1, which patients with chronic hepatitis B need antiviral therapy (including interferon therapy):.
General indications for antiviral therapy: both the following two points are met.
① e antigen (HBeAg) positive patients with hepatitis B DNA quantification ≥ 105copies/ml (2×104IU/ml).
e antigen (HBeAg) negative person, hepatitis B DNA quantification ≥ 104copies/ml (2000 IU/ml).
② Glutathione aminotransferase (ALT) ≥ 2 times the upper limit of normal (ULN).
Patients treated with interferon should have ALT ≤ 10 ULN and total bilirubin < 2 ULN.
Liver biopsy is recommended for patients with only mildly elevated or normal glutathione (ALT) who are older than 40 years, have a family history of hepatocellular carcinoma or an enlarged spleen. Antiviral therapy is recommended for those whose pathology shows more pronounced inflammatory necrosis. Interferon therapy is generally no longer considered in those older than 55 years of age.
For patients with ALT > 10 times the upper limit of normal and wishing to receive interferon therapy, liver protection or treatment with nucleoside (acid) analogs (NA) (except for tibivudine) may be used first, followed by interferon therapy when liver function meets the criteria (the two treatments may overlap for several weeks).
2, which patients can prefer interferon therapy.
Those who are relatively young, wish to have children in the near future, wish to complete treatment in a short period of time, have a strong immune response, and have a heavy inflammatory response in the liver with a mild degree of fibrosis. In addition, it is necessary to be financially viable (the monthly cost is close to 5,000 yuan, which can be partially reimbursed for patients with medical insurance).
Hepatitis B DNA quantification <2×108copies/ml (4×107IU/ml), high glutamate transaminase (ALT) level, female, short duration of disease, non-maternal-to-child transmission, good compliance, and genotype A have better efficacy.
3. What is the efficacy of interferon therapy?
According to the data cited in the guidelines for slow hepatitis B, the rate of HBeAg serological conversion (commonly known as “major triplet” to “minor triplet”) in patients with positive e antigen (HBeAg) treated with pegylated interferon for 48 weeks was 32% at 24 weeks of discontinuation and 43% at 48 weeks of discontinuation. In HBeAg-negative patients treated with pegylated interferon for 48 weeks, the rate of hepatitis B DNA quantification <2000 IU/ml was 43% at 24 weeks of discontinuation and 42% at 48 weeks of discontinuation; the rate of disappearance of surface antigen (HBsAg) was 3% at 24 weeks of discontinuation and 8% at 3 years of follow-up. (Clinical trials in recent years have yielded better efficacy data)
Overall, the HBeAg serological conversion rate is similar to or slightly better than that of nucleoside (acid) analogs (NA), and the hepatitis B DNA negative rate is not as high as that of NA. In selected patient populations, the surface antigen (HBsAg) disappearance rate can reach about 10%, with some reports of 30%, depending on the selection of patients enrolled and the treatment regimen.
The advantages of interferon therapy are the relatively constant duration of treatment, better immunomodulation of the body, and the prospect of HBsAg seroconversion (i.e., complete cure of hepatitis B) in some patients. The disadvantages are more adverse reactions, the need for subcutaneous injections, and the relatively high cost of short-term treatment.
4.What are the contraindications to interferon therapy?
Absolute contraindications: pregnancy, history of psychiatric disorders (including major depression), uncontrolled epilepsy, unabated alcoholics/drug users, uncontrolled autoimmune diseases, decompensated cirrhosis, symptomatic heart disease.
Relative contraindications: thyroid disease, retinopathy, psoriasis, previous history of depression, uncontrolled diabetes mellitus or hypertension, neutrophils <1×109/L or platelets <50×109/L, total bilirubin >51umol/L before treatment (especially those with predominantly elevated indirect bilirubin).
5.What tests are generally required during the treatment.
Routine blood count: 1 every 1-2 weeks in the 1st month, and 1 every month thereafter.
Biochemistry and liver function: once a month for 3 consecutive times, and once every 3 months afterwards as the condition improves.
Hepatitis B two-to-half (preferably quantitative) and hepatitis B DNA quantitative: once every 3 months.
Thyroid function, blood sugar, urine routine: once every 3 months. (Those with abnormal thyroid function or diabetes before treatment should be controlled first and checked once a month)
6.What are the adverse effects of interferon therapy and how to deal with them.
Flu-like symptoms: fever, chills, headache, muscle aches, weakness, etc. Can be injected at bedtime, drink more water, and take antipyretic and analgesic drugs at the same time if necessary. Usually it will gradually decrease after 2~3 injections.
Hemocytopenia: leukocytes ≤ 1.5×109/L or neutrophils ≤ 0.75×109/L or platelets ≤ 50×109/L, the dose should be reduced to 135ug/week (or extend the dosing interval) and monitoring should be strengthened.
For leukocytes ≤1.0×109/L or neutrophils ≤0.5×109/L or platelets ≤25×109/L, dosing should be suspended for 1 time and rechecked after 1 week, and treatment should be resumed or started from a small dose after the indexes rebound.
Those with significant decline in neutrophils can be injected with whitening injections (e.g. Rui Bai, Hui Er blood, Ji Gefen, etc.).
Those with significant platelet decline may be given recombinant platelet production factor (e.g., Tebteo).
Psychiatric abnormalities: depression, delusions, anxiety, etc. Consult with psychiatrist and discontinue in severe cases.
Autoimmune diseases: some patients may develop autoantibodies, only a few patients may develop hypothyroidism, hyperthyroidism, diabetes, psoriasis, rheumatoid arthritis, lupus erythematosus-like syndrome, etc. Consult with the physician of the relevant department and discontinue the drug in serious cases.
Rare serious adverse reactions: renal damage (interstitial nephritis, renal syndrome, acute renal failure, etc.), cardiovascular complications (arrhythmia, ischemic heart disease, cardiomyopathy, etc.), retinopathy, hearing loss, interstitial pneumonia, etc., should be discontinued.
Other adverse reactions: hair loss, loss of appetite, wasting, nausea and vomiting, diarrhea, fatigue, etc. They can be recovered after stopping the drug and treated symptomatically if necessary.
7.How to individualize treatment and what is guided treatment according to response to treatment (RGT).
(1) According to hepatitis B DNA quantification.
Complete response: Hepatitis B DNA is undetectable or below the lower limit of detection.
Partial response: Hepatitis B DNA quantification decreased ≥2logIU/ml from baseline but did not turn negative.
Non-responder: Hepatitis B DNA quantification decreased <2logIU/ml from baseline
For those who achieve complete response, it is recommended to maintain consolidation for at least another 6 months; for partial responders, it is recommended to continue treatment until complete response and maintain consolidation for 6 months even if the basic course of treatment has been completed for 1 year; for those who still have no response after 6 months of treatment, it is recommended to change the treatment regimen by combining or switching to nucleoside (acid) analogs (NA).
(2) HBeAg-positive individuals based on two-and-a-half pair quantitative results at 24 weeks of treatment.
HBeAg quantification at 24 weeks.
Those who have decreased to ≤10 PEIU/ml: Treatment can be extended to 72 weeks for those who have not undergone HBeAg serological conversion but have a stable decrease in HBeAg potency up to 48 weeks.
Decrease to 10~100 PEIU/ml: Treatment can be extended to 72 weeks.
Those with ≥100 PEIU/ml and hepatitis B DNA ≥5log copies/ml: combination or switch to NA is recommended.
HBsAg quantification at 24 weeks.
Those who have decreased to ≤1500 IU/ml: treatment can be extended to 72 weeks if HBeAg serological conversion has not occurred until 48 weeks.
Those who have decreased to 1500~20,000IU/ml can extend the treatment to 72 weeks.
Those ≥20,000 IU/ml and HBV-DNA ≥5log copies/ml: combination or switch to NA is recommended.
(3) HBeAg-negative patients according to the two-and-a-half quantification results at 24 weeks of treatment.
HBsAg quantification at 24 weeks.
Decline >1logIU/ml: treatment to 48 weeks, where HBsAg quantification is still >10IU/ml but continues to decline steadily can extend treatment to 72 weeks.
Those with a decrease of <1logIU/ml: coadministration or change to NA is recommended.
(4) For those who are on NA because of poor efficacy at 24 weeks of pegylated interferon treatment, how to deal with them after 24 weeks of combination therapy (by this time 48 weeks of pegylated interferon treatment).
If hepatitis B DNA is negative and there is HBeAg serological conversion or HBsAg quantification is close to disappearance, consider discontinuing NA and continue pegylated interferon therapy until 72 weeks.
If the hepatitis B DNA is negative, but the HBeAg or HBsAg quantitative decrease is not obvious, then discontinue pegylated interferon and continue NA long-term treatment can be considered.
8. Regarding hepatitis B vaccination in patients with negative HBsAg but still negative HBsAb.
Based on expert recommendations (not the references in this article), such patients are recommended to receive hepatitis B vaccine (e.g., when An is present) once a month, as many times as necessary, until HBsAb is positive. The immune effect of hepatitis B vaccine administered simultaneously with pegylated interferon is better than that of those who use hepatitis B vaccine alone after discontinuation of pegylated interferon.