Expert consensus on antiviral therapy of HBV/HCV associated hepatocellular carcinoma

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I. IntroductionHepatitis B virus (HBV) and hepatitis C virus (HCV) infection play an important role in the occurrence and development of hep

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I. Introduction

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection play an important role in the occurrence and development of hepatocellular carcinoma (HCC). In recent years, our country issued "guidelines for prevention and treatment of chronic hepatitis B (2010 Edition)" and "primary liver cancer diagnosis standard (2011 Edition)" have emphasized the importance of antiviral therapy in patients with hepatocellular carcinoma, hepatitis C prevention guide "(2004 Edition)" has also noted that antiviral therapy can delay HCC.

At present, there is no unified understanding of the specific implementation and evaluation of antiviral therapy. In view of this, Hepatology liver cancer study group held the three Symposium of Chinese Medical Association, the system collects and analyses the clinical research literatures of antiviral treatment of comprehensive treatment in the existing HCC, reviews the progress of antiviral drugs in the treatment of HCC clinical application, on the basis of the existing treatment of HCC virus related clinical data on antiviral medicine.

Integrated part of experts, in accordance with the GRADE system of evidence-based medicine grading (Table 1) to refine and supplement, application of antiviral therapy in these patients has launched the "expert HBV/H CV antiviral therapy of hepatocellular carcinoma: correlation between proposal", for domestic experts to discuss, revise and supplement.

In January 2013 Wu Mengchao Tang Zhaoyou academicians and direct participation in and under the guidance of the Chinese Medical Association of Hepatology liver cancer study group, liver surgery branch of study group, radiology intervention group, intervention group and ultrasound medical branch Chinese cancer association Specialized Committee, HCC clinical oncology collaboration Specialized Committee (now known as Chinese Clinical Oncology), tumor intervention group Specialized Committee / Specialized Committee (subsequently oncology liver cancer study group and liver transplantation group and organ transplantation will have to participate in the credit of the Chinese Medical Association) experts to discuss.

Further exchanges in the "expert advice" basis, after repeated modifications added, forming a "expert consensus on antiviral treatment of HBV/HCV related hepatocellular carcinoma (hereinafter as" "the expert consensus"), in order to provide guidance for the clinical application of antiviral treatment, and further improve the "primary standard", the diagnosis and treatment of liver cancer "chronic hepatitis B prevention guide" and "guide" the implementation of prevention and control of hepatitis C.

HBV and (or) HCV infection is an important risk of HCC occurrence, development and recurrence factors, more risk factors of death in patients with HCC, thus reducing the level of HBV/HCV replication is one of the key means of prevention and treatment of I{BV/HCV related HCC. Inhibition of viral replication can reduce the inflammatory activity of liver, reverse liver fibrosis, reduce the incidence of end-stage liver disease, reduce the incidence of HCC, and help to improve the overall survival of patients with HBV/HCV associated HCC.

The overall goal of recommendation 1:HBV/HCV related application of antiviral therapy in patients with HCC is: in the basis of comprehensive treatment for HCC, through antiviral therapy will HBV/HCV replication inhibition to the lowest level, to reduce the recurrence of HCC, and decreased activation in HBV/HCV, control the disease progress, improve the quality of life and prolong the survival time (1, A); antiviral therapy can improve liver function, reduce end-stage liver disease events, create conditions for the comprehensive treatment of HCC (1, B).

Two, HBV/HCV related HCC of the two levels of prevention

HBV chronic infection is one of the main pathogens of HCC. A large sample of natural history studies in Taiwan showed that the incidence of HCC in patients with chronic hepatitis B (CHB) was (403 - 470) / 105. The virological factors that lead to the occurrence of HBV associated HCC include HBV DNA level, HBeAg positive duration, viral genotype, C promoter mutation, X gene mutation, and so on. The incidence of HCC in patients with HBV associated cirrhosis was as high as 820 (- 2247) / 105.

HCV infection is closely related to HCC. At present, there are about 1.3 - HCV chronic infection in the world, about lO% ~ 40% of patients with chronic hepatitis C (CHC) is progressing to liver cirrhosis, l% - 5% is progressing to (HCC). The incidence of HCC in patients with chronic HCV infection was 15 - to 20 fold higher than that in the general population, and the incidence of HCC in the HCV infected patients at the follow-up of 30 years was 1% - 3%.

The positive rate of anti -HCV in Chinese patients with HCC is about 4% - 10%, and the incidence of HCC in patients with HCV related cirrhosis is l%~4%HCC (HCV RNA) and HCV (LB). Available evidence suggests that any level of serum HCV RNA positivity is an important risk factor for HCC, and HCV clearance may reduce the incidence of HCC.

There is strong evidence that antiviral therapy reduces the risk of HCC in patients with cHB and CHC. A number of clinical guidelines will be antiviral therapy as an important means to prevent the occurrence of HBV/H CV associated HCC. Antiviral therapy can be considered as the two level of prevention and treatment of HBV/HCV associated with HCC.

Recommendation 2: HBV. of chronic HCV infection in accordance with the "guidelines for the prevention and treatment of chronic hepatitis B (2010 Edition)" or "hepatitis C prevention guide (2004 Edition)" treatment options to antiviral treatment is an important two level prevention measures to prevent HBV / HcV related HCC (1, A).

Three. Antiviral therapy in patients with HBV associated HCC

There are two classes of antiviral drugs used in HBV related HCC: alpha (IFN) and nucleoside (acid) analogs (NAs). The current anti HBV treatment NAs: lamivudine (LAM), Fu Wei ester (ADV), entecavir and telbivudine (ETV) (LdT). Tenofovir (TDF) have recently received Chinese food and Drug Administration (CFDA) approved the listing application to anti HBV therapy.

Randomized controlled clinical trial (RCT) showed that the use of NAs can improve the survival rate of patients with V associated HCC. Study of HBV HCC RCT Koda small sample showed that LAM treatment group mean Child-Pugh score significantly improved compared with the control group (p=0.023), the cumulative survival rate was significantly higher than the control group (p=0.02), but the cumulative relapse free survival between the two groups were not statistically significant.

Koda also found that 39.3% of patients with drug resistance during the application of LAM mutation, HBV should be given priority because of the high efficiency of the drug resistant barriers. Meta analysis showed that the use of NAs in patients with HBV associated with HCC can reduce the recurrence rate and mortality. Wong et al. 9 patients were collected from the cohort of 551 patients, of whom was used in NAs.

The results showed that the recurrence rate of HCC in the NAs group (55%) was lower than that in the control group (p=o. 04), OR was (95%CI0.35~ = 0.97), and the overall mortality rate was significantly lower in the NAs group (38%) than in the control group (42%) (P)

Wu et al. Reported a large sample of NAs applications in HBV associated HCC radical surgery in 2012, HCC. The research group collected from 2003 to 2010 in Taiwan area, the 100938 Hcc patients, including 4569 cases of HBV associated HCC were radical resection, 518 cases were given NAs treatment (for an average time of 1.45 years), the control group of 4051 cases without NAS.

After follow up observation, the recurrence rate of HCC in the NAs group was 20.5%, and that of the control group was (P)

Cox regression analysis showed that NAs was an independent factor to reduce the recurrence of HCC (HR, 0.67; 95%CI, 0.55~;; p<). Li case control study of HBV related HCC radical surgery to NAs

Observation on the treatment of residual liver volume, 6 months after operation in NAs group (43 cases) residual liver volume increment (78 + 40.1) cm3/m3, the control group (36 cases) for (35.8 + 56) cm3/m2 (p=0.009), suggesting that the application of NAs are helpful to increase the remnant liver volume, improve the tolerability of sequential therapy. To improve the overall prognosis. Patients with Jang were randomly divided into two groups. The patients in the treatment group were treated with LAM (TACE).

The results showed that in the control group (37 cases), HBV (P=0.002) was found to be active in the liver of the patients () in 11 cases (29.7%), but only in the LAM group (36 cases).

The study suggests that LAM may reduce the risk of liver failure in patients with TACE after an inflammatory response. Xia's study showed that percutaneous radiofrequency ablation of small hepatocellular carcinoma (RFA) after treatment, HBV DNA high load group (more than 105 copies / ml) 1, 3, 5 year survival rates were 86.8%, 41.2% and 22.8%, the cumulative overall survival rates were 64.3% and 32.2% 88.5%.

While the low load group (< 105 copies /ml) 1, 3 and 5 years disease-free survival rate was 96.4%, 65.8% and 36.7%, the cumulative survival rates were 90.9%, 66.7% and 21.7%. tips for treatment of liver cancer recurrence after radical effect of high viral load, but does not affect the overall survival rate.

IFN has a certain effect on preventing the recurrence of HCC after radical treatment. Sun RCT of HCC patients after radical operation, IFN a group of 18 months of treatment the recurrence rate was 36.40%, and 49.2% in the control group (p=0.0485); disable IFN alpha after 18 months of follow-up, the IFN alpha group the recurrence rate was 32.9%, the control group was 23.2% (P=o.2292).

Lo and other RCT study, the same TNM stage of patients with HCC after resection were randomly divided into lFN group and control group, treatment plan for IFN alpha -2b, 10MIU/m2, 3 times a week, treatment for 16 weeks. After 5 years of follow-up, the treatment group 20% (8/40) in patients with death or liver transplantation, 33% in the control group (13/40); the survival rate of IFN group was 1, 3 alpha and 5 years were 97%, 79% and 79% in the control group were 85%, 70% and 61%, there was no significant difference between the two groups. (p=o.137).

But for TNM stage III / IV A patients, 1, 3 and 5 year survival rate of IFN group were 95%. and 68%, respectively, the control group was 47%24%, respectively, the difference between the two groups (P=o.038).

Therefore, the application of IFN alpha in patients with HBV associated HCC can reduce the recurrence rate of HCC, which is helpful to improve the survival rate of patients. The main virological factors of HBV associated HCC recurrence were high viral load and HBeAg positive.

A comprehensive study of the role of antiviral therapy. Kim reviewed 12 years (April 1999 to April 2011) in 1305 cases of HCC patients with the treatment of choice for RFA 0, the group of patients with a total of 1502 lesions, the mean lesion size was 2.2cm (0.5~4.9cm), including 206 cases of liver biopsy pathology.

1077 patients (82.5%) had cirrhosis background, and HBV infection was found in 912 patients (69.6%), and 233 patients (17.8%) were infected with HCV. 1305 patients completed RFA and survived more than 30d, of which 795 (62%) relapsed. 154 of the patients with recurrence of focal lesions (19.4%), the distant recurrence of liver in 535 cases (673%).

After a variety of treatment options, 245 cases of recurrence, more than 2 cases (67.5%) recurrence occurred in more than 509 cases, recurrence occurred in more than 344 cases. Multivariate analysis showed that age, Child_Pugh B level, RFA treatment did not use antiviral therapy and RFA treatment before the presence of extrahepatic metastasis is the main risk factor for low survival rate. The study suggests that even in patients with RFA (BCLC) in Barcelona, who are 0 or A stage of stage HCC in the clinical stage, they should be treated with antiviral therapy in order to reduce the recurrence of HCC and improve the survival rate.

Detection of HBV negative DNA should be prevented by HBV in patients with HBV related HCC. The mechanism is that the covalently closed circular DNA (CCE DNA) persists in the nucleus of the liver. Foreign Studies in 1990s showed that the incidence of HBV reactivation in patients with HBV associated with HCC was about 2%, and the rate of HBV reactivation was reported to be about.

The rate of HBV reactivation in patients with HBV associated with TACE was higher, which was about 15% - 30% (HCC). Jang et al. Reported that HBV reactivation rate was 33.7% after TACE. Lao et al retrospectively investigated a group of 172 patients with HBV associated with HCC, HBV reactivation occurred after TACE, and multivariate analysis showed that preoperative baseline and HBeAg status of HBV DNA were the main factors affecting HBV reactivation.

Kim et al. Reported that HBV reactivation rate was 21.8% in patients with HBV associated HCC after three dimensional conformal radiotherapy (3D-CRT). Yeo et al. Reported that HBV reactivation rate was 36% in patients with HBV associated HCC after chemotherapy. TACE application of NAs before and after operation can reduce the reactivation of HBV, and NAs can be used to prevent and treat the reactivation of HBV before and after radiotherapy.

Antiviral therapy has been paid more and more attention in the clinical practice of HCC. In 2013, more and more clinical data have been confirmed in our country. It is proved that antiviral therapy can reduce the recurrence rate and fatality rate of HBV related HCC. Yin et al. Evaluate the impact of NAs antiviral therapy on the outcome of surgical treatment of patients with HBV associated HCC by using the two stage longitudinal study of RCT. High load HBV DNA was a predictor of overall survival (OS) and relapse free survival (RFS) in patients with HCC, and antiviral therapy significantly improved the prognosis of patients.

In the non RCT group NAs and RFS were 59.6% and 4 in the control group (Os) and the difference between the two groups was 46.6% and 16.6%, respectively. The difference was statistically significant (P)

Research shows that closely related to recurrence in response to antiviral therapy with HCC after surgery, 24 weeks after taking the HBV DNA level still remain undetectable in patients with postoperative recurrence rate was significantly higher than has been reduced to undetectable patients, the drug resistance of patients with postoperative recurrence rate is significantly higher than that in non resistant patients.

Surgical treatment for low viral load (HBV DNA< 2000IU/ml) reactivation in patients with HCC may also cause HBV, the overall survival rate and disease-free survival rate were significantly lower than those without HBV reactivation in patients, therefore should be preferred quick and powerful antiviral drugs and low drug resistance.

The incidence of HBV reactivation after RFA treatment was significantly lower than that of patients undergoing hepatectomy. Prophylactic antiviral therapy can effectively reduce the incidence of HBV reactivation in patients undergoing hepatectomy for HCC.

In conclusion, antiviral therapy in the patients with HBV related HCC has clinical significance in two aspects: (L) to prevent or reduce the recurrence of HCC, especially the recurrence, improve liver function, improve the survival rate; (2) decrease due to tumor treatment HBV reactivation, the incidence of lower end liver disease at the end of the event. The timing and the program of antiviral therapy (the application of antiviral therapy and anti tumor treatment measures, or the application of anti tumor therapy after the phased implementation) should be decided according to the specific circumstances of the patient.

3: recommendation HBV associated HCC patients with NAs (LAM). The choice of lamivudine adefovir dipivoxil (ADV), telbivudine (LdT) and entecavir (ETV), tenofovir (TDF) after the listing can choose. Recommendations for the selection of highly potent drug resistance (ETV or TDF). Monitoring, side effects and principles of treatment in the course of treatment of NAs: guidelines for the prevention and treatment of chronic hepatitis B (2010 Edition).

Patients with 1.HBV associated HCC were detected positive for FBV, and antiviral therapy should be given on the basis of comprehensive treatment of NAs (1, A) (HCC, DNA). Recommendations refer to the "chronic hepatitis B prevention and treatment guidelines (2010 Edition)" HBV related cirrhosis treatment principle, choose NAs long-term use (2a, A). Patients in the treatment of anti-tumor, should be given as soon as possible NAs treatment, reduce the level of HBV DNA in order to reduce the reactivation of HBV (2a, A).

2.HBV related HCC after the diagnosis of HBV negative TACE, radiation therapy or systemic chemotherapy, it is recommended that before the start of treatment with NAs treatment in order to avoid the reactivation of HBV in the treatment of DNA. During treatment and after treatment need to closely monitor the HBV DNA, such as the treatment period and after treatment two times (one month apart) HBV DNA are negative can be stopped according to the condition of NAs treatment or continuous treatment for 6 months;

For example, if HBV DNA appears in the monitoring process, the patients need long-term treatment (2a, B). HBV HCC HBV DNA negative correlation detection surgery or ablation treatment, attention should be paid to HBV reactivation, and close monitoring of HBVDNA; such as HBV DNA in the monitoring process of positive and interval of 2 weeks check is still positive, you can choose NAs long-term treatment (2a, B).

3.HBV related HCC was diagnosed in accordance with the criteria for liver transplantation and was intended for liver transplantation patients, such as the positive results of HBV DNA, should be given to patients with preoperative NAs as far as possible to reduce the level of FBV DNA (1, A). Liver transplantation as early as possible before taking LAM, such as preoperative DNA or has high load resistance, should be timely selection of other NAs; anhepatic phase HBV high titer immune globulin (HBIG) in operation: after long-term use of LAM and HBIG in the prevention of reactivation of HBV (2a, B).

For patients with LAN resistance, can be combined with ADV (2a, B). The use of ETV or TDF alone, combined with or without combination with low-dose FBIG, may also prevent HBV recurrence after liver transplantation (2a, B).

Recommendation 4.HBV related HCC patients in the comprehensive treatment program, such as no contraindications, can choose FNa (1, A) adjuvant therapy. The liver function of patients with decompensated according to routine dose application of IFN alpha; Child-Pugh score of B patients should start from dose application, gradually increased to 5 MU, 3 times a week, 18 month course of 6-. Treatment with IFN alpha for up to 12 weeks, such as detection of patients with HBV DNA is still positive, it is recommended to add NAs (except LdT), or switch to NAs treatment (2a, B).

The monitoring items, side effects and treatment principles in the course of treatment were all in accordance with the guidelines for prevention and treatment of chronic hepatitis B (2010 Edition). If the patient confirmed that there is no cirrhosis background, you can choose polyethylene glycol (Peg) IFN alpha treatment.

Four. Antiviral therapy in patients with HCV associated HCC

Retrospective studies suggest antiviral therapy improves survival in patients with HCV associated HCC. Tanimoto 2012 review of the prognosis of 175 cases of resection of HCV associated HCC patients after surgery, in order to avoid selection bias, the standard treatment (sOc) group (Peg-IFN alpha 2b (1.5 u g/kg) and Leigh Bhave Lin (RBV) and the control group according to gender, age, tumor diameter by 1:1 paired analysis.

A total of 38 patients were included in the analysis, comparing the treatment group of 3 years and 5 years survival rates were 100% and 76.6%, the treatment group was 91.7% and 50.6%, there were statistically significant differences between the two groups, but between the two groups of the recurrence free survival rate comparison, the difference was not statistically significant (p=0.886). Haghara et al. Retrospective analysis of the role of Peg-IFN alpha in patients with HCV associated HCC.

The treatment group of 37 cases after Peg-IFN treatment, the control were 145 cases in the treatment group, the follow-up results showed that 5 year survival rate of treatment group and control group were 91% and 56% (P < 0.01; after Peg-IFN treatment to obtain sustained virological response (SVR) in patients with the second recurrence rate was significantly lower than the control group (p=0.03).

Meta analysis showed that antiviral therapy can reduce the recurrence rate of HCV related HCC and improve the survival rate of patients. Singal et al. Collected 10 clinical studies for meta-analysis, and effective analysis was performed in 645 patients with HCV associated HCC, of whom only one was treated with IFN or combined with RBV in 301 patients.

The analysis results show that after the application of IFN can decrease the recurrence rate of HCC alpha, OR 0.26 (95% CI0.15~0.45, P < 0.00001; for the 5 year survival rate of 6 of the 505 patients showed that IFN treatment is an important prognostic factor. The HCC recurrence rate was significantly lower (P=0.005) and SVR (P=0.03) was significantly higher in patients with IFN than those without SVR.

A meta-analysis of Miyake patients with primary HCC lesions within the Milan criteria, a total of 5 clinical studies of 355 patients, including 167 cases after radical surgery to IFN treatment, the results showed that IFN treatment significantly reduced the recurrence rate of HCC (RR0.33; 95%CI0.19~0.58, P< 0.0001). < p=" " >

More studies have confirmed that IFN antiviral therapy can improve the survival rate of patients with HBV/HCV associated HCC. Zhang summary of the 6 RCT study, 600 patients with HBV/HCV related HCC patients: a meta analysis results show that can prevent early recurrence after radical resection by IFN alpha (OR=0.62,95%CI0.42~0.93, P=0.02), to improve the survival rate of 1 years (OR=3.14,95%CI1.79~5.52, p< 0.0001). < p=" " >

Study on Application of RCT Breitenstein IFN alpha HBV/HCV correlation of HCC postoperative meta-analysis, including 7 clinical studies of 620 cases analysis showed that can improve the survival rate of 2 years, the application of IFN alpha after operation, the relative risk ratio (RR) 0.65 (95%CI0.52~0.80, P< 0.001); IFN alpha reduce HCC patients 2 years recurrence rate of RR was 0.86 (95%CI0.76~0.97, P=0.013).

Analysis also pointed out that about 8%~20% of patients with adverse reactions due to excessive IFN can not complete treatment. Therefore, attention should be paid to the role of antiviral therapy in the treatment of virus associated HCC.

Patients with HCV associated HCC can be treated with antiviral therapy according to the condition before liver transplantation. After transplantation, the patients with HCV recurrence must be treated with anti HCV therapy. Watt in HCV related liver disease treatment guidelines for transplantation antiviral that pathology criteria for liver biopsy of HCV recurrence after transplantation, serum HCV or RNA positive patients with liver fibrosis (METAVIR score = 3). Only to meet the above criteria recommended by the IFN alpha as the core drug treatment options, SOC.

Recommendation 5:HCV correlation of HCC application of anti HCV therapy: SOC (Peg-IFN alpha -2a/2b combined with RBV) or IFN alpha and RBV, can not tolerate RBV can be single Peg-IFN / alpha IFN alpha, the scheme can be chosen according to the specific circumstances of patients. Test items, side effects, and treatment principles in the course of anti HCV therapy were performed according to the guidelines for prevention and treatment of hepatitis C (2004 Edition) (, A).

1.HCV RNA positive HCC patients should be treated with anti HCV therapy (2a, A) on the basis of surgical resection, local ablation and TACE. Antiviral treatment should be assessed before the patient's liver pathological state of physiology, by the specialist arrangements for antiviral treatment;

Child-Pugh score of liver function B grade patients should use low dose to start gradually increase the amount of strategy, and gradually increase the IFN /Peg- alpha IFN alpha dose in order to obtain high SVR, and improve the tolerance against treatment in patients with HCV (2a, B); the Child-Pugh score was C, does not recommend the application of IFN /Peg- alpha IFN alpha, so as not to cause serious adverse events. Serum HCV RNA negative without antiviral therapy.

2 liver function Child-Pugh score less than or equal to 7 and undergoing liver transplantation HCV associated HCC patients for antiviral therapy before surgery (2a, B). After liver transplantation, serum HCV RNA levels should be detected, such as the occurrence of HCV RNA positive liver biopsy should be carried out, there are active liver fibrosis, according to the Child-Pugh score reference 5.1 of the recommendations for antiviral therapy (2a, B).

Recommendation 6: for HBV/HCV patients with HCC infection, the degree of liver cirrhosis and liver function should be evaluated on the basis of comprehensive treatment. For patients with grade Child-Pugh, such as serum HBV DNA and HCV RNA are positive, we should first determine what is the dominant virus and then determine the treatment plan. High levels of HBV DNA and can be detected HCV RNA, it is advisable to use Peg- IFN alpha and RBV treatment for 3 months, such as HBV DNA no response or elevated, then add NAs treatment.

Such as HCV RNA positive and HBV negative, it is advisable to first use anti HCV treatment; such as HCV RNA negative and HBV DNA positive, it is recommended to refer to the above HBV related HCC antiviral regimen (2a, C).

Five, HBV/HCV related HCC patients with antiviral application prospects

In summary, the results of clinical application in antiviral therapy based on HBV/HCV correlation in HCC, the group of experts agreed that such patients should pay attention to diagnosis and treatment during antiviral therapy, and incorporated into the scheme of comprehensive treatment of the HCC specification. HBV/HCV HCC is the correlation of antiviral therapy in patients with significance: to reduce the recurrence rate of HCC virus associated with end-stage liver disease, reduce the event rate, improve the safety of patients with comprehensive treatment, to create conditions for other comprehensive treatment.

However, there are still many problems in this field need to be clarified: virus replication was inhibited or reduced with HCC recurrence of a causal relationship between HBV and DNA negative HCC antiviral therapy indications and optimal selection and treatment scheme, how to improve the safety and tolerability of HCC in patients with liver cirrhosis background IFN alpha application, IFN (IFN-free) treatment the effectiveness in the treatment group of HCC patients with HCV correlation, the antiviral therapy of HCC long-term comprehensive management, these problems still need further clinical studies provide new evidence summary.

In short, in the process of diagnosis and treatment of HBV/HCV related HCC must pay attention in antiviral therapy, multidisciplinary physician to discuss detection and treatment, control the disease progression through comprehensive treatment including antiviral treatment, prevention of recurrence of HCC, improve the quality of life of patients, reduce the mortality rate.

Member of the expert group on antiviral therapy of hepatocellular carcinoma: liver cancer group, Department of Hepatology, Chinese medical association. Department of interventional radiology, interventional group of ultrasound medicine, oncology branch. Department of organ transplantation, liver transplantation group, China Association for the prevention of cancer, Specialized Committee, clinical oncology collaboration committee, and cancer Interventional Specialized Committee

Directed by: Wu Mengchao, Tang Zhaoyou

The pen, finishing: Ye Sheng Longjiang Ji Dong Jing

 

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