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Background: Artificial intelligence (AI) has been widely applied in the diagnosis and therapy of chronic liver disease (CLD), but there is currently little insight into the trials registered on ClinicalTrials.gov. Thus, this cross-sectional study was focused on analyzing the progress in the use of AI in CLD., Methods: Registered trials of AI applied in CLD on ClinicalTrials.gov were searched firstly. All available information was downloaded to Excel (Microsoft Excel, Rong, Rong, China), and duplicates were removed. We extracted the data of the included trials, then analyzed the characteristics of them finally., Results: Up to the 27th of May 2021, 6835 trials were identified following an initial search, and 20 registered trials were included after screening for inclusion and exclusion criteria. Among those trials, hepatocellular carcinoma (HCC, 40.0%) and nonalcoholic fatty liver disease (NAFLD, 20.0%) were the most widely applied CLDs for AI. Trials started in 2013 until 2021, with 17 trials (85%) registered after 2016. There was a large trend in trial enrolment, with 40% of them including samples more than 500. Five trials (25%) have been completed, but only one of these had available results. The most frequent sponsors and collaborators were both hospitals at 55%, followed by universities at 35% and institutes at 11%, respectively. Of the 20 trials included, 35% (7 trials) were interventional trials and 65% (13 trials) were observational trials. Among 7 interventional trials, most trials were for diagnosis purpose (42.86%, 3 trials); 4 trials (57.14%) were randomized; 3 trials (42.86%) applied behavioral intervention, 1 trial (14.29%) was in device intervention, 2 trials (28.57%) were in diagnostic test, and 1 trial intervention was unknown. Among 13 observational trials, 8 (61.54%) were cohort studies; 6 (46.15%) were prospective studies, 4 (30.77%) were retrospective studies, 2 (15.38%) were cross-sectional studies, and 1 (7.69%) did not involve a temporal perspective., Conclusion: The study is the first to focus on AI registration trials in CLD, which will aid relevant scholars in understanding the current state of the subject. This study demonstrates that additional research on AI used in the diagnosis and treatment of CLD is required, and timely publication of accessible results from registered trials is essential., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Gezhi Zheng et al.)

Purpose: Monocarboxylate transporter 4 (MCT4) is a critical component in the glycolytic metabolism of cancer cells, and is also important for malignant behavior. We investigated the expression profile of MCT4, its prognostic value in hepatocellular carcinoma (HCC) patients, its role in HCC cell proliferation and metastasis, and associated initial molecular mechanism., Methods: MCT4 expression was examined through immunohistochemical staining of pathological specimens from 318 HCC patients who had undergone hepatectomy. The HCC cell lines were used to validate the relationship between MCT4 expression and cell proliferation, migration, and invasion., Results: The results show that high MCT4 expression is indicative of elevated alpha fetoprotein levels and larger tumor size, which leads to poorer disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis shows that MCT4 expression is an independent prognostic factor for DFS and OS in HCC patients. In 91 recurrent HCC patients who underwent transarterial chemoembolization (TACE) treatment, low MCT4 expression predicted an effective treatment response and improved OS. Furthermore, in cell line experiments with MCT4 siRNA, cancer cell proliferation, migration, and invasion were closely correlated with the MCT4 expression. Knockdown of MCT4 was associated with down-regulation of phosphorylated AKT and HIF-1α., Conclusions: MCT4 expression can predict survival and TACE treatment response for HCC patients. Furthermore, MCT4 plays an important role in HCC cell proliferation, migration, and invasion. The inhibition of MCT4 can induce inactivation of HIF-1α and inhibit phosphorylation of AKT. MCT4 may be a potential therapeutic target for the treatment of HCC.

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus formation in the main vasculature is extremely poor. Sorafenib combined with transarterial chemoembolization is a novel treatment approach for advanced HCC. In this study, we report two HCC patients with inferior vena cava tumor thrombus who underwent the combination treatment. The overall survival times for these two patients were 44 months and 35 months, respectively. Our report suggests that sorafenib combined with transarterial chemoembolization may be a viable choice for patients with advanced HCC even with inferior vena cava tumor thrombus. Further studies are required to verify the efficacy and safety of this combination therapy for patients with advanced HCC with inferior vena cava tumor thrombus.

Objective: To evaluate the efficacy and safety of percutaneous radiofrequency ablation (PRFA) and combined with other minimally invasive treatments for recurrent hepatocellular carcinoma (RHCC) after hepatectomy., Methods: Eighty-four patients with RHCC after hepatectomy who were treated with PRFA or combined with other minimally invasive therapies between August 1999 and February 2008 were analyzed retrospectively., Results: There was no treatment related mortality in the study population, and the morbidity was 2.4% (2/84). The complete ablation rate was 94.0% (79/84), and the 1-, 3- and 5-year overall survival rates were 74.9%, 54.9% and 48.2%, respectively. The 1-, 3- and 5-year overall survival rates of patients with recurrent interval after hepatectomy less than 1 year and over 1 year were 72.1%, 36.2%, 24.2% and 76.8%, 70.6% and 65.1%, respectively (P = 0.040). The 1-, 3- and 5-year overall survival rates of patients with tumor size 3 cm were 83.2%, 67.7%, 67.7% and 59.1%, 24.2%, 12.1%, respectively (P = 0.003). The 1-, 3- and 5-year overall survival rates of patients treated with PRFA alone and combined with percutaneous ethanol injection (PEI) were 66.7%, 33.3%, 22.2% and 76.5%, 57.3%, 57.3%, respectively (P = 0.017). The 1-, 3- and 5-year overall survival rates of patients treated with PRFA alone and combined with transcatheter hepatic arterial chemoembolization (TACE) were 55.6%, 24.7%, 24.7% and 81.6%, 66.0%, 57.5%, respectively (P = 0.001)., Conclusions: PRFA is an effective and safe treatment for RHCC, and tumor size and recurrent interval after hepatectomy are important prognostic factors. Combination with PEI or TACE may improve the efficacy of PRFA for treatment of RHCC.

Objective: To analyze the short-term and long-term effectiveness of radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC)., Methods: The clinical data of 114 HCC patients, 104 males and 10 females, aged 55 (30 - 81), treated by RFA combined with TACE and followed up for 20 (1 - 82) months were analyzed., Results: Complete necrosis was achieved in 101 patients (88.6%). 10 patients showed incomplete necrosis and 3 patients showed new neoplasm, and they all underwent repeated RFA or TACE. No therapy-relative death was found. The overall 1-, 2-, 3-, 4-, and 5-year survival rates were 90.4%, 82.6%, 73.2%, 63.5%, and 49.1%respectively. The 1-, 2-, 3-, 4-, and 5-year tumor progression-free survival rates were 77.1%, 64.6%, 54.6%, 46.8%, and 36.4% respectively. The overall 1-, 2-, 3-, 4-, and 5-year survival rates for the tumors with the size < or = 5 cm and the tumors with the size of 5.1 - 7 cm were 95.5%, 84.6%, 73.1%, 61.5%, and 50.6% and 80.2%, 64.9%, 56.3%, 45.3%, and 39.5% respectively (P = 0.041). The overall 1-, 2-, 3-, 4-, and 5-year survival rates for the solitary tumor and multiple tumors (no more than 3 tumors) were 95.8%, 89.1%, 78.1%, 67.1%, and 56.7% and 80.0%, 60.6%, 46.6%, 33.4%, and 21.5% respectively (P = 0.001). The levels of albumin and alpha-fetoprotein, and boundary and number of tumors were proved to be independent risk factors of survival., Conclusion: RFA combined with TACE is an effective treatment for HCC with satisfactory short-term and long-term effects, especially for the patients with tumor of the size of 5.1 - 7 cm or multiple lesions.

Aim: To investigate the hepatitis B virus (HBV)x gene (HBx) state in the tissues of HBV-related hepatocellular carcinoma (HCC) in Chinese patients and whether there were particular HBx mutations., Methods: HBx gene was amplified and direct sequencing was used in genomic DNA samples from 20 HCC and corresponding non-cancerous liver tissues from HBsAg-positive patients. HBV DNA integration and HBx deleted mutation were validated in 45 HCC patients at different stages by Southern blot analysis and polymerase chain reaction methods., Results: The frequencies of HBx point mutations were significantly lower in HCC than their corresponding non-cancerous liver tissues (11/19 vs 18/19, P=0.019). In contrast, deletions in HBx gene were significantly higher in HCC than their non-cancerous liver tissues (16/19 vs 4/19, P<0.001). The deletion of HBx COOH-terminal was detected in 14 HCC tissues. A specific integration of HBx at 17p13 locus was also found in 8 of 16 HCC, and all of them also exhibited full-length HBx deletions. Integrated or integrated coexistence with replicated pattern was obtained in 45.5% (20/45)-56.8% (25/45) tumors and 40.9% (18/45)-52.3% (23/45) non-tumor tissues., Conclusion: HBx deletion, especially the COOH-terminal deletion of HBx is a frequent event in HBV-associated HCC tissues in China. HBV integration had also taken place in partial HCC tissues. This supporting the hypothesis that deletion and probably integrated forms of the HBx gene may be implicated in liver carcinogenesis.

Objectives: To analyze the differential expression genes (DEGs) among hepatocellular carcinoma (HCC), para-cancerous tissue (PCT) and normal liver tissue (NLT) and explore the target genes related to the development and progression of HCC., Methods: The total RNAs of matched HCC, PCT and NLT of HCC patients were isolated using one step Trizol method. Matched RNAs were qualified using 10 g/L agarose gel electrophoresis and lab-on-chip. cRNAs were synthesized, fluorescence labeled and purified after total RNAs were purified. The RNAs of HCC and NLT, HCC and PCT were hybridized with Agilent oligo microarray (21,074 probes). The fluorescence intensity features were detected by Agilent scanner and quantified by feature extraction software. The selected candidate genes were confirmed by SYBR Green I stained real time RT-PCR., Results: (1) The total RNA, reverse transcription product and fluorescence labeled cRNA were all of high quality; (2) There were 420 up-regulated genes and 552 down-regulated genes among 2-fold DEGs, including DKK1 (dickkopf homolog 1) which was 5-fold up-regulated; (3) The results of real time RT-PCR, using beta-actin as an internal control, showed that the 2-Delta Ct values of DKK1 in HCC, PCT and NLT were 0.089 504, 0.007,65 and 0.000,631 respectively., Conclusion: (1) The high throughput and effective Agilent oligo microarray can screen novel therapy targeted genes by analyzing the DEGs in development and progression of HCC; (2) The development and progression of HCC is a complicated process involving multigenes and multiprocedures; (3) DKK1, as a novel gene, is involved in the development and progression of HCC and may be a new therapy target.