hepatitis%20b
HEPATITIS B

Hepatitis B is transmitted through perinatal, percutaneous, sexual, and close person-to-person contact, ie by open cuts and sores.

Human hepatitis B virus belongs to the family of Hepadnaviridae of small, enveloped, primarily hepatotropic DNA viruses. The virus replicates in the host and assembles exclusively in the hepatocytes and virions are released non-cytopathically through the cellular secretory pathway.

Chronic hepatitis B is defined as a chronic necroinflammatory liver disease due to persistent hepatitis B virus infection.

Hepatitis D infection is found only in patients with hepatitis B as it requires the hepatitis B outer coat. It is transmitted through sexual and percutaneous (especially IV drug use) routes.

Hepatitis B and D both have an incubation period of 30-180 days.

Principles of Therapy

Hepatitis D

  • Aim of treatment is to eradicate or to achieve long-term suppression of both hepatitis D virus and hepatitis B virus
  • Supportive care
  • Consider hospitalization if there is vomiting, dehydration, signs of hepatic decompensation
  • Screen for other sexually-transmitted diseases in cases of sexually-acquired hepatitis or if otherwise appropriate
  • Consider expert referral

Acute Hepatitis B

  • Main goal of treatment is to prevent the risk of acute or subacute hepatic failure
    • Other relevant goal of treatment is to improve the quality of life by shortening disease duration associated with symptoms as well as the risk of chronicity
  • Supportive care
    • Treatment with antivirals is generally not recommended
  • Consider hospitalization if there is vomiting, dehydration, signs of hepatic decompensation
    • Consider treatment with nucleoside or nucleotide analogues in severe acute hepatitis

Chronic Hepatitis B

  • Vaccination against hepatitis B for non-immune patients
  • Periodic screening for hepatocellular carcinoma in high-risk carriers
    • HCC may have a long asymptomatic stage lasting 2 years or longer
    • Carriers of HBV at high risk for developing HCC include Asian men >40 years, Asian women >50 years, patients with cirrhosis, co-infected with HCV, with HBV genotype C, with HDV infection, persistent HBV DNA >2000 IU/mL, or those with family history of HCC in 1st-degree relative
    • Screening methods are ultrasound with or without alpha-fetoprotein (AFP) determination every 6 months
  • Liver biopsy
    • Purposes are to assess the degree of liver damage, to rule out other causes of liver disease and to help predict prognosis
    • Recommended for chronic hepatitis B patients who are candidates for antiviral therapy

Patients For Whom Treatment is Not Recommended

  • Without clinical evidence of cirrhosis, with PNALT, HBV DNA <2,000 IU/mL, regardless of HBeAg status or age

Patients For Whom Treatment is Recommended

  • Evidence of compensated or decompensated cirrhosis regardless of HBeAg status or HBV DNA or ALT levels
  • Without clinical evidence of cirrhosis but with persistently abnormal ALT, HBV DNA >20,000 IU/mL, regardless of HBeAg status
  • Chronic HBV severe reactivation

Goals of Treatment

  • Continued viral suppression is necessary to reduce or prevent hepatic disease and disease progression
  • Primary goal of treatment is to permanently suppress HBV or to eliminate it
    • Short-term goals are to sustain suppression of HBV DNA, ALT normalization, to prevent decompensation and to decrease hepatic necroinflammation and fibrosis during and after therapy
    • Long-term goals of therapy are to avoid hepatic decompensation, reduce or prevent progression to cirrhosis and/or HCC and to prolong survival
  • Endpoints used to assess response:
    • Biochemical response: Normalization of serum ALT
    • Virological response: HBV DNA <104 copies/mL and sustained seroconversion from HBeAg to anti-HBe
    • Histological response: Decrease in histology activity compared to pretreatment liver biopsy or a reduction of at least 1 point in fibrosis by Metavir staging
    • Complete response: Fulfill criteria of biochemical and virological response and loss of HBsAg
  • Current treatments of chronic hepatitis B have limited long-term efficacy

Considerations Prior to Initiation of Treatment

  • Age of patient
  • Severity of liver disease
  • Likelihood of response
  • Potential adverse events and complications
  • HBeAg-positive patients with elevated ALT levels and compensated liver disease should be observed for 3-6 months for spontaneous seroconversion from HBeAg to anti-HBe prior to initiation of treatment
  • Choice of therapy will depend on availability, cost of medication, necessary number of clinic visits, expected duration of treatment and patient/clinician preference

Other Considerations in Pharmacological Therapy

  • There is no evidence that combination therapy of 2 direct antiviral agents results in better viral suppression compared to single agent
  • Antiviral therapy does not remove the risk of hepatocellular carcinoma and thus hepatocellular carcinoma surveillance must continue 
  • In treating concurrent infections such as hepatitis C virus, hepatitis D virus and HIV infection, it is important to identify the dominant virus as this will determine the therapeutic regimen
    • Concurrent hepatitis C infection may be treated with same antiviral therapy for HCV monoinfection
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