What are the World Health Organization (WHO) guidelines for treating chronic hepatitis B?

WHO Guidelines for Treating Chronic Hepatitis B

The World Health Organization (WHO) strongly recommends antiviral therapy for all adults, adolescents, and children with chronic hepatitis B (CHB) who have clinical evidence of compensated or decompensated cirrhosis, regardless of ALT levels, HBeAg status, or HBV DNA levels. 1

Treatment Indications According to WHO Guidelines

Priority Populations for Treatment

1. Cirrhotic Patients:

   • All patients with clinical evidence of compensated or decompensated cirrhosis should be treated regardless of ALT levels, HBeAg status, or HBV DNA levels 1
   • This is a strong recommendation with moderate quality evidence

2. Non-cirrhotic Adults:

   • Treatment is recommended for adults with CHB who do not have clinical evidence of cirrhosis but have:
     • Persistently abnormal ALT levels
     • Evidence of high-level HBV replication (HBV DNA >20,000 IU/mL)
     • Age >30 years 1, 2

Special Populations

1. Pregnant Women:

   • WHO did not make specific recommendations for antiviral therapy to reduce mother-to-child transmission due to lack of evidence when the guidelines were drafted 1
   • This differs from other guidelines like AASLD and EASL which recommend treatment in the third trimester for women with high viral loads

2. Children:

   • WHO suggests a conservative approach for children due to:
     • Low cure rates with nucleos(t)ide analogues (NAs) and interferon
     • Concerns over long-term safety
     • Potential drug resistance 1
   • Treatment is recommended only for children with severe disease such as cirrhosis or histological evidence of severe necro-inflammatory disease

3. Co-infected Patients:

   • HBV/HIV: Antiretroviral therapy (ART) should be initiated in all those with:
     • Evidence of severe chronic liver disease, regardless of CD4 count
     • CD4 count ≤500 cells/mm³, regardless of liver disease stage 1
   • HBV/HCV: HBV DNA monitoring is necessary due to risk of HBV reactivation during or after HCV treatment 1
   • HBV/HDV: No specific WHO recommendations are provided for HDV co-infection

4. Acute Hepatitis B:

   • Persons with fulminant or severe acute hepatitis B may benefit from NA therapy with entecavir or tenofovir to improve survival and reduce risk of recurrent hepatitis B 1

Diagnostic Approach

1. Fibrosis Assessment:

   • WHO recommends APRI (AST-to-platelet ratio index) as the preferred non-invasive test to assess for cirrhosis in resource-limited settings, with a cutoff of 2 1
   • More advanced non-invasive tests like transient elastography (Fibroscan) can be used when available 1

2. Monitoring Parameters:

   • ALT and HBV DNA levels should be monitored regularly
   • HBeAg/anti-HBe status should be checked periodically 2

Treatment Options

1. First-line Agents (based on FDA labels):

   • Entecavir: Indicated for CHB infection in adults with evidence of active viral replication and either persistent elevations in serum aminotransferases or histologically active disease 3
   • Tenofovir: Used for treatment of CHB in people 12 years of age and older 4

2. Treatment Duration:

   • The optimal duration of treatment is unknown
   • The relationship between treatment response and long-term prevention of outcomes such as hepatocellular carcinoma is not fully established 4

Important Clinical Considerations

1. Risk of Discontinuation:

   • Severe acute exacerbations of hepatitis have been reported in patients who discontinued treatment 4
   • Do not stop treatment without physician supervision

2. Monitoring During Treatment:

   • Regular monitoring of renal function is necessary, especially with tenofovir
   • Bone mineral density monitoring should be considered in patients at risk for osteopenia 4

3. Treatment Goals:

   • Primary goals include preventing progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma 2
   • Viral suppression (undetectable HBV DNA) is the main surrogate marker of treatment success

Pitfalls to Avoid

1. Undertreatment of Cirrhotic Patients: All patients with cirrhosis and any detectable HBV DNA should be treated, as failure to do so significantly increases mortality risk

2. Treatment Interruption: Abrupt discontinuation can lead to severe hepatitis flares and decompensation

3. Inadequate Monitoring: Regular follow-up is essential to assess treatment response and detect resistance

4. Inappropriate Drug Selection: Using agents with low genetic barrier to resistance (like lamivudine) as first-line therapy should be avoided 2

5. Overlooking Co-infections: Patients should be tested for HIV, HCV, and HDV co-infections as these require specific management approaches

The WHO guidelines provide a framework for treatment that prioritizes patients at highest risk for disease progression while considering resource limitations in many settings. They are generally more conservative than other international guidelines but focus on evidence-based interventions that can reduce morbidity and mortality from chronic hepatitis B.