Chronic Hepatitis B infection

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Defined as persistence of hepatitis B surface antigen (HBsAg) for six months or more after acute  infection with HBV. 

Clinical presentation 

  • Usually asymptomatic
  • Right upper quadrant abdominal pains
  • Fatigue, malaise, anorexia, low grade fever; jaundice is frequent in severe disease
  • Ascites, variceal bleeding, encephalopathy, coagulopathy, and hypersplenism
  • Urticaria, arthritis, vasculitis, polyneuropathy, glomerulonephritis, thyroiditis

Investigations 

  • HBsAg, HBsAb, HBeAg, HBeAb, HBV DNA PCR
  • LFT, RFT, FBP, HIV
  • Alfa Feto Protein (AFP)
  • Colour Doppler ultrasonography or duplex Doppler ultrasonography or real time ultrasonography
  • CT scan
  • Fibroscan (if available)

Treatment of Chronic Hepatitis B infection 

Pre Treatment Considerations – Who to Treat: 

  • Patient in chronic active/ reactivation phase characterized by elevated liver enzymes ALT >2X ULN, HBeAg +ve, viral load >20,000
  • ALT > 2X ULN, HBeAg –ve, HBeAb –ve, viral load>2000 (mutant strain)
  • Patients  with  evidence  of  fibrosis  development  (APRI  score  >2)/cirrhosis  should  receive treatment irrespective of age, and viral loads
  • Adults aged > 30 years with three determinations of persistently abnormal ALT levels above ULN made at unspecific intervals during 6-12month period  with DNA viral load > 20,000 IU/ml irrespective of HBeAg status
  • Patients co-infected with HIV

Pre Treatment Considerations – Who not treat: 

  • Treatment  should not be given to patients with persistently normal ALT levels and APRI score < 2 regardless of age and HBeAg status
  • Immunotolerant  patients  characterized  by  high  viremia  with  normal  liver  chemistry, age less than 30 years old require no treatment. Reassess after 24weeks interval.
  • Patient in latent or inactive phase characterized by low viremia, normal liver chemistry with or  without  HBeAg  sero-conversion  requires  no  treatment.  Reassess  after  2  weeks’ intervals.

Pharmacological Treatment 

(For eligible adults with no contraindications to tenofovir) 

A: tenofovir (TDF) (PO) 300mg 24hourly; for at least 48weeks

Note: 

  • Reassess at 24 weeks for evidence of biochemical and viral replication remission (normalization of ALT, viral suppression to undetected level and seroconversion to anti-HBe)
  • Offer a consolidated TDF therapy for extended 48 weeks for patients with evidence of HBeAb sero-conversion and biochemical remission at the end of the first 48 weeks. For patients still with detectable viral load and or not yet seroconverted to HBeAb, continue with Tenofovir 300mg daily dose and reassess every 6 to 12 months for HBV DNA, HBeAg/Ab status
  • Absolute contraindications to Tenofovir in patients aged < 12 Years

OR 

S: entecavir in the following groups: Children and adolescents between age 2 to 18 years  weighing between 10kg and 32kg 

 

Adults with renal insufficiency (CrCl<49ml/min)

Entecavir dose considerations 

  • Children age 2 to 18 years weighing between 10kg and 32kg - 0.5mg (PO) 24hourly
  • Adults naive to nucleoside therapy (PO) 0.5mg 24hourly
  • Adults with Lamivudine resistance/previous exposure; and decompensated cirrhosis - 1mg (PO)
  • Adults with renal insufficiency (CrCl<49ml/min); dose should be adjusted according to calculated GFR 

A: Tenofovir (PO) 300mg 24hourly for patients who have treatment failure with other nucleotides analogues with low resistance barrier (i.e. lamivudine) OR Interferon based  therapy. 

Note: Lamivudine should not be prioritized due to low resistance barrier. Interferon based therapy is not  recommended  in  our  setting  due  to  undesirable side  effects,  route  of administration and high cost.

When to Stop Treatment 

  • Patient who has been put on Nucleotides analogues therapy without evidence of cirrhosis or APRI< 2 should be given a follow up plan.
  • Patients  who  are  HBeAb  sero-converted  after  48  weeks  of  consolidation  therapy,  with persistently  normal  ALT  and  undetectable  DNA  levels  should  stop  treatment  and be monitored closely
  • Patients  with  evidence  of  HBsAb  sero-conversion  after  completing  consolidated  therapy regardless of their DNA and HBeAg status should stop treatment
  • Treatment in patient with liver cirrhosis or significant fibrosis is indefinite

Monitoring and evaluation of therapeutic response and toxicity. 

  • HBsAg, HBeAb, HBeAg, HBV DNA, AFP, ALT should be monitored pre, during, and post treatment. PLUS (Fibrosis assessment by APRI scores) at 24/ 48weeks interval
  • Renal  functions  in  adults  and  growth  development  in  children  should  be  monitored annually   for renal toxicity for patients on Tenofovir and Entecavir respectively
  • Abdominal  Ultrasound  (AUS)  and  Alpha  Feto  Protein  (AFP)  should  be  done  at  24- 48 weeks’ interval for   HCC surveillance

Note: Screening all close contacts is important. All at risk individuals e.g. healthcare workers, men who have sex with men, patients on hemodialysis, prisoners, children born to mothers with HBV and  patients requiring multiple transfusions, patients with non-B viral hepatitis should be tested for HBV and vaccinated if found negative for HBsAg and no evidence of natural immunity  to HBV.