hepatitis b management update
TRANSCRIPT
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DR. EMRUL KAISERIMO
MEDICINE UNIT II
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• Hepatitis B virus (HBV) has been classified into eight genotypes (A–H) based on genome sequence divergence .
• HBeAg expression lasts longer and liver disease is more severe with graver outcomes in carriers of genotype C than B in Asia.
• Accumulating lines of evidence indicate a better response to interferon and lamivudine in patients with chronic hepatitis B who are infected with genotype B rather than C.
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• PATHOGENESIS
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ROUTE OF TRANSMISSION
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• ACUTE HEPATITIS B
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WHEN TO GIVE RX• Anti viral are generally unnecessary until the
patient develops fulminant hepatiC failure• HBeAg present >12 wks.
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• CHRONIC HEPATITIS B
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IMMUNE TOLERANT PHASE• The AASLD suggests that ALT levels be tested
at least every 6 months for adults with immunetolerant CHB to monitor for potential transition to immune-active or inactive CHB.
• The AASLD suggests antiviral therapy in theselect group of
• adults >40 years of age with normal ALT • elevated HBV DNA (1,000,000 IU/mL) • liver biopsy showing significant necroinflammation
or fibrosis.
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IMMUNE ACTIVE PHASEImmune active CHB is defined by • an elevation of ALT >2 ULN or evidence of
significant histological disease plus • elevated HBV DNA above 2,000 IU/mL (HBeAg
negative) or above 20,000 IU/mL (HBeAg positive).•
AASLD recommends Peg-IFN, entecavir,or tenofovir as preferred initial therapy for adults with immune-active CHB.
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Additional factors included in the decision to treat persons with immune-active CHB but ALT <2 ULN and HBV DNA below thresholds are:• Age: Older age (>40 years) is associated with higher
likelihood of significant histologicaldisease.
• Family history of HCC• Presence of extrahepatic manifestations
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N
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TREATMENT OPTIONS
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DRUG DOSE USE IN CHILDREN
PREGNANCY CATEGORY
PEG INF 2α
PEG INF β180 mcg Wkly s/c
> 1YR ( PEG INF β)
C
LAMIVUDINE 100mg >2YR C
TELBIVUDINE 600mg B
ENTECAVIR 0.5mg1mg
>2YR C
ADEFOVIR 10mg >12YR C
TENOFOVIR 300mg >12YR B
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GENERIC BRAND NAME
LAMIVUDINE 100MG HEPAVIR LAMIVIR
ADEFOVIR 10 MG ADOVIR ANTIVA INFOVIR
TENOFOVIR 300 MG T FOVIR XYNOVIR
TELBIVUDINE 600MG SEBIVO
ENTECAVIR 0.5MG CAVIR BARCAVIR TECAVIR
PEG INF α PEGASYS
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PEG INF NUCLEOSIDE ANALOGUE
ADMINISTRATION WEEKLY , S/C INJ DAILY , ORALTOLERABILITY poor Well toleratedDURATION Finite , 48 wks >1 yr , indefinite in
most patientsEffective in high-level HBVDNA (≥109 IU/ mL)
no yes
HBeAg seroconversionDuring 1 year of therapy
~30% ~20%
Resistance none presentUse in cirrhosis, transplantation, immunosuppressed
no yes
cost ++++ +
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CIRRHOSIS • 1. Entecavir and tenofovir are preferred drugs.
2. Peg-IFN is contraindicated in persons with decompensated cirrhosis owing to safety concerns.3. Concurrent consideration for liver transplantation is indicated in eligible persons.
Treatment with antivirals does not eliminate therisk of HCC and surveillance for HCC shouldcontinue.
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DURATION OF TREATMENT The AASLD suggests that HBeAg-positive adults without cirrhosis with CHB who seroconvert to anti-HBe on therapy discontinue NAs after a period of treatment consolidation.The period of consolidation therapy generally involves treatment for at least 12 months of persistently normal ALT levels and undetectable serum HBV DNA levels
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• Persons with cirrhosis who stop antiviral therapyshould be monitored closely (e.g., monthly forfirst 6 months, then every 3 months) for recurrent viremia, ALT flares, seroreversion, and clinical decompensation.
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• Indefinite antiviral therapy for adults with HBeAg-negative immune-active CHB unless there is a competing rationale for treatment discontinuation. HBeAgnegative adults without cirrhosis requires careful consideration of risks and benefits for health outcomes including:
• (i) risk for virological relapse, hepatic decompensation, liver cancer, and death;(ii) burden of continued antiviral therapy, financial concerns associated with medication costs and long-term monitoring, adherence, and potential for drug resistance with treatment interruptions.
• (iii) patient and provider preferences.
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RX OF CHB IN PREGNANCY• Telbivudine & tenofovir are the safest. • The AASLD suggests antiviral therapy to
reduce the risk of perinatal transmission of hepatitisB in HBsAg-positive pregnant women with an HBVDNA level >200,000 IU/mL.
• Antiviral therapy was started at 28-32 weeks ofgestation in most of the studies.
• Antiviral therapy was discontinued at birth to 3months postpartum in most of the studies. Withdiscontinuation of treatment, women should bemonitored for ALT flares every 3 months for 6months.
• Breastfeeding is not contraindicated .
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• Neonates born to hepatitis B-infected mothers should be immunised at birth and immunoglobulin is given.
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VACCINATION SCHEDULE• A series of 3 doses (0.5 mL each) on a 0-, 1-, 6-month
schedule.
• Alternative dosage schedule 0, 1, 2 & 12 month
• Accelerated schedule 0, 7 , 21 days & 12 month.
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• If there is an interruption between doses of hepatitis B vaccine, does the vaccine series need to be restarted?
• No, the series does not need to be restarted. If the vaccine series was interrupted after the first dose, the second dose should be administered as soon as possible. The second and third doses should be separated by an interval of at least eight weeks. If only the third dose is delayed, it should be administered as soon as possible.
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Booster doses of hepatitis B vaccine are recommended only in certain circumstances:
• For hemodialysis patients• For other immunocompromised persons (e.g. HIV-
infected persons, hematopoietic stem-cell transplant recipients, and persons receiving chemotherapy)
• A booster dose should be administered when anti-HBs levels decline to <100 mIu/ ml
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VACCINATION SCHEDULE
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POST EXPOSURE PROPHYLAXIS• Unvaccinated persons or persons known not to have
responded to a complete hepatitis B vaccine series should receive both hepatitis B immune globulin (HBIG) and hepatitis B vaccine as soon as possible after exposure (preferably <24 hours). For sexual exposures, HBIG should not be administered more than 14 days after exposure. Hepatitis B vaccine is administered simultaneously with HBIG in a separate injection site.
• Persons who are in the process of being vaccinated but who have not completed the vaccine series should receive the appropriate dose of HBIG and should complete the vaccine series.
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NEW DRUG
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MYRCLUDEX B• The HBV uses its surface lipopeptide pre-S1 for docking
to mature hepatocyte via their sodium taurochlorate co transporter (NTCP) and subsequently entering the cells. Myrcludex B is a synthetic N-acetylated pre-S1 that can also dock to NTCP, blocking the virus's entry mechanism.[
• Reduce the intrahepatic cccDNA loads.
• This drug is still under phase II clinical trial.
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