Antivirals given for chronic hepatitis B include nucleos(t)ide analog monotherapy and pegylated interferon-alpha therapy, but the safety of interferon in patients with cirrhosis has been unclear. A study in Portal Hypertension and Cirrhosis analyzed data from two large Chinese cohorts, including 920 patients with compensated cirrhosis, and found that interferon therapy was not associated with a higher risk of serious complications, supporting its use with appropriate monitoring.
Hepatitis B is a viral infection that affects the liver and can lead to a chronic diseased stage. Antiviral treatments aim to reduce complications such as liver failure and liver cancer, making long-term disease control a key goal. While hepatitis B can be prevented with a vaccine administered soon after birth, individuals with chronic infection are typically treated with antiviral medications.
Currently, the main treatments for chronic hepatitis B include nucleos(t)ide analog (Nuc) monotherapy and pegylated interferon-alpha (Peg-IFN-α) therapy. IFN-based treatments are widely used, especially in Asian populations, and some studies have linked them to a comparatively long-lasting control of the virus and a lower risk of liver cancer.
However, the use of IFN-based therapy in patients with cirrhosis remains debated due to concerns that it may be associated with worsening liver function or increased side effects, such as low platelet counts and liver abnormalities.
To examine this further, a team of researchers in China led by Professor Wenhong Zhang of Huashan Hospital, Fudan University, and Professor Xiaolong Qi of Zhongda Hospital, Southeast University, evaluated the safety of Peg-IFN-α therapy in patients with chronic hepatitis B and compensated cirrhosis. Their findings were published online in the journal Portal Hypertension & Cirrhosis on March 06, 2026.
“We assessed the safety of Peg-IFN-α therapy in patients with compensated hepatitis B cirrhosis by evaluating whether it led to higher decompensation events, more severe adverse events, or worse outcomes compared to nucleos(t)ide analog therapy (the standard treatment for hepatitis B), or to patients without cirrhosis,” the authors note.
The researchers analyzed data from two large studies conducted in China. One, the OASIS Project, followed patients with chronic hepatitis B to understand how different antiviral treatments perform in real-world settings. The other, CHESS 2306, focused on patients with compensated cirrhosis receiving IFN-based therapy between 2018 and 2024. The study included adults aged 18 to 65 who had been on treatment for at least 12 weeks.
In total, the analysis included 920 patients with Child-Pugh class A hepatitis B cirrhosis who received IFN therapy. This stage refers to an early compensated stage of cirrhosis in which the liver is still functioning relatively well. These patients were compared with those receiving Nuc therapy and those without cirrhosis, with outcomes assessed over up to 48 weeks.
The researchers examined serious complications such as liver decompensation, which includes fluid buildup, bleeding, and brain-related symptoms, as well as other side effects. These complications were rare and occurred at similar rates in both IFN and standard treatment groups, with no treatment-related hospitalizations or deaths reported.
Severe side effects, such as low blood cell counts and liver-related abnormalities, were also similar between groups. When comparing groups with and without cirrhosis who received IFN, most side effects were comparable. However, patients with cirrhosis who already had elevated bilirubin levels were more likely to experience further increments during treatment.
Overall, the results suggest that IFN-based therapy was generally safe for patients with compensated cirrhosis. The researchers did not find it to be associated with a higher risk of serious complications compared to standard treatment; however, milder side effects were more common and required closer monitoring. The authors note that careful patient selection and follow-up remain important, and that IFN-based therapy should be used with caution in patients with cirrhosis and elevated bilirubin levels.
“The findings of this study indicate that IFN‐ based therapy has acceptable safety in a population with Child-Pugh class A cirrhosis. However, in cirrhotic patients with CHB and abnormal TBIL levels, IFN administration is more likely to lead to severe TBIL level elevation,” the study reports.
IFN-based therapy is a promising strategy for achieving long-term viral control and reducing liver cancer risk in chronic hepatitis B. These findings offer encouraging evidence on the safety of IFN-based therapy in patients with compensated cirrhosis and may help inform treatment decisions.
About Fudan University, China
Fudan University was established in 1905 as Fudan Public School and was renamed Fudan University in 1917, which has been kept ever since. It is a comprehensive research-oriented university, which upholds the spirit of patriotism, solidarity, service, and sacrifice. lts motto is scientia et studium, quaestio et cogitatio , which means rich in knowledge and tenacious of purposes, inquiring with earnestness and reflecting with self-practice. It houses closes to 40,000 undergraduate and graduate students, including nearly 4,000 international students. The university strives to provide top-quality education and obtain similar achievements and aims to be one of the top universities in the world.
Website: https://www.fudan.edu.cn/en/main.htm
About Southeast University , China
Southeast University (SEU), located in Nanjing, is a prestigious university with an outstanding reputation both at home and abroad. Over its 120-year history, SEU has always embraced a spirit of patriotism and global vision, striving for scientific progress and national rejuvenation. It has cultivated the school spirit of “Rigour, Truthfulness, Unity, and Diligence” and the educational philosophy of “Renown through Science, Service through Talent”, while embodying the motto: “Strive for Perfection.” At present, SEU has 38 schools, which offer 85 bachelor’s degree programs, 53 Master’s degree programs, and 44 doctoral degree programs, across three campuses, Sipailou Campus, Jiulonghu Campus and Dingjiaqiao Campus. Their goal is to build a world-class university with distinctive Chinese characteristics and the unique spirit of SEU that is satisfactory to the people, making outstanding contributions to realizing the great rejuvenation of the Chinese nation and promoting the progress and advancement of human civilization.
Website: https://www.seu.edu.cn/english/
About Professor Wenhong Zhang from Huashan Hospital, Fudan University
Professor Zhang is the head of the Center for Infectious Diseases at Huashan Hospital, Fudan University, China. He currently serves as chair of the Society of Infectious Diseases of the China Medical Association in Shanghai and chair of the Association of Infectious Diseases Doctors of Shanghai. His research focuses on the pathogenesis, diagnosis, and treatment of viral hepatitis, tuberculosis, bacterial infections, and drug-resistant pathogens. He has led numerous multicenter clinical trials involving multidrug-resistant tuberculosis, sepsis, and drug-resistant bacterial infections.
About Professor Xiaolong Qi from Zhongda Hospital, Southeast University
Professor Xiaolong Qi serves as Assistant Dean of Zhongda Hospital affiliated with Southeast University and Director of the Liver Disease Center. His research focuses on patient-oriented clinical and translational studies for the whole-course management of portal hypertension and cirrhosis. He is the founder and Chair of Liver Health Consortium in China (CHESS) and Editor-in-Chief of Portal Hypertension & Cirrhosis. Prof. Qi has published over 200 SCI papers with an h-index of 54 and has led the development of three guidelines, including the Expert Consensus on Clinical Application of Hepatic Venous Pressure Gradient in China.
Funding information
This research was supported by National Natural Science Foundation of China Grant (82100636, 82402413); Shanghai Municipal Health Commission (GWVI‐11.1‐07); Tianjin Health Research Project (TJWJ2022XK029); Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK‐034A); Major Science and technology projects for liver disease research found of Ningbo (2016C51008); Research Personnel Cultivation Program of Zhongda Hospital, Southeast University (CZXM‐GSP‐RC135 and CZXM‐GSP‐RC125); 2021 High‐level Personnel Project Funding of Jiangsu Province (JSSCBS20210073); Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High‐Level Hospital Pairing Assistance Construction Funds (zdlyg24); Fundings for Clinical Trials from Zhongda Hospital, School of medicine, Southeast University (ZDYYGSPLCYJ02); China Association of Chinese Medicine Launches 2025 Joint Research Initiative on Priority Diseases (NCIM25‐4); Key Research and Development Program of Jiangsu Province (BE2023767); the Fundamental Research Fund of Southeast University (4090002502); Special medical experts of Jiangsu Province (CZXM‐RC‐43); and Natural Science Foundation of Jiangsu Province (BK20241681).
Portal Hypertension & Cirrhosis
Observational study
People
The Safety of Interferon‐Based Therapies in Chronic Hepatitis B Patients With Compensatory Cirrhosis
6-Mar-2026
Xiaolong Qi is the Editor‐in‐Chief of Portal Hypertension & Cirrhosis. He is therefore excluded from the peer‐review process and all editorial decisions related to the publication of this manuscript. The other authors declare no conflicts of interest.