中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

2022 No.5
Theme Issue: New Progress in the Treatment of Hepatobiliary Tumors in the New Era of Immunotherapy
Executive Chief Editor: ZHOU Jian  
Zhongshan Hospital Affiliated to Fudan University

Display Method:
Editorial
Opportunities and challenges for the treatment of malignant hepatobiliary tumors in the new era of immunotherapy
Xiaoyong HUANG, Guoming SHI, Jian ZHOU
2022, 38(5): 977-979. DOI: 10.3969/j.issn.1001-5256.2022.05.001
Abstract(786) HTML (199) PDF (1944KB)(208)
Abstract:
Malignant hepatobiliary tumors mainly include hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) and are common malignancies in China that seriously threaten the life and health of the Chinese people. Malignant hepatobiliary tumors often have an insidious onset, and most patients have lost the opportunity for surgery due to the advanced stage at initial diagnosis. The treatment of advanced HCC mainly depends on systemic therapy such as sorafenib, lenvatinib, donafenib, regorafenib, apatinib, and systemic chemotherapy, but such treatment often has a limited effect. The treatment of advanced BTC mainly relies on systemic chemotherapy, which often has an unsatisfactory effect. The advent of the era of immunotherapy brings new hope to the treatment of advanced malignant hepatobiliary tumors. Atezolizumab combined with bevacizumab and sintilimab combined with a bevacizumab biosimilar IBI305 have been approved as the first-line treatment of advanced HCC. The treatment regimens, such as Chemotherapy-based immune checkpoint inhibitor (ICI) or ICI combined with targeted drugs, have made great progress in the treatment of advanced BTC, and although these regimens can significantly improve the overall survival of patients, they often bring obvious and even life-threatening adverse reactions, which should be taken seriously by clinicians. In addition, further studies are needed to investigate the value of ICI-based combination therapy in the perioperative treatment of malignant hepatobiliary tumors.
Discussions by Experts
Perioperative immunotherapy for hepatocellular carcinoma
Bin XU, Meiling LI, Huichuan SUN
2022, 38(5): 980-984. DOI: 10.3969/j.issn.1001-5256.2022.05.002
Abstract(700) HTML (352) PDF (1893KB)(170)
Abstract:
Hepatocellular carcinoma (HCC) greatly threatens the life and health of Chinese people. Most patients with HCC are already in the advanced stage when attending the hospital and are not eligible for radical treatment, and patients in the early stage of HCC who are eligible for radical treatment still face a high risk of recurrence after surgery. In recent years, immunotherapy based on immune checkpoint inhibitors (ICIs) has made great progress in the treatment of advanced HCC, and perioperative immunotherapy for HCC is attracting more and more attention. Immunotherapy in the perioperative period of HCC can improve the feasibility of hepatectomy, reduce the recurrence rate after hepatectomy, and prolong the survival of patients. This article discusses the application of ICIs-based immunotherapy in the perioperative period of HCC and the issues that need to be considered, so as to provide new ideas for perioperative immunotherapy for HCC.
Adverse reactions associated with immune checkpoint inhibitor in treatment of liver cancer and related treatment measures
Hanping WANG
2022, 38(5): 985-991. DOI: 10.3969/j.issn.1001-5256.2022.05.003
Abstract(917) HTML (315) PDF (1918KB)(220)
Abstract:
Immune checkpoint inhibitors (ICIs) exert a therapeutic effect on liver cancer by enhancing the body's anti-tumor immunity and have become an important treatment method in the field of liver cancer. However, while ICIs activate the anti-tumor immunity, they also bring a series of special toxic and side effects, i.e., immune-related adverse events (irAEs). With the wide application of ICIs, irAEs have become a major challenge in clinical practice. Such irAEs have a wide potential disease spectrum and include more than 70 different pathological states, and the most common types of irAEs associated with PD-1/PD-L1 inhibitors are skin toxicity, endocrine toxicity, pneumonia, and digestive tract toxicity, while rare irAEs include the toxicity of the central nervous system and the cardiovascular, renal, and blood systems. The wide disease spectrum of irAEs requires multidisciplinary collaborative management, and at present, many academic institutions or platforms in China and globally have formulated various guidelines for irAE management. However, the management of irAEs currently lacks the support of the results of high-level prospective trials, and the characteristics of irAEs are different from the original immune diseases of various systems; therefore, its management needs to be further optimized. This article elaborates on the epidemiology of irAEs in immunotherapy for liver cancer, related risk and predictive factors, clinical features of irAEs involving different systems, and precautions for treatment and management.
Advances in targeted therapy combined with immunotherapy for advanced hepatocellular carcinoma
Xiufeng LIU, Jue ZHANG, Lin YAO, Chaoxu YANG
2022, 38(5): 992-997. DOI: 10.3969/j.issn.1001-5256.2022.05.004
Abstract(1119) HTML (364) PDF (3145KB)(189)
Abstract:
The IMbrave 150 study opened the door of immunotherapy combined with targeted therapy, and then the data of ORIENTAL-32, a Phase Ⅲ clinical trial for Chinese patients, was released, which confirmed the efficacy of immunotherapy combined with targeted therapy, especially significant survival benefits in Chinese patients. At present, there are many ongoing studies on PD-1/PD-L1 inhibitors combined with small-molecule tyrosine kinase inhibitors, and their corresponding early data provide a considerable objective response rate, which provides an opportunity for conversion therapy/sequential therapy for hepatocellular carcinoma in different stages and courses, as well as a basis for further exploration of neoadjuvant/adjuvant therapy. Combined immunotherapy has entered the era of version 3.0, in which reasonable local therapy can be implemented at different stages in combination with targeted drugs. However, there are still no accurate predictive indicators for efficacy, and it requires comprehensive consideration of the features such as the natural course of the disease, clinicopathological parameters, genomics, and radiomics. Compared with single-drug immunotherapy or single-drug targeted therapy, immunotherapy combined with targeted therapy had a relatively complex spectrum of adverse reactions and difficult identification of correlation, and whole-process management, comprehensive judgment, and timely treatment should be performed within the framework of multidisciplinary team.
Immune checkpoint inhibitors for treatment of biliary malignant tumors
Guoming SHI, Yanzhi PEI, Pinxiang LU, Jun CAO, Jian ZHOU, Jia FAN
2022, 38(5): 998-1001. DOI: 10.3969/j.issn.1001-5256.2022.05.005
Abstract(651) HTML (233) PDF (1877KB)(138)
Abstract:
Biliary malignant tumors have an insidious onset and rapid development, and most patients have lost the opportunity for radical surgery at initial diagnosis and often have poor prognosis. Gemcitabine-based chemotherapy is the first-line treatment for biliary malignant tumors, but with a limited clinical effect. The improvement in next-generation sequencing technology provides the possibility for the precise treatment of biliary malignant tumors, but the application and development of the precise treatment of biliary malignant tumors are limited by the low positive rate of targets and the poor accessibility of therapeutic drugs. The advent of the era of immunotherapy represented by the immune checkpoint inhibitor PD1/PD-L1 monoclonal antibody brings a promising future for the treatment of malignant tumors, including biliary malignant tumors. Combined chemotherapy and/or targeted therapy based on immune checkpoint inhibitors has shown a good effect in the treatment of biliary malignant tumors, which is the direction of the treatment of advanced biliary malignant tumors in the future.
Hotspot·Perspective·Viewpoint
Liver cirrhosis: Decompensation and "recompensation"
Zhiying HE, Bingqiong WANG, Hong YOU
2022, 38(5): 1002-1005. DOI: 10.3969/j.issn.1001-5256.2022.05.006
Abstract(1528) HTML (1188) PDF (1882KB)(313)
Abstract:
The evolution concept of decompensated cirrhosis rebuilds the clinical staging system for decompensated cirrhosis, which changes the focus from the pattern of disease progression to refining the status of acute decompensation onset and proposing "recompensation" of decompensated cirrhosis. During the process, factors such as portal hypertension and systemic inflammatory changes can affect the clinical outcome of decompensated cirrhotic patients. Significantly, more evidence is warranted to elucidate the clinical characteristics and potential mechanisms of achieving "recompensation" after etiology control, such as in viral hepatitis patients.
Guidelines
Standard for diagnosis and treatment of pancreatic cancer (2022 edition)
General Office of National Health Commission
2022, 38(5): 1006-1015. DOI: 10.3969/j.issn.1001-5256.2022.05.007
Abstract(1851) HTML (1007) PDF (2008KB)(535)
Abstract:
An excerpt of Asian Pacific Association for the Study of Liver (APASL) guidelines: Hepatitis B virus in pregnancy (2022)
Chao CHEN, Chenxu WANG, Guanlun ZHOU, Yuhao JU, Deping YUAN, Xiajun YE, Guorong HAN
2022, 38(5): 1023-1026. DOI: 10.3969/j.issn.1001-5256.2022.05.009
Abstract(563) HTML (122) PDF (1871KB)(142)
Abstract:
Guideline Interpretation
Interpretation of Standard for diagnosis and treatment of primary liver cancer (2022 edition)
Zhao LI, Jiye ZHU
2022, 38(5): 1027-1029. DOI: 10.3969/j.issn.1001-5256.2022.05.010
Abstract(1288) HTML (228) PDF (1893KB)(529)
Abstract:
Original Articles_Viral Hepatitis
Value of HBsAg level in predicting liver inflammation in patients with HBeAg-positive chronic hepatitis B virus infection and normal alanine aminotransferase
Zhan ZENG, Yuanjiao GAO, Xiaoyue BI, Fengxin CHEN, Wen DENG, Tingting JIANG, Yanjie LIN, Liu YANG, Minghui LI, Yao XIE
2022, 38(5): 1030-1034. DOI: 10.3969/j.issn.1001-5256.2022.05.011
Abstract(563) HTML (191) PDF (1912KB)(69)
Abstract:
  Objective  To investigate the onset of liver inflammation and related predictive factors in patients with HBeAg-positive chronic hepatitis B virus (HBV) infection who have normal alanine aminotransferase (ALT) and a high viral load.  Methods  A retrospective analysis was performed for the clinical data of 183 patients with HBeAg-positive chronic HBV infection who had normal ALT and a high viral load and were treated from October 2008 to May 2015, and according to the results of liver biopsy, they were divided into hepatitis group and non- hepatitis group. The t-test or Mann-Whitney U testwas used for comparison of normally distributed continuous data between groups, the chi-square test was used for comparison of categorical data. The predictive factors were analyzed by univariate binary logistic regression, the multivariate binary logistic regression was carried out by stepback method, and the cut-off values were analyzed by receiver operating characteristic curve (ROC) and Jordan index.  Results  There were 37 patients (20.2%) in the hepatitis group and 146 patients (79.8%) in the non-hepatitis group. Compared with the non-hepatitis group, the hepatitis group had a significantly lower proportion of male patients (45.9% vs 68.5%, χ2=6.508, P=0.011), a significantly higher level of aspartate aminotransferase [24 (21.25~35.55) U/L vs 21.2 (18.08~ 24.65) U/L, Z=-3.344, P=0.001], and a significantly lower log(HBsAg) value [4.4(4.28~4.49) vs 4.46(4.4~4.74), Z=-2.184, P=0.029]. Log(HBsAg) value was a predictive factor for hepatitis (odds ratio=0.077, P=0.017), and the cutoff value of HBsAg was 33884.4I U/mL.  Conclusion  Among the patients with HBeAg-positive chronic HBV infection who have normal ALT and a high viral load, 20.2% have liver inflammation, and HBsAg may be a predictive factor for liver inflammation.
Comparison of two quantitative real-time PCR methods for serum HBV RNA in patients with HBeAg-positive chronic hepatitis B: A propensity score matching study
Yang WANG, Hao LIAO, Zhongping DENG, Dandan BIAN, Yan REN, Yingying JIANG, Shuang LIU, Yu CHEN, Fengmin LU, Zhongping DUAN, Sujun ZHENG
2022, 38(5): 1035-1040. DOI: 10.3969/j.issn.1001-5256.2022.05.012
Abstract(610) HTML (122) PDF (2241KB)(56)
Abstract:
  Objective  To investigate the consistency between Shengxiang (S) and Xinbo (X) real-time PCR methods in the quantification of HBV RNA.  Methods  In the prospective follow-up cohort of 108 chronic hepatitis B (CHB) patients established from July 2007 to August 2008, 20 patients with HBeAg seroconversion were selected, and 20 patients without seroconversion were selected by propensity score matching at a ratio of 1∶ 1. The two quantification methods from S and X companies were used, and a retrospective analysis was performed for HBV RNA in serum samples at baseline and weeks 12, 24, and 48. The paired t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data. The Pearson correlation coefficient, intraclass correlation coefficient (ICC), and the Bland-Altman method were used to evaluate the consistency of the two quantification methods.  Results  A total of 132 serum samples were tested by S reagent, and 154 were tested by X reagent; the detection rate of HBV RNA was 100% by both reagents. A total of 131 serum samples were tested by both reagents, with 34 samples at baseline and 29, 35, and 33 samples, respectively, at weeks 12, 24, and 48 of follow-up; at these four time points, the HBV RNA quantification data detected by X reagent were significantly higher than those detected by S reagent (5.75±1.64/5.43±1.73/5.13±1.54/4.76±1.55 log10 copies/mL vs 4.80±1.48/4.52±1.53/4.10±1.50/3.92± 1.43 log10 copies/mL, t=8.348, t=5.341, Z=-5.086, Z=-4.762, all P < 0.001). The correlation analysis of the two methods showed a Pearson correlation coefficient of 0.915 (95% confidence interval [CI]: 0.836-0.957) and an ICC of 0.771(95%CI: -0.021 to 0.931) at baseline, a Pearson correlation coefficient of 0.849(95%CI: 0.701-0.927) and an ICC of 0.733(95%CI: 0.138-0.902) at week 12, a Pearson correlation coefficient of 0.951(95%CI: 0.905-0.975) and an ICC of 0.776(95%CI: -0.058 to 0.942) at week 24, and a Pearson correlation coefficient of 0.933(95%CI: 0.867-0.967) and an ICC of 0.804(95%CI: -0.014 to 0.944) at week 48 (all P < 0.05). The Bland-Altman analysis showed that the difference of 96.18%(126/131) samples tested by the two methods was within the mean difference±1.96 standard deviation.  Conclusion  HBV RNA quantification by X reagent is higher than that by S reagent, while the two real-time PCR quantification methods show a good consistency in CHB patients with HBeAg seroconversion and those without seroconversion.
Risk factors for osteopenia/osteoporosis and the diagnostic value of CT value in patients with chronic hepatitis B
Jingyi ZHANG, Yingmei TANG, Jiaqi LI, Qian WANG, Chenrui ZHANG
2022, 38(5): 1041-1047. DOI: 10.3969/j.issn.1001-5256.2022.05.013
Abstract(370) HTML (153) PDF (2526KB)(43)
Abstract:
  Objective  To investigate the value of the CT values of thoracolumbar vertebrae measured by abdominal CT in the diagnosis of osteopenia/osteoporosis in patients with chronic hepatitis B, as well as the risk factors for osteopenia/osteoporosis in such patients.  Methods  A retrospective analysis was performed for 112 patients with chronic hepatitis B in the Second Affiliated Hospital of Kunming Medical University from January 2019 to December 2020. All patients underwent abdominal CT, and some patients underwent dual-energy X-ray absorptiometry (DXA). The CT values of T12 vertebral body to L3 vertebral body were measured, and the value of CT value of each vertebral body in the diagnosis of osteopenia/osteoporosis was analyzed in comparison with T-score of L1-L4 vertebral bodies measured by DXA. With the CT values of vertebral bodies as the diagnostic criteria, the patients with chronic hepatitis B enrolled were divided into osteopenia/osteoporosis group with 55 patients and normal bone mass group with 57 patients. Clinical features and biochemical parameters were compared between the two groups to analyze the risk factors for osteopenia/osteoporosis in patients with chronic hepatitis B. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test, the Fisher's exact test, and the Bonferroni correction test were used for comparison of categorical data between groups. A Pearson correlation analysis was performed to investigate correlation, and a binary logistic regression analysis was used for multivariate analysis. The receiver operating characteristic (ROC) curve was used to investigate the value of CT values of T12-L3 vertebral bodies in the diagnosis of osteopenia/osteoporosis in patients with chronic hepatitis B. The Kappa test was used check consistency.  Results  A total of 46 patients who completed abdominal CT and DXA during the same time of hospitalization were analyzed, and their CT values of T12-L3 vertebral bodies were significantly positively correlated with the T-score values of L1-L4 vertebral bodies in DXA (rT12=0.694, rL1=0.661, rL2=0.781, rL3=0.685, all P < 0.001). The ROC curve analysis showed that the CT value of L2 vertebral body had the largest area under the ROC curve of 0.863 and showed a good accuracy in the diagnosis of osteopenia/osteoporosis, which was consistent with the results of DXA (K=0.648, P < 0.001). The clinical features and biochemical parameters of 112 patients with chronic hepatitis B were analyzed, and it was suggested that old age (odds ratio [OR]=1.108, 95% confidence interval [CI]: 1.026-1.196, P=0.009) and sarcopenia (OR=2.788, 95% CI: 1.009-7.707, P=0.048) were the risk factors for osteopenia/osteoporosis.  Conclusion  The patients with chronic hepatitis B often need regular abdominal CT to evaluate the progression of liver disease, and it is of high clinical significance to identify the presence or absence of osteopenia/osteoporosis and sarcopenia by measuring the CT value of L2 vertebral body and skeletal muscle area of L3 vertebrae plane, thereby giving timely intervention and improving patients' prognosis and quality of life.
Determination of a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-associated acute-on-chronic liver failure
Hongmin WANG, Jingjing TONG, Xiang XU, Jing CHEN, Zifeng LIU, Haibin SU, Xiaoyan LIU, Jinhua HU
2022, 38(5): 1048-1052. DOI: 10.3969/j.issn.1001-5256.2022.05.014
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Abstract:
  Objective  To investigate a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and to realize accurate early diagnosis.  Methods  A retrospective analysis was performed for the clinical data of 1232 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from September 2008 to September 2018, and according to the baseline serum level of total bilirubin (TBil), the patients were divided into group A (TBil < 205.2 μmol/L) and group B (TBil ≥205.2 μmol/L). the two groups were compared in terms of clinical features and 28-day, 90-day, 1-year, and 3-year survival. The t-test or the Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The Kaplan-Meier method was used to analyze survival rate, and the log-rank test was used for comparison.  Results  There were significant differences between the two groups in age(t=3.188, P=0.001) male sex(χ2=33.833, P < 0.001), liver failure classification(χ2=39.987, P < 0.001), white blood cell count(Z=6.586, P < 0.001), hemoglobin(Z=4.272, P < 0.001), platelet count(Z=3.680, P < 0.001), creatinine(Z=4.505, P < 0.001), total cholesterol(Z=8.644, P < 0.001), Na(Z=2.335, P=0.020), albumin(Z=2.592, P=0.010), HBV DNA(Z=3.703, P < 0.001), Mo