Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Pegylated interferon alfa

11 evidence topics · 8 sources

Current role: AASLD/IDSA 2025 guideline

“Peginterferon is rarely used, given its limitations of applicability, safety and tolerability, compared with NA therapy.” (opens the source at this quote in a new tab)
“Role of peginterferon add-on or switch therapy to NA as strategy to achieve functional cure” (opens the source at this quote in a new tab)

Recommendations on administration, stopping rules, and add-on therapy: EASL 2025 guideline

“Predictive factors should be used to guide the decision to initiate PEG-IFNα treatment. In addition, PEG-IFNα-associated side effects should be considered, and the patient's treatment preferences should be taken into account to support the decision-making process (LoE 2, strong recommendation, strong consensus).” (opens the source at this quote in a new tab)
“PEG-IFNα should be administered once a week, typically for a duration of 48 weeks. The dose of PEG-IFNα-2a should be 180 μg weekly (s.c.) (LoE 1, strong recommendation, strong consensus).” (opens the source at this quote in a new tab)
“Stopping rules should be considered based on the quantitative determinations of HBV DNA and HBsAg at treatment week 12 and 24 (LoE 2, strong recommendation, strong consensus).” (opens the source at this quote in a new tab)
“De novo combination therapy with PEG-IFNα and NAs cannot be generally recommended. PEG-IFNα as an add-on therapy can be considered in selected HBeAg-negative patients undergoing NA therapy with low HBsAg levels (LoE 2, weak recommendation, consensus).” (opens the source at this quote in a new tab)

Patient selection and duration: AASLD 2018 guidance

“Comorbidities: peg-IFN is contraindicated in persons with autoimmune disease, uncontrolled psychiatric disease, cytopenia, severe cardiac disease, uncontrolled seizures, and decompensated cirrhosis.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote
“For patients treated with peg-IFN, 48 weeks’ duration is used in most studies and is preferred. This treatment duration yields HBeAg seroconversion rates of 20% to 31% and sustained off-treatment HBV DNA suppression of <2,000 IU/mL in 65% of persons who achieve HBeAg to anti-HBe seroconversion. The combination of peg-IFN and NAs has not yielded higher rates of off-treatment serological or virological responses and is not recommended.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote

Differences between peginterferon and nucleos(t)ide analogue therapy

Feature	ETV, tenofovir (TDF, TAF)	PEG-IFNα
Strategy	“Preventing disease progression through persistent HBV suppression”	“Induction of an off-treatment response through finite treatment”
Administration	“Oral, once daily”	“Subcutaneous, once weekly”
Treatment duration	“Long-term”	“Finite (48 weeks)”
Side effects	“Very low”	“Moderate to high”
Contraindications	“Very few (e.g. ETV in pregnancy)”	“Numerous”
HBsAg loss	“Very low”	“Low, higher compared to NAs”
Risk of viral resistance	“Very low”	“Absent”

HBsAg loss with peginterferon monotherapy: HBeAg-negative pivotal trial

“We compared the efficacy and safety of peginterferon alfa-2a (180 microg once weekly) plus placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), and lamivudine alone in 177, 179, and 181 patients with HBeAg-negative chronic hepatitis B, respectively. Patients were treated for 48 weeks and followed for an additional 24 weeks.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quote
“Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups, as compared with 0 patients in the group given lamivudine alone.” (opens the original PubMed page at this quote in a new tab)View highlighted excerpt for this quote

HBsAg seroconversion with peginterferon: HBeAg-positive pivotal trial

“Sixteen patients receiving peginterferon alfa-2a (alone or in combination) had hepatitis B surface antigen (HBsAg) seroconversion, as compared with 0 in the group receiving lamivudine alone (P=0.001).” (opens the source at this quote in a new tab)
“In this study, HBsAg seroconversion was identified in 8 of 473 Asian patients (2 percent) and 8 of 47 white patients (17 percent) receiving peginterferon alfa-2a alone or in combination with lamivudine, as compared with none receiving lamivudine alone.” (opens the source at this quote in a new tab)

Durable HBsAg loss after finite peginterferon: 2022 AASLD-EASL endpoints conference

“Historically, a finite course of pegIFNa monotherapy (48 weeks) can result in durable off-treatment HBsAg loss in up to approximately 11% of patients (mostly HBeAg positive) although these results vary by genotype and baseline serum ALT.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote

Peginterferon added to or switched from nucleos(t)ide analogues: EASL 2025 evidence review

“HBsAg loss rates can be improved by PEG-IFNα therapy. However, overall HBsAg loss rates were only 8% for the "add-on" therapy and 14% for the "switch" therapy.” (opens the source at this quote in a new tab)
“Tolerance and acceptance of add-on PEG-IFNα may be a concern as a recent multicentre, open-label, randomised-controlled trial in France found this regimen to be poorly tolerated, leading to early discontinuation of PEG-IFNα in 20% of patients but no significant increase in HBsAg clearance.” (opens the source at this quote in a new tab)
“Notably, a randomised-controlled trial demonstrated that in HBeAg-negative patients with HBV DNA <60 IU/ml for ≥2.5 years, switching from NAs to PEG-IFNα for 48 weeks significantly reduced virological relapse rates (7.8% vs. 20.9%) and increased HBsAg loss (21.5% vs. 9.0%) compared to NA cessation alone,” (opens the source at this quote in a new tab)

Peginterferon add-on to nucleos(t)ide analogues: individual participant data meta-analysis

“581 patients were included. At the start of peg-IFN therapy (SOT), 44% were hepatitis B envelope antigen (HBeAg) positive, mean HBsAg level was 3.03 log10 IU/mL (HBsAg<100: 12%; 100–1000: 28%; ≥1000: 60%), and planned duration of peg-IFN was 48 weeks in 496 patients (85%).” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote
“At EOF, 50 (8.6%) patients achieved HBsAg loss (HBsAg<100/100–1000/≥1000: 37.7/9.8/2.3%, p<0.001) Findings were consistent across ethnicities (Caucasian: 30.0/8.7/3.6%; Asian: 39.3/9.2/2.2%).” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote
“Peg-IFN add-on results in HBsAg loss in 18% of patients with SOT HBsAg<1000 IU/mL, and in 38% if SOT HBsAg<100 IU/mL.” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote
“57 (10%) patients discontinued peg-IFN prior to the planned end-date, and these rates varied between 0% and 21% in the included studies (online supplemental table S1).” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote

Adverse effects and safety monitoring

“Flu-like symptoms, fatigue, mood disturbances, cytopenia, autoimmune disorders in adults, anorexia and weight loss in children” (opens the original PMC page at this quote in a new tab)View highlighted excerpt for this quote

“A decline in leukocytes and platelets is common during PEG-IFNα-based therapy.” (opens the source at this quote in a new tab)
“ALT flares can also occur during treatment despite suppression of HBV DNA, particularly in the early treatment phase” (opens the source at this quote in a new tab)
“Psychiatric side effects, including depression, are significant concerns with PEG-IFNα treatment and should be carefully considered both during patient selection and throughout therapy to ensure proper management.” (opens the source at this quote in a new tab)

“Thirty-three patients had serious adverse events during treatment and up to eight weeks after therapy: 12 patients (4 percent) receiving peginterferon alfa-2a monotherapy, 16 patients (6 percent) receiving peginterferon alfa-2a plus lamivudine, and 5 patients (2 percent) receiving lamivudine monotherapy (Table 4).” (opens the source at this quote in a new tab)
“However, the rate of withdrawal from peginterferon alfa-2a therapy was less than 5 percent.” (opens the source at this quote in a new tab)

Concomitant use with bepirovirsen

“Concomitant administration of HIBSAGO and peginterferon alfa-2a is not recommended.” (opens the prescribing information at this quote)