Clonorchis sinensis is considered a class I carcinogen for cholangiocarcinoma, but an increasing number of studies have found that it is also closely associated with hepatocellular carcinoma. This paper reviews the discovery and prevalence, historical studies, key regional studies, animal models and complications of Clonorchis sinensis, and summarizes the possible molecular mechanisms of Clonorchis sinensis contributing to hepatocellular carcinoma development, in order to gain insight into the correlation between Clonorchis sinensis and hepatocellular carcinoma, and thus to provide new ideas for the study of the effects of Clonorchis sinensis infection on hepatocellular carcinoma.

The onset of primary hepatic carcinoma (PHC) is usually occult, and early symptoms are not obvious. Most patients are at advanced stages of disease at diagnosis, and the prognosis is poor. Paraneoplastic syndrome (PNS) refers to the clinical manifestations indirectly caused by tumor metabolites or abnormal immune reactions that cannot be explained by the primary lesion, local tumor spread or distant metastasis. Hypercholesterolemia, hypercalcemia and hypoglycemia are the most commonly seen clinical presentations of PNS in PHC patients. Adequate understanding of PNS is of great importance in early diagnosis and treatment of PHC. In this review, we summarized the clinical manifestations and prognostic mechanisms of PNS in patients with PHC.

Objective:To study the impact of preoperative serum HBV DNA levels on prognosis of hepatocellular carcinoma (HCC) patients undergoing hepatectomy with curative intent.Methods:The clinical data of patients with HCC treated by hepatectomy with curative intent at the Guangxi Medical University Cancer Hospital from January 2010 to December 2016 were retrospectively analyzed. According to the preoperative serum HBV DNA levels, patients were divided into three groups: the control group (HBV DNA negative), the low load group (<10 4 copy/ml) and the high load group (≥10 4 copy/ml). The clinical data of these patients were collected and long-term survival outcomes of these patients were followed-up. The Kaplan-Meier method was used to compare the overall survival (OS) and recurrence-free survival (RFS) rates among the three groups. Using the Barcelona clinic liver cancer classification (BCLC), patients with different serum HBV DNA levels were further divided into three subgroups: stage 0/A, stage B and stage C. The OS and RFS rates of patients in each of these subgroups were compared. Results:Of 1 180 patients who were enrolled in the study, there were 1 024 males and 156 females, aged (48.6±10.8) years. The 1-, 3- and 5-year OS rates for patients in the control group ( n=258) were 91.5%, 79.3% and 74.9%, respectively; while those in the low load group ( n=289) were 87.2%, 68.6% and 61.6%, respectively; and those in the high load group ( n=633) were 85.4%, 68.9% and 60.7%, respectively. The 1-, 3- and 5-year OS rates in the control group were significantly better than those in the low load group and the high load group ( P<0.05). The 1-, 2- and 3-year RFS rates in the control group were significantly higher than those in the high load group ( P<0.05). Subgroup analysis showed that in the BCLC 0/A subgroup ( n=786) the 1-, 3- and 5-year OS rates in the control group were significantly better than those in the high load group ( P<0.05). In the BCLC B subgroup ( n=181), the 1-, 2- and 3-year RFS rates in the control group were significantly higher than those in the high load group ( P<0.05). In the BCLC C subgroup ( n=214), there were no significant differences in the 1-, 3- and 5-year OS and 1-, 2- and 3-year RFS rates among the three groups ( P>0.05). Conclusion:For HCC patients undergoing hepatectomy with curative intent, the higher the preoperative serum HBV-DNA level, the worse the long-term survival outcomes.

Objective:To investigate the clinical impact factors of liver regeneration after hemihepatectomy in patients with hepatocellular carcinoma (HCC).Methods:Patients who underwent hemihepatectomy due to HCC from Sep 2013 to Sep 2018 were included in the study. Liver volumes were calculated by perioperative simulations to analyze the influencing factors of postoperative liver regeneration, and to compare the albumin bilirubin (ABLI) score and the end-stage liver disease (MELD) score at weeks 1, 5, 9, and 13 after operation.Results:A total of 163 patients were included, of which 13 developed postoperative liver failure. The median liver regeneration rates at 1, 5, 9 and 13 weeks after operation were 22.0%, 32.2%, 33.7% and 35.4%, respectively. Multivariate analysis showed that remnant liver volume (RLV) <611.1 cm 3, %RLV and liver cirrhosis were the influencing factors of liver regeneration. ALBI score and MELD score were lower in the low regeneration group compared to the high regeneration group in the first 5 weeks after operation. Conclusion:RLV and cirrhosis are influential factors in postoperative liver regeneration. Liver regeneration proceeded rapidly within 1 week and slowed down until week 5.

Objective:To investigate the risk factors for overall survival in operable hepatocellular carcinoma with portal vein tumor thrombus (PVTT-HCC) patients and establish a scoring system.Methods:Survival data in 253 PVTT-HCC patients were retrospectively analyzed in Guangxi Medical University Affiliated Tumor Hospital. Survival curves were analyzed using the Kaplan-Meier method and log-rank test. Cox stepwise regression analysis was used to identify independent preoperative risk factors affecting overall survival. A prognostic scoring system based on independent risk factors and their relative coefficients was established to screen patients with greater hepatic resection benefits, and the identification ability of the model was based on ROC.Results:A total of 253 patients with PVTT-HCC were enrolled in this study, there were 222 males and 31 females, with a median age 44 years. The median survival time in all patients was (13.00±2.15) months. Rate of overall survival was 51.8% at 1 year, 25.0% at 3 years and 17.7% at 5 years. Multivariable Cox regression analyses showed four risk factors including: AST≥40 U/L, ALP (≥80 U/L), tumor number (>1), and incomplete tumor capsule. A prognostic scoring system was established based on these variables. The area under curve of the scoring system was 0.780 (95% CI: 0.715-0.845). Patients were classified as low- or high-risk group for hepatic resection depending on whether their score was <3 ( n=77) or ≥3 ( n=176), respectively. High-risk patients had a median survival of 10 months, compared to 29 months in low-risk patients. Low-risk patients also had better survival rates at 1 year (75.3% vs 41.5%), 3 years (47.6% vs 15.2%), and 5 years (34.7% vs 10.5%), P<0.05. Conclusion:A prognostic scoring system for hepatic resection in PVTT-HCC patients has been developed based entirely on preoperative variables. Using this system, patients belong to the low risk group have better prognosis after surgery, which can provide a basis for surgical treatment of PVTT-HCC patients.

Objective:To study the relationship between preoperative serum carbohydrate antigen 19-9 (CA19-9) levels and long-term prognosis after partial hepatectomy in patients with hepatocellular carcinoma (HCC).Methods:The clinical data of 1102 patients with HCC who underwent partial hepatectomy at the Affiliated Tumor Hospital of Guangxi Medical University from January 2012 to December 2017 were retrospectively analyzed. There were 960 males and 142 females, with an average age of 51 years. The X-tile software determined the best cut-off value of CA19-9 to be 55U/ml. The enrolled patients were then divided into the low-level (CA19-9≤55 U/ml, n=956) and high-level (CA19-9 >55 U/ml, n=146) groups. The Kaplan-Meier method was used to analyze survival, and the log-rank test was performed to evaluate survival rates. The prognostic risk factors of HCC were calculated by the Cox proportional hazards model. Results:The 1, 3, and 5-year survival rates for the low-level group were 85.0%, 68.2%, and 60.9%, respectively, which were significantly higher than those of the high-level group of 80.1%, 58.2%, and 47.0%, respectively ( P<0.05) . The 1, 3, and 5-year recurrence-free survival rates of the low level group were 60.5%, 44.6%, and 37.9% respectively, which were significantly higher than those in the high-level group of 53.4%, 33.3%, and 25.1%, respectively ( P<0.05). Cox regression analysis showed that patients with CA19-9 >55 U/ml ( HR=1.323, 95% CI: 1.070-1.636, P=0.010) had a higher risk of recurrence after hepatectomy, while patients with CA19-9 >55 U/ml ( HR=1.511, 95% CI: 1.163-1.964, P=0.002) had a poor prognosis after hepatectomy. Conclusions:Preoperative serum level of CA19-9>55 U/ml was an independent risk factor for survival and recurrence of HCC patients after partial hepatectomy. CA19-9 had a significant predictive value for prognosis of HCC patients who underwent partial hepatectomy.

ObjectiveTo investigate the safety and efficacy of re-hepatic resection (rHR) versus radiofrequency ablation (RFA) in the treatment of recurrent hepatocellular carcinoma (RHCC) in Asia through a meta-analysis. MethodsPubMed, CNKI, and Wanfang Data were searched for related studies published up to June 15, 2020. Two reviewers independently searched for the articles and extracted related data, and RevMan 5.4.1 was used to perform the meta-analysis. ResultsA total of 2 randomized controlled trials and 18 retrospective cohort studies met the inclusion criteria and involved 2903 patients with RHCC from Asian countries. The mortality rate in the perioperative period was 2% in the rHR group and 0 in the RFA group, and the incidence rate of perioperative complications was 22.4% in the rHR group and 3.3% in the RFA group. The 1-, 3-, and 5-year overall survival rates were 92.3%, 66.3%, and 51.1%, respectively, in the rHR group and 91.4%, 69.2%, and 39.9%, respectively, in the RFA group. The 1-, 3-, and 5-year disease-free survival rates were 67.9%, 48.3%, and 34.4%, respectively, in the rHR group and 57.5%, 27.9%, and 14.0%, respectively, in the RFA group. The Meta-analysis showed that there was no significant difference in overall survival rate between the two groups (hazard ratio ［HR］=089, 95% confidence interval ［CI］: 0.77-1.02, P=0.10), while the rHR group had a significantly higher disease-free survival rate than the RFA group (HR=0.79, 95% CI: 0.72-0.87, P＜0.001). ConclusionCurrent evidence shows that rHR may help to achieve a higher disease-free survival rate than RFA in the treatment of RHCC, while rHR and RFA have a similar overall survival rate.

Objective To study the correlation between serum prealbumin level before liver resection and prognosis of patients with primary hepatocellular carcinoma (HCC).Methods The clinical data of patients with HCC who underwent liver resection at the Affiliated Tumor Hospital of Guangxi Medical University from August 2007 to October 2016 were retrospectively analyzed.The previous albumin of 200 mg/L and the pre-albumin as predicted by the maximum selection rank statistic method were used as the bounding group,and reduced groups and the correlation between pre-operative serum pre-albumin levels and clinicopathological characteristics were analyzed.The Kaplan-Meier method was used to calculate the overall survival rate of patients with the different cutoff levels.The Cox proportional regression model was used to analyze,and cirrhosis,alpha-fetoprotein levels and Barcelona Clinic Liver Cancer staging were used to adjust the relationship between serum prealbumin and prognosis of liver resection for HCC patients.Analysis of stratified variables was performed and their interactions with serum prealbumin were analyzed.Results Of the 2 022 patients included in this study,there were 1 739 males and 283 females.Their age was 49.5 ± 11.2 years.The median follow-up was 37.4 months.The optimal cutoff value of prealbumin predicted by the maximum selection rank statistic method was 166 mg/L.Regardless of the cutoff values of previous albumin 200 mg/L or prealbumin 166 mg/L,multivariate analysis showed that preoperative serum prealbumin level was an independent prognostic risk factor for patients (P ＜0.05).The prognosis of patients with ＞200 mg/L (＞ 166 mg/L) serum prealbumin before surgery was significantly better than that of patients with ≤200 mg/L (≤166 mg/L) prealbumin,the differences were significant (all P ＜ 0.05).After adjusting for confounding factors,the prealbumin level correlated with prognosis of patients with HCC [cutoff value 200 mg/L:HR (95％ CI) was 1.59 (1.35-1.86),cutoff value 166 mg/L:HR (95％ CI) was 1.69 (1.44-1.98),all P ＜ 0.05].The results of stratified analysis showed that the relationship between prealbumin levels and the prognosis of HCC patients became more robust.Conclusions Preoperative serum prealbumin was an independent risk factor for prognosis of HCC patients,and it had predictive value on prognosis of HCC patients.

Objective:To analyze the impact of gender on prognosis in patients with primary hepatocellular carcinoma (HCC) after hepatectomy.Methods:The data of 1 796 patients with HCC who underwent liver resection at the Guangxi Medical University Cancer Hospital from January 2010 to December 2016 were retrospectively analyzed. There were 1 548 males and 248 females, the average age were 49.6 years. Patients were followed up for recurrence and survival. After propensity score matching, the postoperative survival rates of male and female patients were compared. Univariate and multivariate Cox regression was used to analyze independent factors affecting prognosis of patients with HCC after hepatectomy. The age and menopause were analyzed by subgroup analyses.Results:The 1-, 3- and 5-years cumulative overall and recurrence-free survival rates of male patients were significantly lower than that of female patients (all P<0.05). Multivariate analysis showed that female was an independent protective factor affecting postoperative recurrence ( HR=0.777, 95% CI: 0.615-0.982) and overall survival ( HR=0.669, 95% CI: 0.520-0.856). Using a cut-off value of 50 years old, the patients were divided into <50 years old ( n=915) and ≥50 years old ( n=881). In patients who were less than 50 years old, the 1-, 3- and 5-years cumulative overall and recurrence-free survival rates of male patients were significantly lower than those of female patients (all P<0.05). In patients ≥50 years old, there were no significant difference in the cumulative overall and recurrence-free survival rates between male and female patients (all P>0.05). Female patients were then divided into the postmenopausal group ( n=152) and the premenopausal group ( n=96). There were no significant differences in the cumulative overall and cumulative recurrence-free survival rates between the two groups ( P>0.05). Conclusion:The prognosis of female patients with HCC after hepatectomy was significantly better than that of male patients.

Objective:To explore the effects and the mechanism of metformin combined with celecoxib on the proliferation and apoptosis of hepatoma HepG2 and Huh7 cells.Methods:Hepatoma cells HepG2 and Huh7 were divided into control group, metformin group, celecoxib group and combination medication group, CCK-8 assay was used to detect cell proliferation; Hoechst33258 staining method was used to investigate the cell apoptosis; wound healing test was used to detect cells migration ability; Transwell invasion chamber test was used to detect cell invasion ability; Western blotting was used to detect the expression of AMPK, PI3K, Akt, mTOR.Results:After metformin and celecoxib treatment, HepG2 and Huh7 cells were gradually contracted, disintegrated and more apoptotic cells were noticed, and cell proliferation was significantly inhibited. The wound healing test results showed that the cell migration was significantly decreased ( P<0.05) under metformin and celecoxib treatment. The results of the transwell invasion chamber test showed that the metformin and celecoxib treatment inhibited the invasion of HepG2 and Huh7 cells ( P<0.05). The expression levels of AKT, AMPK, and mTOR were decreased in HepG2 cells in the combinational treatment group, and the expression level of PI3K was decreased and then increased; the expression levels of AKT, AMPK, PI3K, and mTOR in Huh7 cells were decreased. Conclusions:Metformin can cooperate with celecoxib to enhance the inhibitory effect on the proliferation, migration and invasion of HepG2 and Huh7 cells. The mechanism may be related to the inhibition of the expression of mTOR signaling pathway.