutes of Health consensus development conference statement: Management of hepatitis B. Ann Intern Med 2009 Jan 20; 150:104. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19124811
Shamliyan TA et al. Antiviral therapy for adults with chronic hepatitis B: A systematic review for a National Institutes of Health consensus development conference. Ann Intern Med 2009 Jan 20; 150:111. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19124812 - ↑ 17.0 17.1 Shim JH et al Efficacy of entecavir in treatment-naive patients with hepatitis B virus-related decompensated cirrhosis. J Hepatol 2010 Feb; 52:176. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20006394
- ↑ 18.0 18.1 ARUP Consult: Hepatitis B Virus - HBV The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/hepatitis-b-virus
Hepatitis B Virus Testing Algorithm https://arupconsult.com/algorithm/hepatitis-b-virus-testing-algorithm - ↑ 19.0 19.1 19.2 19.3 19.4 Holmberg SD, Suryaprasad A, Ward JW Updated CDC Recommendations for the Management of Hepatitis B Virus-Infected Health-Care Providers and Students MMWR July 6, 2012 / 61(RR03);1-12 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6103a1.htm (corresponding NGC guideline withdrawn Jan 2018
- ↑ 20.0 20.1 Marcellin P et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: A 5-year open-label follow-up study. Lancet 2012 Dec 7 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23234725
- ↑ 21.0 21.1 21.2 Zoutendijk R et al. Virological response to entecavir is associated with a better clinical outcome in chronic hepatitis B patients with cirrhosis. Gut 2013 May; 62:760 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22490523
- ↑ Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007 Feb;45(2):507-39 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17256718
- ↑ Centers for Disease Control and Prevention (CDC) CDC Guidance for Evaluating Health-Care Personnel for Hepatitis B Virus Protection and for Administering Posteexposure Management/ MMWR Weekly. Dec 20, 2013 http://www.cdc.gov/mmwr/PDF/rr/rr6210.pdf
- ↑ 24.0 24.1 24.2 24.3 WHO News RElease. 12 March 2015 WHO issues its first hepatitis B treatment guidelines http://www.who.int/mediacentre/news/releases/2015/hepatitis-b-guideline/en/
Guideline for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. World Health Organization. March 2015 http://apps.who.int/iris/bitstream/10665/154590/1/9789241549059_eng.pdf?ua=1&ua=1 - ↑ Vassilopoulos D, Calabrese LH Viral hepatitis: review of arthritic complications and therapy for arthritis in the presence of active HBV/HCV. Curr Rheumatol Rep. 2013 Apr;15(4):319. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23436024
- ↑ Lok AS, Ward JW, Perrillo RP, McMahon BJ, Liang TJ. Reactivation of hepatitis B during immunosuppressive therapy: potentially fatal yet preventable. Ann Intern Med. 2012 May 15;156(10):743-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22586011
- ↑ Jindal A, Kumar M, Sarin SK. Management of acute hepatitis B and reactivation of hepatitis B. Liver Int. 2013 Feb;33 Suppl 1:164-75. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23286861
- ↑ 28.0 28.1 Harris AM et al Increases in Acute Hepatitis B Virus Infections - Kentucky, Tennessee, and West Virginia, 2006-2013 MMWR. Weekly / January 29, 2016 / 65(3);47-50 http://www.cdc.gov/mmwr/volumes/65/wr/mm6503a2.htm
- ↑ 29.0 29.1 Pan CQ et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med 2016 Jun 16; 374:2324 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27305192
- ↑ Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004 Mar 11;350(11):1118-29. Review. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15014185 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMra031087
- ↑ 31.0 31.1 31.2 COMMITTEE ON INFECTIOUS DISEASES, COMMITTEE ON FETUS AND NEWBORN Elimination of Perinatal Hepatitis B: Providing the First Vaccine Dose Within 24 Hours of Birth Pediatrics Aug 2017, e20171870; PMID: https://www.ncbi.nlm.nih.gov/pubmed/28847980
- ↑ 32.0 32.1 Jourdain G, Ngo-Giang-Huong N, Harrison L et al. Tenofovir versus placebo to prevent perinatal transmission of hepatitis B. N Engl J Med 2018 Mar 8; 378:911. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29514030 <Internet> http://www.nejm.org/doi/10.1056/NEJMoa1708131
Dusheiko G. A shift in thinking to reduce mother-to-infant transmission of hepatitis B. N Engl J Med 2018 Mar 8; 378:952. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29514035 <Internet> http://www.nejm.org/doi/10.1056/NEJMe1801662 - ↑ 33.0 33.1 Yeo YH, Ho HJ, Yang HI et al. Factors associated with rates of HBsAg seroclearance in adults with chronic HBV infection: A systematic review and meta-analysis. Gastroenterology 2018 Oct 17 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30342034 https://www.gastrojournal.org/article/S0016-5085(18)35158-8/pdf
- ↑ Chronic hepatitis B (AASLD guidelines) 2007 https://www.aasld.org/eweb/docs/chronichep_B.pdf
Hepatitis B https://www.niddk.nih.gov/health-information/liver-disease/viral-hepatitis/hepatitis-b - ↑ 35.0 35.1 Terrault NA, Bzowej NH, Chang KM AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2016 Jan;63(1):261-83. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26566064 Free PMC Article
- ↑ 36.0 36.1 Alawad AS, Auh S, Suarez D, Ghany MG. Durability of spontaneous and treatment-related loss of hepatitis B s antigen. Clin Gastroenterol Hepatol 2019 Jul 16 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31323381 https://www.cghjournal.org/article/S1542-3565(19)30751-7/pdf
- ↑ 37.0 37.1 Henderson DK et al. Management of healthcare personnel living with hepatitis B, hepatitis C, or human immunodeficiency virus in US healthcare institutions. Infect Control Hosp Epidemiol 2020 Oct 14 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33050959 https://www.cambridge.org/core/journals/infection-control-and-hospital-epidemiology/article/management-of-healthcare-personnel-living-with-hepatitis-b-hepatitis-c-or-human-immunodeficiency-virus-in-us-healthcare-institutions/71C331662FBEDDF7F62369E22A22E4F0
- ↑ Ly KN, Yin S, Spradling PR Regional Differences in Mortality Rates and Characteristics of Decedents With Hepatitis B Listed as a Cause of Death, United States, 2000-2019. JAMA Netw Open. 2022;5(6):e2219170. June 28 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35763293 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793633
- ↑ 39.0 39.1 Yuen M-F et al. Efficacy and safety of bepirovirsen in chronic hepatitis B infection. N Engl J Med 2022 Nov 8; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36346079 https://www.nejm.org/doi/10.1056/NEJMoa2210027
Hoofnagle JH. A modern therapy for an ancient disease. N Engl J Med 2022 Nov 8; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36346068 https://www.nejm.org/doi/10.1056/NEJMe2213449 - ↑ 40.0 40.1 40.2 40.3 40.4 40.5 NEJM Knowledge+ Gastroenterology
Reddy KR, Beavers KL, Hammond SP et al American Gastroenterological Association Institute guideline on the prevention and treatment of hepatitis B virus reactivation during immunosuppressive drug therapy. Gastroenterology. 2015 Jan;148(1):215-9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25447850 Review. No abstract available.
Di Bisceglie AM, Lok AS, Martin P et al Recent US Food and Drug Administration warnings on hepatitis B reactivation with immune-suppressing and anticancer drugs: just the tip of the iceberg? Hepatology. 2015 Feb;61(2):703-11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25412906 PMCID: PMC5497492 Free PMC article. Review.
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