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Objective: To compare the postoperative liver function injury condition in patients with intermediate-and advanced-stage hepatocellular carcinoma (HCC) treated with hepatic artery infusion chemotherapy (HAIC) and hepatic artery chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and multi-target tyrosine kinase inhibitors (TKIs). Methods: Patients with intermediate-and advanced-stage HCC who were admitted and treated with HAIC/TACE+ICIs+TKIs therapy at Nanfang Hospital of Southern Medical University from January 2019 to November 2021, with follow-up up to July 2023, were retrospectively enrolled. The results of liver function tests within one week before interventional surgery and on the first day after surgery were recorded. The degree of postoperative liver injury was graded according to the common terminology criteria for adverse events 5.0 (CTCAE 5.0). The treatment efficacy was evaluated according to RECIST 1.1 criteria. Measurement data were compared between groups using a t-test or a non-parametric rank sum test. Enumeration data were compared between the groups using the χ (2) test or Fisher's exact probability method. The survival condition differences were analyzed by the log-rank method. Results: This study included 82 and 77 cases in the HAIC and TACE groups. There were no statistically significant differences between the two groups of patients in terms of gender, age, physical condition score, number of tumors, presence or absence of liver cirrhosis, Child-Pugh grade, albumin-bilirubin (ALBI) grade, and combined ICIs and TKIs . The HAIC group had later tumor staging, a greater tumor burden, poorer liver reserve function, and a larger proportion of patients in stage C (81.7% vs. 63.6%), χ (2)=6.573, P = 0.01). There were 53 cases (64.6% vs. 32.5%) with a maximum tumor diameter of ≥ 10cm, χ (2)=16.441, P < 0.001), and more patients had a retention rate of ≥ 10% for indocyanine green (ICG) at 15 minutes (68.3% vs. 51.9%, P = 0.035). The postoperative incidence rate of increased levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin was significantly lower in the HAIC group than that in the TACE group (28.0% vs. 63.6%, χ (2)=20.298, P < 0.001, 54.9% vs. 85.7%, χ (2)=17.917, P < 0.001;40.2% vs. 55.8%, χ (2)=3.873, P = 0.049). The number of patients with postoperative ALBI grade 3 was significantly lower in the HAIC group than that in the TACE group (6.1% vs. 16.9%, χ (2)=4.601, P = 0.032). There was no statistically significant difference in the incidence rate of postoperative hypoalbuminemia, activated partial thromboplastin time, or increased international standardized ratio between the two groups of patients. There was no statistically significant difference in median progression-free survival (7.3 months vs. 8.2 months, P = 0.296) or median overall survival (16.5 months vs. 21.9 months, P = 0.678) between the two groups of patients. Conclusion: The incidence rate of postoperative liver injury is higher in patients with intermediate-and advanced-stage HCC treated with TACE combined with ICIs and TKIs than in patients with HAIC combined with ICIs and TKIs.

Objective: To explore the clinical effect of microwave ablation in the treatment of early small liver cancer (≤3 cm). Methods: 103 cases with small liver cancer (tumor number < 3 and maximum tumor diameter < 3 cm) who underwent microwave ablation from November 2016 to November 2018 were retrospectively collected. The rate of residual lesions, recurrence rate one-year after the operation, and surgical complications were observed and grouped according to tumor size (< 2 cm and≥2 cm group) and tumor numbers (solitary and 2 ~ 3 lesion groups). The therapeutic effects of each group were compared and analyzed. Results: The tumor residual rate and one-year recurrence rate of small liver cancer after microwave ablation were 11.7% and 35.0%, respectively. The post-ablation syndrome incidence rate was 52.4%, with no serious adverse events. Compared with tumors < 2 cm, patients with≥2 cm had a higher postoperative residual rate ( χ (2) = 7.651, P = 0.006), and the one-year recurrence rate of more solitary nodular tumors was lower ( χ (2) = 10.125, P = 0.001). Conclusion: Microwave ablation is a safe and effective treatment for early small liver cancer, and it is more effective for small solitary nodules (< 2 cm).

Molecular targeted drugs are the first choice for systemic treatment of liver cancer. In the past decade, several anti-liver cancer targeted drugs have been launched. More recently, immunotherapy has become a dazzling nova in the field of systemic treatment of liver cancer. Nivolumab and pembrolizumab have been approved as second-line treatments for patients with advanced hepatocellular carcinoma treated with sorafenib. However, the effect of single-agent treatment is always unsatisfactory in advanced liver cancer. An increasing number of evidences suggests that molecular targeted drugs have important immunomodulatory effects for liver cancer, and several targeted combined immunotherapies have also shown promising clinical effectiveness. This paper reviews the immunomodulatory effects of several molecular targeted drugs in the field of liver cancer.

Objective: The aMAP score is a hepatocellular carcinoma (HCC) risk prediction model based on an international cooperative cohort, which can be applied to various liver diseases. The aim of this study is to use the aMAP score to stratify the risk of HCC in patients with chronic liver disease (combined or non-combined metabolic diseases) admitted to People's Hospital of Yudu County, Ganzhou City, Jiangxi Province, in order to guide personalized HCC screening. Methods: The demographic information, laboratory test results (platelets, albumin, and total bilirubin) and combined disease information of patients with chronic liver disease who were admitted to People's Hospital of Yudu from January 2016 to December 2020 were collected, and the aMAP score was calculated to stratify HCC risk in this population. Results: A total of 3629 cases with chronic liver disease were included in the analysis, including 3 452 (95.1%) cases with hepatitis B virus (HBV) infection, 177 (4.9%) cases with fatty liver, and 22 (0.6%) cases with HBV infection and fatty liver. There were 2 679 (73.8%) male and the median age was 44 (35, 54). In the overall population, low, medium and high risk of HCC accounted for 52.6%, 29.0%, and 18.4% respectively. In the HBV-infected population, the proportion of high risk of HCC was significantly higher than that of fatty liver (18.9% vs. 9.6%, P = 0.001). The proportion of chronic liver disease patients with combined hypertension or diabetes was significantly higher than that of those with non-combined metabolic diseases (combined hypertension: 32.3% vs. 17.9%, P < 0.001; combined diabetes: 36.5% vs. 18.1%, P < 0.001). Moreover, the proportion of high-risk population with two metabolic diseases was significantly higher than that with one and no metabolic diseases (40.9% vs. 31.8% vs. 17.7%, P < 0.001). Conclusion: The aMAP score can be used as a simple tool for HCC screening and management of chronic liver disease in primary hospitals, and it is helpful to improve the personalized follow-up management system of chronic liver disease population. Chronic liver disease patients with metabolic diseases have a higher risk of HCC, and people with high risk of HCC should be given special priority in follow-up visits, so as to improve the rate of HCC early diagnosis and reduce the mortality rate.

The comprehensive management of hepatocellular carcinoma (HCC) is a complete, dynamic and personalized process. Therefore, how to scientifically determine the HCC high-risk/extremely high-risk populations and develop a stratified monitoring plan is the key link to early detection, diagnosis and improvement of overall survival. In addition, accurately identifying high-risk/extremely high-risk groups based on the HCC risk prediction model, and applying it to establish an integrated hospital-community pyramid for HCC screening through the implementation of interdisciplinary scientific management and treatment may ultimately reduce HCC-related mortality rate.

Objective: To analyze the prognostic factors on multidisciplinary team patients for diagnosis, and treatment of hepatocellular carcinoma. Methods: This retrospective study enrolled 132 HBsAg positive patients with HCC. MDT diagnostic approach was conducted at our hospital between 1 January 2015 and 31 December 2015, and all patients were followed up to 31 December 2017. Groups were arranged according to variables such as Barcelona stage, MDT compliance, and multidisciplinary combination therapy. TTP and OS were statistically analyzed. Results: The survival of the MDT compliance group was better than the non-compliance group. The difference in survival curves was statistically significant ( χ (2) = 4.062, P < 0.05). The 1- and 2-year survival rates of the former group were 72.0%, 60.9%, and the latter was 64.3%, 40.3%. The survival of the combined treatment group was better than the non-combination group. The survival curves of the two groups were statistically significant ( χ (2) = 9.502, P < 0.05), and they were independent influencing factors of survival ( HR = 0.451, 95% CI , 0.210-0.968). The 1- and 2-year survival rates of the former group were 82.2% and 75.4%, and the latter was 63.1% and 44.6%. The median survival time of the follow-up group was 29.4 months, and the non-compliance and the uncombined group were 17.0 months. The difference was statistically significant ( χ (2) = 13.336, P < 0.001). The median tumor progression time was 15.7 months in the combination group and 10.1 months in the non-compliance group ( χ (2) = 7.263, P < 0.05). Conclusion: An advanced MDT compliance with implementation of multidisciplinary combination therapy may help to improve the prognosis of MDT patients with liver cancer.

Objective: To study the effect of ozonized saline on the activation of the Keap1-Nrf2-ARE signaling pathway in rat liver cells., Methods: Twenty male Sprague-Dawley rats were randomly divided into ozonized saline (OS) group, model group, ozonized saline control (OSC) group and normal control (NC) group. The rats in OS group and model group were intravenously administered with OS or oxygen saline (5 ml/kg) respectively, once a day for 15 days, and then intraperitoneally injected with CCl4 dissolved in oliver oil. The rats in OSC group were pretreated with OS for 15 days. The rats in NC group were fed normally for 15 days. On the 16th day, the rats in OSC group and NC group were intraperitoneally injected with oliver oil (2 ml/kg) without CCl4. After 24 hours of CCl4 or olive oil intraperitoneal injection, the serum levels of alanine transaminase (ALT) and aspertate aminotransferase (AST) were measured. The liver tissues were also collected for detection of total anti-oxygen capability (TAOC), glutathione (GSH), catalase (CAT), Glutathione peroxidase (GPx). Western Blot was used to detect Nrf2 and immunofluorescence staining assay to display intracelluar distribution of Nrf2., Results: Compared with the rats in model group,the serum ALT and AST levels of rats in OS group were significantly lower (P < 0.01) ,which were (1240.4 ± 188.2) U/L and (1245.4 ± 176.9) U/L vs (539.8 ± 175.3) U/L and (546.0 ± 130.2) U/L, and the TAOC, CAT, GPx and GSH activity of rats in OS group were significantly higher, which were (0.72 ± 0.24) U/mg, (1.05 ± 0.21) mg/g, (676.9 ± 115.1) U/mg and (45.2 ± 14.3) U/mg vs (1.37 ± 0.19) U/mg, (2.23 ± 0.55) mg/g, (1024.6 ± 162.9) U/mg and (68.2 ± 9.9) U/mg, respectively. In contrast with NC group, pretreatment of OS in OSC group elevated TAOC, CAT, GPx and GSH activity (P < 0.01 or P < 0.05). Ozonized saline can strengthen the Nrf2 expression in liver cells., Conclusion: Preconditioning injection of ozonized saline can reduce rat's liver injury induced by CCl4. The ozonized saline, as a novel Nrf2 activator, can reduce the oxidative damage of radical oxygen species (ROS) and the deleterious substance by activating the Keap1-Nrf2-ARE signaling pathway and its downstream genes expression.

Objective: HBsAg loss is rare in chronic hepatitis B patients, even in the patients with long-term nucleos(t)ide analogue therapy; therefore information about serum HBsAg kinetics will be of value in understanding this unusual occurrence., Methods: Forty-five consecutive patients were studied, which were all HBeAg positive and never had antiviral therapy prior to lamivudine treatment; they then achieved rapid and good viral responses (defined as undetectable HBV DNA [Roche Lightcycler, less than 1000 copies/ml] at treatment week 24 and they remained so until week 156). Abbott Architect HBsAg assay was used to quantify serum HBsAg and HBV genotypes were determined by direct sequencing., Results: Twenty-six (57.8%) patients had HBeAg loss during the observation and one patient had HBsAg loss following his HBeAg seroconversion. Serum HBsAg levels decreased to 39.5% (median) of their baseline values at week 12, but no further significant reductions of serum HBsAg were found afterwards. Changes of serum HBsAg were comparable between patients with or without HBeAg loss. Serum HBsAg levels at their baselines were higher in HBV genotype B (HBV/B, n = 21) patients than in genotype C (HBV/C, n = 24) patients. HBV/B patients achieved many more HBsAg reductions than HBV/C ones (75.5 vs. 26.0%, median, P less than 0.05) in the first 12 treatment weeks, however HBsAg levels at week 156 were comparable between these two subgroups. HBsAg changes mainly showed two distinct patterns: a biphasic pattern (HBsAg levels were less than 60% of baseline ones at week 12 and 24, n = 25) and a maintaining pattern (HBsAg levels were greater than 80% of the baseline ones at week 12 and 24, n = 14). Logistic regression analysis showed that low serum HBsAg at baseline (odds ratio 0.020, 95% confidence interval 0.002-0.743, P less than 0.05) and HBV/C infection (odds ratio 8.206, 95% confidence interval 1.070-62.948, P less than 0.05) were the determinants of the occurrences of the maintaining pattern., Conclusion: In patients we examined, their HBsAg changes were mainly presented as either a biphasic pattern or a maintaining pattern, which were associated with HBV genotypes (B/C) but not with HBeAg loss. This might explain that why HBsAg loss is a rare occurrence even with long-term lamivudine therapy.

Objective: To study the effects of genotypes of HBV and HBeAg on the response to PEG-interferon alpha (PEG-IFN) in chronic hepatitis B (CHB) patients., Methods: PCR-RFLP and S gene sequencing were conducted in 42 CHB patients., Results: The sustained response (SR) rates were 66.7% in genotype B and 27.3% in genotype C group. The P value was 0.039 by the Pearson Chi-square test, while it was 0.06 by the Fisher's exact test. The results suggested a trend that patients with genotype B HBV compared to genotype C had better SR to PEG-IFN therapy, although the difference was not significant. Results also showed that SR rate in patients with HBeAg-negative CHB (7/8 87.5%) was significantly higher than that in HBe+ CHB patients (8/21 38.1%, P < 0.05)., Conclusion: Our results indicate that HBV genotype and HBeAg, especially the later, are main factors for predicting PEG-IFN therapy response in CHB patients.

Objective: To investigate the efficacy of interferon-alpha (IFN-alpha) therapy for HBeAg-negative chronic hepatitis B., Methods: Sixty-five Chinese HBeAg-negative chronic hepatitis B patients were treated with 5 MU recombinant rIFN-alpha 1b subcutaneously thrice weekly for 5 to 24 months, followed by 12 months of treatment-free follow-up; one hundred and eighty-eight Chinese HBeAg-positive patients served as controls. For each patient, serum alanine transaminase (ALT) was measured biochemically and serum HBV DNA level was detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay every 1 to 3 months during therapy and during the follow-up period. HBeAg loss (only for HBeAg-positive cases), HBV DNA undetectable, and ALT normalization: the three together were considered a combined response., Results: Rates of combined response were similar in HBeAg-negative patients (58.5%, 38/65) or HBeAg-positive ones at the end of treatment (weighted chi square test, chi2 = 1.878, P<0.05), but were higher at the end of the follow-up period in the HBeAg-negative cases (75.4%, 49/65) (weighted chi square test, chi2 = 4.796, P<0.05). Furthermore, relapse rates at the end of the follow-up period, were also similar in HBeAg-negative patients (15.8%, 6/38) or HBeAg positive (chi2 = 0.205, P>0.05). Combined response was achieved at a median of 6.0 months (2-16 months) of treatment course in HBeAg-negative patients while at a median of 6.0 months (1-22 months) in HBeAg-positive cases (Z = -0.186, P>0.05, by the Wilcoxon rank sum test). The only factor predictive of combined response, by binary logistic regression analysis, was inflammatory activity in the liver biopsy. Gender, age, baseline ALT level, baseline HBV DNA level, and anti-HBe were not predictive factors., Conclusion: Interferon-alpha therapy induces a similar primary and sustained response in HBeAg-negative and in HBeAg-positive chronic hepatitis B patients.

Objective: To investigate the clinical effect of oxymatrine on chronic viral hepatitis B and to look for new methods for treating hepatitis B., Methods: Multi-center, controlled study was used. In this study, 196 patients were allocated to oxymatrine, oxymatrine with Ara-AMP, IFN-a1b, and glucose groups to observe ALT, AST and viral marker changes., Results: At the end of treatment, the rate of normal ALT, the negative rate of HBV DNA and HBeAg, and the positive rate of HBeAb were similar in oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b groups. It was higher than that of glucose group. After 12 months follow up, the total effective rate is 40.8%, 60.8% and 43.1% in oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b groups, respectively., Conclusions: Oxymatrine, oxymatrine with Ara-AMP, and IFN-a1b are effective to treat hepatitis B with a good negative rate of HBV DNA and HBeAg and positive rate of HBeAb.