International Hepatology

The reduction of hepatitis B surface antigen (HBsAg) levels in treated chronic hepatitis B (CHB) patients is closely linked to decreased risks of cirrhosis and even liver cancer. However, spontaneous HBsAg clearance occurs in less than 1% of patients per year. As CHB prevention and treatment guidelines continue to evolve both domestically and internationally, more patients are now pursuing "functional cures" through nucleos(t)ide analogs (NAs) combined with or followed by pegylated interferon (PEG-IFN) treatment. This approach offers the possibility of reducing or eliminating long-term or lifelong medication use. Clinically, even when patients use similar regimens aimed at achieving a functional cure, many continue to struggle along the difficult path to achieving HBsAg seroclearance, let alone reaching the ideal treatment endpoint of HBs seroconversion. Thus, understanding and recognizing the potential factors influencing functional cure is crucial for timely evaluation and intervention. This article summarizes the possible factors affecting CHB functional cure based on both domestic and international research to date.

China is a major country with liver cancer, and the incidence rate and mortality rate of liver cancer account for about half of the world's total. Early identification of high-risk populations and early diagnosis of liver cancer are key to improving the overall survival rate of patients. Since the discovery of vitamin K in 1929, researchers have gradually confirmed the important role of serum abnormal prothrombin caused by its deficiency in the diagnosis of liver cancer. In 2019, Dr. Feng Shen and his team from Eastern Hepatobiliary Surgery Hospital, the third affiliated hospital of the Naval Medical University, collaborated with other top hospital teams in China to establish and validate the ASAP risk prediction model. Since then, the ASAP model has continuously broken through the prediction limitations of hepatitis B-related liver cancer, and has achieved frequent success in predicting hepatitis C-related liver cancer, non-alcoholic fatty liver disease-related liver cancer, and early recurrence diagnosis of liver cancer.

Primary liver cancer ranks as the fourth most common malignancy and the second leading cause of cancer-related deaths in China, posing a severe threat to people's lives and health. Early detection, diagnosis, and treatment are crucial for improving treatment outcomes. In 2019, Dr. Feng Shen and Dr. Tian Yang research team from Eastern Hepatobiliary Surgery Hospital, collaborating with 11 renowned tertiary hospitals in China, developed the ASAP (Alpha-Fetoprotein, Age, Sex, and PIVKA-II) liver cancer risk assessment model, making a significant contribution to Chinese clinical practice.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, characterized by high mortality rates and limited treatment options. Immunotherapy, particularly immune checkpoint blockade (ICB), has shown remarkable efficacy in treating cancers like melanoma and non-small cell lung cancer. However, many PDAC patients exhibit poor responses to ICB, mainly due to the tumor’s low immunogenicity and its immunosuppressive tumor microenvironment (TME). Inhibiting epigenetic regulators, such as SETDB1, KDM5B, and PHF8, has been shown to induce retrotransposon-mediated immune responses, thereby enhancing sensitivity to immunotherapy. While this approach shows promise in cancer treatment, its role in PDAC remains unclear. A recent study published in Gut identifies the key role of MED12 in modulating TME through the epigenetic silencing of retrotransposons, thus reshaping the immune TME in PDAC.