The Association of Glycemic Index, Glycemic Load, and Daily Carbohydrates Intake with the Risk of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Glycemic index (GI), glycemic load (GL) and daily carbohydrates intake have been associated with a variety of cancers, but their implications in hepatocellular carcinoma (HCC) remain controversial. The purpose of our study is to investigate the association of GI, GL and daily carbohydrates intake with the risk of HCC. Methods: Systematic searches were conducted in PubMed, Embase and Web of Science until November 2020. According to the degree of heterogeneity, random effect model or fixed effect model was chosen to obtain the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Results: Four cohort studies and three case-control studies were eventually included. The pooled results showed no significant association of GI (RR = 1.11, 95% CI = 0.80-1.53), GL (RR = 1.09, 95% CI = 0.76-1.55), and daily carbohydrates intake (RR = 1.09, 95% CI = 0.84-1.32) with the risk of HCC in the general population. Subgroup analysis revealed that in hepatitis B virus (HBV) or/and hepatitis C virus (HCV)-positive group, GI was irrelevant to the risk of HCC (RR = 0.65, 95% CI = 0.32-1.32), while a high GL diet was associated with a higher risk of HCC (RR = 1.52, 95% CI = 1.04-2.23). In contrast, in HBV and HCV-negative group, both GI (RR = 1.23, 95% CI = 0.88-1.70) and GL (RR = 1.17, 95% CI = 0.83-1.64) were not associated with the risk of HCC. Conclusion: A high GL diet increases the risk of HCC in those with viral hepatitis. A low GL diet is recommended for them to reduce the risk of HCC.

Prognostic value of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND: Preliminary studies have suggested that soluble programmed death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) have prognostic implications in many malignant tumors. However, the correlation between sPD-1/sPD-L1 level and prognosis of hepatocellular carcinoma (HCC) is still unclear. METHODS: We searched several electronic databases from database inception to October 7, 2021. Meta-analyses were performed separately for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), time to progression (TTP), and tumor-free survival (TFS). Random effects were introduced to this meta-analysis. The correlation between sPD-1/sPD-L1 level and prognosis was evaluated using hazard ratios (HRs) with 95% confidence intervals (95%CIs). RESULTS: A total of 11 studies (1291 patients) were incorporated into this meta-analysis, including seven on sPD-L1, two on sPD-1, and two about both factors. The pooled results showed that high sPD-L1 level was associated with worse OS (HR = 2.46, 95%CI 1.74-3.49, P < 0.001; I2 = 31.4, P = 0.177) and poorer DFS/RFS/TTP/TFS of patients with HCC (HR = 2.22, 95%CI 1.47-3.35, P < 0.001; I2 = 66.1, P = 0.011), irrespective of method of detection, study type, treatment, cut-off value and follow-up time. In contrast, the level of sPD-1 was not correlated to the OS (HR = 1.19, 95%CI 0.55-2.56, P = 0.657) and DFS/TFS of patients with HCC (HR = 0.94, 95%CI 0.36-2.49, P = 0.906). CONCLUSION: sPD-L1 rather than sPD-1 could be a good predictor for recurrence and survival after treatment for HCC. More high-quality prospective studies are warranted to assess the prognostic value of sPD-1 or sPD-L1 for HCC.

Comments on validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease.

To evaluate and predict liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), several non-invasive scoring systems were built and widely used in the progress of diagnosis and treatment, which showed great diagnostic efficiency, such as aspartate aminotransferase to platelet ratio index, fibrosis-4 index, body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes score and NAFLD fibrosis score. Since the new concept of metabolic associated fatty liver disease (MAFLD) was proposed, the clinical application value of the non-invasive scoring systems mentioned above has not been assessed in MAFLD. The evaluation of the diagnostic performance of these non-invasive scoring systems will provide references for clinicians in the diagnosis of MAFLD.

Efficacy and Safety of Aspirin for Prevention of Hepatocellular Carcinoma: An Updated Meta-analysis.

Background and Aims: Previous meta-analyses have shown that aspirin use may reduce the risk of hepatocellular carcinoma (HCC). However, the optimal dose, frequency, and duration of aspirin use or the safety and efficacy of aspirin in target populations for HCC prevention remain unclear. The study aim was to investigate the efficacy and safety of aspirin for prevention of HCC. Methods: Publications were retrieved by a comprehensive literature research of several databases. Based on a random-effects model, hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship between aspirin use and HCC risk was assessed with a restricted cubic spline model. Results: Twenty-two studies were included in the meta-analysis. Aspirin use was associated with a reduced risk of HCC (HR=0.64, 95% CI: 0.56-0.75). The effect was robust across sex and age; however, women and the non-elderly had the greatest benefit from aspirin use. The preventive effect was well reproduced in those with comorbidities. Daily use and long-term use of aspirin appeared to offer greater benefits. Aspirin 100 mg/d was associated with maximum reduction of HCC risk. Aspirin use did slightly increase the risk of bleeding (HR=1.14, 95% CI: 1.02-1.27). Conclusions: Our meta-analysis confirmed that use of aspirin significantly reduced the incident risk of HCC. Regular and long-term aspirin use offers a greater advantage. Aspirin use was associated with an increased risk of bleeding. We recommend 100 mg/d aspirin as a feasible dose for further research on primary prevention of HCC in a broad at-risk population.

The Prognostic Value of Natural Killer Cells and Their Receptors/Ligands in Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Background: Natural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear. Methods: Several electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI). Results: 26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57-0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57+ NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56+ NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear. Conclusion: NK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.

Sex and regional disparities in incidence of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis.

BACKGROUND: Recent studies have identified an increased risk of hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH). Sex and regional disparities in incidence of HCC in AIH continue to be reported worldwide. Nevertheless, the magnitude of this gap remains unknown. METHOD: We searched several databases including PubMed, Embase, Web of Science, Cochrane Library, Wanfang Data, CNKI and SinoMed. Incidence rates of HCC in AIH were combined and analyzed following the EBayes method. Incidence rate ratios were pooled to assess the sex differences. The impact of population difference, sex, age, cirrhotic condition was further analyzed with subgroup analysis and linear regression analysis. RESULT: 39 studies meeting our eligibility criteria were chosen for the analysis. The pooled incidence rate of HCC in AIH was 3.54 per 1000 person years (95% CI 2.76-4.55). Pooled IRR for the risk of HCC in male AIH patients compared to female was 2.16 (95% CI 1.25-3.75), with mild heterogeneity among studies. The pooled HCC incidence rate in AIH by continents was as follows: Europe 2.37 per 1000 person-years (95% CI 1.45-3.88), Asia 6.18 per 1000 person-years (95%CI 5.51-6.93), North America 2.97 per 1000 person-years (95%CI 2.40-3.68), Oceania 2.60 (95%CI 0.54-7.58). The pooled HCC incidence rate in AIH-related cirrhosis by continent was as follows: Europe 6.35 per 1000 person-years (95%CI 3.94-10.22), Asia 17.02 per 1000 person-years (95%CI 11.18-25.91), North America 10.89 per 1000 person-years (95%CI 6.69-17.74). CONCLUSION: A higher HCC incidence in AIH was observed among male and in Asian populations. Cirrhosis status at AIH diagnosis is significantly associated with an increased incidence rate for HCC, and routine HCC surveillance is recommended for patients with AIH cirrhosis, especially for those in Asia.

Clinical Benefit of Antiviral Agents for Hepatocellular Carcinoma Patients With Low Preoperative HBV-DNA Loads Undergoing Curative Resection: A Meta-Analysis.

BACKGROUND AND AIMS: The clinical benefit of adjuvant antiviral therapy after curative therapy for HCC in patients with high preoperative HBV-DNA loads has been studied widely but that in patients with low preoperative HBV-DNA loads remains controversial. The purpose of this study was to determine the effect of antiviral treatment prophylaxis on HBV reactivation, overall survival (OS), and postoperative liver function in patients with low preoperative HBV-DNA levels undergoing curative resection. METHODS: A meta-analysis was conducted by searching Web of Science, PubMed, Embase, and Cochrane Library until May 2020. We used REVMAN for data analysis and completed the study under the PRISMA guidelines. RESULTS: Three randomized trials and seven cohort studies, comprising of 1,131 individuals, were included in the meta-analysis. Antiviral treatment significantly reduced the rate of HBV reactivation after curative treatment of HCC, with a pooled risk ratio of 0.12 (95% c.i. 0.07 to 0.21; P < 0.00001). The trials were consistently favorable for the antiviral group, with a pooled hazard ratio of 0.52 (95% c.i. 0.37 to 0.74; P = 0.0002) in respect of OS rate. However, by pooling the data from studies that reported ALT on the 30th day postoperatively, the result didn't reach statistical significance (mean difference -4.38, 95% c.i. -13.83 to 5.07; P = 0.36). The I² values of the heterogeneity test for the above three comparisons are zero. CONCLUSION: Antiviral therapy during curative resection is effective in reducing HBV reactivation and improving OS rate in HCC patients with low viral load.

RECK expression is associated with angiogenesis and immunogenic Tumor Microenvironment in Hepatocellular Carcinoma, and is a prognostic factor for better survival.

Angiogenesis and immunosuppression have been described as closely related processes that can occur in parallel. As an inhibitor of matrix metalloproteinase, whether the level of reversion-inducing cysteine-rich protein with Kazal motifs (RECK) in hepatocellular carcinoma (HCC) reflects a link between angiogenesis and immunosuppression is still unknown. We analyzed RNA expression, immune infiltration and survival of HCC from The Cancer Genome Atlas databases. Immune scores and stromal scores were calculated based on the ESTIMATE algorithm to quantify the immune and stromal components in HCC. The association between RECK and clinicopathological features was further investigated by immunohistochemistry on tissue microarray. We found that the prognosis of patients with high RECK expression was significantly better than that of patients with low RECK expression. High RECK expression was associated with high ESTIMATE Score, recruitment of more tumor-infiltrating lymphocytes, low tumor purity, and high PD-L1 expression. In addition, positive RECK expression was associated with a lower incidence of vascular invasion and recurrence, a lower level of alpha fetoprotein (AFP) and microvessel density and a better tumor differentiation. Multivariate analyses revealed that reduced RECK expression was an independent prognostic factor for recurrence and poor prognosis. In conclusion, high RECK expression reflects an immunogenic and hypovascularity status in HCC. RECK is a promising prognostic marker for survival of HCC and may act as a complementary indicator for patients to receive anti-angiogenic therapy or immunotherapy.

Development and clinical application of a length-adjustable water phantom for total body irradiation.

A new type of water phantom which would be specialised for the absorbed dose measurement in total body irradiation (TBI) treatment is developed. Ten millimetres of thick Plexiglas plates were arranged to form a square cube with 300 mm of edge length. An appropriate sleeve-type piston was installed on the side wall, and a tabular Plexiglas piston was positioned inside the sleeve. By pushing and pulling the piston, the length of the self-made water phantom could be varied to meet the required patients' physical sizes. To compare the international standard water phantom with the length-adjustable and the Plexiglas phantoms, absorbed dose for 6-MV X ray was measured by an ionisation chamber at different depths in three kinds of phantoms. In 70 cases with TBI, midplane doses were metered using the length-adjustable and the Plexiglas phantoms for simulating human dimensions, and dose validation was synchronously carried out. There were no significant statistical differences, p > 0.05, through statistical processing of data from the international standard water phantom and the self-designed one. There were significant statistical differences, p < 0.05, between the two sets of data from the standard and the Plexiglas one. In addition, the absolute difference had a positive correlation with the varied depth of the detector in the Plexiglas phantom. Comparing the data of clinical treatment, the differences were all <1 % among the prescription doses and the validation data collected from the self-design water phantom. However, the differences collected from the Plexiglas phantom were increasing gradually from +0.77 to +2.30 % along with increasing body width. Obviously, the difference had a positive correlation with the body width. The results proved that the new length-adjustable water phantom is more accurate for simulating human dimensions than Plexiglas phantom.

Postoperative intraportal vein antieoagulation in the prevention of portal vein thrombosis in portal hypertensive patients / 中国普通外科杂志

Objective To investigate the clinical significance of intraportal vein anticoagulation for the prevention of portal vein thrombosis after portaazygous devascularization and splenorenal shunt. Methods In this study 67 patients of portal hypertension undergoing surgery were randomly divided into two groups,receiving respectively intraportal vein heparin injection by 100 U?kg~(-1)?d~(-1)?7 d in group A (32 patients)and placebo in group B(35 patients).Portal vein thrombosis,the recurrent bleeding after operation and portal hypertensive gastropathy were compared between the two groups.Results The occurrence of portal vein thrombosis after operation in group A(0)was significantly lower than that in group B(20%,X~2=5.169,P