Managing Chronic Hepatitis B

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Managing Chronic Hepatitis B

• Akash Ajmera PG Y-III
• 10/1/10

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Hepatitis B

• Double-stranded DNA virus
• Family of hepadnaviruses
• Eight genotypes (A to H) geographical variance
• 300 million HBV carriers in the world
• 500,000 die annually from related liver disease
• Related hospitalizations, cancers, and deaths in
  the US have more than doubled in past decade

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Outcome

• Progression to chronic hepatitis determined by
  the age at infection
• 90 for a perinatally acquired infection
• 20 to 50 for infections 1-5 years
• lt5 for an adult-acquired infection
• Complete eradication rare after recovery
• HBV DNA nt in blood, liver with evidence of
  liver damage

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HbeAg positive patients

• Treat those with ALT gt2 x ULN
• Recurrent hepatitis flares, icteric flares,
  advanced histologic findings (moderate/severe
  inflammation or bridging fibrosis/cirrhosis),
  gt40y with persistently high HBV DNA levels.
• Delay for 3-6 mth in newly diagnosed HBeAg ve
  with compensated liver disease spontaneous HBeAg
  seroconversion

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HbeAg negative patients

• Treat immediately if HBeAg -ve chronic hepatitis
  (ALT gt2 x ULN and HBV DNA gt2000 IU/mL) as
  sustained remission is rare in the absence of
  treatment
• Fluctuating course serial f/u to differentiate
  an inactive carrier state from HBeAg ve chronic
  hepatitis

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Interferon

• Standard interferon thrice weekly
• Pegylated interferon once a week
• Finite duration of Rx
• No resistant mutants, more durable response
• Young patients with well compensated liver
  disease
• Genotype A

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Lamivudine

• Lower cost
• Safety profile, many years of experience
• Safer in Pregnancy
• Higher resistance
• Lower remission rates compared to newer drugs
• Diminishing role with newer Rx

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Adefovir

• For lamivudine resistant HBV
• Virus suppression is slow and low
• Upto 30 resistance with 5 yr treatment
• Nephrotoxic
• Diminishing role with newer Rx

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Entecavir

• Potent antiviral activity
• Low rate of drug resistance
• May have role in decompensated cirrhosis
• Upto 50 resistance in lamivudine-resistant
  patients

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Tenofovir

• Can be used as first line treatment in
  treatment-naïve patients
• Also in patients with lamivudine or
  entecavir resistance
• Will probably replace adefovir in countries where
  it is approved because of its more potent
  antiviral activity
• Resistance rare after upto two years Rx

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Duration of Rx

• Standard interferon
• HbeAg ve 4-8 months
• HbeAg ve 12-24 months
• Pegylated interferon 12 months

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Duration of Rx (NI)

• HbeAg ve Endpoint is loss of HbeAg. Continue 6
  mo after seroconversion
• HbeAg ve Endpoint not established. Rx can stop
  in pts with loss of HbsAg
• Most patients require 4-5 yrs of Rx
• Lifelong Rx recommended in cirrhosis

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Special situations

• Entecavir better in renal failure or patients at
  risk for renal failure
• Interferon contraindicated in decompensated
  cirrhosis
• Any oral agent for interferon failed therapy,
  response similar to Rx naive patients
• In HIV co-infected patients, can use Truvada
  (emtricitabine tenofovir)

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Resistance prevention

• Avoid unnecessary treatment
• Initiate treatment with potent antiviral with low
  rate of drug resistance or combination therapy
• Switch to alternative therapy in patients with
  primary non-response

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Resistance monitoring

• Test for serum HBV DNA (PCR assay) every 3-6
  months during treatment
• Check for medication compliance in patients with
  virologic breakthrough
• Confirm antiviral resistance with genotypic
  testing

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Resistance

• Lamivudine-resistance ? Add adefovir or tenofovir
  
• Adefovir-resistance ? Add lamivudine Switch to
  or add entecavir
• Entecavir-resistance ? Switch to tenofovir

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Surveillance for HCC

• HCC can develop in normal liver
• RCT on 20,000 Chinese patients showed decreased
  mortality with surveillance over 20 year period
• Due to early detection Rx of HCC
• 6-12 monthly US /- AFP is recommended for
  surveillance in chronic hepatitis B

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• Nodules lt1 cm usually NOT HCC monitored every
  three months
• Nodules gt1 cm evaluated by CT scan and/or MRI
  with contrast
• If both show the typical radiological features of
  HCC (hypervascularity with washout in
  venous/portal phase) or AFP gt 200 ng/ml, the
  diagnosis is confirmed biopsy not necessary
• If one or neither show the typical features of
  HCC, a biopsy is required