NCCVH Guidelines for the Management
of Patients with HBV Infection
June 2022

1. Initial Assessment of Patients with Chronic HBV Infection

  • Clinical assessment (history/physical examination)
  • Laboratory investigations:
    • ALT
    • AST
    • CBC
    • Random blood sugar
    • Serum total bilirubin
    • Serum albumin
    • PT and INR
    • Serum phosphorus
    • Serum creatinine, and estimated glomerular filtration rate (eGFR) calculated by the CKD-EPI equation
    • Anti-HCV
    • Anti-HIV
    • HBeAg
    • Quantitative HBV DNA serum level
    • AFP
  • Abdominal ultrasound
  • Transient elastography (TE):
    • It is only recommended if: 
      • HBV DNA ≥ 2,000 IU/ml + normal transaminases,
      • HBV DNA < 2,000 IU/ml + elevated transaminases, or
      • HBV DNA < 2,000 IU/ml + normal transaminases + imaging suggestive of liver cirrhosis.
    • If it is not available in the treatment center, FIB-4 can be used.

2. Patients who should be treated:

HBV DNA (IU/ml) ALT Other Factors
≥ 2000 > ULN Negative HBeAg
≥ 20000 > ULN Positive HBeAg
≥ 2000 Persistently normal Positive HBeAg and age > 30 years
< 2000 > ULN TE > 7 kPa, or
FIB4 > 1.45
≥ 2000 Normal TE > 7 kPa, or
FIB4 > 1.45
Any Any
  • Family history of HCC,
  • cirrhosis (FIB4 > 3.25, or TE > 12 KPa),or
  •  severe extra-hepatic manifestations(documented by specialty consultation)
ULN, upper limit of normal.

3. Treatment Strategies

a. Treatment-naïve patients:
  • Tenofovir disoproxil fumarate (TDF) 300 mg once daily, tenofovir alafenamide (TAF) 25 mg once daily, or entecavir (ETV) 0.5 mg once daily.
  • ETV or TAF is preferred in patients over 60 years or with bone disease (chronic steroid use or use of other medications that worsen bone density, osteoporosis).
b. Treatment-experienced patients:
  • Patients on lamivudine (LAM): shift to TDF 300 mg once daily or TAF 25 mg once daily.
  • Patients on combined LAM and adefovir: shift to TDF 300 mg once daily or TAF 25 mg once daily.
c. Treatment failure:
  • Primary non-response: < 1 log10 decrease in HBV DNA after 3 months of therapy.
  • Partial virological response: HBV DNA decreased by > 1 log10, but still detectable after ≥ 12 months of therapy.
  • Virological breakthrough: HBV DNA increase of > 1 log10 above on-therapy lowest level.
  • Compliance should be confirmed.
  • ETV should not be used in LAM experienced patients.
Resistance/failure Recommended strategies
LAM Switch to TDF or TAF
ETV (very rare except in patients withprevious LAM failure) Switch to TDF or TAF
ADV • If LAM-naive: switch to ETV or TDF
or TAF
• If LAM-failure: switch to TDF or TAF
TDF or TAF (very rare if any) • If LAM-naive: switch to ETV
• If LAM-failure: add ETV
Multidrug Switch to ETV + TDF or TAF
ADV, adefovir; ETV, entecavir; LAM, lamivudine; TDF, tenofovir disoproxil
fumarate TAF tenofovir alafenamide.

Follow-up of patients with chronic HBV

a. Currently on treatment
  • Every month: to receive medication and monitor for compliance and side effects.
  • Every 3 months during the first year, and every 6-12 months thereafter:
    • ALT
    • AST
    • Serum total bilirubin
    • Serum albumin
    • PT and INR
    • Quantitative serum HBV DNA level
    • AFP
    • Abdominal ultrasound
    • Serum phosphorus
    • Serum creatinine and eGFR
    • Closer renal monitoring is required in patients who develop eGFR < 60 ml/min or serum phosphorus levels < 2 mg/dl
  • Long-term follow-up: HCC surveillance for all patients under effective long-term nucleos(t)ide analogue (NA) therapy (AFP, U/S every 4 months).
b. Currently not on treatment
  • Every 6 months:
    • ALT
    • Quantitative serum HBV DNA
    • AFP
    • Abdominal ultrasound
  • Every 2 years: TE or FIB-4 to assess liver fibrosis.

5. NAs discontinuation rules

Discontinuation strategy
No cirrhosis
Positive HBeAg HBeAg seroconversion and undetectable HBV DNA after:
• 12 months of consolidation therapy,
• 3 years of continuous treatment, and
• age > 40 years
Negative HBeAg  Indefinitely, or until HBsAg seroconversion and after 12
months of consolidation treatment
Cirrhosis Do not stop anti-viral therapy

Special groups:

a. Acute Infection
  • Antiviral treatment is indicated in patients with acute liver failure or who have a severe course indicated by the presence of 2 out of the following 3 criteria:
    • serum total bilirubin > 10 mg/dl
    • INR > 1.6
    • encephalopathy
  • Entecavir 0.5 mg daily for:
    • at least 6 months after seroconversion to anti-HBs, or
    • at least 12 months after seroconversion to anti-HBe without HBsAg loss.
b. Liver Cirrhosis

All patients with cirrhosis should receive oral antiviral therapy if HBV DNA is detectable.

  • Compensated cirrhosis: ETV 0.5 mg or TDF 300 mg or TAF 25 mg once daily.
  • Decompensated cirrhosis: ETV 1 mg once daily.
  • The dose of antiviral therapy needs to be adjusted in patients with low creatinine clearance (< 50 ml/min).
c. Co-infection with other viruses

HBV/HCV co-infection

  • Treatment of HCV with DAAs may cause reactivation of HBV.
  • Patients fulfilling the standard criteria for HBV treatment should receive NA:
    • Patients with positive HBsAg undergoing DAA therapy should be considered for concomitant NA prophylaxis and continue until 12 weeks after completion of DAA, then re-evaluated.
    • Patients with negative HBsAg and positive anti-HBc undergoing DAA therapy should be monitored (and tested for HBV reactivation in case of ALT elevation) every 4 weeks during treatment.

HBV/HIV co-infection

  • All HIV-positive patients with HBV co-infection should start antiretroviral therapy (ART):
    • irrespective of CD4 cell count.
    • with a TDF or TAF-based ART regimen.

HBV/HDV co-infection

  • Should be suspected if there is:
    • re-rise of serum transaminases (double peak pattern) in acute viral hepatitis B.
    • on-treatment with unexplained increase of transaminases.
    • failure to achieve virologic response with potent NAs.
  • Active HDV infection should be confirmed by HDV RNA assays.
  • Peg-INFα is the only effective drug against HDV.
  • Optimal duration of therapy is at least 48 wks.
  • Oral antiviral therapy for HBV should be considered in patients with:
    • HBV DNA levels persistently > 2,000 IU/ml.
    • evidence of advanced liver disease.

d. Pregnancy
  • All pregnant females should be screened for HBsAg in the first trimester and if negative, they should be vaccinated (test anti-HBc IgG and anti-HBs).
  • Criteria for NA use during pregnancy:
    • HBV DNA level ≥ 200,000 IU/ml at the end of the second trimester:
      • TDF (class B drug) 300 mg once daily should start at gestational week 24-28, and
      • continue to 12 weeks after delivery, then re-evaluate.
    • Females who become pregnant while on treatment: continue or shift to TDF.
    • FIB-4 > 1.45 (if not already on treatment): start TDF 300 mg once daily.
  • Pregnant women not fulfilling the criteria for NA use should be followed during pregnancy and after delivery for HBV reactivation.
  • Cesarean section does not decrease chances of MTC transmission compared to normal delivery and is not indicated to reduce this chance.
  • Newborns for chronic HBV mothers should receive hepatitis B immunoglobulin (HBIG) and the first dose of HBV vaccine at birth (6-12 hours after delivery).
  • Breastfeeding is not contraindicated in mothers who are HBsAg-positive and untreated or on TDF.
e. Renal impairment, dialysis and renal transplantation

All dialysis and renal transplant recipients should be screened for HBsAg.

  • Seronegative patients should be vaccinated.
  • TAF is preferred in naïve patients.
  • Patients who were already on TDF or ETV, should shift to TAF.
  • No TAF dose adjustment is needed in patients with eGFR ≥ 15 ml/min or in those who are on hemodialysis.
  • In patients with LAM failure or decompensated cirrhosis, ETV is used with dose adjustment according to eGFR as follows:
    • eGFR (ml/min) Entecavir dose
    • ≥ 50 1 mg / day
    • 30 - 49 1 mg / 2 days
    • 10 - 29 1 mg / 3 days
    • < 10 or on hemodialysis 1 mg / week
eGFR (ml/min) Entecavir dose
≥ 50 1 mg / day
30 - 49  1 mg / 2 days
10 - 29  1 mg / 3 days
< 10 or on hemodialysis 1 mg / week

• In patients undergoing dialysis, ETV (once weekly) and TAF should be given
after the dialysis session.

f. Immunosuppressed patients
  • All candidates for chemotherapy and immunosuppressive therapy should be screened for HBsAg, anti-HBs, and anti-HBc prior to initiation of treatment.
  • Vaccination is mandatory for seronegative patients. Higher vaccine doses may be needed.
HBsAg   Other conditions Strategy
Positive Irrespective of the viral load NA at the onset of chemotherapy
and for 12 months after cessation
of treatment
Negative Anti-HBc positive, and
HBV DNA positive
Anti-HBc positive, and
HBV DNA negative
• Follow-up every 3 months.
• Start NA if DNA becomes

NA, nucleos(t)ide analogue.

g. Liver Transplantation
  • Pre-transplant: All patients with HBV who are candidates for liver transplantation should receive an NA to achieve undetectable HBV DNA and reduce the risk of graft infection.
  • Post-transplant: Combination of hepatitis B immunoglobulin (HBIG) and a potent NA is recommended to prevent HBV recurrence.
  • Patients with a low risk of recurrence can discontinue HBIG but need continued monoprophylaxis with a potent NA.
  • HBsAg-negative patients receiving livers from donors with evidence of past HBV infection (anti-HBc positive) are at risk of HBV activation and should receive antiviral prophylaxis with NA.

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