Dataset Information

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology.

SUBMITTER: Haberl EM

PROVIDER: S-EPMC8157577 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma.

Haberl Elisabeth M EM Weiss Thomas S TS Peschel Georg G Weigand Kilian K Köhler Nikolai N Pauling Josch K JK Wenzel Jürgen J JJ Höring Marcus M Krautbauer Sabrina S Liebisch Gerhard G Buechler Christa C

International journal of molecular sciences 20210518 10

Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholest ...[more]

PMID: 34069902

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Project description:Background: The combined effect of hepatitis B virus infection and metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatocellular carcinoma (HCC) risk remains unclear. The current study sought to elucidate the impact of MASLD on HCC progression in chronic hepatitis B (CHB) patients. Method: This retrospective cohort study included CHB patients who had undergone liver biopsy and abdominal imaging at the Guangdong Provincial Hospital of Chinese Medicine between 2013 and 2019. We investigated the correlation between MASLD and HCC risk, and inverse probability treatment weighting (IPTW) was used to adjust for patient characteristics. Results: A total of 1,613 patients were included, and 483 (29.9%) were diagnosed with MASLD. Over a median follow-up period of 5.02 years, 36 (2.2%) developed HCC, comprising 4.8% (23/483) of those with MASLD and 1.2% (13/1,130) of those without. Those with MASLD had a significantly higher cumulative incidence of HCC than those without (p < 0.001). The presence of MASLD was associated with a higher risk of HCC (adjusted hazard ratio [HR], 3.996; 95% confidence interval [CI], 2.007-7.959; p < 0.001). After adjustment using IPTW, the patients with MASLD retained a higher cumulative incidence of HCC (p < 0.001). Moreover, MASLD was found to be an independent risk factor for the development of HCC (adjusted HR, 10.191; 95% CI, 4.327-24.002; p < 0.001). However, among patients with MASLD, there were no significant differences in the cumulative risk of HCC between patients with and without overweight, between those with <2 and ≥2 cardiometabolic risk factors (CMRFs), between those with <3 and ≥3 CMRFs, or between those with <4 and ≥4 CMRFs (p = 0.110, p = 0.087, p = 0.066, and p = 0.490, respectively). Conclusion: The presence of MASLD is associated with a higher risk of HCC in patients with CHB. Notably, this higher risk is present in patients with MASLD, irrespective of the presence or absence of overweight or the number of CMRFs they have.

Project description:Hepatocellular carcinoma (HCC) is a worldwide health problem. HCC patients show a 50% mortality within two years of diagnosis. To better understand the molecular pathogenesis at the level of lipid metabolism, untargeted UPLC MS-QTOF lipidomics data were acquired from resected human HCC tissues and their paired nontumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to chronic liver disease (CLD) (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The lipidomics data yielded 604 identified lipids that were divided into six super classes. Five-hundred and twenty-four blood lipids were found as significantly differentiated (p < 0.05 and qFDR p < 0.1) between the three study groups. In the blood of CLD patients compared to healthy control subjects, almost all lipid classes were significantly upregulated. In CLD patients, triacylglycerides were found as the most significantly upregulated lipid class at qFDR p = 1.3 × 10-56, followed by phosphatidylcholines at qFDR p = 3.3 × 10-51 and plasmalogens at qFDR p = 1.8 × 10-46. In contrast, almost all blood lipids were significantly downregulated in HCC patients compared to CLD patients, and in HCC tissues compared to nontumor hepatic tissues. Ceramides were found as the most significant lipid class (qFDR p = 1 × 10-14) followed by phosphatidylglycerols (qFDR p = 3 × 10-9), phosphatidylcholines and plasmalogens. Despite these major differences, there were also common trends in the transitions between healthy controls, CLD and HCC patients. In blood, several mostly saturated triacylglycerides showed a continued increase in the trajectory towards HCC, accompanied by reduced levels of saturated free fatty acids and saturated lysophospatidylcholines. In contrast, the largest overlaps of lipid alterations that were found in both HCC tissue and blood comparisons were decreased levels of phosphatidylglycerols and sphingolipids. This study highlights the specific impact of HCC tumors on the circulating lipids. Such data may be used to target lipid metabolism for prevention, early detection and treatment of HCC in the background of viral-related CLD etiology.

Dataset Information

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma.

Publications

Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma.

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