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1.
Heliyon ; 10(10): e31412, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38831828

ABSTRACT

Background: /Aim: Chronic hepatitis B patients often develop concomitant fatty liver disease, which is associated with increased risk of liver cirrhosis and hepatocarcinoma. Our previous studies have shown that apolipoprotein H (APOH) levels are gradually decreased in patients with chronic HBV infection at different stages of disease progression, and APOH deficiency disrupted hepatic lipid metabolism and caused fatty liver. We focus on the relationship between APOH and hepatocellular carcinoma (HCC) in the context of chronic HBV infection. Methods and results: APOH was downregulated at the transcriptional level in HBV-related HCC patients from open-source human liver transcriptome databases, and relatively high expression of APOH might be a favourable prognostic marker in HCC. APOH downregulation was positively associated with tumour grade and HCC subtypes. The analysis result of CHCC-HBV database showed that APOH-associated differential expression genes (DEGs) enriched in lipid metabolic pathways and downregulated APOH correlated with macrophage, neutrophil and CD8 T cell infiltration levels. Next, in vitro experiments were performed and APOH gene was silenced in HepG2.2.15 cells, an HBV producing human HCC cells. Further transcriptomic assay and analysis revealed the DEGs were enriched in cholesterol metabolism. The subsequent RT-qPCR experiments identified that CYP7A1 expression was higher upregulated in APOH silencing HepG2.2.15 cells than vehicle control cells (p < 0.05). Finally, demographic data of patients with HBV-related HCC were enrolled, and serum APOH levels were analysed using ELISA. Serum APOH levels were significantly lower in patients with HCC than in healthy controls (p < 0.05), and positively correlated with triglyceride level in healthy controls (p < 0.05). In HBV-HCC patients, serum APOH levels were positively correlated with albumin levels and negatively correlated with alkaline phosphatase (ALP), total bilirubin, and INR levels (p < 0.05). Conclusion: APOH downregulation disrupted liver lipid metabolism to potentially affect the overall survival in patients with HBV-related HCC.

2.
J Lipid Res ; 65(1): 100483, 2024 01.
Article in English | MEDLINE | ID: mdl-38101620

ABSTRACT

Apolipoprotein H (APOH) downregulation can cause hepatic steatosis and gut microbiota dysbiosis. However, the mechanism by which APOH-regulated lipid metabolism contributes to metabolic dysfunction-associated steatotic liver disease (MASLD) remains undetermined. Herein, we aim to explore the regulatory effect of APOH, mediated through various pathways, on metabolic homeostasis and MASLD pathogenesis. We analyzed serum marker levels, liver histopathology, and cholesterol metabolism-related gene expression in global ApoH-/- C57BL/6 male mice. We used RNA sequencing and metabolomic techniques to investigate the association between liver metabolism and bacterial composition. Fifty-two differentially expressed genes were identified between ApoH-/- and WT mice. The mRNA levels of de novo lipogenesis genes were highly upregulated in ApoH-/- mice than in WT mice. Fatty acid, glycerophospholipid, sterol lipid, and triglyceride levels were elevated, while hyodeoxycholic acid levels were significantly reduced in the liver tissues of ApoH-/- mice than in those of WT mice. Microbial beta diversity was lower in ApoH-/- mice than in WT mice, and gut microbiota metabolic functions were activated in ApoH-/- mice. Moreover, ApoH transcripts were downregulated in patients with MASLD, and APOH-related differential genes were enriched in lipid metabolism. Open-source transcript-level data from human metabolic dysfunction-associated steatohepatitis livers reinforced a significant association between metabolic dysfunction-associated steatohepatitis and APOH downregulation. In conclusion, our studies demonstrated that APOH downregulation aggravates fatty liver and induces gut microbiota dysbiosis by dysregulating bile acids. Our findings offer a novel perspective on APOH-mediated lipid metabolic dysbiosis and provide a valuable framework for deciphering the role of APOH in fatty liver disease.


Subject(s)
Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Humans , Male , Mice , Animals , Lipid Metabolism/genetics , beta 2-Glycoprotein I/genetics , beta 2-Glycoprotein I/metabolism , beta 2-Glycoprotein I/pharmacology , Down-Regulation , Dysbiosis/metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , Liver/metabolism , Fatty Acids/metabolism
3.
Oncol Lett ; 16(3): 3690-3698, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30127979

ABSTRACT

The objective of the present study was to investigate the tumor-associated vascular changes in hepatocellular carcinoma (HCC) following treatment with transarterial chemoembolization (TACE) combined with sorafenib. The data of 20 patients were retrospectively analyzed. Patients underwent treatment depending on their chosen regimens (orally administered sorafenib was recommended, however the cost prevented some study articipants from selecting this course). Based on this, the patients were divided into TACE combined with sorafenib (TS) (n=10) and TACE-only treatment groups (n=10). Digital subtraction angiography images of all patients were analyzed by 2 radiologists who were blind to the type of treatment administered. The diameters of the hepatic and proper hepatic arteries, and hepatic artery branches (tumor-associated arteries), the splenic, left gastric and gastroduodenal arteries or portal veins (non-tumor-associated arteries) and the number of microvascular vessels were compared prior to and following sorafenib treatment in the TS group, between the first and second sessions of TACE in the TACE-only group and between the TS and TACE-only groups. In the TS group, the diameters of the hepatic and proper hepatic arteries, their branches and the number of microvascular vessels were significantly decreased following sorafenib treatment (P<0.05), while the diameters of the splenic, gastroduodenal and left gastric arteries were not significantly altered (P>0.05). In the TACE-only group, the diameters of the hepatic, proper hepatic, splenic, left gastric and gastroduodenal arteries were not significantly different between the first and second TACE sessions (P>0.05), while the diameters of the hepatic artery branches and the number of microvascular vessels were significantly altered (P<0.05). TACE combined with sorafenib significantly decreased the diameters of the tumor-associated arteries and the number of tumor microvascular vessels when compared with TACE treatment alone (P<0.05). No significant difference in the diameters of the portal vein and its branches between the two groups was observed (P>0.05). Treatment with TACE combined with sorafenib may significantly affect the tumor-associated vasculature compared with treatment with TACE alone in HCC.

4.
Eur J Radiol ; 89: 277-283, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27908612

ABSTRACT

PURPOSE: To evaluate the safety and efficacy of polyvinyl alcohol (PVA) terminal chemoembolization and to identify the prognostic factors associated with survival in hepatocellular carcinoma (HCC) patients with hepatic arteriovenous shunts (HAVS). MATERIALS AND METHODS: Of 133 patients' managements were retrospectively analyzed. HAVS was classified into three types: slow-flow, intermediate-flow and high-flow. The size of the PVA used was determined following the scheme: slow-flow HAVS: 300-500µm PVA; intermediate-flow HAVS: 500-710µm PVA; high-flow HAVS: 710-1000µm PVA. The HCCs with slow-flow and intermediate-flow HAVS were embolized by PVA plus chemotherapeutic agents lipiodol emulsion, while the high-flow HAVS were treated by PVA with chemotherapeutic agents. Survival curves were calculated by Kaplan-Meier method and compared by log-rank test. The influence of possible prognostic factors on survival were analyzed by multivariate Cox proportional-hazards method. RESULTS: The median overall survival (OS) of 133 patients was 9.1 months. The median OS of the slow-flow type, intermediate-flow type and high-flow type patients were 10.8, 9.1 and 7.3 months, respectively. There was no statistically significant difference among different HAVS types (P=0.239). The 30-day mortality was 3.8%. Cox multivariate survival analysis revealed that initial preoperative AFP value≥400ng/ml (HR=2.105, P=0.006) was an independent risk factor. While multiple embolization (HR=0.482, P=0.011), tumor remission (HR=0.431, P=0.041) and multimodality therapy (HR=0.416, P=0.004) were independent protection factors. CONCLUSION: It is safe and effective for HCCs with HAVS treated by terminal chemoembolization therapy with PVA plus chemotherapeutic agents lipiodol emulsion (or PVA plus chemotherapeutic agents). The HCCs with HAVS achieves good prognosis with multiple embolization, tumor remission and multimodality therapy, while achieves poor prognosis with inital preoperative high AFP value (≥400ng/ml).


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Liver Neoplasms/therapy , Polyvinyl Alcohol/administration & dosage , Adult , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Chemoembolization, Therapeutic/mortality , Ethiodized Oil/administration & dosage , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Portasystemic Shunt, Surgical/mortality , Prognosis , Retrospective Studies , Risk Factors , Treatment Outcome
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