Table of Content

30 September 2021, Volume 8 Issue 3

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Review of experts

To establish a comprehensive prevention and treatment system based on rapamycin for cancer recurrence after liver transplantation

He Qiang, Zhou Lin

2021, 8(3):  1-7. 

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Liver transplantation (LT) represents one of the most effective radical therapy for hepatocellular carcinoma (HCC), particularly for advanced HCC. With the standardized development of organ acquisition and transplantation, the number of LT for HCC in China has far exceeded that of the United States in the past five years. However, postoperative recurrence and metastasis remains the key issues to improve the long-term prognosis. Meanwhile, immunosuppressive regimens based on calcineurin inhibitors are considered to be an independent risk factor of tumor recurrence after LT for HCC, early rapamycin conversion therapy is currently recommended for immunosuppression in recommended so as to avoid long-term high exposure to hormones and calcineurin inhibitors. Nevertheless, this option failed to improve the long-term survival of 3 to 5 years or the benefit was limited. Therefore, it is important and urgent to establish a personalized comprehensive prevention and treatment system to maximize the survival benefit of rapamycin and delay the recurrence of HCC. Based on the recent progress of HCC treatment including LT, targeted therapy and biological immunotherapy, our study aims to explore the necessity of establishing a comprehensive prevention and treatment system of tumor recurrence after LT.

Original article

Clinical study on individualized medication of tacrolimus after liver transplantation guided by CYP3A5 gene polymorphism for hepatocellular carcinoma

Jiang Tao, Pan Fei, Chen Qing, Huang Jincan, He Qiang, Lang Ren

2021, 8(3):  8-11. 

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Objective: To evaluate the safety and efficacy based on CYP3A5 gene polymorphisms in guiding the individualized tacrolimus therapy after liver transplantation for hepatocellular carcinoma. Methods: Clinical data of 120 patients with primary hepatocellular carcinoma were analyzed who underwent orthotopic liver transplantation from January 2018 to December 2019. According to whether the donor and recipient CYP3A5 gene was detected before operation, they were divided into individualized medication group and conventional medication group. The initial dose of tacrolimus was determined according to CYP3A5 genotype and previous experience in the two groups. The recovery rates of liver function at 14, 21, 28 days and 3, 6, 9, 12 months after operation were observed. The incidence of acute rejection, acute kidney injury, neurological symptoms, infection, de novo hypertension, de novo diabetes and the overall survival rate were recorded. Results: The differences of recovery rate of liver function between the two groups of recipients at 14 days and 21 days after was statistically significant (all P<0.05). There was no significant difference in the incidence of complications and overall 1-year and 2-year survival rates between the two groups (P> 0.05). Conclusion: It is safe to guide individualized tacrolimus after liver transplantation according to CYP3A5 gene polymorphism and beneficial to long-term survival for hepatocellular carcinoma recipients.

Comparison of comprehensive therapy and local therapy of recurrence after liver transplantation in patients with hepatocellular carcinoma beyond Milan criteria

Xie Yan, Zhang Weiqi, Sun Jisan, Jiang Wentao

2021, 8(3):  12-16. 

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Objective: To compare the efficacy of different treatments of recurrence after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) beyond Milan criteria (MC). Methods: The clinical data of 57 patients with HCC beyond MC who underwent LT for the first time and had tumor recurrence after operation in Tianjin First Central Hospital from March, 2016 to August, 2019 were analyzed retrospectively. According to the different treatment methods after recurrence, the patients were divided into comprehensive treatment group and local treatment group. Local treatment includes surgical resection, transarterial chemoembolization, radioactive ¹³¹I seed implantation, arterial infusion chemotherapy, radiofrequency ablation and radiotherapy. The comprehensive treatment is the addition of sorafenib or lenvatinib on the basis of local treatment. The differences of tumor remission and survival between comprehensive treatment group and local treatment group were compared and analyzed. Results: In the local treatment group, 1 patient (4.35%) and 8 patients (34.78%) achieved partial remission (PR) and stable disease (SD) respectively, and 14 patients (60.87%) happened progressive disease (PD) after treatment. In the comprehensive treatment group, 7 patients (20.59%) achieved PR, 17 patients (50%) achieved SD, and 10 patients (29.41%) had PD after treatment, which was better than that of local treatment group (P < 0.05). The median survival timeafterrecurrencein the comprehensive treatment group was 12 months, which was higher than that in the local treatment group (7 months) (P < 0.01). In the comprehensive treatment group, 3 patients (15.79%), 9 patients (47.37%) and 7 patients (36.84%) achieved PR, SD and PD in lenvatinib respectively. In sorafenib group, 4 patients (26.67%), 8 patients (53.33%) and 3 patients (20.00%) achieved PR, SD and PD, respectively. There was no significant difference in tumor remission between the two groups (P=0.548). However, the median survival time after recurrence in the lenvatinib group (13 months) was higher than that in the sorafenib group (10 months) (P=0.047). Conclusion: Patients with tumor recurrence after LT for HCC beyond MC are more likely to benefit from the comprehensive treatment, in which lenvatinib may be sorafenib to sorafinib in the long-term survival of such patients.

HIF-1α is a negative prognostic indicator associated with poor survival benefits of HCC patients

Zhou Lin, Wang Jing, Zhao Yang, Li Han, Du Guosheng, Shi Xianjie, He Qiang, Lang Ren

2021, 8(3):  17-25. 

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Objective: To explore the survival benefits of hypoxia-inducible factor-1α (HIF-1α) inpatients with hepatocellular carcinoma (HCC). Methods: We enrolled 136 patients who performed liver resection.Liver tissue were collected to analyze the expression of HIF-1α and others with immunohistochemistry (IHC). Mean integral optical density (MIOD) of tissue IHC was used to measure the expression level of different differentiated tumors. Survival rates were calculated using the Kaplan-Meier method and evaluated with the log-rank test. Cox proportional model was used to analyze the independent risk factors affecting the survival time. Results: HIF-1α, VEGF, GLUT1, LDHA, p-Akt and p-mTOR were highly expressed in poorly differentiated HCC and carcinoma tissue. HIF-1α was positive associated with VEGF, GLUT1, LDHA, p-Akt and p-mTOR, respectively. Meanwhile, high-middle differentiated HCC patients suggested a well survival benefits over that low differentiated HCC patients. Cox regression analysis indicated that tumor differentiation, HIF-1α and Ki-67 were the prognostic independent risk factors. Conclusion: HIF-1α is an independent risk factor for prognosis of HCC.Low differentiated HCC with high HIF-1α expression and high Ki-67displayed a poor prognostic survival.

Review

Progress on liver transplantation in the treatment of liver metastases

Lyu Shaocheng, Lang Ren

2021, 8(3):  26-29. 

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Liver transplantation has become an acceptable and effective treatment for primary malignant liver tumors according to Milan criteria. In recent years, with the development of comprehensive treatment, the emergence of targeted drugs and immunotherapy, the long-term prognosis of liver transplantation for some liver metastases has been significantly improved. And a new era of “Transplant Oncology” has begun. This article reviews the current status of liver transplantation for patients with liver metastases.

Immune checkpoint inhibitors in liver transplantation patients with hepatocellular carcinoma

Xiong Jun, Wan Chidan

2021, 8(3):  30-34. 

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Hepatocellular carcinoma (HCC) is one of the most malignant solid tumors. Liver transplantation is currently the most effective treatment for HCC. However, most of the patients have exceeded the transplantation standards when they are first diagnosed. Besides, the recurrence of tumors after surgery also seriously affects the long-term survival of patients who have accepted transplantation. Immunotherapy is a new treatment of solid tumors. Some HCC patients who received immunotherapy achieved tumor downgrading or elimination in previous reports. In this review, we mainly discuss current research progress of immune checkpoint inhibitors in the downstage or bridging therapy before liver transplantation, as well as in the treatment of recurrence cancer after liver transplantation.

The prognostic value of simple inflammation-related indexes in predicting liver transplantation for hepatocellular carcinoma

Cao Yin, Wang Zhongxia, Jiang Chunping

2021, 8(3):  35-40. 

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Liver transplantation is an important treatment for hepatocellular carcinoma, but the recurrence rate remains unsatisfied. Systemic inflammatory response can be reflected by a number of common serological markers including neutrophils, lymphocytes, platelets, C-reactive protein and simple inflammatory indexes constructed by these factors. Many researches reported that these inflammatory indexes are important to predict the prognosis of HCC patients underwent liver transplantation. The purpose of this review is to summarize the published work on the prognostic value of simple inflammation based markers such as neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, systemic immune inflammation index, prognostic nutrient index, and Glasgow prognostic score in HCC patients following liver transplantation.

How to evaluate donors' liver volume: a review of researches

Lin Xin, Xiao Min, Li Qiyong

2021, 8(3):  41-45. 

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Liver transplantation (LT) is the best treatment for patients with end-stage liver diseases, but the shortage of organs limits the development of LT. At present, the liver donation in China mainly includes organ donation after citizen's death and living donors. The whole or partial grafts could be transplanted into recipients in condition of different donations. Partial LT includes living donor liver transplantation, split liver transplantation and reduced-sized liver transplantation et al. Accurate assessment of liver volume (LV) is the important risk factor of LT. Rough LV evaluation through the formula based on donor's basic parameters and accurate LV evaluation by digital measurement are the two major methods to estimate the LV of donors, which are of great importance to the safety of patients. In this review, we will represent the different ways to evaluate the LV, as well as their advantages and disadvantages.

Discussion on the whole course management of preventing recurrence of liver cancer after liver transplantation

Zheng Yuanwen, Liu Jun

2021, 8(3):  46-50. 

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Liver transplantation is one of the important measures for the treatment of hepatocellular carcinoma, especially for patients with end-stage liver disease. However, tumor recurrence after transplantation severely restricts the patient's long-term survival. Therefore, how to prevent the recurrence of liver cancer after transplantation is the key to improve the long-term efficacy of liver transplantation for liver cancer. This article discusses the prevention of postoperative recurrence of liver cancer patients after liver transplantation from the perspective of perioperative management of the entire treatment process, and reviews relevant clinical progress from multiple dimensions such as surgery and medication.

Research progress of serum markers for early diagnosis of hepatocellular carcinoma

Fu Zuojun, Liu Guisheng

2021, 8(3):  51-54. 

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Hepatocellular carcinoma is a malignant tumor originating from liver cells, which is characterized by high degree of malignancy, difficulty in early diagnosis, and poor clinical prognosis. In recent years, more and more studies have found that the sensitivity of serum alpha-fetoprotein for the diagnosis of hepatocellular carcinoma is reduced, and the early diagnostic efficacy is poor. Therefore, the study of new serum tumor markers for hepatocellular carcinoma has become a hot spot. For example, the presence of alpha-fetoprotein heteroplasmy, heat shock protein 90, and Golgi protein 73 may effectively improve the early diagnosis rate of hepatocellular carcinoma. This article reviews the research progress of serum markers for early diagnosis of hepatocellular carcinoma in recent years.

Research progress on Pringle maneuver and half hepatic vascular exclusion in hepatectomy

Huang Xiaozhun, Wang Chunling, Huang Zhangkan, Xu Lin, Ma Teng, Yin Xin, Bi Xinyu, Che Xu

2021, 8(3):  55-58. 

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As we all know, it is complex and difficult in doing hepatic surgery. Thus, how to apply blocking technology effectively in intraoperative bleeding control had become the key factor for liver resection. Consider that the hepatic blood flow occlusion modes usually were chosen by surgeons according to their preferences, this paper, based on the existing evidence, is to make a review on research and application of blood flow blocking method and half hepatic inflow blocking method in liver surgery.