Summary

AASLD 2018 guidance updates the 2016 Hepatitis B Treatment Guidelines, adding tenofovir alafenamide (TAF) as a preferred first-line NA and elevating tenofovir disoproxil fumarate (TDF) to preferred therapy for prevention of mother-to-child transmission. It covers screening, counseling, prevention, virological assays, monitoring of untreated patients, and management in special populations (HCV/HDV/HIV coinfection, immunosuppression, acute HBV, pregnancy, cirrhosis, transplant recipients, children). Preferred antivirals remain peg-IFN, entecavir, TDF, and TAF; TAF offers improved renal and bone safety vs TDF with comparable efficacy.

Key Recommendations

Screen high-risk groups (Table 3) with both HBsAg and anti-HBs; vaccinate anti-HBs–negative persons.
Preferred first-line therapies for immune-active CHB are peg-IFN, entecavir, TDF, or TAF; avoid lamivudine, adefovir, telbivudine as initial therapy.
Treat HBeAg-positive or HBeAg-negative immune-active CHB when ALT ≥2× ULN and HBV DNA above threshold; treat all patients with cirrhosis and detectable HBV DNA.
Do not treat immune-tolerant adults; monitor ALT every 6 months. Consider treatment in patients >40 with normal ALT, HBV DNA >1,000,000 IU/mL, and significant histologic disease.
Use TAF or entecavir preferentially over TDF in patients at risk for or with renal dysfunction or bone disease.
Treat HBsAg-positive pregnant women with HBV DNA >200,000 IU/mL starting at 28–32 weeks gestation with TDF to prevent perinatal transmission; infants receive HBIG plus vaccine within 12 hours of birth.
Screen all immunosuppression candidates with HBsAg and anti-HBc; give prophylaxis to all HBsAg-positive patients and to anti-HBc–positive patients receiving rituximab/anti-CD20 or stem cell transplant, continuing 6 months (12 months if anti-CD20) after completion.
In HBV/HIV coinfection, use ARVT containing two HBV-active drugs—tenofovir (TAF or TDF) plus lamivudine or emtricitabine.
For HBV/HCV coinfection initiating DAA therapy, give concurrent HBV antiviral prophylaxis (entecavir, TDF, or TAF) if HBsAg-positive and meet HBV treatment criteria; monitor HBsAg-negative/anti-HBc–positive patients for reactivation.
For HDV coinfection: screen high-risk HBsAg-positive patients with anti-HDV; treat HDV-RNA positive patients with peg-IFN-α for 12 months, adding NA if HBV DNA elevated.
Treat acute hepatitis B only if acute liver failure or protracted severe course (bilirubin >3 mg/dL, INR >1.5, encephalopathy, or ascites) with entecavir, TDF, or TAF; peg-IFN contraindicated.
All HBsAg-positive liver transplant recipients require lifelong NA prophylaxis (entecavir, TDF, or TAF) with or without HBIG; HBIG monotherapy is inadequate.
Surveillance for HCC with ultrasound every 6 months in cirrhotics and high-risk non-cirrhotics; continue HCC surveillance even after HBsAg loss in those with cirrhosis or other risk factors.

Thresholds & Doses

TAF dose: 25 mg PO daily; no dose adjustment unless CrCl <15 mL/min.
TDF dose: 300 mg PO daily (adults); approved in children ≥12 years.
Entecavir dose: 0.5 mg PO daily (1 mg if lamivudine-experienced or decompensated cirrhosis).
Peg-IFN-α-2a: 180 mcg SC weekly; pediatric 6 million IU/m² 3 times weekly.
Lamivudine adult dose 100 mg daily; adefovir 10 mg daily; telbivudine 600 mg daily.
ALT ULN for management: 35 U/L (men), 25 U/L (women).
Treatment threshold HBeAg-positive: HBV DNA >20,000 IU/mL with ALT ≥2× ULN.
Treatment threshold HBeAg-negative: HBV DNA ≥2,000 IU/mL with ALT ≥2× ULN.
Immune-tolerant CHB: HBV DNA typically >1,000,000 IU/mL with normal ALT.
Antiviral prophylaxis in pregnancy: HBV DNA >200,000 IU/mL; start at 28–32 weeks.
HBsAg-positive HCWs performing exposure-prone procedures: HBV DNA must stay <1,000 IU/mL.
HBV reactivation (HBsAg+): ≥2 log rise in HBV DNA, or HBV DNA ≥3 log IU/mL if previously undetectable, or ≥4 log IU/mL if baseline detectable.
Hepatitis flare definition: ALT >3× baseline and >100 U/L.
Virological breakthrough: >1 log10 rise in HBV DNA from nadir on therapy.
Inactive CHB: HBV DNA <2,000 IU/mL, normal ALT, HBeAg-negative; qHBsAg <1,000 IU/mL supports diagnosis.
Post-immunosuppression prophylaxis duration: ≥6 months after completion (≥12 months after anti-CD20).
HBV vaccine schedules: standard 3-dose 0/1/6 months; HEPLISAV-B 2-dose at 0 and 1 month; Twinrix accelerated 0/7/21–30 days plus 12-month booster.
Post-vaccination protective anti-HBs titer: ≥10 mIU/mL.
HCC surveillance: ultrasound every 6 months; AFP every 6 months only if US unavailable.
Alcohol risk threshold: >7 drinks/week women, >14 drinks/week men associated with increased cirrhosis/HCC.

Citations

Interim Data Section — TAF phase 3 trial efficacy and renal/bone safety vs TDF.
Section 1A & Table 3 — Screening high-risk groups; HBsAg + anti-HBs as initial tests.
Table 4 — Interpretation of HBsAg/anti-HBc/anti-HBs serology patterns.
Section 1C & Guidance Statements on Pregnancy — TDF for prevention of mother-to-child transmission when HBV DNA >200,000 IU/mL.
Figure 1 / Treatment Algorithms — ALT and HBV DNA thresholds for HBeAg-positive and HBeAg-negative CHB.
Section 6D & Guidance Statements on Immunosuppression — Prophylaxis vs on-demand therapy; anti-CD20 and HSCT exceptions.
Section 6E — Treatment of acute hepatitis B (entecavir/TDF/TAF only in ALF or protracted severe disease).
Section 6H–6I & Table 9 — Liver and nonliver transplant prophylaxis with NA ± HBIG.
Recommendation 5 (Renal/Bone) — TAF preferred over TDF in patients with renal/bone disease.
Table 6 — Diagnostic criteria and definitions of CHB phases, reactivation, and flare.