Recommendation 1: General management
Adequate assessment and counseling (IIA) must be performed before considering drug therapy.
● Counseling includes: infectiousness or transmission, prevention, lifestyle, importance of monitoring, benefits or risks and advantages or disadvantages of treatment.
Recommendation 2: Indications
Viral replication but persistently normal or mildly elevated ALT levels do not require treatment; unless there is severe liver fibrosis or cirrhosis. These patients need to be adequately followed and monitored for hepatocellular carcinoma every 3 to 6 months (IA).
Recommendation 3: Evaluation of liver fibrosis
Assessment of liver fibrosis (IIA) is recommended for those with viremia, high limit of normal or slightly elevated ALT, and those older than 40 years (except for those with clinical signs of cirrhosis).
A liver biopsy is recommended for grading, staging and excluding other etiologies; non-invasive assessment methods are also available.
Recommendation 4: When to start treatment
ALT ≥ 2 × upper limit of normal (ULN) and HBV DNA ≥ 2 × 104 IU/mL (HBeAg positive) or ≥ 2000 IU/mL (HBeAg negative), and patients with severe liver fibrosis or cirrhosis should be considered for antiviral therapy (ⅠA) regardless of ALT level.
Patients with progressive ALT elevation or ALT > 5×ULN may experience: ① deterioration with heavy hepatitis or liver loss, requiring early treatment (ⅠA); ② spontaneous HBeAg serologic conversion or elimination, observed for 3~6 months (ⅡA).
Recommendation 5: Drug or strategy selection
IFN-α (ⅠB), PEG-IFN-α (ⅠA), entecavir (ⅠA), tenofovir (ⅠA), adefovir (ⅠB), telbivudine (ⅠB), or lamivudine (ⅠB) are available for nucleoside primary patients. Thymidine alpha (IB) may also be used. Entecavir or tenofovir preference.
● The duration of treatment, cost, speed of onset of action, and adverse effects need to be weighed.
Recommendation 6: How to monitor during treatment
ALT, HBeAg, and/or HBV DNA should be monitored during treatment, at least every 3 months (IA).
If tenofovir or adefovir is used, renal function needs to be monitored (IA).
If telbivudine is used, special attention needs to be paid to the development of myasthenia gravis (IIIA).
Monitoring of complete blood counts and other adverse effects is mandatory during IFN-based therapy (ⅠA).
Recommendation 7: How to monitor after the end of treatment
ALT and HBV markers (including HBV DNA) are tested once per month for the first 3 months after the end of treatment, and then every 3 months for the first year. If no events occur, test every 3 months (for those with cirrhosis) to 6 months (IIA).
For non-responders, further monitoring of HBV markers should be performed to identify delayed response and re-treatment if indicated (IIA).
Recommendation 8: Limited course of therapy
Plain IFN-α: 4-6 months of treatment for HBeAg-positive patients (ⅠA) and at least one year for HBeAg-negative patients (ⅠA).
PEG-IFN-α: treatment for 12 months (IA).
Thymidine α1: 6 months for both HBeAg-positive patients (IA) and negative patients (IIB).
● Observation for 6 to 12 months after the end of treatment.
Recommendation 9: When to stop oral antiviral drugs
HBeAg-positive patients: Obtain HBeAg serologic conversion and HBV DNA negativity and maintain for 12 months or more (IIA).
HBeAg-negative patients: 3 tests negative for HBV DNA, each 6 months apart (IIA).
With lamivudine, telbivudine or adefovir, if primary treatment failure occurs at 3 months of therapy or if response is poor at 6 months of therapy, discontinue and switch to a more effective nucleoside (acid) analogue or add a nucleoside (acid) analogue without cross-resistance (IIIA).
Recommendation 10: Women of childbearing age
Preference for IFN-α-based therapy is given to those who are not pregnant if treatment is needed (IA), and pregnancy is contraindicated during IFN-α therapy (IA). For those who require treatment during pregnancy, consider telbivudine or tenofovir (IIA).
To interrupt mother-to-child transmission, pregnant women with HBV DNA >2×106 IU/mL can be treated with tenifovudine (IIA) or tenofovir (IIIA) in late pregnancy.
Recommendation 11: Co-infection with HIV
For most patients with hepatitis B co-infection with HIV, the primary treatment modality is antiretroviral therapy including tenofovir and emtricitabine or lamivudine. Adefovir or PEG-IFN therapy (IIA) may be an option if CD4+ cell counts are >500/mL and antiretroviral therapy is not required.
Recommendation 12: Co-infection with HCV or HDV
Pay attention to identify which virus is the main cause of liver damage, and give treatment according to the appropriate treatment plan in case of separate infection (IA).
Recommendation 13: Decompensated liver disease
Entecavir or tenofovir (ⅠA) is used in patients with significant liver failure or imminent significant liver failure. Patients with nucleoside priming may also be treated with telbivudine, lamivudine, or adefovir (IB).
Renal function and lactic acidosis need to be monitored during treatment, especially in those with MELD score >20 (IIIA).
● Treatment should be started as early as possible; IFN is usually contraindicated.
Recommendation 14: Treatment of drug resistance
Lamivudine or telbivudine resistance: add adefovir (ⅠA) or switch to tenofovir (ⅡA). Lamivudine-resistant patients may be treated with entecavir 1 mg/d instead (ⅠB).
Adefovir-resistant: add or switch to lamivudine, telbivudine or entecavir (if the patient has not used these drugs previously) or switch to tenofovir (IIIA).
Entecavir resistance: add tenofovir disoproxil or adefovir (IIIA).
Lamivudine or both telbivudine and adefovir resistance: switch to entecavir plus tenofovir (IIA) is recommended.
Resistant patients may also switch to IFN-based therapy (IIIA).
Recommendation 15-1: When receiving immunosuppressive therapy or chemotherapy
Before receiving immunosuppressive therapy or chemotherapy, patients should be screened for HBsAg (IVA). If HBsAg is positive, oral nucleoside (acid) analogue therapy (IA) may be initiated when clinically indicated. Alternatively, prophylactic treatment with lamivudine may be initiated before the start of immunosuppressive therapy or chemotherapy and continued until at least 6 months after the end of immunosuppressive therapy or chemotherapy (IA).
Entecavir and tenofovir disoproxil may also be used for prophylaxis (IIIA).
Recommendation 15-2: Treatment with biologics or corticosteroids
Anti-HBc should be screened, and if anti-HBc is positive, HBV DNA levels need to be monitored closely (IIIA), and nucleoside (acid) analogs should be given for antiviral therapy if needed.
Biological agents such as anti-CD20, anti-TNF-α, etc.
Recommendation 16-1: Liver transplantation
All patients awaiting liver transplantation who test positive for HBV DNA should be started on nucleoside (acid) analogue therapy (IIA).
Lamivudine + low-dose HBIG (400-800 U/d for the first week, i.m.; then 400-800 U once a month for long-term use) is safe and effective in preventing HBV reinfection (IIA)
Lamivudine combined with adefovir or entecavir may also be considered for prevention (IIA).
● Antiviral therapy may save some patients from liver transplantation and may reduce hepatitis recurrence after transplantation (IIA).
Recommendation 16-2: Liver transplantation
Replacement of HBIG with adefovir in the late phase of liver transplantation (at least 1 year after surgery) provides safe and cost-effective prophylaxis (IIA).
For “low-risk” patients, lamivudine alone may also be considered in the late phase of liver transplantation (IA).
Low risk is defined as.
(i) Pre-transplant HBV DNA negativity;
② initial anti-HBs titer is protective.
Recommendation 16-3: Anti-HBc-positive donors
Patients who have not been infected with HBV and who receive a liver from an anti-HBc-positive donor should be given long-term prophylaxis with lamivudine or HBIG (IIIA).
Recommendation 17: Patients before and after radical or local treatment for HCC
For all patients with HCC with HBV DNA > 2000 IU/mL, oral nucleoside (acid) analogs should be given before and after the administration of radical therapy (IIIB), as in other patients with hepatitis B. Empirical nucleoside (acid) analogue therapy (IIA) should be given to all patients with HCC treated with transarterial chemoembolization.