Chronic hepatitis B: treatment and what thymosin alpha-1 shows

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What is chronic hepatitis B and how many people have it?

Hepatitis B is a liver infection caused by the hepatitis B virus (HBV). It is considered chronic when surface antigen (HBsAg) persists, and it can progress to cirrhosis and liver cancer¹³. According to the World Health Organization, 240 million people were living with chronic infection in 2024, with about 0.9 million new infections a year and around 1.1 million deaths, mostly from cirrhosis and liver cancer¹.

The route of infection varies by region: the WHO lists mother-to-child transmission at birth, contact with infected body fluids in early childhood, sexual contact, unsafe injections and sharp instruments¹. Age matters greatly: infection in infancy or early childhood becomes chronic in about 95% of cases, compared with under 5% when acquired in adulthood¹. The Global Burden of Disease 2019 analysis provides country-level and yearly estimates of the disease burden⁵.

Symptoms and how chronic hepatitis B is diagnosed

Most people have no symptoms when first infected; when present, the WHO lists jaundice, dark urine, extreme fatigue, nausea, vomiting and abdominal pain¹. Diagnosis is therefore laboratory-based: guidelines build the assessment on HBsAg, the e antigen (HBeAg), HBV DNA viral load, aminotransferases (ALT) and assessment of liver fibrosis, and distinguish phases of infection from those results³⁴.

The 2024 WHO guideline expands and simplifies treatment criteria, recommends point-of-care viral load and reflex HBV DNA testing to improve diagnosis, and addresses who should be tested for hepatitis delta (HDV)².

Standard treatment today: what the guidelines recommend

The aim is to prevent progression to cirrhosis, decompensation and liver cancer. The 2018 guidance of the American Association for the Study of Liver Diseases (AASLD) and the 2017 guideline of the European Association for the Study of the Liver (EASL) describe high-barrier nucleos(t)ide analogues and peginterferon alfa in selected candidates as first-line options³⁴. Both predate the most recent updates, so the current version should be consulted. The WHO names tenofovir or entecavir among the oral options and notes that most people who start must continue treatment for life¹.

Pivotal trials support those options. In 715 treatment-naive HBeAg-positive patients, entecavir produced histologic improvement in 72% versus 62% with lamivudine, and undetectable HBV DNA in 67% versus 36% at 48 weeks, with no resistance to entecavir⁷. Tenofovir alafenamide was non-inferior to tenofovir disoproxil (HBV DNA <29 IU/mL in 64% versus 67% at week 48; 873 treated) with smaller bone density loss and creatinine rise⁸. Peginterferon alfa-2a, in 814 HBeAg-positive patients treated for 48 weeks, produced HBeAg seroconversion in 32% versus 19% with lamivudine at 24 weeks of follow-up, and HBsAg seroconversion in 16 peginterferon-treated patients versus none with lamivudine alone⁶.

This section is about the disease, not peptides: none of the first-line options mentioned is a peptide, and interferon is a protein. The role of immunomodulation such as thymosin alpha-1 is discussed next.

What peptide research has shown: thymosin alpha-1 and bulevirtide

Thymosin alpha-1 (thymalfasin). It is a synthetic 28-amino-acid peptide that modulates the immune response; the peptide's general history and its sepsis use (the TESTS trial and a later meta-analysis¹⁴¹⁵) are covered in Thymosin alpha-1 after TESTS. A 2009 review states it is approved in more than 35 countries for hepatitis B and C and as an immune stimulant and adjuvant¹³. The sources consulted here show no FDA or EMA approval for hepatitis B, and the AASLD and EASL guidance name nucleos(t)ide analogues and peginterferon as first line, not thymosin³⁴.

The 2026 Cochrane review included 10 randomized trials (1349 participants, published between 1991 and 2018, in Bangladesh, China, Italy, Korea, Singapore and Taiwan). Thymosin alpha-1, compared with controls, was observed to possibly reduce all-cause mortality (RR 0.53; 95% CI 0.29 to 0.96; 3 studies, 907 participants) and serious adverse events (RR 0.72; 95% CI 0.53 to 0.99; 5 studies), but certainty was very low, except for serious adverse events (low); there was no clear effect on quality of life or histological improvement, and HBV-related morbidity is very uncertain⁹. The authors conclude they are not sure of its effects⁹.

Earlier meta-analyses describe short-term virological results. In 8 trials with 583 HBeAg-positive patients, lamivudine plus thymosin alpha-1 was associated with more HBeAg seroconversion than lamivudine alone (45.1% versus 15.2%) and more virological response (84.7% versus 74.9%)¹⁰. In 4 trials with 199 patients, against interferon alfa thymosin showed no advantage at the end of 6 months (complete response was lower, OR 0.54), but virological, biochemical and complete responses were higher 6 months later (odds ratios of 3.71, 3.12 and 2.69)¹¹. In 7 trials with 1144 subjects with HBV-related cirrhosis, entecavir plus thymosin alpha-1 was associated with a higher complete response than entecavir alone (RR 1.18), with higher undetectable HBV DNA and HBeAg loss at 24 weeks, but no differences at 48 and 52 weeks and no difference in HBsAg loss¹². All those patients came from mainland China and the authors call for larger studies¹².

Bulevirtide. It is a lipopeptide that blocks the entry receptor of the hepatitis delta virus, which needs HBV to infect. The EMA granted it conditional authorization on 31 July 2020 and standard authorization on 18 July 2023, for chronic hepatitis delta with compensated liver disease and detectable HDV RNA; it is not a treatment for hepatitis B itself¹⁸. In the phase 3 MYR301 trial (150 patients), the combined response at week 48 was 45% with 2 mg, 48% with 10 mg and 2% with no treatment; no HBsAg loss occurred in the bulevirtide groups by week 48¹⁶. In an open-label phase 2b trial, 10 mg of bulevirtide plus peginterferon alfa-2a reached undetectable HDV RNA in 46% at 24 weeks after treatment ended, versus 12% with bulevirtide alone¹⁷.

Safety: adverse effects and precautions

For oral antivirals, the tenofovir alafenamide trial showed that tenofovir disoproxil was associated with greater loss of bone mineral density (hip -1.72% versus -0.10%) and a larger creatinine rise than the alternative⁸. Peginterferon causes the known adverse effects of interferon alfa; in the 814-patient trial, serious adverse events occurred in 4% and 6% of peginterferon-treated groups and 2% with lamivudine alone, and two lamivudine patients had irreversible liver failure after stopping treatment⁶.

With thymosin alpha-1, the Cochrane review describes fewer serious and non-serious adverse events than controls, with low to very low certainty, which does not amount to a demonstrated safety profile⁹. With bulevirtide, the MYR301 trial recorded more headache, pruritus, fatigue, eosinophilia, injection-site reactions, upper abdominal pain, arthralgia and asthenia than the control group, no treatment-related serious events, and dose-dependent increases in bile acids¹⁶. The EMA lists as common effects (more than 1 in 10) raised bile salts, headache, itching and injection-site reactions¹⁸.

Summary by agent

Frequently asked questions

How many people have chronic hepatitis B? The WHO estimated 240 million people in 2024, with around 1.1 million deaths a year¹.

Is there an approved peptide for hepatitis B? No FDA or EMA approval for hepatitis B was identified in the sources consulted. Bulevirtide is EMA-authorized for chronic hepatitis delta, and a 2009 review states thymosin alpha-1 is approved in more than 35 countries for hepatitis B and C¹³¹⁸.

Does thymosin alpha-1 cure hepatitis B? There is no evidence that it does. The 2026 Cochrane review concluded it is not sure of its effects, with very low certainty, and with entecavir there was no difference in HBsAg loss⁹¹².

Can antiviral treatment be stopped? The WHO states that most people who start treatment must continue it for life¹; individual decisions fall to the guidelines and the treating physician³⁴.

What is the difference between hepatitis B and hepatitis delta? Delta is a coinfection that needs HBV; the MYR301 trial studied patients with chronic hepatitis D, and bulevirtide blocks HDV entry¹⁶¹⁸.