Background: Primary liver cancer, of which around 75–85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the “Health China 2030 Blueprint.”

Hepatitis B virus (HBV) infection is associated with 70% to 90% of patients with hepatocellular carcinoma (HCC) in the highly endemic Asia-Pacific regions, particularly China.¹ Liver resection and liver transplantation are potentially curative treatments in select patients.² Previous studies³ showed the prevalence of microvascular invasion (MVI) in specimens obtained from liver resection or transplantation to be between 15.0% and 57.1%. The presence of MVI is a histopathologic feature that indicates aggressive behavior of the HCC and predicts worse prognosis after liver resection and transplantation.^4,5

Hepatocellular carcinoma (HCC) is a common malignancy, ranking sixth among the most common neoplasms and third among the leading causes of cancer-related mortality worldwide.^1-4 In China, HCC ranks second only to lung cancer in cancer-related deaths.⁵ Liver resection remains the mainstay of curative treatment.^6,7 The long-term prognosis after HCC resection still remains unsatisfactory because of the high rate of cancer recurrence of up to 60% to 70% in patients within 5 years after surgery.^8-11 Identifying risk factors of recurrence is of vital importance to improve long-term survival outcomes after HCC resection.

Intrahepatic cholangiocarcinoma (ICC) is a primary liver cancer with high aggressiveness and extremely poor prognosis. The role of circular RNAs (circRNAs) in ICC carcinogenesis and progression remains to be determined. CircRNA microarray was performed to screen significantly upregulated circRNAs in paired ICC and non-tumor tissues. Colony formation, transwell, and xenograft models were used to examine the role of circRNAs in ICC proliferation and metastasis. RNA pulldown, mass spectrometry, chromatin immunoprecipitation, RNA-binding protein immunoprecipitation, chromatin isolation by RNA purification, electrophoretic mobility shift assay, and luciferase reporter assays were used to explore the molecular sponge role of the circRNA (via miRNA binding), and the interaction between circRNA and RNA-binding proteins. Hsa_circ_0050898, which originated from exon 1 to exon 20 of the ACTN4 gene (named circACTN4), was significantly upregulated in ICC. High circACTN4 expression was associated with enhanced tumor proliferation and metastasis in vitro and in vivo, as well as a worse prognosis following ICC resection. In addition, circACTN4 upregulated Yes-associated protein 1 (YAP1) expression by sponging miR-424-5p. More importantly, circACTN4 also recruited Y-box binding protein 1 (YBX1) to stimulate Frizzled-7 (FZD7) transcription. Furthermore, circACTN4 overexpression in ICC cells enhanced the interaction between YAP1 and β-catenin, which are the core components of the Hippo and Wnt signaling pathways, respectively. CircACTN4 was upregulated in ICC and promoted ICC proliferation and metastasis by acting as a molecular sponge of miR-424-5p, as well as by interacting with YBX1 to transcriptionally activate FZD7. These results suggest that circACTN4 is a potential prognostic marker and therapeutic target for ICC. Intrahepatic cholangiocarcinoma is a primary liver cancer associated with aggressiveness and extremely poor prognosis. It is essential for therapeutic development that we uncover relevant pathogenic pathways. Herein, we showed that a circular RNA (circACTN4) was highly expressed in intrahepatic cholangiocarcinoma and was positively associated with tumor growth and metastasis through key developmental signaling pathways. Thus, circACTN4 could be a prognostic biomarker and therapeutic target for intrahepatic cholangiocarcinoma.

Surgical resection remains the mainstay treatment for hepatocellular carcinoma (HCC).¹ However, the incidence of tumor recurrence can be as high as 70% at 5 years after surgery.² Advances in postoperative surveillance have led to detection of recurrent HCC (RHCC) at an early stage when multiple treatments may still be available. Among possible treatments, salvage liver transplant has been beneficial for a limited number of patients owing to donor shortage.¹ Repeat hepatectomy and percutaneous radiofrequency ablation (PRFA) have been more commonly used to treat RHCC.^1,3-5