1.Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang LI ; Chujun CAI ; Chendong WANG ; Xiaoping CHEN ; Bixiang ZHANG ; Zhao HUANG
Clinical and Molecular Hepatology 2025;31(2):350-381
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.
2.Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang LI ; Chujun CAI ; Chendong WANG ; Xiaoping CHEN ; Bixiang ZHANG ; Zhao HUANG
Clinical and Molecular Hepatology 2025;31(2):350-381
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.
3.Gut microbiota-mediated gut-liver axis: a breakthrough point for understanding and treating liver cancer
Chenyang LI ; Chujun CAI ; Chendong WANG ; Xiaoping CHEN ; Bixiang ZHANG ; Zhao HUANG
Clinical and Molecular Hepatology 2025;31(2):350-381
The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.
4.Current status and progress of immunotherapy in biliary tract cancer
Tumor 2023;43(6):541-551
Biliary tract cancer(BTC)is an aggressive cancer that arises from the epithelium of the biliary tract with high degree of malignancy,strong heterogeneity,insidious onset and poor prognosis.It has been on the rise globally in recent years,and its incidence is generally higher in Asian countries than in Western countries.Surgical resection remains the only current potentially curative treatment option for early-stage BTC.However,the surgical resection rate is low and the risk of recurrence after surgery is high.For patients with inoperable advanced or recurrent BTC,systemic chemotherapy is the preferred treatment recommendation,but treatment outcomes are still unsatisfactory.In recent years,immunotherapy has revolutionized the field of cancer treatment.Immunotherapy for advanced BTC mainly includes immune checkpoint inhibitors targeting PD-1,PD-L1 and CTLA-4,cancer vaccines and adoptive cell therapy.The review provides insights into the current status of clinical research and future research directions for immunotherapy in advanced BTC.
5.Bone metastasis of hepatocellular carcinoma: facts and hopes from clinical and translational perspectives.
Zhao HUANG ; Jingyuan WEN ; Yufei WANG ; Shenqi HAN ; Zhen LI ; Xuemei HU ; Dongling ZHU ; Zhenxiong WANG ; Junnan LIANG ; Huifang LIANG ; Xiao-Ping CHEN ; Bixiang ZHANG
Frontiers of Medicine 2022;16(4):551-573
Patients with hepatocellular carcinoma (HCC) and bone metastasis (BM) suffer from greatly reduced life quality and a dismal prognosis. However, BM in HCC has long been overlooked possibly due to its relatively low prevalence in previous decades. To date, no consensus or guidelines have been reached or formulated for the prevention and management of HCC BM. Our narrative review manifests the increasing incidence of HCC BM to sound the alarm for additional attention. The risk factors, diagnosis, prognosis, and therapeutic approaches of HCC BM are detailed to provide a panoramic view of this disease to clinicians and specialists. We further delineate an informative cancer bone metastatic cascade based on evidence from recent studies and point out the main factors responsible for the tumor-associated disruption of bone homeostasis and the formation of skeletal cancer lesions. We also present the advances in the pathological and molecular mechanisms of HCC BM to shed light on translational opportunities. Dilemmas and challenges in the treatment and investigation of HCC BM are outlined and discussed to encourage further endeavors in the exploration of underlying pathogenic and molecular mechanisms, as well as the development of novel effective therapies for HCC patients with BM.
Bone Neoplasms/secondary*
;
Carcinoma, Hepatocellular/therapy*
;
Humans
;
Liver Neoplasms/therapy*
;
Prognosis
6.Standardized establishment and informationized management of liver cancer biobank
Jingjing YU ; Wei XIAO ; Yani LI ; Bixiang ZHANG ; Xiaoping CHEN ; Chang SHU
Journal of Clinical Hepatology 2022;38(5):1092-1096
Objective To establish a small liver cancer biobank with a standard operating procedure and the function of informationized management. Methods According to the inclusion and exclusion criteria, blood, tissue, and stool samples were collected from the patients with liver cancer who attended Liver Surgery Center, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, from August 2012 to December 2020 and signed the informed consent. In-and-out-of-storage management was performed based on the standard procedure for whole blood, serum, frozen tissue, paraffin-embedded tissue, and stool samples, and related clinical and follow-up data were collected. The frozen samples of liver cancer tissue and adjacent tissue in different years were randomly selected, and the concentration and completeness of total RNA were examined to ensure the quality of frozen samples stored in the biobank. Results The samples were collected from 4190 liver cancer patients who underwent surgery within a period of 101 natural months, and there were 41718 frozen tissue samples, 18950 paraffin-embedded tissue samples, 24389 whole blood samples, 20060 serum samples, and 5392 stool samples. The liver cancer patients had an age range of 13-88 years, and male patients accounted for 85.1%. The patients with hepatitis B accounted for 83.3%, and those with liver cirrhosis accounted for 73.5%. A standard operating procedure and an electronic data capture system were developed according to the collection, processing, storage, application, and informationized management of samples. Among the 18 frozen tissue samples randomly selected from the biobank, 16 samples had high RNA quality, which could meet the requirements of subsequent experiments. Conclusion A standardized and informationized biobank has been established for liver cancer, which provides high-quality samples for the basic research on liver cancer and helps to explore the research value of samples.
7.Clinical characteristics and risk factors for mortality in cancer patients with COVID-19.
Junnan LIANG ; Guannan JIN ; Tongtong LIU ; Jingyuan WEN ; Ganxun LI ; Lin CHEN ; Wei WANG ; Yuwei WANG ; Wei LIAO ; Jia SONG ; Zeyang DING ; Xiao-Ping CHEN ; Bixiang ZHANG
Frontiers of Medicine 2021;15(2):264-274
Patients with cancer are at increased risk of severe infections. From a cohort including 3060 patients with confirmed COVID-19, 109 (3.4%) cancer patients were included in this study. Among them, 23 (21.1%) patients died in the hospital. Cancer patients, especially those with hematological malignancies (41.6%), urinary carcinoma (35.7%), malignancies of the digestive system (33.3%), gynecological malignancies (20%), and lung cancer (14.3%), had a much higher mortality than patients without cancer. A total of 19 (17.4%) cancer patients were infected in the hospital. The clinical characteristics of deceased cancer patients were compared with those of recovered cancer patients. Multivariate Cox regression analysis indicated that a Nutritional Risk Screening (NRS2002) score ⩾ 3 (adjusted hazard ratio (HR) 11.00; 95% confidence interval (CI) 4.60-26.32; P < 0.001), high-risk type (adjusted HR 18.81; 95% CI 4.21-83.93; P < 0.001), tumor stage IV (adjusted HR 4.26; 95% CI 2.34-7.75; P < 0.001), and recent adjuvant therapy (< 1 month) (adjusted HR 3.16; 95% CI 1.75-5.70; P < 0.01) were independent risk factors for in-hospital death after adjusting for age, comorbidities, D-dimer, and lymphocyte count. In conclusion, cancer patients showed a higher risk of COVID-19 infection with a poorer prognosis than patients without cancer. Cancer patients with high-risk tumor, NRS2002 score ⩾ 3, advanced tumor stage, and recent adjuvant therapy (< 1 month) may have high risk of mortality.
COVID-19
;
Hospital Mortality
;
Humans
;
Neoplasms
;
Prognosis
;
Retrospective Studies
;
Risk Factors
;
SARS-CoV-2
8.Adjuvant treatment strategy after curative resection for hepatocellular carcinoma.
Wei ZHANG ; Bixiang ZHANG ; Xiao-Ping CHEN
Frontiers of Medicine 2021;15(2):155-169
Hepatic resection represents the first-line treatment for patients with resectable hepatocellular carcinoma (HCC). However, the 5-year recurrence rates of HCC after surgery have been reported to range from 50% to 70%. In this review, we evaluated the available evidence for the efficiency of adjuvant treatments to prevent HCC recurrence after curative liver resection. Antiviral therapy has potential advantages in terms of reducing the recurrence rate and improving the overall survival (OS) and/or disease-free survival of patients with hepatitis-related HCC. Postoperative adjuvant transarterial chemoembolization can significantly reduce the intrahepatic recurrence rate and improve OS, especially for patients with a high risk of recurrence. The efficacy of molecular targeted drugs as an adjuvant therapy deserves further study. Adjuvant adoptive immunotherapy can significantly improve the clinical prognosis in the early stage. Randomized controlled trial (RCT) studies evaluating adjuvant immune checkpoint inhibitors are ongoing, and the results are highly expected. Adjuvant hepatic artery infusion chemotherapy might be beneficial in patients with vascular invasion. Huaier granule, a traditional Chinese medicine, has been proved to be effective in prolonging the recurrence-free survival and reducing extrahepatic recurrence. The efficiency of other adjuvant treatments needs to be further confirmed by large RCT studies.
Carcinoma, Hepatocellular/therapy*
;
Chemoembolization, Therapeutic
;
Chemotherapy, Adjuvant
;
Hepatectomy
;
Humans
;
Liver Neoplasms/therapy*
;
Neoplasm Recurrence, Local
;
Treatment Outcome
9.Evaluation of infrahepatic inferior vena cava clamping in robot-assisted laparoscopic liver resection
Qi CHENG ; Peng ZHU ; Wei LIAO ; Lin CHEN ; Bixiang ZHANG ; Xiaoping CHEN
Chinese Journal of Surgery 2021;59(1):18-23
Objective:To evalutate the safety and efficacy of infrahepatic inferior vena cava clamping robot-assisted laparoscopic liver resection.Methods:All data about 24 patients with robotic liver resection at Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology between February 2015 and December 2017 were collected and analyzed. These patients were divided into two groups based on different methods to decrease central venous pressure. Eight patients(6 males and 2 females,aged 49 years(range:50 to 56 years)) were applied with infrahepatic inferior vena cava clamping,and the other 16 matched cases (15 males and 1 female,aged 53 years(range:38 to 69 years)) were categorized into lowering central venous pressure group. Intraoperative blood loss,blood transfusion,intraoperative hemodynamic parameters,postoperative complications,and renal function were compared by t-test,non-parametric test,χ 2test,or Fisher exact test. Results:There was significantly difference in the intraoperative blood loss between the infrahepatic vena cava clamping group and the lowering central venous group(200(220) ml (range:100 to 400 ml) vs.750(800) ml (range:100 to 2 000 ml), Z=?2.169, P=0.030). The clamping time of portal triad and infrahepatic inferior vena cava were 24 (18) minutes and 29 (20) minutes in the infrahepatic inferior vena cava clamping group, and portal triad clamping time was 23 (23) minutes in the low central venous group. There was no significant difference between the two groups ( Z=?0.323, P=0.747). There was no intraoperative blood transfusion in the infrahepatic inferior vena cava clamping group, and 5 cases in the low central venous group, with a transfusion volume of 1.5(1.5)U. The difference between the two groups was statistically significant ( Z=?3.353, P=0.001). However, the mean arterial pressure in the infrahepatic vena cava clamping group decreased from (88.6±4.9) mmHg to (67.4±3.8) mmHg(1 mmHg=0.133 kPa), which was lower than that of lowering central venous group (72.4±3.3) mmHg ( t=2.315, P=0.003). And there were no significant differences related to postoperative complications rate or hepatic and renal function in both groups. Conclusion:The infrahepatic inferior vena cava technology is safe and feasible to decrease central venous pressure during robotic liver resections,which will not affect the recovery of hepatic and renal functions.
10.Evaluation of infrahepatic inferior vena cava clamping in robot-assisted laparoscopic liver resection
Qi CHENG ; Peng ZHU ; Wei LIAO ; Lin CHEN ; Bixiang ZHANG ; Xiaoping CHEN
Chinese Journal of Surgery 2021;59(1):18-23
Objective:To evalutate the safety and efficacy of infrahepatic inferior vena cava clamping robot-assisted laparoscopic liver resection.Methods:All data about 24 patients with robotic liver resection at Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology between February 2015 and December 2017 were collected and analyzed. These patients were divided into two groups based on different methods to decrease central venous pressure. Eight patients(6 males and 2 females,aged 49 years(range:50 to 56 years)) were applied with infrahepatic inferior vena cava clamping,and the other 16 matched cases (15 males and 1 female,aged 53 years(range:38 to 69 years)) were categorized into lowering central venous pressure group. Intraoperative blood loss,blood transfusion,intraoperative hemodynamic parameters,postoperative complications,and renal function were compared by t-test,non-parametric test,χ 2test,or Fisher exact test. Results:There was significantly difference in the intraoperative blood loss between the infrahepatic vena cava clamping group and the lowering central venous group(200(220) ml (range:100 to 400 ml) vs.750(800) ml (range:100 to 2 000 ml), Z=?2.169, P=0.030). The clamping time of portal triad and infrahepatic inferior vena cava were 24 (18) minutes and 29 (20) minutes in the infrahepatic inferior vena cava clamping group, and portal triad clamping time was 23 (23) minutes in the low central venous group. There was no significant difference between the two groups ( Z=?0.323, P=0.747). There was no intraoperative blood transfusion in the infrahepatic inferior vena cava clamping group, and 5 cases in the low central venous group, with a transfusion volume of 1.5(1.5)U. The difference between the two groups was statistically significant ( Z=?3.353, P=0.001). However, the mean arterial pressure in the infrahepatic vena cava clamping group decreased from (88.6±4.9) mmHg to (67.4±3.8) mmHg(1 mmHg=0.133 kPa), which was lower than that of lowering central venous group (72.4±3.3) mmHg ( t=2.315, P=0.003). And there were no significant differences related to postoperative complications rate or hepatic and renal function in both groups. Conclusion:The infrahepatic inferior vena cava technology is safe and feasible to decrease central venous pressure during robotic liver resections,which will not affect the recovery of hepatic and renal functions.

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