HBV Management

Views:
 
     
 

Presentation Description

No description available.

Comments

By: ZIAHAYDER (17 month(s) ago)

nice presentation. can i download it

By: urbanhawk (25 month(s) ago)

hi ,i need ur presentation desperately im a HCP from pakistan email Shahbaz_rafiq1@yahoo.com ,ur name will remain on slide

By: ket053 (28 month(s) ago)

You can copy by using printscreen

By: jpeet (29 month(s) ago)

Dear, very nice presentation.Please consider to provide me with permission to download. Much appreciated. THNX and best regards

By: tomor (46 month(s) ago)

please help me for download, i need it very much

See all

Presentation Transcript

Chronic Hepatitis B: The Disease and Its Management : 

Chronic Hepatitis B: The Disease and Its Management

Outline : 

Outline Introduction to the hepatitis B virus Epidemiology Hepatitis B disease burden in Europe/EMEA Natural history of chronic hepatitis B Long-term outcomes of chronic hepatitis B Hepatitis B screening and vaccination European approaches to chronic hepatitis B management

Introduction to the hepatitis B virus : 

Introduction to the hepatitis B virus

Hepatitis B virus (HBV) : 

Ott MJ et al. J Pediatr Health Care 1999; 13(5):211–216 Ribeiro RM et al. Microbes Infect 2002; 4:829–835 MMWR 2003; 52:1–33 Hepatitis B virus (HBV) Hepadnaviridae member that primarily infects liver cells 100 times more infective than HIV Found in blood and body fluids Able to survive in dried blood for > 1 week

Hepatitis B nomenclature : 

MMWR 2003; 52:1–33 Mahoney FJ Clin Microbiol Rev 1999; 12:351–366 Funk ML et al. J Viral Hepat 2002; 9:52–61 Conjeevaram HS et al. J Hepatol 2003; 38:S90–S103 Hepatitis B nomenclature

Structure of HBV illustrating source and key antigen particles : 

Structure of HBV illustrating source and key antigen particles Adapted from Ganem D et al. N Engl J Med 2004; 350:1118–1129 Adapted from Liang TJ et al. N Engl J Med 2002; 347:208–210 Fung SK et al. Hepatology 2004; 40:790–792 HBsAg HBcAg Partially double Stranded DNA DNA polymerase HBeAg ~41nm (smallest known DNA virus) 8 HBV genotypes (A-H) based on ≥8% divergence in sequence identity

Slide 7: 

Adapted from Lai et al. J Med Virol 2000; 61:368 The Life Cycle of HBV in the Hepatocyte Subviral particles Infectious HBV virion cccDNA Partially dsDNA Viral polymerase converts pg RNA to partially ds DNA Encapsulated pre-genomic mRNA ER Nucleus HBsAg HBcAg HBeAg Precore/core Hepatocyte Minus strand DNA Cytoplasm

HBV mutants : 

Four relevant HBV mutants Naturally occurring Precore mutation Abolished HBeAg production (e-CHB) Core promoter mutation Down-regulates HBeAg production (e-CHB) Treatment-induced mutations YMDD: induced by L-nucleoside analogue RT-inhibitors e.g. Lamivudine N236T and A181V: induced by Adefovir HBV mutants

Epidemiology : 

Epidemiology

Global impact of hepatitis B : 

WHO Fact Sheets, available at www.who.int Accessed July 26 2005 Conjeevaram HS et al. J Hepatol 2003; 38:S90–S103 Lee WM N Engl J Med 1997; 337:1733–1745 Lok AS N Engl J Med 2002; 346:1682–1683 Global impact of hepatitis B World population 6 billion 2 billion with evidence of HBV infection 350–400 million with chronic hepatitis B (CHB) 25–40% (75–160 million) die of cirrhosis or liver cancer

World’s hepatitis B disease burden is high : 

World’s hepatitis B disease burden is high Lavanchy D J Viral Hepat 2004; 11:97–107 Conjeevaram HS et al. J Hepatol 2003; 38:S90–S103

Geographic prevalence of chronic hepatitis B : 

³8% – High 2-8% – Intermediate <2% – Low Geographic prevalence of chronic hepatitis B World Health Organisation. Geographical Prevalence of HBsAg. Data 1996 (unpublished) http://www.who.int/vaccines-surveilllance/graphics/htmls/hepbprev.htm

Geographical distribution of HBV genotypes (1) : 

McMahon BJ Semin Liver Dis 2004; 24:17–21 Chu CJ et al. Gastroenterology 2003; 125:444–451 Geographical distribution of HBV genotypes (1)

Geographical distribution of HBV genotypes (2) : 

Geographical distribution of HBV genotypes (2) Over-simplification of distribution – populations are not static F C D E A D D D C Ba F A,B,C,D Bj A,B,C,D F A D

Possible clinical significance of HBV genotypes : 

Nucleoside analogues Lamivudine Data contradictory Mutants may emerge more rapidly in A vs D* Adefovir HBV DNA suppression equal with all genotypes** Standard IFN therapy HBeAg seroconversion higher with A vs D HBeAg seroconversion higher with B vs C * Correlation with response was not reported ** Correlation with HBeAg seroconversion could not be determined “…the story of HBV genotypes continues to unfold…” Possible clinical significance of HBV genotypes Fung SK et al. Hepatology 2004; 40:790–792

Transmission of HBV : 

CDC Fact Sheet http://www.cdc.gov/ncidod/diseases/hepatitis/b/fact.htm Accessed July 26 2005 Lee WM N Engl J Med 1997; 337:1733–1745 Lavanchy D J Viral Hepat 2004; 11:97–107 Transmission of HBV Host Recipient Mother Infant Horizontal Transmission Vertical Transmission Child-to-Child Contaminated Needles Sexual Health Care Worker Transfusion Perinatal 6% infected after age 5 years become chronically infected 90% infected infants become chronically infected No clear risk factors in 2030% of patients

Risk groups for hepatitis B : 

Children of immigrants from a country with high HBV prevalence Intravenous drug users History of a sexually transmitted disease/ multiple sex partners Men who have sex with men Household contact with chronically infected persons Infants born to infected mothers Healthcare workers Haemodialysis patients Sexual contact with infected persons CDC Fact Sheet http://www.cdc.gov/ncidod/diseases/hepatitis/b/fact.htm Accessed July 26 2005 Risk groups for hepatitis B

Natural history of chronic hepatitis B : 

Natural history of chronic hepatitis B

Hepatitis B: a variable disease : 

Natural history influenced by: Age at infection Viral mutations Level of HBV replication Gender Host immune status Alcohol use Infection with other hepatotropic viruses Clinical spectrum varies Acute hepatitis Subclinical Acute symptomatic Fulminant HBsAg carrier (low level replication) Chronic hepatitis Cirrhosis HCC Fattovich G Semin Liver Dis 2003; 23:47–58 Hepatitis B: a variable disease

Phases of chronic hepatitis B : 

McMahon BJ Semin Liver Dis 2004; 24:17–21 Phases of chronic hepatitis B

Dynamics of HBV replication and clinical disease : 

Dynamics of HBV replication and clinical disease Immune Tolerant Immune Active Non-replicative

Multiple outcomes of chronic hepatitis B : 

Hsu YS et al. Hepatology 2002; 35:1522–1527 Multiple outcomes of chronic hepatitis B (n = 283) Spontaneous seroconversion 67% Sustained remission 24% e-CHB with detectable HBV DNA 5% Undetermined causes 4% HBeAg reversion 33% ALT elevation (>2xULN)

Natural history after spontaneous seroconversion : 

McMahon BJ et al. Ann Intern Med 2001; 135:759–768 Natural history after spontaneous seroconversion HBeAg+ (n = 641) 100 (16%) Persistent HBeAg+ 432 (67%) Seroconversion 109 (17%) HBeAg Reversion

HBeAg-negative CHB characteristics : 

Hadziyannis SJ et al. N Engl J Med 2003; 348:800–807 Fattovich G Semin Liver Dis 2003; 23:47–58 HBeAg-negative CHB characteristics Growing prevalence Liver disease typically advanced Male Age range 36–45 years Sustained spontaneous remission is rare Persistent or intermittent HBV replication Fluctuations in ALT and viraemia levels Severe liver necroinflammation Progressive fibrosis ~40% of patients in some studies have cirrhosis

ALT levels fluctuate during the course of HBV infection : 

ALT levels followed monthly in 164 HBsAg+/HBeAg- patients for 1 year: 64.1% had recurrent flares 69.5% returned to normal values between flares HBV DNA levels indicating viral load track the biochemical course of HBeAg- CHB Brunetto MR et al. J Hepatol 2002; 36:263–270Hadziyannis SJ et al. Hepatology 2001; 34:617–624 ALT levels fluctuate during the course of HBV infection

“Liver injury seems to be particularly severe and rapidly progressive in patients who are negative for HBeAg and positive for anti-HBe, but in whom clinically significant HBV replication persists” : 

“Liver injury seems to be particularly severe and rapidly progressive in patients who are negative for HBeAg and positive for anti-HBe, but in whom clinically significant HBV replication persists” Hadziyannis SJ et al. N Engl J Med 2003; 348(9):800–807

Long-term outcomes of chronic hepatitis B : 

Long-term outcomes of chronic hepatitis B

Chronic hepatitis B disease progression : 

Chronic hepatitis B disease progression Liver Cancer (HCC) Cirrhosis Liver Failure Chronic Infection Liver Transplantation Death 30% 5–10% 23% in 5 years Acute flare Torresi J et al. Gastroenterology 2000; 118:S83-S103 Fattovich G et al. Hepatology 1995; 21:77-82 Perrillo RP et al. Hepatology 2001; 33:424-32

Pathogenesis of HBV infection : 

Pathogenesis of HBV infection Averett et al. Viral Hepatitis Reviews 1995; 1:129–142 Keeffe EB et al. Clin Gastroenterol Hepatol 2004; 2:87–106 Clinical hepatitis HBV production Hepatocyteregeneration Infection Immune response Re-infection Coinfection Inflammation & cell death HBV-infected hepatocytes Uninfected hepatocytes

Significance of HBV DNA/viral replication : 

Significance of HBV DNA/viral replication Presence of HBV DNA/viral replication precedes Elevated ALT Worsening histology HCC

Association of past viral load to current liver disease*¥ : 

Association of past viral load to current liver disease*¥ *Nominal logistics regression, unadjusted for age and sex ¥Reference group “not detected normal” category Undetectable < 1.6x103 copies/mL; low ≥ 1.6x103-9.9x104 copies/mL; High ≥1x105 copies/mL Chen et al. Hepatology 2004; 40(51):594A

Undetectable/low viral load associated with clinically apparent liver disease after 10 years : 

Adapted from Chen et al. Hepatology 2004; 40(51):594A Undetectable/low viral load associated with clinically apparent liver disease after 10 years 10 year, prospective cohort 1,681 patients included in current liver disease analysis Liver disease found in 33.5% (322/960) of chronic HBV patients with low (1.6x103–9.9x104 copies/mL) or undetectable (< 1.6x103 copies/mL) viral loads Liver Disease 34% No Liver Disease 66%

HBV DNA cut-off in HBeAg-negative CHB : 

HBV DNA cut-off in HBeAg-negative CHB Manesis et al. Cut-off of 105 copies/mL may be too high 30,000 copies/mL may be more sensitive cut-off for liver inflammation in e-CHB patients Sensitivity 93% All persons with inactive HBV had DNA levels < 30,000 copies/mL Manesis EK et al. Am J Gastroenterol 2003; 98:2261–2267

Risk factors for progression to cirrhosis : 

Older age Ongoing HBV Replication Persistent or intermittent non-PCR HBV DNA detection Severity of fibrosis/necroinflammation stage at diagnosis Concurrent clinical conditions HBV, HCV, HIV, heavy alcohol consumption Fattovich G et al. Semin Liver Dis 2003; 23:47–58 Risk factors for progression to cirrhosis

Histology progression in the placebo arm of a 1-year pivotal trial : 

NDA 21-449. 2002 http://www.fda.gov/ohrms/dockets Accessed July 26 2005 Histology progression in the placebo arm of a 1-year pivotal trial n = 145 untreated HBeAg-positive patients with blinded ranked assessment of baseline and week 48 biopsies 34% 26% 41% 24% 26% 50% Necroinflammation Fibrosis Improved Worsened Same

Histology progression in the placebo arm of a pivotal trial: HBeAg-negative patients at 48 weeks : 

Hadziyannis SJ et al. N Engl J Med 2003; 348:800–807 Histology progression in the placebo arm of a pivotal trial: HBeAg-negative patients at 48 weeks n = 55 HBeAg-negative untreated patients with blinded ranked assessment of baseline and week 48 biopsies 51% 7% 42% 25% 38% 36% Necroinflammation Fibrosis Improved Worsened Same

Progression to cirrhosis : 

Progression to cirrhosis Progression to cirrhosis 10 years after seroconversion (HBeAg to anti-HBe) in CHB patients: Cumulative incidence HBeAg reversion: 45% HBeAg-negative disease: 5% Sustained remission: 0% Cirrhosis progression in patients with CHB: 215 patients untreated vs 436 patients treated with lamivudine: 5% vs 2% at 12 months 12% vs 6% at 24 months 17% vs 7% at 32 months (p=0.001) Hsu YS et al. Hepatology 2002; 35:1522–1527Liaw YF et al. N Engl J Med 2004; 351:1521–1531

Hepatocellular carcinoma : 

Primary liver carcinoma is the 5th most frequent cancer in the world HCC is the major type of primary liver carcinoma HCC is mainly associates with viral hepatitis In many areas of the world > 85% of HCC retain markers of HBV and/or HCV Kim JW et al. Hepatology 2004; 39:518–527 Hepatocellular carcinoma

Risk factors for HCC : 

Risk factors for HCC Cirrhosis Male gender Older age Viral replication HBeAg-positive or HBeAg-negative Alcohol consumption Concurrent infection with HCV Family history with HCC Fattovich G et al. Semin Liver Dis 2003; 23:47–58 Yang HI et al. N Engl J Med 2002; 347:168–174

HBV DNA associated with increased risk of HCC : 

Likelihood of HCC in men with detectable HBV DNA is 3.9 times greater than those with undetectable HBV DNA Increased risk associated with increased HBV DNA levels Yang HI et al. N Engl J Med 2002; 347:168–174Ohata K et al. J Gastroenterol Hepatol 2004; 19:670–675 HBV DNA associated with increased risk of HCC

“Approximately 15–40% of infected patients will develop cirrhosis, liver failure, or HCC” : 

“Approximately 15–40% of infected patients will develop cirrhosis, liver failure, or HCC” Lok AS N Engl J Med 2002; 346(22):1682–1683

Hepatitis B screening and vaccination : 

Hepatitis B screening and vaccination

HBV immunization : 

World Health Organisation, Hepatitis B – department of communicable diseases surveillance and response HBV immunization Two types of HBV immunization: Passive immunization Inject the individual with ready-made HBV-specific Immunoglobulin (HBIG) Provides immediate short-term protection Involves large injection volumes Can be given at birth to reduce perinatal transmission Active immunization Currently HBV vaccines are based on recombinant HBsAg with or without preS The aim of giving therapeutic vaccines to HBV-infected patients is to increase the efficiency of the natural immune response – in particular the T-helper or cytotoxic T lymphocyte response

HBV vaccination (1) : 

Hollinger FB and Liang TJ. Fields Virology 2001 Chapter 87: Hepatitis B virus Lai CL et al. Hepatitis B Virus: Human virus guidelines 2002 IMP World Health Organization, Hepatitis B – department of communicable diseases surveillance and response The HBV vaccine currently used is a synthetically prepared recombinant DNA vaccine Recombinant DNA vaccines contain sections of HBV proteins (antigenic regions such as outer protein or surface antigen) to stimulate a natural immune response All but one of the licensed vaccines consist of the major S-gene product Live virus not used – eliminates risk of vaccine-acquired infection HBV vaccination (1)

HBV vaccination (2) : 

HBV vaccination (2) Hepatitis D virus relies on Hepatitis B for productive infection, so the HBV vaccine also protects against HDV The HBV vaccine can be given in combination with other vaccines, Hepatitis A for example Vaccine efficacy is extremely high with 80–90% of recipients mounting a natural immune response Protection is also long lasting but the exact time period of protection is unknown CDC Hepatitis B fact sheet, http://www.cdc.gov/ncidod/diseases/hepatitis/b/factvax.htm Accessed July 26 2005 Immunisation against infectious disease 1996 Department of Health Welsh Office, Scottish Office, Department of Health DHSS (Northern Ireland)

HBV vaccine: not always efficacious : 

HBV vaccine: not always efficacious Seroprotection: anti-HBs titre ≥10mIU/mL Immunity inadequate <10mIU/mL Protection rates after completion of 3 dose series: >95% for infants of HBsAg-negative women and adolescents 90% in adults <40 years Risk factors for suboptimal response Age >40 years IVDU Immunocompromised state Obesity Smoking Mahoney FJ Clin Microbiol Rev 1999; 12:351–366 Ott MJ et al. J Pediatr Health Care 1999; 13:211–216

Summary of recommendations : 

Summary of recommendations 2 different treatment strategies applicable: Finite treatment duration with pegIFN-α or NAs Long-term treatment with NAs ETV and TDF are potent HBV inhibitors and have high barrier to resistance, they can be confidently used as first-line monotherapies Treatment indication based on HBV DNA, ALT, histological grade and stage Baseline and on-treatment predictors of subsequent response have been identified Monitor HBV DNA and adjust therapy accordingly Pattern of resistance mutations should be used to adapt therapy Adding a second drug without cross-resistance is the only option European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001 EASL (2009) guidelines

DiagnosisHow should patients be diagnosed and evaluated? : 

DiagnosisHow should patients be diagnosed and evaluated? Biochemical markers AST, ALT, gamma glutamyl transpeptidase (GGT), alkaline phosphatase, prothrombin time, serum albumin, blood counts, hepatic ultrasound Virological HBV DNA Liver biopsy To determine degree of inflammation and fibrosis in patients with raised ALT and/or HBV DNA >2,000 IU/ml Other causes Co-infection with HCV, HDV, HIV; co-morbid alcoholism etc should be investigated EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

DiagnosisDiagnostic criteria : 

DiagnosisDiagnostic criteria EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Recommended treatment choices : 

Recommended treatment choices Finite treatment: PegIFN-α mainly recommended in HBeAg(+) patients Use most potent NA with highest barrier to resistance (ETV or TDF) to rapidly reduce levels of viraemia to undetectable levels and avoid rebounds due to HBV resistance Long-term treatment Use most potent NA with highest barrier to resistance (ETV or TDF) for HBeAg(+) patients who do not develop HBe seroconversion or in HBeAg(-) patients EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Which patients to treatHBeAg(+) : 

Which patients to treatHBeAg(+) EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Which patients to treatHBeAg(-) : 

Which patients to treatHBeAg(-) EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Treatment endpoints : 

Treatment endpoints EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

On-treatment monitoring : 

On-treatment monitoring (Peg)IFN-α treatment Full blood count and serum ALT monitored monthly HBV DNA level should be monitored at weeks 12 and 24 to verify primary response* HBeAg(+) patients: HBeAg and anti-HBe antibodies at weeks 24 and 48, and 24 weeks post-treatment HBsAg checked every 6 months after HBe seroconversion if HBV DNA is undetectable HBeAg(-) patients: Monitor for safety and efficacy through 48 weeks’ treatment NAs Finite treatment in HBeAg(+) patients: HBV DNA every 12 weeks Long-term treatment [HBeAg(+) and HBeAg(-) patients]: HBV DNA levels at week 12 then every 12 to 24 weeks EASL (2009) guidelines *Primary response: >1 log10 IU/ml decrease in HBV DNA level from baseline European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

When to stop therapy : 

When to stop therapy EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Management of antiviral resistancePrevention and monitoring : 

Management of antiviral resistancePrevention and monitoring The use of the most potent drugs with the optimal resistance profile (ie ETV and TDF) should be used as first-line monotherapies Resistance should be identified as early as possible by monitoring HBV DNA level Check for compliance in patients with primary non-response* and partial response† The pattern of resistance mutations should be used to adapt therapy Add a second drug without cross-resistance to decrease the risk of developing multiple drug-resistant strains EASL (2009) guidelines *Primary non-response: <1 log10 IU/ml decrease in HBV DNA level from baseline†Partial response: HBV DNA >1 log10 IU/ml but detectable HBV DNA by PCR European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Management of antiviral resistanceTreatment modification : 

Management of antiviral resistanceTreatment modification EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Management of patients with cirrhosis : 

Management of patients with cirrhosis Compensated Treat even if HBV DNA <2,000 IU/ml and normal ALT Use potent NA with very low risk of resistance, ie ETV or TDF If using LVD, combine with ADV or preferably TDF Use IFN only if well compensated Closely monitor for resistance and flares Decompensated Require urgent antiviral treatment Rapid and profound viral suppression and efficacious prevention of resistance needed Use potent NA with good resistance profile (ETV or TDF) Treat in specialised liver units EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Management in liver transplant : 

Management in liver transplant HBsAg-positive patients should receive pre-transplant therapy with a potent NA with a high barrier to resistance Achieve lowest possible HBV DNA level before transplantation Profound suppression and low rates of resistance are advantageous Antiviral therapy for prophylaxis of recurrent hepatitis B probably requires lifelong continuation of treatment EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Management in immunosuppressive/cytotoxic chemotherapy : 

Management in immunosuppressive/cytotoxic chemotherapy Screen all candidates for immunosuppressive/chemotherapy for HBsAg and anti-HBc antibodies prior to treatment HBV vaccination in seronegative patients highly recommended Measure HBV DNA in all HBsAg-positive candidates Pre-emptive NA during therapy + 12 months after treatment cessation Use NA with high antiviral potency and high barrier to resistance, ie ETV or TDF, especially if high HBV DNA HBsAg-negative patients with anti-HBc antibodies and undetectable HBV DNA Monitor HBV DNA and ALT Treat with NA if HBV reactivation before ALT elevation EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Management in HBV-HCV and HBV-HDV co-infections : 

Management in HBV-HCV and HBV-HDV co-infections HBV-HCV co-infection Use pegIFN-α + ribavirin Use NA if HBV reactivation during/after HCV clearance HBV-HDV co-infection Treat with (peg)IFN-α Assess efficacy at 24 weeks ≥1 year of therapy may be necessary (unproven efficacy) EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Management in HBV-HIV co-infections : 

Management in HBV-HIV co-infections Indications for therapy same as HIV-negative patients, ie based on HBV DNA, ALT and histological lesions Treat both HIV and HBV de novo (most patients) TDF + emtricitabine, plus a third agent against HIV If HBV treatment before HIV (small number of patients) ADV and LdT should be preferred ETV, LVD and TDF contraindicated as single agents for HBV in co-infected patients If undetectable HBV DNA not achieved, treatment of HIV infection should be envisaged EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Management in pregnancy : 

Management in pregnancy ADV, ETV and LVD are category C drugs in pregnancy LdT and TDF are category B drugs in pregnancy Considerable safety data in HIV-positive women treated with TDF and/or LVD or emtricitabine Reports suggest LVD therapy during last trimester in HBsAg-positive women with high levels of viraemia reduces risk of intra-uterine and perinatal HBV transmission if given in addition to passive and active vaccination by HBIg and HBV vaccination TDF or TDF with emtricitabine or ETV could be considered Requires further confirmation for safety Monitor closely after delivery as exacerbations of CHB may occur EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001

Management of children : 

Management of children Only conventional IFN-α, ADV and LVD have been evaluated for use in children Studies of other NAs ongoing to better define treatment strategies EASL (2009) guidelines European Association for the Study of the Liver. J Hepatol 2009;50: DOI:10.1016/j.jhep.2008.10.001