Practice GuidelinesClinical practice guidelines on liver transplantation for hepatocellular carcinoma in China (2018 edition)
Introduction
Over 3 00 000 people in China die each year of hepatocellular carcinoma (HCC), which accounts for approximately half of HCC-related deaths worldwide. Liver transplantation (LT) is generally recognized as one of the most effective therapeutic approaches for end-stage liver diseases. Since the beginning of the second LT boom in the 1990s, LT in China has been developed rapidly with professional and large-scale trends, and it is approaching or has reached the level of developed countries in terms of quantity and quality. According to the China Liver Transplant Registry, the number of transplants for HCC accounted for 36.8% of the total number of LT cases during the past 5 years in the mainland of China. In order to develop an effective, safe and standardized protocol to guide the national LT practice, the clinical guidelines of LT for HCC was launched in 2014 by multidisciplinary experts from Chinese Society of Organ Transplantation, Chinese Medical Association and Chinese Association of Organ Transplantation, Chinese Medical Doctor Association. Recently, there have been new clinical and scientific advances in the field of LT and to keep abreast of these achievements, the original clinical practice guidelines need to be updated.
This guideline is covering the following aspects: criteria for LT in HCC patients, preoperative downstaging treatment, antiviral therapy, application of immunosuppressants and prevention and treatment of post-LT HCC recurrence. The adopted classification of evidence in this guideline mainly refers to the 2001 Oxford evidence classification (Table 1), and the strength of recommendation mainly refers to the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) [1], [2], [3].
Section snippets
Criteria of LT for HCC (Table 2)
The shortage of donor livers remains a serious problem worldwide. Although this shortage has been slightly eased in China due to the propagation of donation after citizen's death (DCD), the number of donor livers is still far from meeting the demands. To overcome this challenge, Mazzaferro et al. proposed the so-called Milan criteria by selection of HCC patients complicated with liver cirrhosis for LT. The Milan criteria requires, in addition to the absence of intrahepatic macrovascular
Preoperative downstaging treatment of HCC for LT (Table 3)
Preoperative downstaging treatment of HCC should be applied to reduce tumor burden and stage, enabling candidates who exceed the LT criteria to obtain the opportunity of LT. The downstaging treatment is mainly indicated to HCC patients who do not meet the existing LT criteria and have no macrovascular invasion in portal vein or inferior vena cava and no distant metastasis [20], [21], [22], [23].
The effective downstaging treatment mainly includes transcatheter arterial chemoembolization (TACE)
Antiviral therapy of HCC patients for LT (Table 4)
More than 90% of HCC patients in China are infected with hepatitis B virus (HBV). Recipients with recurrent HBV infection or high HBV load before LT are at higher risk of HCC recurrence. Therefore, to reduce the risk of HBV recurrence and improve long-term survival after LT, antiviral drugs should be administered for LT candidates with HBV infection as early as possible [37], [38], [39]. Hepatitis B immunoglobulin (HBIG) should be administered in the anhepatic phase during the operation. The
Application of immunosuppressants to HCC patients post-LT (Table 5)
Usage of immunosuppressants such as calcineurin inhibitor (CNI) is an independent risk factor for HCC recurrence after LT. For LT recipients with HCC, the risk of HCC recurrence is related to the invasiveness of the tumor and the immune homeostasis of the body. When the recipients receive high-dose immunosuppressants, their homeostasis of immune system were disturbed which promote tumor recurrence and metastasis; on the other hand, if the immunosuppressant dose is insufficient, the grafts will
Prevention and treatment of post-LT HCC recurrence (Table 6)
Among different studies, the 5-year recurrence rate of HCC after LT ranged between 20% and 57.8% [17], [29], [73]. Thus, a proper management of HCC patients after LT is critical to reduce the postoperative recurrence. With the global trend of continuous attempts to expand LT indications of HCC, an increase in the recurrence rate after transplantation is inevitable [72]. The most common HCC recurrence sites after LT are lung (37.2%−55.7%), transplanted liver (37.8%−47.9%), abdomen (27.3%−37.7%)
Acknowledgments
A sincere gratitude for Chinese Society of Organ Transplantation, Chinese Medical Association and Chinese Association of Organ Transplantation, Chinese Medical Doctor Association for their continuous support. A great appreciation for the Guideline Committee for their active advice and peer-review that greatly improved the guidelines. Members of the Guideline Committee included Gui-Hua Chen, Zhi-Shui Chen, Guo-Shan Ding, Jia-Hong Dong, Jian Dou, Ke-Feng Dou, Guo-Sheng Du, Zhi-Ren Fu, Wen-Zhi
Funding
This guideline was supported by grants from the National Science and Technology Major Project (2017ZX10203205), and The Changjiang Scholar Award (T2014146).
Competing interest
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
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2023, Digestive and Liver DiseaseCitation Excerpt :Surgical resection is the most important and effective treatment for HCC. However, surgical resection is only appropriate for patients with early-stage of HCC [2–4]. Recently, there are more and more studies focused on targeted therapy for HCC.
Conversion therapy in liver transplantation for hepatocellular carcinoma: What's new in the era of molecular and immune therapy?
2023, Hepatobiliary and Pancreatic Diseases InternationalCitation Excerpt :Hepatectomy potentially improves the survival of patients listed for LT by decreasing the risk of dropout [19]; moreover, laparoscopic or robotic hepatectomy has a minor impact on a subsequent LT [20,21]. “Clinical practice guidelines on liver transplantation for hepatocellular carcinoma in China” has recommended preoperative downstaging treatment of HCC for LT [22]. The China National Health Commission's “Guidelines for the diagnosis and treatment of hepatocellular carcinoma (2019 edition)” recommended conversion therapy as an option for uHCC [23].
Reply to ‘How to select eligible hepatocellular carcinoma patients with portal vein tumor thrombus for deceased donor liver transplantation?’
2022, European Journal of Surgical OncologyDownstaging treatment for patients with hepatocelluar carcinoma before transplantation
2021, Transplantation ReviewsCitation Excerpt :Its advantage is that it provides more LT opportunities for HCC patients with poor initial tumor biology characteristics. Especially in patients who exceed the Hangzhou criteria, it seems sufficient to downstage to the Hangzhou criteria before LT [46]. In conclusion, studies show that using different criteria and treatments, the downstaging success rate ranges from 23.7% to 70% (Table 1).
Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China
2020, Hepatobiliary and Pancreatic Diseases InternationalCitation Excerpt :Theoretically, the HC as the endpoint of LRT may allow more patients to gain an access to LT. Recently, we published the clinical practice guidelines on LT for HCC in China (2018 edition) [16]. The HCC patients exceeding the LT criteria who met the criteria after receiving downstaging treatment are recommended for LT [16].